Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 103
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
2.
EMBO Rep ; 23(7): e54772, 2022 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-35620860

RESUMO

Research needs a balance of risk-taking in "breakthrough projects" and gradual progress. For building a sustainable knowledge base, it is indispensable to provide support for both.

3.
Xenotransplantation ; 31(1): e12841, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38864375

RESUMO

INTRODUCTION: Orthotopic cardiac xenotransplantation has seen notable improvement, leading to the first compassionate use in 2022. However, it remains challenging to define the clinical application of cardiac xenotransplantation, including the back-up strategy in case of xenograft failure. In this regard, the heterotopic thoracic technique could be an alternative to the orthotopic procedure. We present hemodynamic data of heterotopic thoracic pig-to-baboon transplantation experiments, focusing on perioperative xenograft dysfunction and xenograft overgrowth. METHODS: We used 17 genetically modified piglets as donors for heterotopic thoracic xenogeneic cardiac transplantation into captive-bred baboons. In all animals, pressure probes were implanted in the graft's left ventricle and the recipient's ascending aorta and hemodynamic data (graft pressure, aortic pressure and recipient's heart rate) were recorded continuously. RESULTS: Aortic pressures and heart rates of the recipients' hearts were postoperatively stable in all experiments. After reperfusion, three grafts presented with low left ventricular pressure indicating perioperative cardiac dysfunction (PCXD). These animals recovered from PCXD within 48 h under support of the recipient's heart and there was no difference in survival compared to the other 14 ones. After 48 h, graft pressure increased up to 200 mmHg in all 17 animals with two different time-patterns. This led to a progressive gradient between graft and aortic pressure. With increasing gradient, the grafts stopped contributing to cardiac output. Grafts showed a marked weight increase from implantation to explantation. CONCLUSION: The heterotopic thoracic cardiac xenotransplantation technique is a possible method to overcome PCXD in early clinical trials and an experimental tool to get a better understanding of PCXD. The peculiar hemodynamic situation of increasing graft pressure but missing graft's output indicates outflow tract obstruction due to cardiac overgrowth. The heterotopic thoracic technique should be successful when using current strategies of immunosuppression, organ preservation and donor pigs with smaller body and organ size.


Assuntos
Transplante de Coração , Hemodinâmica , Xenoenxertos , Papio , Transplante Heterólogo , Animais , Transplante Heterólogo/métodos , Transplante de Coração/métodos , Suínos , Hemodinâmica/fisiologia , Sobrevivência de Enxerto , Transplante Heterotópico/métodos , Animais Geneticamente Modificados , Rejeição de Enxerto , Humanos
4.
Nature ; 564(7736): 430-433, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30518863

RESUMO

Heart transplantation is the only cure for patients with terminal cardiac failure, but the supply of allogeneic donor organs falls far short of the clinical need1-3. Xenotransplantation of genetically modified pig hearts has been discussed as a potential alternative4. Genetically multi-modified pig hearts that lack galactose-α1,3-galactose epitopes (α1,3-galactosyltransferase knockout) and express a human membrane cofactor protein (CD46) and human thrombomodulin have survived for up to 945 days after heterotopic abdominal transplantation in baboons5. This model demonstrated long-term acceptance of discordant xenografts with safe immunosuppression but did not predict their life-supporting function. Despite 25 years of extensive research, the maximum survival of a baboon after heart replacement with a porcine xenograft was only 57 days and this was achieved, to our knowledge, only once6. Here we show that α1,3-galactosyltransferase-knockout pig hearts that express human CD46 and thrombomodulin require non-ischaemic preservation with continuous perfusion and control of post-transplantation growth to ensure long-term orthotopic function of the xenograft in baboons, the most stringent preclinical xenotransplantation model. Consistent life-supporting function of xenografted hearts for up to 195 days is a milestone on the way to clinical cardiac xenotransplantation7.


Assuntos
Transplante de Coração , Xenoenxertos/transplante , Papio , Suínos , Transplante Heterólogo , Animais , Anticorpos/análise , Anticorpos/sangue , Proteínas do Sistema Complemento/análise , Enzimas/sangue , Fibrina/análise , Galactosiltransferases/deficiência , Galactosiltransferases/genética , Xenoenxertos/patologia , Humanos , Fígado/enzimologia , Masculino , Proteína Cofatora de Membrana/genética , Proteína Cofatora de Membrana/metabolismo , Miocárdio/enzimologia , Necrose , Perfusão , Contagem de Plaquetas , Tempo de Protrombina , Trombomodulina/genética , Trombomodulina/metabolismo , Fatores de Tempo
5.
Thorac Cardiovasc Surg ; 72(4): 273-284, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38154473

RESUMO

This report comprises the contents of the presentations and following discussions of a workshop of the German Heart Transplant Centers in Martinsried, Germany on cardiac xenotransplantation. The production and current availability of genetically modified donor pigs, preservation techniques during organ harvesting, and immunosuppressive regimens in the recipient are described. Selection criteria for suitable patients and possible solutions to the problem of overgrowth of the xenotransplant are discussed. Obviously microbiological safety for the recipient and close contacts is essential, and ethical considerations to gain public acceptance for clinical applications are addressed. The first clinical trial will be regulated and supervised by the Paul-Ehrlich-Institute as the National Competent Authority for Germany, and the German Heart Transplant Centers agreed to cooperatively select the first patients for cardiac xenotransplantation.


Assuntos
Sobrevivência de Enxerto , Transplante de Coração , Xenoenxertos , Imunossupressores , Transplante Heterólogo , Animais , Transplante de Coração/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Resultado do Tratamento , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/imunologia , Animais Geneticamente Modificados , Fatores de Risco , Alemanha , Suínos , Seleção de Pacientes
6.
Pneumologie ; 2024 May 24.
Artigo em Alemão | MEDLINE | ID: mdl-38788761

RESUMO

The number of adults with congenital heart defects (CHD) is steadily rising and amounts to approximately 360,000 in Germany. CHD is often associated with pulmonary hypertension (PH), which may develop early in untreated CHD. Despite timely treatment of CHD, PH not infrequently persists or recurs in older age and is associated with significant morbidity and mortality.The revised European Society of Cardiology/European Respiratory Society 2022 guidelines for the diagnosis and treatment of PH represent a significant contribution to the optimized care of those affected. However, the topic of "adults with congenital heart disease" is addressed only relatively superficial in these guidelines. Therefore, in the present article, this topic is commented in detail from the perspective of congenital cardiology.

7.
Plant Biotechnol J ; 21(1): 109-121, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36121345

RESUMO

Aegilops tauschii is the diploid progenitor of the wheat D subgenome and a valuable resource for wheat breeding, yet, genetic analysis of resistance against Fusarium head blight (FHB) and the major Fusarium mycotoxin deoxynivalenol (DON) is lacking. We treated a panel of 147 Ae. tauschii accessions with either Fusarium graminearum spores or DON solution and recorded the associated disease spread or toxin-induced bleaching. A k-mer-based association mapping pipeline dissected the genetic basis of resistance and identified candidate genes. After DON infiltration nine accessions revealed severe bleaching symptoms concomitant with lower conversion rates of DON into the non-toxic DON-3-O-glucoside. We identified the gene AET5Gv20385300 on chromosome 5D encoding a uridine diphosphate (UDP)-glucosyltransferase (UGT) as the causal variant and the mutant allele resulting in a truncated protein was only found in the nine susceptible accessions. This UGT is also polymorphic in hexaploid wheat and when expressed in Saccharomyces cerevisiae only the full-length gene conferred resistance against DON. Analysing the D subgenome helped to elucidate the genetic control of FHB resistance and identified a UGT involved in DON detoxification in Ae. tauschii and hexaploid wheat. This resistance mechanism is highly conserved since the UGT is orthologous to the barley UGT HvUGT13248 indicating descent from a common ancestor of wheat and barley.


Assuntos
Aegilops , Fusarium , Triticum/genética , Triticum/metabolismo , Glucosiltransferases/genética , Difosfato de Uridina , Melhoramento Vegetal , Doenças das Plantas/genética , Resistência à Doença/genética
8.
Theor Appl Genet ; 136(4): 79, 2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-36952008

