Evaluierung einer neuen Hybrid-Technik zum Verschluss muskulärer Ventrikelseptumdefekte im chronischen Tiermodell

OBJECTIVE: Therapy for muscular ventricular septal defects beyond the moderator band, especially in neonates and infants, has always been challenging for both surgeons and cardiologists. Recently, we established a patch closure hybrid therapy for muscular ventricular septal defects. In this study, we evaluated it in a long-term porcine model. METHODS: Thirteen minipigs underwent anterolateral thoracotomy to expose the left ventricle. Muscular ventricular septal defects were created under 2- and 3-dimensional echocardiographic guidance with a 7.5-mm sharp punch instrument. Closure of the defects was undertaken with our new patch system in hybrid technique. Animals were observed for 3 months. Echocardiographic evaluation and pathologic examination, including immunohistochemical staining, were undertaken. RESULTS: Defects were successfully created in 12 pigs and closed in 10 pigs. Seven survived for 3 months. Residual shunting was noticed in 1 animal. Neither left ventricular dysfunction nor relevant damage to the valves could be detected. Pathologic examination showed complete endothelialization of the patch and the nitinol anchors without protruding parts of the system. Cellular organization was proceeding. Immunohistochemical staining demonstrated endothelial cells on the surface of the patch and fibromuscular cells around the patch. CONCLUSION: Our hybrid therapy was efficacious in closing muscular ventricular septal defects without impairment of cardiac function. The patch system and nitinol anchors demonstrated good integration into the septum. Further development of the system for human application is already being undertake

Evaluierung einer neuen Hybrid-Technik zum Verschluss muskulärer Ventrikelseptumdefekte im chronischen Tiermodell

OBJECTIVE: Therapy for muscular ventricular septal defects beyond the moderator band, especially in neonates and infants, has always been challenging for both surgeons and cardiologists. Recently, we established a patch closure hybrid therapy for muscular ventricular septal defects. In this study, we evaluated it in a long-term porcine model. METHODS: Thirteen minipigs underwent anterolateral thoracotomy to expose the left ventricle. Muscular ventricular septal defects were created under 2- and 3-dimensional echocardiographic guidance with a 7.5-mm sharp punch instrument. Closure of the defects was undertaken with our new patch system in hybrid technique. Animals were observed for 3 months. Echocardiographic evaluation and pathologic examination, including immunohistochemical staining, were undertaken. RESULTS: Defects were successfully created in 12 pigs and closed in 10 pigs. Seven survived for 3 months. Residual shunting was noticed in 1 animal. Neither left ventricular dysfunction nor relevant damage to the valves could be detected. Pathologic examination showed complete endothelialization of the patch and the nitinol anchors without protruding parts of the system. Cellular organization was proceeding. Immunohistochemical staining demonstrated endothelial cells on the surface of the patch and fibromuscular cells around the patch. CONCLUSION: Our hybrid therapy was efficacious in closing muscular ventricular septal defects without impairment of cardiac function. The patch system and nitinol anchors demonstrated good integration into the septum. Further development of the system for human application is already being undertake

Results of the Fontan operation with no early mortality in 248 consecutive patients

Background: The Fontan operation has undergone several modifications and today is the primary way to treat a broad spectrum of congenital heart defects. Aim: The purpose of this study is to present the results of treatment of children with a single ventricle operated by the same surgical team and managed according to a uniform strategy. Methods: In the years 2007-2015, in 248 children aged 3.7 +/- 2.6 years and weighing 14.6 +/- 6.1 kg with a single ventricle, Fontan surgery was performed. In 56 (22.6%) children surgery was based on the creation of an intra-atrial lateral tunnel, and in 192 (77.4%) patients extracardiac modification was performed. In most patients, the operation was carried out with the normothermic cardiopulmonary bypass, on a "beating heart" without aortic cross-clamp. The average cardiopulmonary bypass time was 53.9 +/- 23.9 min. The most common indication for surgery was hypoplastic left heart syndrome (53.6%). All patients with a single ventricle referred to our hospital for the Fontan procedure were enrolled into the surgery programme. Results: All patients survived the operation and were discharged home. Thirty-six (14.5%) patients were extubated in the operating room, in other patients the mean duration of the mechanical ventilation was 9.7 +/- 16.1 h (median 7 h). The average time of hospitalisation in the whole study group was 17.5 +/- 18.5 days (median 15 days). After surgery, in four children transient seizures occurred, and three patients had an ischaemic stroke. Conclusions: Developing and obeying a fixed perioperative protocol is crucial for low mortality and small number of complications after Fontan operation

Percutaneous pulmonary valve implantation in a dysfunctional Trifecta® bioprothesis after high‐pressure balloon fracturing

A percutaneous pulmonary valve‐in‐valve (PPVIV) implantation in small surgical tissue valves may be limited due to the valve's initial diameter. Fracturing of the valve's integrity by high‐pressure balloons may enhance the diameter and facilitate subsequent PPVIV with a large valve. To the best of our knowledge, the Trifecta® valve seemed not to be accessible for fracturing. We report a case of successful 19‐mm Trifecta valve fracturing, followed by PPVIV using a 26‐mm Edwards SAPIEN 3 valve in pulmonary position. By repetitively using a high‐pressure balloon 5 mm larger than the labeled valve size, we were able to fracture the valve's integrity and implant a 26‐mm valve thereafter. Therefore, Trifecta valve appears to be suitable for valve ring fracturing and subsequent PPVIV in certain patients

