[Lung transplantation: current situation and developments]. / Lungentransplantation: aktueller Stand und Entwicklungen.

Lung transplantation is currently the gold standard treatment for end-stage lung diseases. Advances in the preservation of donor lungs, the surgical technique and immunosuppressive therapy have led to lung transplantation now being a routine procedure. Nevertheless, the shortage of donor organs, the acute and particularly chronic lung allograft dysfunction (CLAD) still represent major challenges even in experienced centers. Research in this area is still necessary to improve the long-term survival of lung recipients.

[Patient transport and networks for use of extracorporeal life support]. / Patiententransport und Netzwerke beim Einsatz des Extracorporeal Life Support.

New technologies and continuous further development of extracorporeal support systems have expanded the range of applications of extracorporeal life support (ECLS) in recent years. In addition to use in cardiogenic shock or resuscitation, the number of requests for the transfer of unstable patients from peripheral hospitals are increasing. Organizational challenges such as the establishment of networks and structured team training for all parties involved mean that the ECLS team is quickly available to reach the patient.

[Indications and strategies in mechanical circulatory support : Rise of the machines?] / Indikationsstellung und Therapieziele der mechanischen Kreislaufunterstützung : Vormarsch der Maschinen?

Terminal heart failure is an emerging problem with a continuously growing number of diseased patients worldwide. Because of the limited number of donor hearts, mechanical circulatory support is increasingly becoming an integral part of surgical treatment for end-stage heart failure, especially in patients deemed for destination therapy. Accurate patient selection, appropriate indication, and the optimal implantation time point guarantee a good outcome for these patients. This review article gives a systematic overview of the possible indication settings and treatment strategies for various patient groups in need of mechanical circulatory support.

Pericardial tissue for cardiovascular application: an in-vitro evaluation of established and advanced production processes.

Pericardial tissue is widely used as a biomaterial, especially for cardiovascular application. Tissue processing plays a key role in developing future scaffolds derived from biological material, yet standardized evaluation is still pending. This study presents a comprehensive assessment of different treatment protocols of bovine pericardium and compares those findings to commercially available decellularized bovine (CAB) and equine (CAE) pericardial patches. Native samples were fixed with glutaraldehyde (GA) or decellularized. These decellularized samples were subsequently either treated with GA (DEC-GA) or sterilized (DEC). Treatment effects were assessed by histological evaluation of structural and biomechanical properties. Furthermore, decellularization efficacy and accuracy of the applied sterilization protocol were evaluated. Cell seeding of processed pericardial samples with human endothelial cells constituted as biocompatibility test.GA-fixed tissue revealed structural deterioration, cytotoxicity and opposed to popular believe, GA-treatment did not lead to sterility of the samples. Biomechanical assessment revealed an increase in tensile strength of GA and a decrease of DEC and DEC-GA. DEC samples were successfully sterilized and showed good decellularization results, with a significant decrease in residual DNA. Comparative assessment revealed overall good results of CAE, yet results of CAB varied largely, e.g. decellularization efficacy or tissue thickness. Biocompatibility of DEC, CAB and CAE was confirmed by successful cell adhesion. Substantial differences of native tissue properties were observed, resulting in varying treatment efficacies. This study provides a first overview describing consequential variations among biomaterials and illustrates the necessity of multidimensional assessment and tissue quality management for biological scaffold development.

[Recommendations for extracorporeal cardiopulmonary resuscitation (eCPR) : Consensus statement of DGIIN, DGK, DGTHG, DGfK, DGNI, DGAI, DIVI and GRC]. / Empfehlungen zur extrakorporalen kardiopulmonalen Reanimation (eCPR) : Konsensuspapier der DGIIN, DGK, DGTHG, DGfK, DGNI, DGAI, DIVI und GRC.

Extracorporeal cardiopulmonary resuscitation (eCPR) may be considered as a rescue attempt for highly selected patients with refractory cardiac arrest and potentially reversible etiology. Currently there are no randomized, controlled studies on eCPR, and valid predictors of benefit and outcome which might guide the indication for eCPR are lacking. Currently selection criteria and procedures differ across hospitals and standardized algorithms are lacking. Based on expert opinion, the present consensus statement provides a proposal for a standardized treatment algorithm for eCPR.

[Recommendations for extracorporeal cardiopulmonary resuscitation (eCPR) : Consensus statement of DGIIN, DGK, DGTHG, DGfK, DGNI, DGAI, DIVI and GRC]. / Empfehlungen zur extrakorporalen kardiopulmonalen Reanimation (eCPR) : Konsensuspapier der DGIIN, DGK, DGTHG, DGfK, DGNI, DGAI, DIVI und GRC.

Extracorporeal cardiopulmonary resuscitation (eCPR) may be considered as a rescue attempt for highly selected patients with refractory cardiac arrest and potentially reversible etiology. Currently there are no randomized, controlled studies on eCPR, and valid predictors of benefit and outcome which might guide the indication for eCPR are lacking. Currently selection criteria and procedures differ across hospitals and standardized algorithms are lacking. Based on expert opinion, the present consensus statement provides a proposal for a standardized treatment algorithm for eCPR.

Ventricular assist device therapy and heart transplantation: Benefits, drawbacks, and outlook.

End-stage heart failure is associated with significant morbidity and mortality. Heart transplantation has the potential to offer a return to daily activities for critically ill patients and is the gold standard therapy. However, heart transplantations are decreasing yearly with a historic low in Germany in 2017. By striking contrast, both waiting list numbers and waiting time have increased owing to a lack of acceptable donor organs. Ventricular assist devices (VAD) represent a reasonable therapeutic alternative for patients on heart transplantation waiting lists. Patients ineligible for transplantation may undergo VAD implantation as a destination therapy. However, the necessity for life-long anticoagulation must be weighed against bleeding complications in potential VAD candidates. VAD-dependent patients also face risks of driveline infections, in addition to restricted activities of daily living owing to limited battery capacities. Given Germany's low transplantation rate, VAD implantation may serve as a middle ground. With the recent events in transplantation medicine, trust among the German population has declined. Transplant centers must ensure graft quality and ongoing care, define minimum caseload for accreditation, and implement specialty care units in heart failure. Furthermore, the legislation shift from extended consent to dissent solution has the potential to end donor organ shortage.

Tissue-engineering acellular scaffolds-The significant influence of physical and procedural decellularization factors.

The importance of decellularized medical products has significantly increased during the last years. In this paper, we evaluated the effects of selected physical and procedural decellularization (DC) factors with the aim to systematically assess their influence on DC results. 72 porcine aortic walls (AW) were divided into three groups and exposed to a DC solution for 4 h and 8 h, either continuously or in repeated cycles. The AW were rocked (90bpm), whirled (10 l/min), sonicated (120W, 45 kHz) or exposed to a combination of these treatments, followed by 10 washing cycles. Defining successful DC as removal of nuclei while keeping an intact extracellular matrix (ECM), we equalized the efficiency to the penetration depth (PD), obtained by DAPI fluorescence and H&E staining. Additionally, we performed scanning electron microscopy (SEM), Pentachrome and Picrosirius-Red staining. Results showed that significantly higher DC depths are achieved on outer compared to inner surfaces (61 ± 7%; p < 0.001). Furthermore, the PD showed a high time dependency for all samples. Compared to continuous rocking, we achieved a significant increase in the DC efficiency through cyclic treatments ( ∼ 43%), whirling ( ∼ 19%) and sonication ( ∼ 49%). The combined treatment supported these results. In all procedures, a skeletonized but intact Collagen fibrous network was obtained as confirmed by SEM analysis. In conclusion, we systematically identified essential factors to significantly enhance DC procedures. We highly recommend considering these factors in future DC protocols. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 153-162, 2018.

Effects of the Cardio First AngelTM on chest compression performance.

BACKGROUND: Survival rates of out-of-hospital cardiac arrest remain poor. Bystander cardiopulmonary resuscitation (CPR) is crucial for survival and feedback devices could improve its quality. OBJECTIVE: We investigated the quality of chest compression when using the Cardio First AngelTM (CFA) feedback device compared to standard basic life support (BLS). The analysis focused on laymen. METHODS: Laymen without (n= 43) and with (n= 96) explanation of the device, medical students (n= 128) and medical staff (n= 27) performed 60 seconds of standard versus assisted chest compression using the CFA on a resuscitation manikin. Compression frequency, depth and position were analyzed according to current guidelines. RESULTS: Laymen showed significantly better success rates regarding correct compression depth when using the CFA (23.3% vs. 55.8%, p= 0.004 and 25.0% vs. 52.1%, p< 0.001, laymen without and with explanation of the device, respectively). Medical students likewise improved (22.7% vs. 42.2%, p= 0.004). Hand positioning was 100% correct in all groups with the device. Improvement in frequency yielded by the CFA was more pronounced for probands with fears of contact (p= 0.02). The benefit of using the device did not differ significantly in laymen with or without explanation. CONCLUSIONS: Chest compression as performed by laymen was significantly improved with regard to compression depth when using the CFA for guidance and feedback. With the device, no cases of incorrect hand positioning occurred in any group.

Transient severe tricuspid regurgitation after transplantation of an extremely oversized donor heart in a child-Does size matter? A case report.

In pediatric heart transplantation, the size of the donor organ is an important criterion for organ allocation. Oversized donor hearts are often accepted with good results, but some complications in relation to a high donor-recipient ratio have been described. Our patient was transplanted for progressive heart failure in dilated cardiomyopathy. The donor-to-recipient weight ratio was 3 (donor weight 65 kg, recipient weight 22 kg). The intra-operative echocardiography before chest closure showed excellent cardiac function, no tricuspid valve regurgitation, and a normal central venous pressure. After chest closure, central venous pressure increased substantially and echocardiography revealed a severe tricuspid insufficiency. As other reasons for right ventricular dysfunction, that is, myocardial ischemia, pulmonary hypertension, and rejection, were excluded, we assumed that the insufficiency was caused by an alteration of the right ventricular geometry. After 1 week, the valve insufficiency regressed to a minimal degree. In pediatric heart transplant patients with a high donor-to-recipient weight ratio, the outlined complication may occur. If other reasons for right ventricular heart failure can be ruled out, this entity is most likely caused by an acute and transient alteration of the right ventricular geometry that may disappear over time.

Established interventions for mitral valve regurgitation. Current evidence.

Severe mitral regurgitation (MR) is a growing medical challenge in today's aging population, leading to increased health expenditure due to the resultant morbidity and mortality. Surgery, either replacement or repair, has been the mainstay of therapy for primary MR. In high-risk or inoperable patients, treatment was limited to medical therapy until 2008. Since then, alternative percutaneous therapies have been introduced and have proven to be safe and effective in patients with secondary MR. Edge-to-edge repair with the MitraClip system is applied worldwide for primary and secondary MR. Randomized data do not support its application in low-risk patients with primary MR. Results from ongoing and future randomized trials will clarify its impact on important clinical endpoints in high-risk and inoperable patients. The Carillon device is a percutaneous indirect annuloplasty technique introduced in 2009 for secondary MR. Clinical data for the novel Cardioband system, using a different intra-atrial annuloplasty technique, have been gathered from more than 40 patients and the system recently received CE mark approval. Other percutaneous repair devices and implantable valves are under development and may be introduced into clinical practice soon. The percutaneous interventional therapy of MR is a highly dynamic field of cardiovascular medicine and has the potential to improve quality of life as well as morbidity and mortality in selected patients.

A single German center experience with intermittent inotropes for patients on the high-urgent heart transplant waiting list.

AIM: Currently, more than 900 patients with end-stage heart failure are listed for heart transplantation in Germany. All patients on the Eurotransplant high-urgent status (HU) have to be treated in intensive care units and have to be relisted every 8 weeks. Long-term continuous inotropes are associated with tachyphylaxia, arrhythmias and even increased mortality. In this retrospective analysis, we report our single center experience with HU patients treated with intermittent inotropes as a bridging therapy. METHODS AND RESULTS: 117 consecutive adult HU candidates were treated at our intensive care heart failure unit between 2008 and 2013, of whom 14 patients (12 %) were stabilized and delisted during follow-up. In the remaining 103 patients (age 42 ± 15 years), different inotropes (dobutamine, milrinone, adrenaline, noradrenaline, levosimendan) were administered based on the patient's specific characteristics. After initial recompensation, patients were weaned from inotropes as soon as possible. Thereafter, intermittent inotropes (over 3-4 days) were given as a predefined weekly (until 2011) or 8 weekly regimen (from 2011 to 2013). In 57 % of these patients, additional regimen-independent inotropic support was necessary due to hemodynamic instabilities. Fourteen patients (14 %) needed a left- or biventricular assist device; 14 patients (14 %) died while waiting and 87 (84 %) received heart transplants after 87 ± 91 days. Cumulative 3 and 12 months survival of all 103 patients was 75 and 67 %, respectively. CONCLUSION: Intermittent inotropes in HU patients are an adequate strategy as a bridge to transplant; the necessity for assist devices was low. These data provide the basis for a prospective multicenter trial of intermittent inotropes in patients on the HU waiting list.

Association between students' personality traits and hand hygiene compliance during objective standardized clinical examinations.

BACKGROUND: Although the need for hand hygiene (HH) is generally accepted, studies continue to document inadequate compliance. Medical students are taught about the importance of HH to prevent nosocomial infections, and receive training in the correct procedures for HH. However, personality traits (social orientation and achievement orientation) may influence HH compliance. People with high social orientation feel socially responsible and act cooperatively, and people with high achievement orientation are ambitious and competitive. AIM: To evaluate the relationship between HH compliance and personality traits of medical students. METHODS: The HH compliance of 155 students was observed during objective standardized clinical examinations (OSCEs). Social orientation and achievement orientation were measured using the corresponding scales of the Freiburg Personality Inventory - Revised. FINDINGS: Social orientation did not differ between students with high HH compliance and students with low HH compliance [F(1) = 3.87, P = 0.052, η(2) = 0.045]. For achievement orientation, a moderate effect was found between low and high HH compliance [F(1) = 11.242, P = 0.001, η(2) = 0.119], and students with high HH compliance were found to be more achievement orientated than students with low HH compliance. CONCLUSION: Achievement orientation plays a major role during OSCEs, while social orientation is less emphasized. To the authors' knowledge, this is the first study to show that HH compliance is associated with achievement orientation in achievement situations.

[Acute jaw-thoracic pain and syncope in a 41-year-old man]. / Akuter Kiefer-Thorax-Schmerz und Synkope bei einem 41-jährigen Patienten.

A 41-year-old physically active man with no significant past medical history presented with sudden thoracic pain. The patient was referred to the next tertiary care hospital. A CT scan showed an ectasia of the ascending aorta with irregularities of the aortic wall without dissection. Despite initial refusal, the patient was referred to a university hospital with experience in aortic surgery. A triphase ECG-synchronized cardiothoracic flash protocol performed on a 256 line CT scanner confirmed an aortic intramural hematoma and a covered aortic perforation. Shortly afterwards the patient collapsed and had to be resuscitated.

Introduction of the lung allocation score in Germany.

The aim of this study was to assess performance of the new lung allocation system in Germany based on lung allocation score (LAS). Retrospective analysis of waitlist (WL) outflow, lung transplantation (LTx) activity and 3-month outcomes comparing 1-year pre- and post-LAS introduction on December 10, 2011 was performed. Following LAS introduction, WL registrations remained constant, while WL mortality fell by 23% (p = 0.04). Reductions in WL mortality occurred in patients with cystic fibrosis (CF; -52%), emphysema (chronic obstructive pulmonary disease [COPD]; -49%) and pulmonary hypertension (PH; -67%), but not idiopathic pulmonary fibrosis (IPF; +48%). LTx activity increased by 9% (p = 0.146). Compared to pre-LAS, more patients with IPF (32% vs. 29%) and CF (20% vs. 18%) underwent transplantation and comparatively fewer with COPD (30% vs. 39%). Median LAS among transplant recipients was highest in PH (53) and IPF (49) and lowest in COPD (34). Transplantation under invasive respiratory support increased to 13% (in CF 28%, +85%, p = 0.017). Three-month survival remained unchanged (pre: 96.1% and post: 94.9%, p = 0.94). Following LAS implementation in Germany, reductions in waiting list size and WL mortality were observed. Composition of transplant recipients changed, with fewer COPD and more IPF recipients. Transplantation under invasive respiratory support increased. Reductions in WL mortality were most pronounced among CF and PH patients.

[Interventional Mitral valve repair with the MitraClip® procedure. Patient selection criteria]. / Interventionelle Mitralklappenrekonstruktion mit dem MitraClip®-Verfahren. Patientenauswahlkriterien.

In current practice the MitraClip® procedure is increasingly being used for patients unsuitable or at high risk for cardiac surgery. This article initially describes the patient groups that are suitable for percutaneous edge-to-edge repair. For this purpose the echocardiographic criteria for severe mitral regurgitation are first characterized and treatment algorithms for patients with primary as well as secondary mitral regurgitation according to current guidelines are illustrated. Basic anatomical requirements for the successful implantation of a MitraClip® are described and a distinction is made between various valve morphologies ranging from optimal to unsuitable anatomical conditions. Finally, three patient groups eligible for percutaneous edge-to-edge repair considering clinical and anatomical criteria are defined: (1) optimal for MitraClip®, (2) MitraClip® could be considered and (3) MitraClip® only in exceptional cases.

Expression and function of the Transforming Growth Factor-b system in the human and rat enteric nervous system.

BACKGROUND: Transforming growth factor-betas (TGF-bs) are pleiotropic growth factors exerting neurotrophic functions upon various neuronal populations of the central nervous system. In contrast, the role of TGF-b isoforms in the enteric nervous system (ENS) is largely unknown. We therefore analyzed the gene expression pattern of the TGF-b system in the human colon and in rat myenteric plexus, and smooth muscle cell cultures and determined the effect of TGF-b isoforms on neuronal differentiation. METHODS: Human colonic samples as well as cultured rat myenteric plexus, and smooth muscle cells were assessed for mRNA expression levels of the TGF-b system (TGF-b1-3, TbR-1-3) by qPCR. The colonic wall was separated into mucosa and tunica muscularis and enteric ganglia were isolated by laser microdissection (LMD) to allow site-specific gene expression analysis. Effects of TGF-b isoforms on neurite outgrowth and branching pattern of cultured myenteric neurons were monitored. KEY RESULTS: mRNA expression of the TGF-b system was detected in all compartments of the human colonic wall as well as in LMD-isolated myenteric ganglia. Cultured myenteric neurons and smooth muscle cells of rat intestine also showed mRNA expression of all ligands and receptors. Transforming growth factor-b2 treatment increased neurite length and branching pattern in cultured myenteric neurons. CONCLUSIONS & INFERENCES: The TGF-b system is abundantly expressed in the human and rat ENS arguing for an auto-/paracrine function of this system on enteric neurons. Transforming growth factor-b2 promotes neuronal differentiation and plasticity characterizing this molecule as a relevant neurotrophic factor for the ENS.

Time course of haemostatic effects of fibrinogen concentrate administration in aortic surgery.

BACKGROUND: There is currently a contrast between the demonstrated benefits of fibrinogen concentrate in correcting bleeding and reducing transfusion, and its perceived thrombogenic potential. This analysis evaluates the effects of fibrinogen concentrate on coagulation up to 12 days after administration during aortic surgery. METHODS: We performed a post hoc analysis of a prospective, randomized, double-blind, controlled trial of fibrinogen concentrate as first-line haemostatic therapy in aortic surgery. After cardiopulmonary bypass (CPB) and protamine administration, subjects with coagulopathic bleeding received fibrinogen concentrate or placebo. The placebo group received allogeneic blood products, including fresh-frozen plasma (FFP; n=32); the fibrinogen concentrate group received fibrinogen concentrate alone (FC; n=14), or fibrinogen concentrate followed by allogeneic blood products (FC+FFP; n=15). Plasma fibrinogen, fibrin-based clotting (ROTEM(®)-based FIBTEM assay), and peri- and postoperative haematological and coagulation parameters were compared. RESULTS: Plasma fibrinogen and FIBTEM maximum clot firmness (MCF) decreased ∼50% during CPB but were corrected by FC or FC+FFP. At last suture, the highest values for plasma fibrinogen (360 mg dl(-1)) and FIBTEM MCF (22 mm) were within normal ranges--below the acute phase increases observed after surgery. In patients receiving only FFP as a source of fibrinogen, these parameters recovered marginally by last suture (P<0.001 vs FC and FC+FFP). All groups displayed comparable haemostasis at 24 h post-surgery. Fibrinogen concentrate did not cause alterations of other haemostasis parameters. CONCLUSIONS: Fibrinogen concentrate provided specific, significant, short-lived increases in plasma fibrinogen and fibrin-based clot firmness after aortic surgery.