RESUMO

KEY MESSAGE: A novel genomic selection strategy offers the unique opportunity to develop qualitative race-specific resistant varieties that possess high levels of the more durable quantitative race-nonspecific resistance in their genetic background. Race-specific qualitative resistance genes (R-genes) are conferring complete resistance in many pathosystems, but are frequently overcome by new virulent pathogen races. Once the deployed R-genes are overcome, a wide variation of quantitative disease resistance (QDR) can be observed in a set of previously race-specific, i.e., completely resistant genotypes-a phenomenon known as "vertifolia effect." This race-nonspecific QDR is considered to be more durable in the long term, but provides merely a partial protection against pathogens. This simulation study aimed to detangle race-specific R-gene-mediated resistance of pending selection candidates and the QDR in their genetic background by employing different genomic selection strategies. True breeding values that reflected performance data for rust resistance in wheat were simulated, and used in a recurrent genomic selection based on several prediction models and training population designs. Using training populations that were devoid of race-specific R-genes was thereby pivotal for an efficient improvement of QDR in the long term. Marker-assisted preselection for the presence of R-genes followed by a genomic prediction for accumulating the many small to medium effect loci underlying QDR in the genetic background of race-specific resistant genotypes appeared furthermore to be a promising approach to select simultaneously for both types of resistance. The practical application of such a knowledge-driven genomic breeding strategy offers the opportunity to develop varieties with multiple layers of resistance, which have the potential to prevent intolerable crop losses under epidemic situations by displaying a high level of QDR even when race-specific R-genes have been overcome by evolving pathogen populations.


Assuntos
Basidiomycota , Resistência à Doença , Resistência à Doença/genética , Melhoramento Vegetal , Locos de Características Quantitativas , Genótipo , Genômica , Doenças das Plantas/genética
9.
Theor Appl Genet ; 136(11): 235, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37878079

RESUMO

KEY MESSAGE: NIRS of wheat grains as phenomic predictors for grain yield show inflated prediction ability and are biased toward grain protein content. Estimating the breeding value of individuals using genome-wide marker data (genomic prediction) is currently one of the most important drivers of breeding progress in major crops. Recently, phenomic technologies, including remote sensing and aerial hyperspectral imaging of plant canopies, have made it feasible to predict the breeding value of individuals in the absence of genetic marker data. This is commonly referred to as phenomic prediction. Hyperspectral measurements in the form of near-infrared spectroscopy have been used since the 1980 s to predict compositional parameters of harvest products. Moreover, in recent studies NIRS from grains was used to predict grain yield. The same studies showed that phenomic prediction can outperform genomic prediction for grain yield. The genome is static and not environment dependent, thereby limiting genomic prediction ability. Gene expression is tissue specific and differs under environmental influences, leading to a tissue- and environment-specific phenome, potentially explaining the higher predictive ability of phenomic prediction. Here, we compare genomic prediction and phenomic prediction from hyperspectral measurements of wheat grains for the prediction of a variety of traits including grain yield. We show that phenomic predictions outperform genomic prediction for some traits. However, phenomic predictions are biased toward the information present in the predictor. Future studies on this topic should investigate whether population parameters are retained in phenomic prediction as they are in genomic prediction. Furthermore, we find that unbiased phenomic prediction abilities are considerably lower than previously reported and recommend a method to circumvent this issue.


Assuntos
Fenômica , Melhoramento Vegetal , Humanos , Genômica , Fenótipo , Produtos Agrícolas , Grão Comestível , Triticum/genética
10.
Theor Appl Genet ; 136(7): 164, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37392221

RESUMO

KEY MESSAGE: A major yellow rust resistance QTL, QYr.nmbu.6A, contributed consistent adult plant resistance in field trials across Europe, China, Kenya and Mexico. Puccinia striiformis f. sp. tritici, causing wheat yellow rust (YR), is one of the most devastating biotrophic pathogens affecting global wheat yields. Owing to the recent epidemic of the PstS10 race group in Europe, yellow rust has become a reoccurring disease in Norway since 2014. As all stage resistances (ASR) (or seedling resistances) are usually easily overcome by pathogen evolution, deployment of durable adult plant resistance (APR) is crucial for yellow rust resistance breeding. In this study, we assessed a Nordic spring wheat association mapping panel (n = 301) for yellow rust field resistance in seventeen field trials from 2015 to 2021, including nine locations in six countries across four different continents. Nine consistent QTL were identified across continents by genome-wide association studies (GWAS). One robust QTL on the long arm of chromosome 6A, QYr.nmbu.6A, was consistently detected in nine out of the seventeen trials. Haplotype analysis of QYr.nmbu.6A confirmed significant QTL effects in all tested environments and the effect was also validated using an independent panel of new Norwegian breeding lines. Increased frequency of the resistant haplotype was found in new varieties and breeding lines in comparison to older varieties and landraces, implying that the resistance might have been selected for due to the recent changes in the yellow rust pathogen population in Europe.


Assuntos
Basidiomycota , Triticum , Adulto , Humanos , Triticum/genética , Estudo de Associação Genômica Ampla , Melhoramento Vegetal , Noruega , Europa (Continente)
11.
Theor Appl Genet ; 136(9): 201, 2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37639019

RESUMO

KEY MESSAGE: FHB resistance of durum wheat was improved by introgression of Fhb1 and resistance genes from emmer wheat and by selection against adverse alleles of elite durum wheat. Durum wheat is particularly susceptible to Fusarium head blight (FHB) and breeding for resistance is impeded by the low genetic variation within the elite gene pool. To extend the genetic basis for FHB resistance in durum wheat, we analyzed 603 durum wheat lines from crosses of elite durum wheat with resistance donors carrying resistance alleles derived from Triticum aestivum, T. dicoccum and T. dicoccoides. The lines were phenotyped for FHB resistance, anthesis date, and plant height in artificially inoculated disease nurseries over 5 years. A broad variation was found for all traits, while anthesis date and plant height strongly influenced FHB severities. To correct for spurious associations, we adjusted FHB scorings for temperature fluctuations during the anthesis period and included plant height as a covariate in the analysis. This resulted in the detection of seven quantitative trait loci (QTL) affecting FHB severities. The hexaploid wheat-derived Fhb1 QTL was most significant on reducing FHB severities, highlighting its successful introgression into several durum wheat backgrounds. For two QTL on chromosomes 1B and 2B, the resistance alleles originated from the T. dicoccum line Td161 and T. dicoccoides accessions Mt. Hermon#22 and Mt. Gerizim#36, respectively. The other four QTL featured unfavorable alleles derived from elite durum wheat that increased FHB severities, with a particularly negative effect on chromosome 6A that simultaneously affected plant height and anthesis date. Therefore, in addition to pyramiding resistance genes, selecting against adverse alleles present in elite durum wheat could be a promising avenue in breeding FHB-resistant durum wheat.


Assuntos
Ascomicetos , Fusarium , Locos de Características Quantitativas , Triticum/genética , Melhoramento Vegetal
12.
Clin Transplant ; 37(3): e14710, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35576323

RESUMO

Tricuspid annular plane systolic excursion (TAPSE) is important in the noninvasive echocardiographic assessment of right heart function. This retrospective observational study shows correlations of TAPSE with invasive right heart catheterization parameters after pediatric heart transplantation (HTx). The study included patients after pediatric HTx with cardiac catheterizations in 2018/2019 and measurement of TAPSE (n = 52 patients with 57 examinations; 50.9% adults, 52.6% female, median age: 18.54 years). TAPSE was compared with normal values. Stepwise, linear and multiple regression were used to show influencing variables on TAPSE. Mean TAPSE z-score was -3.48 (SD: 2.25) and 68.4% of HTx-recipients showed abnormally reduced TAPSE (z-score ←2) compared to normal values. Multiple regression (p-value <0.001; corrected R2 = 0.338) showed significant correlations of time since HTx (p-value <0.001) and mPAP (p-value: 0.008) with TAPSE z-scores. Divided into subgroups (time since HTx <10 and ≥10 years), TAPSE and mPAP correlated only ≥10 years after HTx (p-value = 0.002). This study provides data of TAPSE even ≥10 years after pediatric HTx. Most patients showed a decreased TAPSE early after HTx, which improved over time. TAPSE z-scores correlated significantly with time since HTx and mPAP, especially ≥10 years post-HTx. Therefore, TAPSE must be used carefully in the early follow-up.