A NON-INVASIVE METHOD TO INVESTIGATE FOOT BONE KINEMATICS

The purpose of this study was to investigate whether image correlation photometry in combination with an inverse dynamics foot model is capable of investigating foot bone kinematics. Thus an explorative test setup with one participant was used to acquire the motion data with ARAMISTM (GOM, Braunschweig, Germany). The motion data enabled a customized inverse dynamics foot model to reproduce the recorded motion and simulate intrinsic movement. Navicular drop was 10.5mm and maximal motion angle did not exceed 23°. The calculated results of navicular drop, range of motion and course of angle over time are promising in comparison to studies using bone pins

Motor outcome, executive functioning, and health‐related quality of life of children, adolescents, and young adults after ventricular assist device and heart transplantation

Objective The aim of the current study is to measure long‐term executive function, motor outcome, and QoL in children, adolescents, and young adults after VAD and Htx. Methods Patients were examined during routine follow‐up. Investigation tools were used as follows: Examination for MND of motor outcomes, Epitrack® for attention and executive functioning, and Kidscreen‐52 and EQ‐5D‐5L questionnaires for QoL. Additional data were retrospectively obtained by an analysis of patient medical records. Results Out of 145 heart transplant recipients at the department of pediatric cardiology of the University Hospital Munich, 39 were implanted with a VAD between 1992 and 2016. Seventeen (43.6%) patients died before or after Htx; 22 (56.4%) patients were included in our study. Mean age at transplant was 9.52 years (range: 0.58‐24.39 years, median 9), and the mean follow‐up time after Htx was 6.18 years (range: 0.05‐14.60 years, median 5.82). MND examination could be performed in 13 patients (normal MND: n = 11, simple MND: n = 1, complex MND: n = 1). Executive functioning was tested in 15 patients. Two (13.3%) patients had good results, six (40%) average results, three (20%) borderline results, and four (26.7%) impaired results. QoL (Kidscreen n = 7, EQ‐5D‐5L n = 8) was similar to a healthy German population. Conclusion Motor outcome, executive functioning and QoL in survivors of VAD bridging therapy and Htx can be good, though underlying diseases and therapies are associated with a high risk of cerebral ischemic or hemorrhagic complications

Early outcomes of percutaneous pulmonary valve implantation using the Edwards SAPIEN XT transcatheter heart valve system

BACKGROUND: Patients with congenital or acquired heart defects affecting the pulmonary valve and right ventricular outflow tract (RVOT) commonly require multiple surgical interventions, resulting in significant morbidity. A less invasive alternative is percutaneous pulmonary valve implantation (PPVI). Though studies have previously reported the safety and efficacy of the early generation transcatheter heart valves (THVs), data on more recent devices are severely lacking. METHODS AND RESULTS: We performed a multinational, multicentre, retrospective, observational registry analysis of patients who underwent PPVI using the Edwards SAPIEN XT THV. Of the 46 patients that were enrolled, the majority had tetralogy of Fallot as the underlying diagnosis (58.7%), and stentless xenograft as the most common RVOT anatomy (34.8%). Procedural success rate was high (93.5%), with a low frequency of periprocedural complications and adverse events (6.5% and 10.9%, respectively). At 30days post-procedure, NYHA class had improved significantly (90.6% were at NYHA I or II). The rate of moderate/severe pulmonary regurgitation had decreased from 76.1% at baseline to 5.0% at 30days, and the calculated peak systolic gradient had decreased from 45.2 (SD±21.3) mmHg to 16.4 (SD±8.0) mmHg, with these values remaining low up to 2years. CONCLUSIONS: The data suggest the efficacy and safety of the SAPIEN XT THV in PPVI in common anatomies in patients with conduits, as well as those with native pulmonary valves or transannular patches. Continued data collection is necessary to verify long-term findings

Onset and progression of diabetes in kidney transplant patients receiving everolimus or cyclosporine therapy: an analysis of two randomized, multicenter trials

Background: Conversion from calcineurin inhibitor (CNI) therapy to a mammalian target of rapamycin (mTOR) inhibitor following kidney transplantation may help to preserve graft function. Data are sparse, however, concerning the impact of conversion on posttransplant diabetes mellitus (PTDM) or the progression of pre-existing diabetes. Methods: PTDM and other diabetes-related parameters were assessed post hoc in two large open-label multicenter trials. Kidney transplant recipients were randomized (i) at month 4.5 to switch to everolimus or remain on a standard cyclosporine (CsA)-based regimen (ZEUS, n = 300), or (ii) at month 3 to switch to everolimus, remain on standard CNI therapy or convert to everolimus with reduced-exposure CsA (HERAKLES, n = 497). Results: There were no significant differences in the incidence of PTDM between treatment groups (log rank p = 0.97 [ZEUS], p = 0.90 [HERAKLES]). The mean change in random blood glucose from randomization to month 12 was also similar between treatment groups in both trials for patients with or without PTDM, and with or without pre-existing diabetes. The change in eGFR from randomization to month 12 showed a benefit for everolimus versus comparator groups in all subpopulations, but only reached significance in larger subgroups (no PTDM or no pre-existing diabetes). Conclusions: Within the restrictions of this post hoc analysis, including non-standardized diagnostic criteria and limited glycemia laboratory parameters, these data do not indicate any difference in the incidence or severity of PTDM with early conversion from a CsA-based regimen to everolimus, or in the progression of pre-existing diabetes. Trial registration: clinicaltrials.gov , NCT00154310 (registered September 2005) and NCT00514514 (registered August 2007); EudraCT ( 2006-007021-32 and 2004-004346-40 )

A time-resolved proteomic and prognostic map of COVID-19

COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease