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1.
Nature ; 614(7949): 664-669, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36623549

RESUMO

Measuring the abundances of carbon and oxygen in exoplanet atmospheres is considered a crucial avenue for unlocking the formation and evolution of exoplanetary systems1,2. Access to the chemical inventory of an exoplanet requires high-precision observations, often inferred from individual molecular detections with low-resolution space-based3-5 and high-resolution ground-based6-8 facilities. Here we report the medium-resolution (R ≈ 600) transmission spectrum of an exoplanet atmosphere between 3 and 5 µm covering several absorption features for the Saturn-mass exoplanet WASP-39b (ref. 9), obtained with the Near Infrared Spectrograph (NIRSpec) G395H grating of JWST. Our observations achieve 1.46 times photon precision, providing an average transit depth uncertainty of 221 ppm per spectroscopic bin, and present minimal impacts from systematic effects. We detect significant absorption from CO2 (28.5σ) and H2O (21.5σ), and identify SO2 as the source of absorption at 4.1 µm (4.8σ). Best-fit atmospheric models range between 3 and 10 times solar metallicity, with sub-solar to solar C/O ratios. These results, including the detection of SO2, underscore the importance of characterizing the chemistry in exoplanet atmospheres and showcase NIRSpec G395H as an excellent mode for time-series observations over this critical wavelength range10.

2.
Nature ; 617(7961): 483-487, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37100917

RESUMO

Photochemistry is a fundamental process of planetary atmospheres that regulates the atmospheric composition and stability1. However, no unambiguous photochemical products have been detected in exoplanet atmospheres so far. Recent observations from the JWST Transiting Exoplanet Community Early Release Science Program2,3 found a spectral absorption feature at 4.05 µm arising from sulfur dioxide (SO2) in the atmosphere of WASP-39b. WASP-39b is a 1.27-Jupiter-radii, Saturn-mass (0.28 MJ) gas giant exoplanet orbiting a Sun-like star with an equilibrium temperature of around 1,100 K (ref. 4). The most plausible way of generating SO2 in such an atmosphere is through photochemical processes5,6. Here we show that the SO2 distribution computed by a suite of photochemical models robustly explains the 4.05-µm spectral feature identified by JWST transmission observations7 with NIRSpec PRISM (2.7σ)8 and G395H (4.5σ)9. SO2 is produced by successive oxidation of sulfur radicals freed when hydrogen sulfide (H2S) is destroyed. The sensitivity of the SO2 feature to the enrichment of the atmosphere by heavy elements (metallicity) suggests that it can be used as a tracer of atmospheric properties, with WASP-39b exhibiting an inferred metallicity of about 10× solar. We further point out that SO2 also shows observable features at ultraviolet and thermal infrared wavelengths not available from the existing observations.

3.
Anal Chem ; 95(32): 11901-11907, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37540774

RESUMO

The inability to identify the structures of most metabolites detected in environmental or biological samples limits the utility of nontargeted metabolomics. The most widely used analytical approaches combine mass spectrometry and machine learning methods to rank candidate structures contained in large chemical databases. Given the large chemical space typically searched, the use of additional orthogonal data may improve the identification rates and reliability. Here, we present results of combining experimental and computational mass and IR spectral data for high-throughput nontargeted chemical structure identification. Experimental MS/MS and gas-phase IR data for 148 test compounds were obtained from NIST. Candidate structures for each of the test compounds were obtained from PubChem (mean = 4444 candidate structures per test compound). Our workflow used CSI:FingerID to initially score and rank the candidate structures. The top 1000 ranked candidates were subsequently used for IR spectra prediction, scoring, and ranking using density functional theory (DFT-IR). Final ranking of the candidates was based on a composite score calculated as the average of the CSI:FingerID and DFT-IR rankings. This approach resulted in the correct identification of 88 of the 148 test compounds (59%). 129 of the 148 test compounds (87%) were ranked within the top 20 candidates. These identification rates are the highest yet reported when candidate structures are used from PubChem. Combining experimental and computational MS/MS and IR spectral data is a potentially powerful option for prioritizing candidates for final structure verification.


Assuntos
Bases de Dados de Compostos Químicos , Espectrometria de Massas em Tandem , Reprodutibilidade dos Testes , Metabolômica/métodos , Aprendizado de Máquina
4.
Pediatr Crit Care Med ; 24(7): 604-613, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-36892305

RESUMO

OBJECTIVES: Renal replacement therapy (RRT) options are limited for small babies because of lack of available technology. We investigated the precision of ultrafiltration, biochemical clearances, clinical efficacy, outcomes, and safety profile for a novel non-Conformité Européenne-marked hemodialysis device for babies under 8 kg, the Newcastle Infant Dialysis Ultrafiltration System (NIDUS), compared with the current options of peritoneal dialysis (PD) or continuous venovenous hemofiltration (CVVH). DESIGN: Nonblinded cluster-randomized cross-sectional stepped-wedge design with four periods, three sequences, and two clusters per sequence. SETTING: Clusters were six U.K. PICUs. PATIENTS: Babies less than 8 kg requiring RRT for fluid overload or biochemical disturbance. INTERVENTIONS: In controls, RRT was delivered by PD or CVVH, and in interventions, NIDUS was used. The primary outcome was precision of ultrafiltration compared with prescription; secondary outcomes included biochemical clearances. MEASUREMENTS AND MAIN RESULTS: At closure, 97 participants were recruited from the six PICUs (62 control and 35 intervention). The primary outcome, obtained from 62 control and 21 intervention patients, showed that ultrafiltration with NIDUS was closer to that prescribed than with control: sd controls, 18.75, intervention, 2.95 (mL/hr); adjusted ratio, 0.13; 95% CI, 0.03-0.71; p = 0.018. Creatinine clearance was smallest and least variable for PD (mean, sd ) = (0.08, 0.03) mL/min/kg, larger for NIDUS (0.46, 0.30), and largest for CVVH (1.20, 0.72). Adverse events were reported in all groups. In this critically ill population with multiple organ failure, mortality was lowest for PD and highest for CVVH, with NIDUS in between. CONCLUSIONS: NIDUS delivers accurate, controllable fluid removal and adequate clearances, indicating that it has important potential alongside other modalities for infant RRT.


Assuntos
Injúria Renal Aguda , Terapia de Substituição Renal Contínua , Hemofiltração , Diálise Peritoneal , Humanos , Lactente , Diálise Renal , Ultrafiltração , Estudos Transversais , Rim
5.
Nucleic Acids Res ; 49(D1): D1496-D1501, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33264401

RESUMO

SoyBase, a USDA genetic and genomics database, holds professionally curated soybean genetic and genomic data, which is integrated and made accessible to researchers and breeders. The site holds several reference genome assemblies, as well as genetic maps, thousands of mapped traits, expression and epigenetic data, pedigree information, and extensive variant and genotyping data sets. SoyBase displays include genetic, genomic, and epigenetic maps of the soybean genome. Gene expression data is presented in the genome viewer as heat maps and pictorial and tabular displays in gene report pages. Millions of sequence variants have been added, representing variations across various collections of cultivars. This variant data is explorable using new interactive tools to visualize the distribution of those variants across the genome, between selected accessions. SoyBase holds several reference-quality soybean genome assemblies, accessible via various query tools and browsers, including a new visualization system for exploring the soybean pan-genome. SoyBase also serves as a nexus of announcements pertinent to the greater soybean research community. The database also includes a soybean-specific anatomic and biochemical trait ontology. The database can be accessed at https://soybase.org.


Assuntos
Bases de Dados Genéticas , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Genótipo , Glycine max/genética , Proteínas de Plantas/genética , Mapeamento Cromossômico , Produtos Agrícolas , Epigênese Genética , Estudos de Associação Genética , Internet , Anotação de Sequência Molecular , Filogenia , Melhoramento Vegetal/métodos , Proteínas de Plantas/metabolismo , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Característica Quantitativa Herdável , Padrões de Referência , Software , Glycine max/classificação , Glycine max/metabolismo , Estados Unidos , United States Department of Agriculture
6.
Health Promot Int ; 38(4)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37590385

RESUMO

Arts engagement is gaining recognition as a non-clinical approach to promote mental health and well-being. However, the perceived utility of the arts to promote mental health among men with low socioeconomic status (SES) and how to best engage them is underexplored. This study explores the lived experiences of men with low SES who engage with the arts in Northern Ireland (n = 41). Data collected via focus groups (n = 5) and interviews (n = 11) were analysed using reflexive thematic analysis to inductively derive four themes. Theme 1 highlights how the arts facilitated friendship, a collective identity, peer support and a reason to socialize. Themes 2 and 3 explore how the arts enhanced self-esteem and emotional regulation by developing a routine, purpose, sense of mastery, a sense of catharsis through immersion in a soothing endeavour and an alternative outlet for self-expression. Theme 4 covers strategies that facilitate male engagement in the arts such as using a familiar space, delivering to an existing male group, framing the programme around male interests not health or creativity, building on existing strengths and capacities, enabling ownership, using tangible action-orientated activities, and being non-authoritative and flexible with delivery. This is one of the first studies to highlight the gendered dimensions in which men with low SES engage with and experience mental health benefits through arts engagement. This study points towards relevant theories to further understand the pathways between the arts and improved mental health among men which can inform development of tailored arts programmes for men.


Assuntos
Regulação Emocional , Saúde Mental , Humanos , Masculino , Saúde do Homem , Grupos Focais , Baixo Nível Socioeconômico
7.
Small ; 18(33): e2202661, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35863913

RESUMO

The family of van der Waals (vdW) materials is large and diverse with applications ranging from electronics and optoelectronics to catalysis and chemical storage. However, despite intensive research, there remains significant knowledge-gaps pertaining to their properties and interactions. One such gap is the interaction between these materials and hydrogen, a potentially vital future energy vector and ubiquitous processing gas in the semiconductor industry. This work reports on the interaction of hydrogen with the vdW semiconductor SnS2 , where molecular hydrogen (H2 ) and H-ions induce a controlled chemical conversion into semiconducting-SnS or to ß-Sn. This hydrogen-driven reaction is facilitated by the different oxidation states of Sn and is successfully applied to form SnS2 /SnS heterostructures with uniform layers, atomically flat interfaces and well-aligned crystallographic axes. This approach is scalable and offers a route for engineering materials at the nanoscale for semiconductor technologies based on the earth-abundant elements Sn and S, a promising result for a wide range of potential applications.

8.
Clin Exp Immunol ; 207(1): 123-139, 2022 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-35020854

RESUMO

LITMUS was a single-centre, Phase 2a study designed to investigate whether the gene biomarker FGL2/IFNG previously reported for the identification of tolerance in murine models could identify operationally tolerant liver transplant recipients. Multiplex RT-PCR was used to amplify eight immunoregulatory genes in peripheral blood mononuclear cells (PBMC) from 69 adult liver transplant recipients. Patients with PBMC FGL2/IFNG ≥ 1 and a normal liver biopsy underwent immunosuppression (IS) withdrawal. The primary end point was the development of operational tolerance. Secondary end points included correlation of tolerance with allograft gene expression and immune cell markers. Twenty-eight of 69 patients (38%) were positive for the PBMC tolerance biomarker and 23 proceeded to IS withdrawal. Nine of the 23 patients had abnormal baseline liver biopsies and were excluded. Of the 14 patients with normal biopsies, eight (57%) have achieved operational tolerance and are off IS (range 12-57 months). Additional studies revealed that all of the tolerant patients and only one non-tolerant patient had a liver gene ratio of FOXP3/IFNG ≥ 1 prior to IS withdrawal. Increased CD4+ T regulatory T cells were detected both in PBMC and livers of tolerant patients following IS withdrawal. Higher expression of SELE (gene for E-selectin) and lower expression of genes associated with inflammatory responses (GZMB, CIITA, UBD, LSP1, and CXCL9) were observed in the pre-withdrawal liver biopsies of tolerant patients by RNA sequencing. These results suggest that measurement of PBMC FGL2/IFNG may enrich for the identification of operationally tolerant liver transplant patients, especially when combined with intragraft measurement of FOXP3/IFNG. Clinical Trial Registration: ClinicalTrials.gov (LITMUS: NCT02541916).


Assuntos
Leucócitos Mononucleares , Transplante de Fígado , Adulto , Biomarcadores/metabolismo , Fibrinogênio , Expressão Gênica , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/genética , Humanos , Tolerância Imunológica/genética , Imunossupressores , Leucócitos Mononucleares/metabolismo , Transplante de Fígado/métodos , Tolerância ao Transplante/genética
9.
Ann Plast Surg ; 89(6): 600-609, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36416684

RESUMO

PURPOSE: The aim of this study was to understand how opioid prescribing practices of plastic surgery residents changed after instituting opioid prescribing education (OPE) interventions. METHODS: Plastic surgery residents at a single academic institution completed a survey (fall 2017) assessing opioid prescribing following 8 common procedures. The Division then completed 3 multidisciplinary OPE interventions over 2.5 years, which provided passive learning to raise awareness without top-down prescribing guidelines. Residents were resurveyed at 2 time points after the interventions (fall 2018 and spring 2020). The primary outcome measure was self-reported morphine milligram equivalents prescribed. RESULTS: Survey response rates were 84% to 100%. Preintervention opioid prescriptions were characterized by high variability and absolute doses for all procedures. We observed statistically significant decreases in prescribed doses for most procedures at 9 months post intervention and further decreases at 2.5 years. In the most recently surveyed cohort, only 3 of 16 residents (18.8%) had OPE before residency, whereas 12 of 16 residents (75.0%) participated in OPE during residency. Eighty-eight percent of respondents "always" (8/16, 50%) or "usually" (6/16, 38%) considered the opioid epidemic when prescribing opioids, suggesting an improved prescribing culture. Barriers to better prescribing included duplicate prescriptions/accessing state-run prescription drug monitoring programs (75.0%), remote prescribing (75%), providing refills (56%), and prescribing opioids for patients on chronic opioid therapy (56%). CONCLUSION: This prospective cohort study demonstrates that a simple multidisciplinary, didactic OPE intervention that aimed to increase residents' awareness has the potential to reduce self-reported opioid prescribing and sustain prescribing practices over many years. We identify persistent barriers facing our resident prescribers today, enabling more opioid educational interventions in the future.


Assuntos
Analgésicos Opioides , Cirurgia Plástica , Humanos , Autorrelato , Analgésicos Opioides/uso terapêutico , Prescrição Inadequada/prevenção & controle , Estudos Prospectivos , Padrões de Prática Médica
10.
Anal Chem ; 93(30): 10688-10696, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34288660

RESUMO

The high-throughput identification of unknown metabolites in biological samples remains challenging. Most current non-targeted metabolomics studies rely on mass spectrometry, followed by computational methods that rank thousands of candidate structures based on how closely their predicted mass spectra match the experimental mass spectrum of an unknown. We reasoned that the infrared (IR) spectra could be used in an analogous manner and could add orthologous structure discrimination; however, this has never been evaluated on large data sets. Here, we present results of a high-throughput computational method for predicting IR spectra of candidate compounds obtained from the PubChem database. Predicted spectra were ranked based on their similarity to gas-phase experimental IR spectra of test compounds obtained from the NIST. Our computational workflow (IRdentify) consists of a fast semiempirical quantum mechanical method for initial IR spectra prediction, ranking, and triaging, followed by a final IR spectra prediction and ranking using density functional theory. This approach resulted in the correct identification of 47% of 258 test compounds. On average, there were 2152 candidate structures evaluated for each test compound, giving a total of approximately 555,200 candidate structures evaluated. We discuss several variables that influenced the identification accuracy and then demonstrate the potential application of this approach in three areas: (1) combining IR and mass spectra rankings into a single composite rank score, (2) identifying the precursor and fragment ions using cryogenic ion vibrational spectroscopy, and (3) the incorporation of a trimethylsilyl derivatization step to extend the method compatibility to less-volatile compounds. Overall, our results suggest that matching computational with experimental IR spectra is a potentially powerful orthogonal option for adding significant high-throughput chemical structure discrimination when used with other non-targeted chemical structure identification methods.


Assuntos
Metabolômica , Bases de Dados Factuais , Íons , Espectrometria de Massas
11.
Clin Transplant ; 35(1): e14155, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33191549

RESUMO

BACKGROUND: Complications after liver transplantation cause additional healthcare costs. The objective of this study was to contrast the length of stay (LOS) costs for recipients with and without surgical site infections (SSIs). METHODS: This retrospective observational cohort study was conducted at a transplant center in Canada, between February 2011 and August 2014. The difference in the LOS costs was assessed by the Mann-Whitney U test, while multiple linear regression analysis was used to identify the variables that may have impacted on the costs. RESULTS: Two hundred and twenty-nine liver transplant recipients were enrolled. Thirty-six recipients developed SSIs (36/229, 15.7%). The median LOS costs in recipients with and without SSIs were $39,456 Canadian dollars (interquartile range $25,696- 59,722) and $31,084 Canadian dollars (interquartile range $22,712-49 610), respectively (p = .072). There was a trend that the costs were higher for those recipients with versus those without SSIs (p = .088). Transfusion of ≥ 5 units of red cells and dialysis before transplantation impacted on cost. CONCLUSION: There was a trend for higher healthcare facility costs for recipients with SSIs. Red cell transfusions and greater dialysis use before transplant were factors associated with the cost. Implementation of cost reduction strategies targeting high-cost recipients is necessary.


Assuntos
Transplante de Fígado , Infecção da Ferida Cirúrgica , Canadá , Custos de Cuidados de Saúde , Humanos , Tempo de Internação , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia
12.
Radiographics ; 41(4): 1022-1042, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34115535

RESUMO

Transthoracic echocardiography (TTE) is the primary initial imaging modality in cardiac imaging. Advantages include portability, safety, availability, and ability to assess the morphology and physiology of the heart in a noninvasive manner. Because of this, many patients who undergo advanced imaging with CT or MRI will have undergone prior TTE, particularly when cardiac CT angiography or cardiac MRI is performed. In the modern era, the increasing interconnectivity of picture archiving and communication systems (PACS) has made these images more available for comparison. Therefore, radiologists who interpret chest imaging studies should have a basic understanding of TTE, including its strengths and limitations, to make accurate comparisons and assist in rendering a diagnosis or avoiding a misdiagnosis. The authors present the standard TTE views along with multiplanar reformatted CT images for correlation. This is followed by examples of limitations of TTE, focusing on potential blind spots, which have been placed in seven categories on the basis of the structures involved: (a) pericardium (thickening, calcification, effusions, cysts, masses), (b) aorta (dissection, intramural hematoma, penetrating atherosclerotic ulcer), (c) left ventricular apex (infarcts, aneurysms, thrombus, apical hypertrophic cardiomyopathy), (d) cardiac valves (complications of native and prosthetic valves), (e) left atrial appendage (thrombus), (f) coronary arteries (origins, calcifications, fistulas, aneurysms), and (g) extracardiac structures (primary and metastatic masses). Online supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article . ©RSNA, 2021.


Assuntos
Cardiopatias , Trombose , Ecocardiografia , Cardiopatias/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X
13.
Crit Care ; 25(1): 226, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193243

RESUMO

BACKGROUND: Rapid response systems aim to achieve a timely response to the deteriorating patient; however, the existing literature varies on whether timing of escalation directly affects patient outcomes. Prior studies have been limited to using 'decision to admit' to critical care, or arrival in the emergency department as 'time zero', rather than the onset of physiological deterioration. The aim of this study is to establish if duration of abnormal physiology prior to critical care admission ['Score to Door' (STD) time] impacts on patient outcomes. METHODS: A retrospective cross-sectional analysis of data from pooled electronic medical records from a multi-site academic hospital was performed. All unplanned adult admissions to critical care from the ward with persistent physiological derangement [defined as sustained high National Early Warning Score (NEWS) > / = 7 that did not decrease below 5] were eligible for inclusion. The primary outcome was critical care mortality. Secondary outcomes were length of critical care admission and hospital mortality. The impact of STD time was adjusted for patient factors (demographics, sickness severity, frailty, and co-morbidity) and logistic factors (timing of high NEWS, and out of hours status) utilising logistic and linear regression models. RESULTS: Six hundred and thirty-two patients were included over the 4-year study period, 16.3% died in critical care. STD time demonstrated a small but significant association with critical care mortality [adjusted odds ratio of 1.02 (95% CI 1.0-1.04, p = 0.01)]. It was also associated with hospital mortality (adjusted OR 1.02, 95% CI 1.0-1.04, p = 0.026), and critical care length of stay. Each hour from onset of physiological derangement increased critical care length of stay by 1.2%. STD time was influenced by the initial NEWS, but not by logistic factors such as out-of-hours status, or pre-existing patient factors such as co-morbidity or frailty. CONCLUSION: In a strictly defined population of high NEWS patients, the time from onset of sustained physiological derangement to critical care admission was associated with increased critical care and hospital mortality. If corroborated in further studies, this cohort definition could be utilised alongside the 'Score to Door' concept as a clinical indicator within rapid response systems.


Assuntos
Deterioração Clínica , Administração Hospitalar/estatística & dados numéricos , Mortalidade/tendências , Tempo para o Tratamento/normas , Idoso , Estudos Transversais , Feminino , Administração Hospitalar/normas , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Análise de Regressão , Estudos Retrospectivos , Medição de Risco/métodos , Medição de Risco/normas , Medição de Risco/estatística & dados numéricos , Tempo para o Tratamento/estatística & dados numéricos
14.
Pediatr Emerg Care ; 37(12): e1259-e1264, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31990851

RESUMO

OBJECTIVES: The aim of the Emergency Triage Assessment and Treatment (ETAT) plus trauma course is to improve the quality of care provided to infants and children younger than 5 years. The curriculum was revised and shortened from 5 to 2.5 days by enhancing simulation and active learning opportunities. The aim of this study was to examine the feasibility and value of the new short-form ETAT course by assessing postcourse knowledge and satisfaction. METHODS: We delivered the short-form ETAT course to a group of interdisciplinary health workers in Malawi. Precourse and postcourse knowledge was assessed using a standardized 20 questions short answer test used previously in the 5-day courses. A 13-statement survey with 2 open-ended questions was used to examine participant satisfaction. RESULTS: Participants' postcourse knowledge improved significantly (P < 0.001) after the shorter ETAT course. Participants reported high levels of satisfaction with the short-form ETAT. CONCLUSIONS: Simulation and other active learning strategies reduced training time by 50% in the short-form ETAT course. Participants with and without previous ETAT training improved their knowledge after participating in the short-form ETAT course. Reduced training time is beneficial in settings already burdened by scarce human resources, may facilitate better access to in-service training, and build capacity while conserving resources in low-resource settings.


Assuntos
Aprendizagem Baseada em Problemas , Triagem , Criança , Competência Clínica , Currículo , Humanos , Lactente , Malaui , Projetos Piloto , Recursos Humanos
15.
Vet Anaesth Analg ; 48(3): 324-333, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33741264

RESUMO

OBJECTIVES: To compare pulmonary gas exchange, tissue oxygenation and cardiovascular effects of four levels of end-expiratory pressure: no positive end-expiratory pressure (ZEEP), positive end-expiratory pressure (PEEP) of maximal respiratory system compliance (PEEPmaxCrs), PEEPmaxCrs + 2 cmH2O (PEEPmaxCrs+2), PEEPmaxCrs + 4 cmH2O (PEEPmaxCrs+4), in isoflurane-anesthetized dogs. STUDY DESIGN: Prospective randomized crossover study. ANIMALS: A total of seven healthy male Beagle dogs, aged 1 year and weighing 10.2 ± 0.7 kg (mean ± standard deviation). METHODS: The dogs were administered acepromazine and anesthesia was induced with propofol and maintained with isoflurane. Ventilation was controlled for 4 hours with ZEEP, PEEPmaxCrs, PEEPmaxCrs+2 or PEEPmaxCrs+4. Cardiovascular, pulmonary gas exchange and tissue oxygenation data were evaluated at 5, 60, 120, 180 and 240 minutes of ventilation and compared using a mixed-model anova followed by Bonferroni test. p < 0.05 was considered significant. RESULTS: Cardiac index (CI) and mean arterial pressure (MAP) were lower in all PEEP treatments at 5 minutes when compared with ZEEP. CI persisted lower throughout the 4 hours only in PEEPmaxCrs+4 with the lowest CI at 5 minutes (2.15 ± 0.70 versus 3.45 ± 0.94 L minute-1 m-2). At 180 and 240 minutes, MAP was lower in PEEPmaxCrs+4 than in PEEPmaxCrs, with the lowest value at 180 minutes (58 ± 7 versus 67 ± 7 mmHg). Oxygen delivery index (DO2I) was lower in PEEPmaxCrs+4 than in ZEEP at 5, 60, 120 and 180 minutes. Venous admixture was not different among treatments. CONCLUSION AND CLINICAL RELEVANCE: The use of PEEP caused a transient decrease in MAP and CI in lung-healthy dogs anesthetized with isoflurane, which improved after 60 minutes of ventilation in all levels of PEEP except PEEPmaxCrs+4. A clinically significant improvement in arterial oxygenation and DO2I was not observed with PEEPmaxCrs and PEEPmaxCrs+2 in comparison with ZEEP, whereas PEEPmaxCrs+4 decreased DO2I.


Assuntos
Cães , Isoflurano , Animais , Estudos Cross-Over , Cães/fisiologia , Masculino , Respiração com Pressão Positiva/veterinária , Estudos Prospectivos , Troca Gasosa Pulmonar , Respiração Artificial/veterinária
16.
Am J Transplant ; 20(2): 504-512, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31550068

RESUMO

Usage of "large-for-size" left lateral segment (LLS) liver grafts in children with high graft to recipient weight ratio (GRWR) is controversial due to concerns about increased recipient complications. During the study period, 77 pediatric living donor liver transplantations (LDLTs) with LLS grafts were performed. We compared recipients with GRWR ≥2.5% (GR-High = 50) vs GRWR <2.5% (GR-Low = 27). Median age was higher in the GR-Low group (40 vs 8 months, P> .0001). Graft (GR-High: 98%, 98%, 98% vs GR-Low: 96%, 93%, 93%) and patient (GR-High: 98%, 98%, 98% vs GR-Low: 100%, 96%, 96%) survival at 1, 3, and 5 years was similar between groups (P = NS). Overall complications were also similar (34% vs 30%; P = .8). Hepatic artery and portal vein thrombosis following transplantation was not different (P = NS). Delayed abdominal fascia closure was more common in GR-High patients (17 vs 1; P = .002). Subgroup analysis comparing recipients with GRWR ≥4% (GR-XL = 20) to GRWR <2.5% (GRWR-Low = 27) revealed that delayed abdominal fascia closure was more common in the GR-XL group, but postoperative complications and graft and patient survival were similar. We conclude that pediatric LDLT with large-for-size LLS grafts is associated with excellent clinical outcomes. There is an increased need for delayed abdominal closure with no compromise of long-term outcomes. The use of high GRWR expands the donor pool and improves timely access to the benefits of transplantation without extra risks.


Assuntos
Doença Hepática Terminal/cirurgia , Transplante de Fígado/métodos , Fígado/anatomia & histologia , Doadores Vivos , Criança , Pré-Escolar , Doença Hepática Terminal/mortalidade , Feminino , Sobrevivência de Enxerto , Humanos , Lactente , Masculino , Tamanho do Órgão , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
17.
Liver Transpl ; 26(6): 799-810, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32189415

RESUMO

Recipients of donation after circulatory death (DCD) grafts are reportedly at higher risk of developing renal dysfunction after liver transplantation (LT). We compared the development of acute kidney injury (AKI) and chronic kidney disease (CKD) after LT in recipients of DCD versus donation after brain death (DBD) or living donor liver transplantation (LDLT) livers. Adult recipients of DBD, LDLT, and DCD between 2012 and 2016 at Toronto General Hospital were included. AKI was defined as a post-LT increase of serum creatinine (sCr) ≥26.5 µmol/L within 48 hours or a ≥50% increase from baseline, and CKD was defined as an estimated glomerular filtration rate <60 mL/minute for >3 months. A total of 681 patients (DCD, n = 57; DBD, n = 446; and LDLT, n = 178) with similar baseline comorbidities were included. Perioperative AKI (within the first 7 postoperative days) was observed more frequently in the DCD group (61%; DBD, 40%; and LDLT, 44%; P = 0.01) and was associated with significantly higher peak AST levels (P < 0.001). Additionally, patients in the DCD group had a significantly higher peak sCr (P < 0.001) and a trend toward higher rates of AKI stage 3 (DCD, 33%; DBD, 21%; LDLT, 21%; P = 0.11). The proportions of recovery from AKI (DCD, 77%; DBD, 72%; LDLT, 78%; P = 0.45) and patients developing CKD (DCD, 33%; DBD, 32%; LDLT, 32%; P = 0.99) were similar. Nevertheless, patients who received DCD or DBD LT and required perioperative renal replacement therapy showed significantly lower patient survival in multivariate analysis (hazard ratio, 7.90; 95% confidence interval, 4.51-13.83; P < 0.001). In conclusion, recipients of DCD liver grafts experience higher rates of short-term post-LT renal dysfunction compared with DBD or LDLT. Additional risk factors for the development of severe kidney injury, such as high Model for End-Stage Liver Disease score, massive transfusions, or donor age ≥60 years should be avoided.


Assuntos
Doença Hepática Terminal , Transplante de Fígado , Adulto , Morte Encefálica , Doença Hepática Terminal/cirurgia , Sobrevivência de Enxerto , Humanos , Transplante de Fígado/efeitos adversos , Doadores Vivos , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Doadores de Tecidos
18.
Vet Surg ; 49(7): 1292-1300, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32790953

RESUMO

OBJECTIVE: To determine the prevalence of subclinical bacteriuria (SBU) in dogs with cranial cruciate ligament (CCL) disease, the clinical variables and clinicopathologic data associated with SBU, and the incidence of surgical site infections (SSI) in dogs with and without SBU. STUDY DESIGN: Prospective, clinical cohort study. ANIMALS: One hundred fifty-five dogs with CCL disease. METHODS: Dogs had a urinalysis, sediment examination, and aerobic urine culture performed. Age, breed, sex, body weight, body condition score, clinical history, and physical examination findings were recorded. Dogs with SBU were not treated for bacteriuria or with postoperative antibiotics. Standard perioperative antimicrobials were provided for all dogs. Dogs that received nonsteroidal anti-inflammatory drugs were not excluded. Dogs that underwent an osteotomy were followed for at least 1 year to determine incidence of SSI. Outcomes and variables associated with SBU were assessed. RESULTS: In 155 dogs with CCL disease, the prevalence of SBU was 6.5%, and SBU occurred exclusively in female dogs (11.4%). The incidence of SSI was 22.3% (25/112). Two of six dogs with SBU and 23/106 dogs without SBU developed SSI. Organisms isolated from SSI were different from those isolated from urine. CONCLUSION: The prevalence of SBU in dogs with CCL disease was similar to that in other studies in which SBU was evaluated in various populations of dogs. CLINICAL SIGNIFICANCE: Screening for and treatment of SBU may not be beneficial prior to tibial osteotomy for CCL disease. Additional studies are required to determine whether dogs with SBU have a greater risk of SSI.


Assuntos
Infecções Bacterianas/veterinária , Bacteriúria/veterinária , Doenças do Cão/microbiologia , Infecção da Ferida Cirúrgica/veterinária , Animais , Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/patologia , Lesões do Ligamento Cruzado Anterior/veterinária , Bacteriúria/microbiologia , Bacteriúria/patologia , Estudos de Coortes , Doenças do Cão/cirurgia , Cães , Feminino , Masculino , Osteotomia/veterinária , Estudos Prospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/microbiologia , Infecção da Ferida Cirúrgica/patologia , Tíbia/cirurgia
19.
Am J Transplant ; 19(11): 2991-3005, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31012532

RESUMO

Normothermic ex situ liver perfusion (NEsLP) offers the opportunity to assess biomarkers of graft function and injury. We investigated NEsLP parameters (biomarkers and markers) for the assessment of liver viability in a porcine transplantation model. Grafts from heart-beating donors (HBD), and from donors with 30 minutes (donation after cardiac death [DCD]30'), 70 minutes (DCD70'), and 120 minutes (DCD120') of warm ischemia were studied. The HBD, DCD30', and DCD70'-groups had 100% survival. In contrast, 70% developed primary nonfunction (PNF) and died in the DCD120'-group. Hepatocellular function during NEsLP showed low lactate (≤1.1 mmol/L) in all the groups except the DCD120'-group (>2 mmol/L) at 4 hours of perfusion (P = .04). The fold-urea increase was significantly lower in the DCD120'-group (≤0.4) compared to the other groups (≥0.65) (P = .01). As for cholangiocyte function, bile/perfusate glucose ratio was significantly lower (<0.6) in all the groups except the DCD120'-group (≥0.9) after 3 hours of perfusion (<0.01). Bile/perfusate Na+ ratio was significantly higher (≥1.2) after 3 hours of perfusion in all the groups except for the DCD120'-group (≤1) (P < .01). Three hours after transplantation, the DCD120'-group had a significantly higher international normalized ratio (>5) compared to the rest of the groups (≤1.9) (P = .02). Rocuronium levels were higher at all the time-points in the animals that developed PNF during NEsLP and after transplantation. This study demonstrates that biomarkers and markers of hepatocellular and cholangiocyte function during NEsLP correlate with the degree of ischemic injury and posttransplant function.


Assuntos
Transplante de Fígado/métodos , Fígado/fisiologia , Preservação de Órgãos/métodos , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/normas , Animais , Morte , Fígado/irrigação sanguínea , Fígado/citologia , Perfusão , Suínos
20.
J Hepatol ; 71(5): 951-959, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31279899

RESUMO

BACKGROUND & AIMS: Death rates on liver transplant waiting lists range from 5%-25%. Herein, we report a unique experience with 50 anonymous individuals who volunteered to address this gap by offering to donate part of their liver to a recipient with whom they had no biological connection or prior relationship, so called anonymous live liver donation (A-LLD). METHODS: Candidates were screened to confirm excellent physical, mental, social, and financial health. Demographics and surgical outcomes were analyzed. Qualitative interviews after donation examined motivation and experiences. Validated self-reported questionnaires assessed personality traits and psychological impact. RESULTS: A total of 50 A-LLD liver transplants were performed between 2005 and 2017. Most donors had a university education, a middle-class income, and a history of prior altruism. Half were women. Median age was 38.5 years (range 20-59). Thirty-three (70%) learned about this opportunity through public or social media. Saving a life, helping others, generativity, and reciprocity for past generosity were motivators. Social, financial, healthcare, and legal support in Canada were identified as facilitators. A-LLD identified most with the personality traits of agreeableness and conscientiousness. The median hospital stay was 6 days. One donor experienced a Dindo-Clavien Grade 3 complication that completely resolved. One-year recipient survival was 91% in 22 adults and 97% in 28 children. No A-LLD reported regretting their decision. CONCLUSIONS: This is the first and only report of the characteristics, motivations and facilitators of A-LLD in a large cohort. With rigorous protocols, outcomes are excellent. A-LLD has significant potential to reduce the gap between transplant organ demand and availability. LAY SUMMARY: We report a unique experience with 50 living donors who volunteered to donate to a recipient with whom they had no biological connection or prior relationship (anonymous living donors). This report is the first to discuss motivations, strategies and facilitators that may mitigate physical, social and ethical risk factors in this patient population. With rigorous protocols, anonymous liver donation and recipient outcomes are excellent; with appropriate clinical expertise and system facilitators in place, our experience suggests that other centers may consider the procedure for its significant potential to reduce the gap between transplant organ demand and availability.


Assuntos
Anonimização de Dados , Transplante de Fígado/psicologia , Doadores Vivos/psicologia , Adolescente , Adulto , Altruísmo , Canadá , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Tempo de Internação , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Autorrelato , Transplantados , Resultado do Tratamento , Adulto Jovem
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