Assuntos
Transplante de Coração , Hipertensão Pulmonar , Adulto , Humanos , Criança , Feminino , Adolescente , Masculino , Artéria Pulmonar , Ecocardiografia , Estudos Retrospectivos , Transplante de Coração/efeitos adversos , Função Ventricular Direita , Volume Sistólico
13.
Clin Transplant ; 37(1): e14850, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36398875

RESUMO

INTRODUCTION: Posterior reversible encephalopathy syndrome is a rare neurologic complication that can occur under immunosuppressive therapy with CNI after organ transplantation. METHODS: We retrospectively reviewed medical records of 545 patients who underwent lung transplantation between 2012 and 2019. Within this group, we identified 30 patients with neurological symptoms typical of PRES and compared the characteristics of patients who were diagnosed with PRES (n = 11) to those who were not (n = 19). RESULTS: The incidence of PRES after lung transplantation was 2%. Notably, 73% of the patients with PRES were female and the mean age was 39.2. Seizure (82% vs. 21%, p = .002) was the most common neurological presentation. The risk of developing PRES was significantly associated with age (OR = .92, p < .0001) and having cystic fibrosis (CF) (OP = 10.1, p < .0001). Creatinine level (1.9 vs. 1.1 mg/dl, p = .047) and tacrolimus trough level (19.4 vs. 16.5 ng/ml, p = .048) within 1 week prior to neurological symptoms were significantly higher in patients with PRES. CONCLUSION: Renal insufficiency and high tacrolimus levels are associated with PRES. A change of immunosuppressive drug should be done after confirmed PRES diagnosis or immediately in case of severe neurological dysfunction to improve neurological outcomes and minimize the risk of early allograft rejection.


Assuntos
Transplante de Pulmão , Síndrome da Leucoencefalopatia Posterior , Humanos , Feminino , Adulto , Masculino , Tacrolimo/efeitos adversos , Síndrome da Leucoencefalopatia Posterior/diagnóstico , Síndrome da Leucoencefalopatia Posterior/etiologia , Estudos Retrospectivos , Transplante de Pulmão/efeitos adversos , Fatores de Risco
14.
Transpl Int ; 36: 11506, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37799668

RESUMO

Prolonged mechanical ventilation (PMV) after lung transplantation poses several risks, including higher tracheostomy rates and increased in-hospital mortality. Mechanical power (MP) of artificial ventilation unifies the ventilatory variables that determine gas exchange and may be related to allograft function following transplant, affecting ventilator weaning. We retrospectively analyzed consecutive double lung transplant recipients at a national transplant center, ventilated through endotracheal tubes upon ICU admission, excluding those receiving extracorporeal support. MP and derived indexes assessed up to 36 h after transplant were correlated with invasive ventilation duration using Spearman's coefficient, and we conducted receiver operating characteristic (ROC) curve analysis to evaluate the accuracy in predicting PMV (>72 h), expressed as area under the ROC curve (AUROC). PMV occurred in 82 (35%) out of 237 cases. MP was significantly correlated with invasive ventilation duration (Spearman's ρ = 0.252 [95% CI 0.129-0.369], p < 0.01), with power density (MP normalized to lung-thorax compliance) demonstrating the strongest correlation (ρ = 0.452 [0.345-0.548], p < 0.01) and enhancing PMV prediction (AUROC 0.78 [95% CI 0.72-0.83], p < 0.01) compared to MP (AUROC 0.66 [0.60-0.72], p < 0.01). Mechanical power density may help identify patients at risk for PMV after double lung transplantation.


Assuntos
Transplante de Pulmão , Respiração Artificial , Humanos , Estudos Retrospectivos , Fatores de Tempo , Desmame do Respirador , Pulmão
15.
Oral Dis ; 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36939725

RESUMO

INTRODUCTION: Poor oral hygiene can cause infections and inflammatory diseases. Data on its impact on outcome after lung transplantation (LuTX) is scarce. Most transplant centers have individual standards regarding dental care as there is no clinical guideline. This study's objective was to assess LuTX-listed patient's dental status and determine its effect on postoperative outcome. METHODS: Two hundred patients having undergone LuTX from 2014 to 2019 were selected. Collected data comprised LuTX-indication, periodontal status, and number of carious teeth/fillings. A preoperative panoramic dental X-ray and a dentist's consultative clarification were mandatory. RESULTS: 63.5% had carious dental status, differing significantly regarding TX-indication (p < 0.001; ILD: 41.7% vs. CF: 3.1% of all patients with carious teeth). Mean age at the time of LuTX differed significantly within these groups. Neither preoperative carious dental status nor periodontitis or bone loss deteriorated post-LuTX survival significantly. No evidence was found that either resulted in a greater number of deaths related to an infectious etiology. CONCLUSION: This study shows that carious dental status, periodontitis, and bone loss do not affect post-TX survival. However, literature indicates that they can cause systemic/pulmonary infections that deteriorate post-LuTX survival. Regarding the absence of standardized guidelines regarding dental care and LuTX, we strongly recommend emphasizing research in this field.

16.
Ultraschall Med ; 44(5): 537-543, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36854384

RESUMO

PURPOSE: The aim of the study was to evaluate whether the quantification of B-lines via lung ultrasound after lung transplantation is feasible and correlates with the diagnosis of primary graft dysfunction. METHODS: Following lung transplantation, patients underwent daily lung ultrasound on postoperative days 1-3. B-lines were quantified by an ultrasound score based on the number of single and confluent B-lines per intercostal space, using a four-region protocol. The ultrasound score was correlated with the diagnosis of primary graft dysfunction. Furthermore, correlation analyses and receiver operating characteristics analyses taking into account ultrasound score, chest radiographs, and PaO2/FiO2 ratio were performed. RESULTS: A total of 32 patients (91 ultrasound measurements) were included, whereby 10 were diagnosed with primary graft dysfunction. The median B-line score was 5 [IQR: 4, 8]. There was a significant correlation between B-line score and the diagnosis of primary graft dysfunction (r = 0.59, p < 0.001). A significant correlation could also be seen between chest X-rays and primary graft dysfunction (r = 0.34, p = 0.008), but the B-line score showed superiority over chest X-rays with respect to diagnosing primary graft dysfunction in the receiver operating characteristics curves with an area under the curve value of 0.921 versus 0.708. There was a significant negative correlation between B-line score and PaO2/FiO2 ratio (r = -0.41, p < 0.001), but not between chest X-rays and PaO2/FiO2 ratio (r = -0.14, p = 0.279). CONCLUSION: The appearance of B-lines correlated well with primary graft dysfunction and outperformed chest radiographs.


Assuntos
Transplante de Pulmão , Disfunção Primária do Enxerto , Síndrome do Desconforto Respiratório , Humanos , Disfunção Primária do Enxerto/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Ultrassonografia , Transplante de Pulmão/efeitos adversos
17.
Pneumologie ; 77(11): 956-961, 2023 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-37963485

RESUMO

The number of adults with congenital heart disease (CHD) is steadily rising and amounts to approximately 360,000 in Germany. CHD is often associated with pulmonary arterial hypertension (PAH), which may develop early in untreated CHD. Despite timely treatment of CHD, PAH often persists or recurs in older age and is associated with significant morbidity and mortality.The revised European Society of Cardiology/European Respiratory Society 2022 guidelines for the diagnosis and treatment of PH represent a significant contribution to the optimized care of those affected. However, the topic of "adults with congenital heart defects" is addressed only relatively superficially in these guidelines. Therefore, this article addresses the perspective of congenital cardiology in greater depth.


Assuntos
Cardiologia , Cardiopatias Congênitas , Hipertensão Arterial Pulmonar , Adulto , Humanos , Hipertensão Arterial Pulmonar/complicações , Hipertensão Arterial Pulmonar/diagnóstico , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/terapia , Alemanha
18.
Eur Respir J ; 59(6)2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34824051

RESUMO

BACKGROUND: The published experience of lung transplantation in acute respiratory distress syndrome (ARDS) is limited. The aim of this study was to investigate the contemporary results of lung transplantation attempts in ARDS in major European centres. METHODS: We conducted a retrospective multicentre cohort study of all patients listed for lung transplantation between 2011 and 2019. We surveyed 68 centres in 22 European countries. All patients admitted to the waitlist for lung transplantation with a diagnosis of "ARDS/pneumonia" were included. Patients without extracorporeal membrane oxygenation (ECMO) or mechanical ventilation were excluded. Patients were followed until 1 October 2020 or death. Multivariable analysis for 1-year survival after listing and lung transplantation was performed. RESULTS: 55 centres (81%) with a total transplant activity of 12 438 lung transplants during the 9-year period gave feedback. 40 patients with a median age of 35 years were identified. Patients were listed for lung transplantation in 18 different centres in 10 countries. 31 patients underwent lung transplantation (0.25% of all indications) and nine patients died on the waitlist. 90% of transplanted patients were on ECMO in combination with mechanical ventilation before lung transplantation. On multivariable analysis, transplantation during 2015-2019 was independently associated with better 1-year survival after lung transplantation (OR 10.493, 95% CI 1.977-55.705; p=0.006). 16 survivors out of 23 patients with known status (70%) returned to work after lung transplantation. CONCLUSIONS: Lung transplantation in highly selected ARDS patients is feasible and outcome has improved in the modern era. The selection process remains ethically and technically challenging.


Assuntos
Oxigenação por Membrana Extracorpórea , Transplante de Pulmão , Síndrome do Desconforto Respiratório , Adulto , Estudos de Coortes , Oxigenação por Membrana Extracorpórea/métodos , Humanos , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório/terapia , Estudos Retrospectivos
19.
Theor Appl Genet ; 135(9): 3103-3115, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35896689

RESUMO

KEY MESSAGE: Association mapping and phenotypic analysis of a diversity panel of 238 bread wheat accessions highlights differences in resistance against common vs. dwarf bunt and identifies genotypes valuable for bi-parental crosses. Common bunt caused by Tilletia caries and T. laevis was successfully controlled by seed dressings with systemic fungicides for decades, but has become a renewed threat to wheat yield and quality in organic agriculture where such treatments are forbidden. As the most efficient way to address this problem is the use of resistant cultivars, this study aims to broaden the spectrum of resistance sources available for breeders by identifying resistance loci against common bunt in bread wheat accessions of the USDA National Small Grains Collection. We conducted three years of artificially inoculated field trials to assess common bunt infection levels in a diversity panel comprising 238 wheat accessions for which data on resistance against the closely related pathogen Tilletia controversa causing dwarf bunt was already available. Resistance levels against common bunt were higher compared to dwarf bunt with 99 accessions showing [Formula: see text] 1% incidence. Genome-wide association mapping identified six markers significantly associated with common bunt incidence in regions already known to confer resistance on chromosomes 1A and 1B and novel loci on 2B and 7A. Our results show that resistance against common and dwarf bunt is not necessarily controlled by the same loci but we identified twenty accessions with high resistance against both diseases. These represent valuable new resources for research and breeding programs since several bunt races have already been reported to overcome known resistance genes.


Assuntos
Basidiomycota , Fungicidas Industriais , Pão , Resistência à Doença/genética , Estudo de Associação Genômica Ampla , Melhoramento Vegetal , Doenças das Plantas/genética , Locos de Características Quantitativas , Triticum/genética , Estados Unidos , United States Department of Agriculture
20.
Theor Appl Genet ; 135(7): 2247-2263, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35597885

RESUMO

KEY MESSAGE: This study identified a significant number of QTL that are associated with FHB disease resistance in NMBU spring wheat panel by conducting genome-wide association study. Fusarium head blight (FHB) is a widely known devastating disease of wheat caused by Fusarium graminearum and other Fusarium species. FHB resistance is quantitative, highly complex and divided into several resistance types. Quantitative trait loci (QTL) that are effective against several of the resistance types give valuable contributions to resistance breeding. A spring wheat panel of 300 cultivars and breeding lines of Nordic and exotic origins was tested in artificially inoculated field trials and subjected to visual FHB assessment in the years 2013-2015, 2019 and 2020. Deoxynivalenol (DON) content was measured on harvested grain samples, and anther extrusion (AE) was assessed in separate trials. Principal component analysis based on 35 and 25 K SNP arrays revealed the existence of two subgroups, dividing the panel into European and exotic lines. We employed a genome-wide association study to detect QTL associated with FHB traits and identify marker-trait associations that consistently influenced FHB resistance. A total of thirteen QTL were identified showing consistent effects across FHB resistance traits and environments. Haplotype analysis revealed a highly significant QTL on 7A, Qfhb.nmbu.7A.2, which was further validated on an independent set of breeding lines. Breeder-friendly KASP markers were developed for this QTL that can be used in marker-assisted selection. The lines in the wheat panel harbored from zero to five resistance alleles, and allele stacking showed that resistance can be significantly increased by combining several of these resistance alleles. This information enhances breeders´ possibilities for genomic prediction and to breed cultivars with improved FHB resistance.


Assuntos
Resistência à Doença , Fusarium , Mapeamento Cromossômico , Resistência à Doença/genética , Estudo de Associação Genômica Ampla , Melhoramento Vegetal , Doenças das Plantas/genética , Triticum/genética
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa