Factor Analyses and Validity of the Transplant Evaluation Rating Scale (TERS) in a Large Sample of Lung Transplant Candidates

Objective: It is well known that the occurrence of mental disorders is more common in lung transplant candidates compared to the general population. After transplantation mental disorders may negatively affect quality of life, adherence to immunosuppressive medication, as well as overall survival. Therefore, the identification of patients at risk is of utmost importance and in Germany pre-transplant psychosocial evaluation of the patients is required. To ensure high quality and comparability of these assessments, the use of psychometrically sound instruments is recommended. We applied the Transplant Evaluation Rating Scale (TERS), a broadly used expert interview. Two research groups have detected a two-factor structure of the TERS in different transplant samples; however, with slightly different results. The present study investigated which of the models would fit best in our sample of lung transplant patients. Additionally, we assessed convergent and predictive validity of the best fitting model to evaluate its clinical usefulness. Methods: Between 2016 and 2019, 390 lung transplant candidates were evaluated and included in the study. The median age was 53 years and 54% were male. TERS interviews were conducted by trained medical doctors and psychologists. The participants completed questionnaires assessing quality of life and levels of depression and anxiety. Transplant- and disease-specific variables (lung disease, listing date, oxygen use) were taken from the patient charts. Confirmatory factor analysis was used to test the two proposed TERS-models in the present sample. Results: The two-factor structure of the TERS reported by Hoodin and Kalbfleisch fit our sample best, showing good psychometric properties. The factor “emotional sensitivity” was highly correlated with quality of life and measures of psychosocial health while the factor “defiance” correlated with obstructive lung disease and older age but not with quality of life. The two factors showed differential predictive validity with regard to time until listing and pulmonary-specific quality of life 1 year after transplantation. Conclusions: The two factors showed good psychometric properties, and differential convergent and predictive validity. However, further studies concentrating on the predictive value of the TERS and its factors regarding somatic outcomes (mortality, graft functioning) are required

Stabilizing A Vascularized Autologous Matrix with Flexible Magnesium Scaffolds to Reconstruct Dysfunctional Left Ventricular Myocardium in a Large-Animal Feasibility Study

The surgical reconstruction of dysfunctional myocardium is necessary for patients with severe heart failure. Autologous biomaterials, such as vascularized patch materials, have a regenerative potential due to in vivo remodeling. However, additional temporary mechanical stabilization of the biomaterials is required to prevent aneurysms or rupture. Degradable magnesium scaffolds could prevent these life-threatening risks. A left ventricular transmural defect was reconstructed in minipigs with a piece of the autologous stomach. Geometrically adaptable and degradable scaffolds made of magnesium alloy LA63 were affixed on the epicardium to stabilize the stomach tissue. The degradation of the magnesium structures, their biocompatibility, physiological remodeling of the stomach, and the heart’s function were examined six months after the procedure via MRI (Magnetic Resonance Imaging), angiography, µ-CT, and light microscopy. All animals survived the surgery. Stable physiological integration of the stomach patch could be detected. No ruptures of the grafts occurred. The magnesium scaffolds showed good biocompatibility. Regenerative surgical approaches for treating severe heart failure are a promising therapeutic alternative to the currently available, far from optimal options. The temporary mechanical stabilization of viable, vascularized grafts facilitates their applicability in clinical scenarios

Psychometric Properties of the German Version of the Pulmonary-Specific Quality-of-Life Scale in Lung Transplant Patients

The Pulmonary-Specific Quality-of-Life Scale (PQLS) is a validated self-report questionnaire assessing health-related quality of life (HRQoL) in patients with end-stage lung disease awaiting lung transplantation. The aim of our study was to evaluate the psychometric properties of the German version of the PQLS. One hundred and forty patients awaiting lung transplantation (55% men) with a median age of 53 years [Interquartile range (IQR) 13] answered the PQLS. A group of the participants (n = 43) was evaluated again 1 year later after transplantation. A confirmatory factor analysis (CFA) of the PQLS was conducted to test the three-factor structure of the PQLS. We examined the internal consistency of the scales using Cronbach’s α. Convergent validity was explored through correlations with generic measures of HRQoL [Short-Form 8 Health Survey (SF-8), 10-item quality of life (QoL) scale], measures of depression (nine-item Patient Health Questionnaire-Depression Scale), anxiety (Generalized Anxiety Scale), and measures of lung disease severity (supplemental oxygen use, stairway steps). In the group of 43 patients assessed before and after transplantation, sensitivity to change was explored. The CFA confirmed the three-factor model with an acceptable fit. The PQLS total and the three subscale scores “task interference,” “psychological,” and “physical” showed acceptable internal consistency. The PQLS and its subscales showed a significant negative correlation with the 10-item QoL measure and the physical component score of the SF-8, whereas the mental component score of the SF-8 showed a significant negative correlation only with the PQLS subscale “psychological.” Negative correlation was found due to the opposed alignment of the PQLS compared to the 10-item QoL and the SF-8. Symptoms of depression and anxiety were significantly and positively correlated with the subscale “psychological.” Measures of lung disease severity also exhibited a significant positive correlation with the subscales “task interference” and “physical” but not “psychological.” In patients 1 year after a successful transplantation, the PQLS scores were significantly reduced by 50%. The three-factor structure of the PQLS could be replicated using CFA. The results indicate good reliability, validity, and sensitivity to change of the German version of the PQLS

Bilateral lung transplantation for pediatric pulmonary arterial hypertension: perioperative management and one-year follow-up

Background: Bilateral lung transplantation (LuTx) remains the only established treatment for children with end-stage pulmonary arterial hypertension (PAH). Although PAH is the second most common indication for LuTx, little is known about optimal perioperative management and midterm clinical outcomes. Methods: Prospective observational study on consecutive children with PAH who underwent LuTx with scheduled postoperative VA-ECMO support at Hannover Medical School from December 2013 to June 2020. Results: Twelve patients with PAH underwent LuTx (mean age 11.9 years; age range 1.9–17.8). Underlying diagnoses included idiopathic (n = 4) or heritable PAH (n = 4), PAH associated with congenital heart disease (n = 2), pulmonary veno-occlusive disease (n = 1), and pulmonary capillary hemangiomatosis (n = 1). The mean waiting time was 58.5 days (range 1–220d). Three patients were bridged to LuTx on VA-ECMO. Intraoperative VA-ECMO/cardiopulmonary bypass was applied and VA-ECMO was continued postoperatively in all patients (mean ECMO-duration 185 h; range 73–363 h; early extubation). The median postoperative ventilation time was 28 h (range 17–145 h). Echocardiographic conventional and strain analysis showed that 12 months after LuTx, all patients had normal biventricular systolic function. All PAH patients are alive 2 years after LuTx (median follow-up 53 months, range 26–104 months). Conclusion: LuTx in children with end-stage PAH resulted in excellent midterm outcomes (100% survival 2 years post-LuTx). Postoperative VA-ECMO facilitates early extubation with rapid gain of allograft function and sustained biventricular reverse-remodeling and systolic function after RV pressure unloading and LV volume loading

Matched comparison of decellularized homografts and bovine jugular vein conduits for pulmonary valve replacement in congenital heart disease

For decades, bovine jugular vein conduits (BJV) and classic cryopreserved homografts have been the two most widely used options for pulmonary valve replacement (PVR) in congenital heart disease. More recently, decellularized pulmonary homografts (DPH) have provided an alternative avenue for PVR. Matched comparison of patients who received DPH for PVR with patients who received bovine jugular vein conduits (BJV) considering patient age group, type of heart defect, and previous procedures. 319 DPH patients were matched to 319 BJV patients; the mean age of BJV patients was 15.3 (SD 9.5) years versus 19.1 (12.4) years in DPH patients (p = 0.001). The mean conduit diameter was 24.5 (3.5) mm for DPH and 20.3 (2.5) mm for BJV (p < 0.001). There was no difference in survival rates between the two groups after 10 years (97.0 vs. 98.1%, p = 0.45). The rate of freedom from endocarditis was significantly lower for BJV patients (87.1 vs. 96.5%, p = 0.006). Freedom from explantation was significantly lower for BJV at 10 years (81.7 vs. 95.5%, p = 0.001) as well as freedom from any significant degeneration at 10 years (39.6 vs. 65.4%, p < 0.001). 140 Patients, matched for age, heart defect type, prior procedures, and conduit sizes of 20–22 mm (± 2 mm), were compared separately; mean age BJV 8.7 (4.9) and DPH 9.5 (7.3) years (p = n.s.). DPH showed 20% higher freedom from explantation and degeneration in this subgroup (p = 0.232). Decellularized pulmonary homografts exhibit superior 10-year results to bovine jugular vein conduits in PVR

Donor NK and T Cells in the Periphery of Lung Transplant Recipients Contain High Frequencies of Killer Cell Immunoglobulin-Like Receptor-Positive Subsets

Introduction For end-stage lung diseases, double lung transplantation (DLTx) is the ultimate curative treatment option. However, acute and chronic rejection and chronic dysfunction are major limitations in thoracic transplantation medicine. Thus, a better understanding of the contribution of immune responses early after DLTx is urgently needed. Passenger cells, derived from donor lungs and migrating into the recipient periphery, are comprised primarily by NK and T cells. Here, we aimed at characterizing the expression of killer cell immunoglobulin-like receptors (KIR) on donor and recipient NK and T cells in recipient blood after DLTx. Furthermore, we investigated the functional status and capacity of donor vs . recipient NK cells. Methods Peripheral blood samples of 51 DLTx recipients were analyzed pre Tx and at T0, T24 and 3wk post Tx for the presence of HLA-mismatched donor NK and T cells, their KIR repertoire as well as activation status using flow cytometry. Results Within the first 3 weeks after DLTx, donor NK and T cells were detected in all patients with a peak at T0. An increase of the KIR2DL/S1-positive subset was found within the donor NK cell repertoire. Moreover, donor NK cells showed significantly higher frequencies of KIR2DL/S1-positive cells (p<0.01) 3wk post DLTx compared to recipient NK cells. This effect was also observed in donor KIR + T cells 3wk after DLTx with higher proportions of KIR2DL/S1 (p<0.05) and KIR3DL/S1 (p<0.01) positive T cells. Higher activation levels of donor NK and T cells (p<0.001) were detected compared to recipient cells via CD25 expression as well as a higher degranulation capacity upon activation by K562 target cells. Conclusion Higher frequencies of donor NK and T cells expressing KIR compared to recipient NK and T cells argue for their origin in the lung as a part of a highly specialized immunocompetent compartment. Despite KIR expression, higher activation levels of donor NK and T cells in the periphery of recipients suggest their pre-activation during the ex situ phase. Taken together, donor NK and T cells are likely to have a regulatory effect in the balance between tolerance and rejection and, hence, graft survival after DLTx

Cardiac Angiogenic Imbalance Leads to Peripartum Cardiomyopathy

Peripartum cardiomyopathy (PPCM) is an often fatal disease that affects pregnant women who are near delivery, and it occurs more frequently in women with pre-eclampsia and/or multiple gestation. The aetiology of PPCM, and why it is associated with pre-eclampsia, remain unknown. Here we show that PPCM is associated with a systemic angiogenic imbalance, accentuated by pre-eclampsia. Mice that lack cardiac PGC-$1\alpha$, a powerful regulator of angiogenesis, develop profound PPCM. Importantly, the PPCM is entirely rescued by pro-angiogenic therapies. In humans, the placenta in late gestation secretes VEGF inhibitors like soluble FLT1 (sFLT1), and this is accentuated by multiple gestation and pre-eclampsia. This anti-angiogenic environment is accompanied by subclinical cardiac dysfunction, the extent of which correlates with circulating levels of sFLT1. Exogenous sFLT1 alone caused diastolic dysfunction in wild-type mice, and profound systolic dysfunction in mice lacking cardiac PGC-$1\alpha$. Finally, plasma samples from women with PPCM contained abnormally high levels of sFLT1. These data indicate that PPCM is mainly a vascular disease, caused by excess anti-angiogenic signalling in the peripartum period. The data also explain how late pregnancy poses a threat to cardiac homeostasis, and why pre-eclampsia and multiple gestation are important risk factors for the development of PPCM

Bilateral lung transplantation for pediatric pulmonary arterial hypertension: perioperative management and one-year follow-up

BackgroundBilateral lung transplantation (LuTx) remains the only established treatment for children with end-stage pulmonary arterial hypertension (PAH). Although PAH is the second most common indication for LuTx, little is known about optimal perioperative management and midterm clinical outcomes.MethodsProspective observational study on consecutive children with PAH who underwent LuTx with scheduled postoperative VA-ECMO support at Hannover Medical School from December 2013 to June 2020.ResultsTwelve patients with PAH underwent LuTx (mean age 11.9 years; age range 1.9–17.8). Underlying diagnoses included idiopathic (n = 4) or heritable PAH (n = 4), PAH associated with congenital heart disease (n = 2), pulmonary veno-occlusive disease (n = 1), and pulmonary capillary hemangiomatosis (n = 1). The mean waiting time was 58.5 days (range 1–220d). Three patients were bridged to LuTx on VA-ECMO. Intraoperative VA-ECMO/cardiopulmonary bypass was applied and VA-ECMO was continued postoperatively in all patients (mean ECMO-duration 185 h; range 73–363 h; early extubation). The median postoperative ventilation time was 28 h (range 17–145 h). Echocardiographic conventional and strain analysis showed that 12 months after LuTx, all patients had normal biventricular systolic function. All PAH patients are alive 2 years after LuTx (median follow-up 53 months, range 26–104 months).ConclusionLuTx in children with end-stage PAH resulted in excellent midterm outcomes (100% survival 2 years post-LuTx). Postoperative VA-ECMO facilitates early extubation with rapid gain of allograft function and sustained biventricular reverse-remodeling and systolic function after RV pressure unloading and LV volume loading

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements