Hypothermic oxygenated perfusion of the donor heart in heart transplantation: the short-term outcome from a randomised, controlled, open-label, multicentre clinical trial.

BACKGROUND: Static cold storage (SCS) remains the gold standard for preserving donor hearts before transplantation but is associated with ischaemia, anaerobic metabolism, and organ injuries, leading to patient morbidity and mortality. We aimed to evaluate whether continuous, hypothermic oxygenated machine perfusion (HOPE) of the donor heart is safe and superior compared with SCS. METHODS: We performed a multinational, multicentre, randomised, controlled, open-label clinical trial with a superiority design at 15 transplant centres across eight European countries. Adult candidates for heart transplantation were eligible and randomly assigned in a 1:1 ratio. Donor inclusion criteria were age 18-70 years with no previous sternotomy and donation after brain death. In the treatment group, the preservation protocol involved the use of a portable machine perfusion system ensuring HOPE of the resting donor heart. The donor hearts in the control group underwent ischaemic SCS according to standard practices. The primary outcome was time to first event of a composite of either cardiac-related death, moderate or severe primary graft dysfunction (PGD) of the left ventricle, PGD of the right ventricle, acute cellular rejection at least grade 2R, or graft failure (with use of mechanical circulatory support or re-transplantation) within 30 days after transplantation. We included all patients who were randomly assigned, fulfilled inclusion and exclusion criteria, and received a transplant in the primary analysis and all patients who were randomly assigned and received a transplant in the safety analyses. This trial was registered with ClicalTrials.gov (NCT03991923) and is ongoing. FINDINGS: A total of 229 patients were enrolled between Nov 25, 2020, and May 19, 2023. The primary analysis population included 204 patients who received a transplant. There were no patients who received a transplant lost to follow-up. All 100 donor hearts preserved with HOPE were transplantable after perfusion. The primary endpoint was registered in 19 (19%) of 101 patients in the HOPE group and 31 (30%) of 103 patients in the SCS group, corresponding to a risk reduction of 44% (hazard ratio 0·56; 95% CI 0·32-0·99; log-rank test p=0·059). PGD was the primary outcome event in 11 (11%) patients in the HOPE group and 29 (28%) in the SCS group (risk ratio 0·39; 95% CI 0·20-0·73). In the HOPE group, 63 (65%) patients had a reported serious adverse event (158 events) versus 87 (70%; 222 events) in the SCS group. Major adverse cardiac transplant events were reported in 18 (18%) and 33 (32%) patients in the HOPE and SCS group (risk ratio 0·56; 95% CI 0·34-0·92). INTERPRETATION: Although there was not a significant difference in the primary endpoint, the 44% risk reduction associated with HOPE was suggested to be a clinically meaningful benefit. Post-transplant complications, measured as major adverse cardiac transplant events, were reduced. Analysis of secondary outcomes suggested that HOPE was beneficial in reducing primary graft dysfunction. HOPE in donor heart preservation addresses the existing challenges associated with graft preservation and the increasing complexity of donors and heart transplantation recipients. Future investigation will help to further elucidate the benefit of HOPE. FUNDING: XVIVO Perfusion.

Author Correction: Consistent success in life-supporting porcine cardiac xenotransplantation.

In this Letter, Mayuko Kurome and Valeri Zakhartchenko have been added to the author list (affiliated with Institute of Molecular Animal Breeding and Biotechnology, Gene Center, LMU Munich, Munich, Germany). The author list and 'Author contributions' section have been corrected online; see accompanying Amendment.

The breakthrough paradox: How focusing on one form of innovation jeopardizes the advancement of science: How focusing on one form of innovation jeopardizes the advancement of science.

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.

Hemodynamics in pig-to-baboon heterotopic thoracic cardiac xenotransplantation: Recovery from perioperative cardiac xenograft dysfunction and impairment by cardiac overgrowth.

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.

An Approach to Controlling Inflammation and Coagulation in Pig-to-Baboon Cardiac Xenotransplantation.

INTRODUCTION: Inflammatory responses and coagulation disorders are a relevant challenge for successful cardiac xenotransplantation on its way to the clinic. To cope with this, an effective and clinically practicable anti-inflammatory and anti-coagulatory regimen is needed. The inflammatory and coagulatory response can be reduced by genetic engineering of the organ-source pigs. Furthermore, there are several therapeutic strategies to prevent or reduce inflammatory responses and coagulation disorders following xenotransplantation. However, it is still unclear, which combination of drugs should be used in the clinical setting. To elucidate this, we present data from pig-to-baboon orthotopic cardiac xenotransplantation experiments using a combination of several anti-inflammatory drugs. METHODS: Genetically modified piglets (GGTA1-KO, hCD46/hTBM transgenic) were used for orthotopic cardiac xenotransplantation into captive-bred baboons (n = 14). All animals received an anti-inflammatory drug therapy including a C1 esterase inhibitor, an IL-6 receptor antagonist, a TNF-α inhibitor, and an IL-1 receptor antagonist. As an additive medication, acetylsalicylic acid and unfractionated heparin were administered. The immunosuppressive regimen was based on CD40/CD40L co-stimulation blockade. During the experiments, leukocyte counts, levels of C-reactive protein (CRP) as well as systemic cytokine and chemokine levels and coagulation parameters were assessed at multiple timepoints. Four animals were excluded from further data analyses due to porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV) infections (n = 2) or technical failures (n = 2). RESULTS: Leukocyte counts showed a relevant perioperative decrease, CRP levels an increase. In the postoperative period, leukocyte counts remained consistently within normal ranges, CRP levels showed three further peaks after about 35, 50, and 80 postoperative days. Analyses of cytokines and chemokines revealed different patterns. Some cytokines, like IL-8, increased about 2-fold in the perioperative period, but then decreased to levels comparable to the preoperative values or even lower. Other cytokines, such as IL-12/IL-23, decreased in the perioperative period and stayed at these levels. Besides perioperative decreases, there were no relevant alterations observed in coagulation parameters. In summary, all parameters showed an unremarkable course with regard to inflammatory responses and coagulation disorders following cardiac xenotransplantation and thus showed the effectiveness of our approach. CONCLUSION: Our preclinical experience with the anti-inflammatory drug therapy proved that controlling of inflammation and coagulation disorders in xenotransplantation is possible and well-practicable under the condition that transmission of pathogens, especially of PCMV/PRV to the recipient is prevented because PCMV/PRV also induces inflammation and coagulation disorders. Our anti-inflammatory regimen should also be applicable and effective in the clinical setting of cardiac xenotransplantation.

High-Risk HLA-DQ Mismatches Are Associated With Adverse Outcomes After Lung Transplantation.

Human leukocyte antigen (HLA) mismatches (MM) between donor and recipient lead to eplet MM (epMM) in lung transplantation (LTX), which can induce the development of de-novo donor-specific HLA-antibodies (dnDSA), particularly HLA-DQ-dnDSA. Aim of our study was to identify risk factors for HLA-DQ-dnDSA development. We included all patients undergoing LTX between 2012 and 2020. All recipients/donors were typed for HLA 11-loci. Development of dnDSA was monitored 1-year post-LTX. EpMM were calculated using HLAMatchmaker. Differences in proportions and means were compared using Chi2-test and Students' t-test. We used Kaplan-Meier curves with LogRank test and multivariate Cox regression to compare acute cellular rejection (ACR), chronic lung allograft dysfunction (CLAD) and survival. Out of 183 patients, 22.9% patients developed HLA-DQ-dnDSA. HLA-DQ-homozygous patients were more likely to develop HLA-DQ-dnDSA than HLA-DQ-heterozygous patients (p = 0.03). Patients homozygous for HLA-DQ1 appeared to have a higher risk of developing HLA-DQ-dnDSA if they received a donor with HLA-DQB1*03:01. Several DQ-eplets were significantly associated with HLA-DQ-dnDSA development. In the multivariate analysis HLA-DQ-dnDSA was significantly associated with ACR (p = 0.03) and CLAD (p = 0.01). HLA-DQ-homozygosity, several high-risk DQ combinations and high-risk epMM result in a higher risk for HLA-DQ-dnDSA development which negatively impact clinical outcomes. Implementation in clinical practice could improve immunological compatibility and graft outcomes.

Consistent success in life-supporting porcine cardiac xenotransplantation.

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.

Current Status of Cardiac Xenotransplantation: Report of a Workshop of the German Heart Transplant Centers, Martinsried, March 3, 2023.

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.

[Pulmonary hypertension in adults with congenital heart disease in light of the 2022-ESC-PAH guidelines - Part II: Supportive therapy, special situations (pregnancy, contraception, non-cardiac surgery), targeted pharmacotherapy, organ transplantation, special management (shunt lesions, left ventricular disorders, univentricular hearts), interventions, intensive care, follow-up, future perspectives]. / Pulmonale Hypertonie bei Erwachsenen mit angeborenen Herzfehlern im Lichte der 2022-ESC-PAH-Leitlinien.

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.

Identification of a UDP-glucosyltransferase conferring deoxynivalenol resistance in Aegilops tauschii and wheat.

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.

Toward combining qualitative race-specific and quantitative race-nonspecific disease resistance by genomic selection.

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.

Predictor bias in genomic and phenomic selection.

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.

A major yellow rust resistance QTL on chromosome 6A shows increased frequency in recent Norwegian spring wheat cultivars and breeding lines.

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.

Pyramiding Fusarium head blight resistance QTL from T. aestivum, T. dicoccum and T. dicoccoides in durum wheat.

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.

Tricuspid Annular Plane Systolic Excursion (TAPSE) correlates with mean pulmonary artery pressure especially 10 years after pediatric heart transplantation.

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.

Posterior reversible encephalopathy syndrome after lung transplantation: Risk factors and management.

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.

Mechanical Power Density Predicts Prolonged Ventilation Following Double Lung Transplantation.

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.

Influence of dental status on outcome after lung transplantation.

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.

Lung Ultrasound as a Promising Diagnostic Tool for Primary Graft Dysfunction after Lung Transplantation.

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.

[Pulmonary arterial hypertension in congenital heart disease - Part I]. / Pulmonale arterielle Hypertonie bei Erwachsenen mit angeborenen Herzfehlern ­ Teil I.

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.