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OBJECTIVES Venoarterial extracorporeal life support (ECLS) has emerged as a potentially life-saving treatment option in therapy-refractory cardiocirculatory failure, but longer-term outcome is poorly defined. Here, we present a comprehensive follow-up analysis covering all major organ systems. METHODS From February 2012 to December 2016, 180 patients were treated with ECLS for therapy-refractory cardiogenic shock or cardiac arrest. The 30-day survival was 43.9%, and 30-day survivors (n = 79) underwent follow-up analysis with the assessment of medium-term survival, quality of life, neuropsychological, cardiopulmonary and end-organ status. RESULTS After a median of 1.9 (1.1–3.6) years (182.4 patient years), 45 of the 79 patients (57.0%) were alive, 35.4% had died and 7.6% were lost to follow-up. Follow-up survival estimates were 78.0% at 1, 61.2% at 3 and 55.1% at 5 years. NYHA class at follow-up was ≤II for 83.3%. The median creatinine was 1.1 (1.0–1.4) mg/dl, and the median bilirubin was 0.8 (0.5–1.0) mg/dl. No patient required dialysis. Overall, 94.4% were free from moderate or severe disability, although 11.1% needed care. Full re-integration into social life was reported by 58.3%, and 39.4% were working. Quality of life was favourable for mental components, but a subset showed deficits in physical aspects. While age was the only peri-implantation parameter significantly predicting medium-term survival, adverse events and functional status at discharge or 30 days were strong predictors. CONCLUSIONS This study demonstrates positive medium-term outcome with high rates of independence in daily life and self-care but a subset of 10–20% suffered from sustained impairments. Our results indicate that peri-implantation parameters lack predictive power but downstream morbidity and functional status at discharge or 30 days can help identify patients at risk for poor recovery.

Treatment with extracorporeal life support (ECLS) in acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) fell short of improving myocardial recovery measured by 30 day ejection fraction in the ECLS-SHOCK trial. However, to date, no data regarding impact of ECLS on long-term outcomes exist. In this randomized, controlled, prospective, open-label trial, 42 patients with CS complicating AMI were randomly assigned to ECLS (ECLS group, n = 21) or no ECLS (control group, n = 21). The primary endpoint was left ventricular ejection fraction (LVEF) after 30 days. Secondary endpoints included mortality and neurological outcome after 12 months. Evaluation of neurological outcome used the modified Rankin Scale. The 12-month all-cause mortality was 19% in the ECLS group versus 38% in the control group (p = 0.31). Only one patient (control group) died after the initial 30 days. Three patients underwent elective percutaneous coronary intervention (PCI) during follow-up (one in the control and two in the ECLS group). Favorable neurological outcome (modified Rankin Score ≤ 2) was seen in 61.9% of patients in the ECLS group versus 57.1% in the control group (p = 1). This pilot study showed that randomized studies with ECLS in CS patients are feasible and safe. Small numbers of included patients impede meaningful conclusions about mortality and neurological outcome. Our findings of numerical differences in mortality and survival with severe neurological impairment give an urgent call for larger multi-centric randomized trials assessing the endpoint of all-cause mortality but also considering the effects on neurological outcome measures.

Background Acute chest syndrome (ACS) is a leading cause of morbidity and mortality among children with sickle cell disease (SCD). Preventing hypoxemia by optimizing lung aeration during sleep remains a challenge. Objectives To explore safety, feasibility, and tolerability of noninvasive, bi-level positive airway pressure ventilation (BiPAP) as preventative, supportive care for hospitalized, medically stable children with SCD on a general pediatric inpatient unit. Methods Retrospective chart review of patients ≤22 years of age with SCD admitted to the general pediatric inpatient unit from February 1, 2017 to March 1, 2020 for whom BiPAP was recommended as supportive care. Hospitalizations were excluded if patients were admitted to the pediatric intensive care unit (PICU), required BiPAP for respiratory failure, or used BiPAP at home for obstructive sleep apnea. Results Twenty-three patients had 53 hospitalizations in which BiPAP was recommended. Fifty-two (98%) hospitalizations included acute SCD pain. Indications for BiPAP included prior ACS (94%), chest or back pain (79%), and/or oxygen desaturation (66%). On 17 occasions, patients already had mild to moderate ACS but were stable when BiPAP was recommended. BiPAP was used successfully during 75% of hospitalizations for a median of two nights. There were no adverse effects associated with BiPAP. PICU transfer for respiratory support occurred during three hospitalizations. In 26 hospitalizations of children at risk for ACS who tolerated BiPAP, 23 (88%) did not develop ACS. Conclusions BiPAP is safe, feasible, and well tolerated as supportive care for hospitalized children with SCD. Next steps include an intervention trial to further assess the efficacy of BiPAP on ACS prevention.

Controversy exists regarding the threshold of recipient twin polyhydramnios required to diagnose twin-twin transfusion syndrome at a gestational age of ≥20 weeks. One criterion set (Quintero staging) requires the amniotic fluid maximum vertical pocket for the recipient twin to measure ≥8 cm, whereas another (European) system uses a maximum vertical pocket for the recipient twin of ≥10 cm.This study aimed to characterize the patients with twin-twin transfusion syndrome who were treated with laser surgery and would be excluded from laser surgery according to the European criteria.A total of 366 monochorionic diamniotic twins diagnosed with twin-twin transfusion syndrome from 20 to 26 weeks' gestation who underwent laser surgery at our center were studied. A maximum vertical pocket for the recipient twin of ≥8 cm was used to diagnose twin-twin transfusion syndrome. Patients were retrospectively divided into the following 2 groups: group A with a maximum vertical pocket for the recipient twin of ≥8 cm and10 cm and group B with a maximum vertical pocket for the recipient twin of ≥10 cm. The association of each of the groups with the survivorship outcomes was tested. Bivariate associations between the patient characteristics and the 30-day donor twin and dual survivorship outcomes were evaluated. Tests used in the analysis were chi-square or Fisher exact tests as appropriate for categorical variables and Kruskal-Wallis tests for continuous variables. Multiple logistic regression models for each of the survivorship outcomes were then assessed. The results are reported as mean±standard deviation.Of the 366 studied patients, 53 (14.5%) had a maximum vertical pocket for the recipient twin of ≥8 and10 cm (group A) and 313 (85.5%) had a maximum vertical pocket for the recipient twin of ≥10 cm (group B). Groups A and B did not differ in the Quintero stage. Notably, 60.4% (32 of 53) of group A patients were stage III or IV. When compared with group B, group A was diagnosed with twin-twin transfusion syndrome at an earlier gestational age (21.7±1.6 vs 22.3±1.6 weeks; P=.0037) and had a higher prevalence of donor growth restriction (81.1% [43 of 53] vs 65.5% [205 of 313]; P=.0260). Rates of at least 1 twin and dual twin survival between group A and B were similar (98.1% [52 of 53] vs 95.8% [300 of 313]; P=.7023, and 79.2% [42 of 53] vs 83.4% [261 of 313]; P=.4369, respectively). Logistic regression models adjusted for perioperative characteristics showed no difference in the outcomes between the groups (group B as reference) (donor twin survival odds ratio, 0.64; 95% confidence interval, 0.29-1.42; P=.2753; and dual survivor odds ratio, 0.90; 95% confidence interval, 0.42-1.91; P=.7757).Restriction of the definition of twin-twin transfusion syndrome to a maximum vertical pocket for the recipient of ≥10 cm beyond 20 weeks gestational age would potentially exclude 14.5% of patients from laser surgery, the majority of whom had advanced stage twin-twin transfusion syndrome. A unifying criterion of a maximum vertical pocket for the recipient of ≥8 cm regardless of gestational age would allow inclusion of these patients and access to surgical management.

Despite multimodal treatment of patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI), the outcome remains poor. Large retrospective analyses and animal models suggest that extracorporeal life support (ECLS) in CS-complicating AMI improves outcome [(1)][1]. However, to

OBJECTIVE This study was meant to analyse the centre experience of the Munich Lung Transplant Group in lung transplantation of patients with severe pulmonary hypertension. Outcome data focus on survival and right heart remodelling. METHODS All patients receiving a lung transplant between 10/2010 and 08/2016 were retrospectively analysed (n = 343). Patients were categorised into individuals with or without severe pre-operative pulmonary hypertension (PH; mPAP ≥ 35 mm Hg or mPAP ≥ 25 mm Hg with cardiac index

Background Surgical treatment of constrictive pericarditis (CP) is particularly challenging because of the increased risk of right heart failure. The necessity of postoperative extracorporeal life support (ECLS) can result in mortality rates of 100%. Preemptive implantation of ECLS may improve postoperative outcomes; however, no data are currently available on its use. We conducted a retrospective study to evaluate the feasibility of our strategy. Methods Between September 2012 and June 2016, ECLS was established percutaneously through the groin vessels in 12 individually selected patients with high-risk CP immediately before pericardiectomy in the operating theater as part of the surgical strategy. Prolonged weaning was performed in the intensive care unit. Demographic characteristics, perioperative data, and survival were analyzed. Results The median patient age was 61.5 years (first quartile, third quartile: 51.3, 68.5 years), with a preoperative central venous pressure of 24 mm Hg (first quartile, third quartile: 21, 28 mm Hg). Furthermore, the pulmonary artery pressure was greater than 60 mm Hg in 50% of patients and a dip plateau sign existed in 75% before surgery. The median duration of ECLS therapy was 132 hours (first quartile, third quartile: 96, 168 hours) with a length of stay on the intensive care unit of 10 days (first quartile, third quartile: 7.0, 16.8 days). There was no intraoperative death. The cumulative 30-day, 1-year, and 5-year survival rates were 83% ± 11%, 75% ± 13%, and 75% ± 13%, respectively. Conclusions From our real-world data, preemptive use of perioperative ECLS, assigned by individual team decision in selected patients with severe CP, is a feasible and safe strategy.

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.

Objectives Diagnosis of prosthetic graft infection after cardiac and proximal aortic surgery is a challenge. Besides technical considerations, redo surgery is associated with substantial morbidity and mortality. Therefore, an accurate diagnosis is mandatory. We report on our experience with hybrid 18-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET)/computed tomography (CT) imaging, which is increasingly used to diagnose infections in the detection of graft infection after cardiac surgery. Methods Twenty-six patients who underwent (18)F-FDG PET/CT imaging after cardiac surgery between February 2010 and September 2014 for suspected graft infection were retrospectively analysed (81% male, age 54.3 ± 13.7 years). PET/CT imaging was performed 36.5 ± 70.5 (0.5-300) months after surgery. 2 patients (8%) had undergone aortic valve replacement (concomitant ascending and proximal arch replacement in 1), 1 (4%) aortic root reconstruction, 9 (35%) aortic root replacement (concomitant partial arch in 4, arch replacement and postoperative TEVAR in 1), 2 (8%) ascending aortic and partial arch replacement and 2 (8%) ascending aortic replacement along with frozen elephant trunk. In 10 (38%), more than one previous cardiac surgical procedure had been performed. Maximum standardized uptake values (SUVmax) were obtained for all patients. If the patients were reoperated on, the final diagnosis was derived from intraoperative findings and/or microbiological results. Otherwise, the longest clinical follow-up available served as a reference. Results Conventional CT was positive for infection in 13 cases (50%). In 22 (85%), PET was indicative of infection (SUVmax 10.5 ± 4.1). PET did not only confirm true-positive CT results in all but 1 case; in almost 30%, it provided substantial additional diagnostic information in comparison with CT alone. Receiver operating characteristic analysis identified an SUVmax of 7.25 to achieve maximum sensitivity (89%) and specificity (100%) in prediction of infection. Twelve patients (46%) required redo surgery for graft infection; in 1 additional patient (4%), sternal re-fixation was necessary. Furthermore, 2 patients had to be reoperated on for torn-out anastomosis and paraprosthetic perfusion (8%). Conclusions PET provides functional data, confirms a CT diagnosis and may even increase diagnostic sensitivity in comparison with CT alone in selected cases. Specificity can be compromised by postoperative changes or chronic inflammatory reactions induced by the graft. CT and/or echocardiography should remain the first diagnostic step in case of a suspected infection because of their broad and fast availability. If confirmation is needed or diagnosis is not achievable using conventional methods, PET might be chosen as the next modality to gain additional information in experienced centres.

No guidelines for mechanical circulatory support in patients with therapy-refractory cardiogenic shock and multiorgan failure including ongoing cardiopulmonary resuscitation (CPR) exist. To achieve immediate cardiopulmonary stabilization, we established an interdisciplinary concept with on-site percutaneous extracorporeal life support (ECLS) implantation. From February 2012 to November 2014, 96 patients were deemed eligible for ECLS implantation. Establishing ECLS was successful in 87 patients (mean age 54 +/- 13 years, 16% female, initial flow 4.4 +/- 0.9 l/min). Aetiologies included acute coronary syndromes (n = 52, 60%), cardiomyopathies (n = 25, 29%) and other pathologies. Fifty-nine patients (68%) had been resuscitated, and in 27 (31%), implantation was performed during CPR;11 patients (13%) were awake at implantation and 20 (23%) underwent implantation in the referring hospital. Metabolic parameters differed in non-survivors versus survivors before ECLS implantation (pH 7.15 +/- 0.23 vs. 7.27 +/- 0.18, P = 0.007;lactate levels 10.90 +/- 6.00 mmol/l vs. 8.79 +/- 5.78 mmol/l, P = 0.091) and 6 h postimplantation (pH 7.27 +/- 0.11 vs. 7.37 +/- 0.11, P < 0.001;lactate levels 10.19 +/- 5.52 mmol/l vs. 5.52 +/- 4.17 mmol/l, P < 0.001). Altogether 44 patients could be weaned, and 9 were bridged to assist device implantation and 1 to heart transplantation. The mean time of support was 6 days, and the 30-day survival rate was 47% (n = 41). ECLS serves as a bridge-to-decision and bridge-to-treatment device. Our interdisciplinary ECLS programme achieved acceptable survival of critically ill patients despite a substantial percentage of patients having been resuscitated and no absolute exclusion criteria. Further studies defining inclusion- and exclusion criteria might additionally improve outcome.

A significant subset of Veterans residing in in VA Community Living Centers (CLCs) demonstrate challenging dementia-related behaviors that affect their quality of life, stress the caregiving staff, and interfere with successful placement in the community. The Behavioral Recovery Outreach (BRO) team was created at the VA Central Iowa Healthcare System to: (1) treat challenging dementia-related behaviors while Veterans reside in the CLC, and (2) ensure successful placements post-discharge. This team, comprised of a psychologist, nurse, social worker, and recreational therapist, facilitates successful placements by communicating effective behavior plans at discharge, providing on-site visits at 1, 3, 6, and 12 months post-discharge, and providing as-needed consultation. The team, working with 66 Veterans to date, has demonstrated 89% success in community placements. The BRO team implementation process and outcomes will be discussed.

The reattachment of the supra-aortic vessels during hybrid arch repair using a branched prosthesis is time consuming and sometimes technically challenging. Here, we describe the surgical technique of bridging the end-to-end anastomoses between the graft branches and the supra-aortic vessels by self-expanding covered stents to reduce suturing time, avoid anastomotic bleeding, enhance true lumen remodeling, and improve vessel alignment to the hybrid graft.

Objective Extracorporeal life support (ECLS) emerges as a salvage option in therapy refractory cardiogenic shock but is limited to highly specialized tertiary care centers. Critically ill patients are often too unstable for conventional transport. Mobile ECLS programs for remote implantation and subsequent air or ground-based transport for patient retrieval could solve this dilemma and make full-spectrum advanced cardiac care available to patients in remote hospitals in whom shock otherwise might be fatal. Methods From December 2012 to March 2016, 40 patients underwent venoarterial ECLS implantation in remote hospitals with subsequent transport to our center and were retrospectively analyzed. The mobile ECLS team was available 24/7, implantation was performed percutaneously bedside, and compact support systems designed for transport were used. Results Twenty percent of the patients were female; the mean age was 55 ± 10 years, and the mean Interagency Registry for Mechanically Assisted Circulatory Support score was 1.3 ± 0.5. Patient retrieval was accomplished via ground-based (n = 29, 72.5%, mean distance = 27.9 ± 29.7 km [range, 5.6-107.1 km]) or air (n = 11, mean distance = 62.4 ± 27.2 km [range, 38.9-116.4 km]) transport. No ECLS-related complications occurred during transport. The ECLS system could be explanted in 65.0% (n = 26) of patients, and the 30-day survival rate was 52.5% (n = 21). Conclusion Remote ECLS implantation and interfacility transport on ECLS are feasible and effective. Interdisciplinary teams and full-spectrum cardiac care are essential to achieve optimal outcomes. Rapid-response ECLS networks have the potential to substantially increase the survival of cardiogenic shock patients.

Objectives Different revascularization strategies for patients with acute myocardial infarction (AMI) exist. It remains unclear whether ventricular unloading using cardiopulmonary bypass (CPB) or extracorporeal life support (ECLS) has an impact on early postischaemic ventricular function. Here, we report on the results of an approach using a miniaturized CPB in a well-established animal model of AMI. Methods In a randomized fashion, 30 male Wistar rats were assigned to temporary left anterior descending (LAD) ligation (30 min) followed by 180 min of reperfusion either with or without 60 min of CPB (70 ml/min, 36°C). The CPB circuit consisted of a venous reservoir, a peristaltic roller pump and a membrane oxygenator with heat exchanger. Cardiac function was measured at 60 and 120 min after reperfusion (F60, F120) using a conductance catheter. Results The mortality rate was 37% (11/30). Thus, 19 animals could be included into the analysis (8 CPB). The mean cardiac output did not differ between the groups at F60 [63 ± 29 vs 54 ± 25 ml/min (CPB), P = 0.56] and F120 [73 ± 27 vs 53 ± 24 ml/min (CPB), P = 0.21]. During reperfusion, the mean left ventricular ejection fraction (LVEF) was stable in both the control (F60 37 ± 5% vs F120 33 ± 8%, P = 0.42) and the CPB groups (F60 52 ± 11% vs F120 51 ± 13%, P = 0.71). CPB animals had a significantly better LVEF after reperfusion (F60 P = 0.007, F120 P = 0.01). Conclusions In this animal model of AMI, the establishment of CPB resulted in a significantly better LVEF in comparison with conventional reperfusion only. This beneficial effect may have an impact on revascularization strategies and timing in patients presenting with AMI in the future.

OBJECTIVES: Therapy refractory cardiogenic shock is associated with dismal outcome. Percutaneous implantation of an extracorporeal life support (ECLS) system achieves immediate cardiopulmonary stabilization, sufficient end-organ perfusion and reduction of subsequent multiorgan failure (MOF). METHODS: Forty-one patients undergoing percutaneous ECLS implantation for cardiogenic shock from February 2012 until August 2013 were retrospectively analysed. Mean age was 52 ± 13 years, 6 (15%) were female. Mean pH values obtained before ECLS implantation were 7.15 ± 0.24, mean lactate concentration was 11.7 ± 6.4 mmol/l. Levels obtained 6 h after ECLS implantation were 7.30 ± 0.14 and 8.7 ± 5.0 mmol/l, respectively. In 23 patients (56%) cardiogenic shock resulted from an acute coronary syndrome in 13 (32%) from cardiomyopathy, in 5 (12%) from other causes. Twenty-seven (66%) had been resuscitated, in 14 (34%) implantation was performed under ongoing cardiopulmonary resuscitation (CPR). Of note, 97% of the acute coronary syndrome patients underwent percutaneous coronary intervention (PCI) either before ECLS implantation or under ECLS support. Extracorporeal life support implantation was performed on scene (Emergency Department, Cath Lab, Intensive Care Unit) by a senior cardiac surgeon and a trained perfusionist, in 8 cases (20%) in the referring hospital. RESULTS: Thirty-day mortality was 51% [21 patients, due to MOF (n= 14), cerebral complications (n= 6) and heart failure (n= 1)]. Logistic regression analysis identified 6-h pH values as an independent risk factor of 30-day mortality (P< 0.001, OR = 0.000, 95% CI 0.000–0.042). Neither CPR nor implantation under ongoing CPR resulted in significant differences. In 26 cases (63%), the ECLS system could be explanted, after mean support of 169 ± 67 h. Seven of these patients received cardiac surgery [ventricular assist device implantation (n= 4), heart transplantation (n= 1), other procedures (n= 2)]. CONCLUSIONS: Due to the evolution of transportable ECLS systems and percutaneous techniques implantation on scene is feasible. Extracorporeal life support may serve as a bridge-to-decision and bridge-to-treatment device. Neurological evaluation before ventricular assist device implantation and PCI under stable conditions are possible. Despite substantial mortality, ECLS implantation in selected patients by an experienced team offers additional support to conventional therapy as well as CPR and allows survival in patients that otherwise most likely would have died. This concept has to be implemented in cardiac survival networks in the future.

Testicular germ cell tumours (GCTs) of adolescents and adults can be subdivided into seminomas (referred to as dysgerminomas of the ovary) and non-seminomas, all referred to as type II GCTs. They originate from carcinoma in situ (CIS), being the malignant counterparts of primordial germ cells (PGCs)/gonocytes. The invasive components mimic embryogenesis, including the stem cell component embryonal carcinoma (EC), the somatic lineage teratoma (TE), and the extra-embryonic tissues yolk sac tumour (YST) and choriocarcinoma (CH). The other type is the so-called spermatocytic seminomas (SS, type III GCT), composed of neoplastic primary spermatocytes. We reported previously that the miRNAs hsa-miR 371-373 cluster is involved in overruling cellular senescence induced by oncogenic stress, allowing cells to become malignant. Here we report the first high-throughput screen of 156 microRNAs in a series of type II and III GCTs (n = 69, in duplicate) using a quantitative PCR-based approach. After normalization to allow inter-sample analysis, the technical replicates clustered together, and the previous hsa-miRNA 371-373 cluster finding was confirmed. Unsupervised cluster analysis demonstrated that the cell lines are different from the in vivo samples. The in vivo samples, both normal and malignant, clustered predominantly based on their maturation status. This parallels normal embryogenesis, rather than chromosomal anomalies in the tumours. miRNAs within a single cluster showed a similar expression pattern, implying common regulatory mechanisms. Normal testicular tissue expressed most discriminating miRNAs at a higher level than SE and SS. Moreover, differentiated non-seminomas showed overexpression of discriminating miRNAs. These results support the model that miRNAs are involved in regulating differentiation of stem cells, retained in GCTs.

Background: Myocardial ischemia due to concomitant coronary artery disease (CAD) or coronary dissection in patients with acute aortic dissection type Stanford A (AADA) is associated with myocardial failure and poor outcomes. Preoperative coronary angiography in this group of patients is still debated. The use of CT scan to diagnose coronary affection along with the establishment of high-pitched dual-spiral CT protocols are essential for improving outcomes.Methods: We retrospectively analyzed six AADA patients with heart failure who were treated using extracorporeal life support (ECLS). Options for diagnosing coronary affection and different therapeutic strategies for postcardiotomy cardiogenic shock in this patient cohort are discussed.Results: Retrospective review of CT images showed coronary abnormalities in 83% (n = 5). Four patients (67%) underwent unplanned coronary artery bypass grafting (CABG). ECLS was instituted in 67% (n = 4) due to left heart failure and in 33% (n = 2) due to right heart failure. Thirty day mortality was 67% (n = 4). The two patients that received ECLS for right ventricular support survived and both had undergone CABG.Conclusion: Besides preoperative evaluation of the extent of the dissection, focus on coronary affection in CT-scans helps to triage the operative procedure. Hybrid operating rooms allow for immediate interventional and/or surgical treatment and enable for immediate control of revascularization results. The use of ECLS over other types of ventricular support systems may allow for myocardial recovery in selected cases.

Background The number of patients presenting with acute myocardial infarction (AMI) and being untreatable by interventional cardiologists increased during the last years. Previous experience in emergency coronary artery bypass grafting (CABG) in these patients spurred us towards a more liberal acceptance for surgery. Following a prospective protocol, patients were operated on and further analysed. Methods Within a two year interval, 127 patients (38 female, age 68±12 years, EuroScore (ES) II 6.7±7.2%) presenting with AMI (86 non-ST-elevated myocardial infarction (NSTEMI), 41 STEMI) were immediately accepted for emergency CABG and operated on within six hours after cardiac catheterisation (77% three-vessel-disease, 47% left main stem stenosis, 11% cardiogenic shock, 21% preoperative intraaortic balloon pump (IABP), left ventricular ejection fraction 48±15%). Results 30-day-mortality was 6% (8 patients, 2 NSTEMI (2%) 6 STEMI (15%), p=0.014). Complete revascularisation could be achieved in 80% of the patients using 2±1 grafts and 3±1 distal anastomoses. In total, 66% were supported by IABP, extracorporal life support (ECLS) systems were implanted in two patients. Logistic regression analysis revealed the ES II as an independent risk factor for mortality (p Conclusions Quo ad vitam, results of emergency CABG for patients presenting with NSTEMI can be compared with those of elective revascularisation. Complete revascularisation obviously offers a clear benefit for the patients. Mortality in patients presenting with STEMI and cardiogenic shock is substantially high. For these patients, other concepts regarding timing of surgical revascularisation and bridging until surgery need to be taken into consideration.

Viral hemorrhagic fevers (VHF) are acute infections with high case fatality rates, associated with the risk of nosocomial transmission (3). A rapid confirmation of the clinical diagnosis is therefore required by methods such as antigen capture enzyme immunoassay and serologic detection of immunoglobulin M. With the development of PCR technology, it has become possible to rapidly test for viruses that cause VHF (4, 5, 10). We have recently confirmed a case of acute yellow fever with fulminating hepatic failure by reverse transcription-PCR (RT-PCR) (2). In spite of the very high viral RNA concentration in the plasma sample, it initially tested negative. A confirmation by PCR would have been missed if we had not tested a duplicate sample, inoculated with in vitro-transcribed yellow fever virus RNA, to detect substances that are inhibitory to RT-PCR (5). When this control reaction failed, we diluted the plasma in log10 intervals, reprepared RNA from the diluted material, and tested it by RT-PCR. The virus was clearly detectable in the patient's plasma diluted 1:100, 1:1,000, and 1:10,000 (Fig. ​(Fig.1).1). Again, no virus was detectable in the undiluted sample, and detection was also partially inhibited in the 1:10 dilution. Quantitative real-time RT-PCR with the diluted material yielded a projected concentration of >106 copies of viral RNA per ml of the undiluted plasma (Fig. ​(Fig.1).1). Interestingly, we have observed a similarly strong inhibition phenomenon with plasma from a moribund patient with acute Ebola hemorrhagic fever from Gulu, Uganda (Fig. ​(Fig.2).2). The viral RNA concentration in this case was 6.9 × 108 copies/ml. No hemolysis, which often causes inhibition of PCR (1), was observed in plasma from the two patients. In both cases, however, the patients were suffering from severe organ manifestation of their disease (aspartate aminotransferase in yellow fever sample, 15,000 IU; alanine aminotransferase, 6,000 IU). FIG. 1. Results of quantitative real-time yellow fever virus RT-PCR (5) with original plasma and prediluted plasma. Closed data points depict the viral RNA concentration in plasma, as determined by testing of each dilution step of the patient sample (y axis). ... FIG. 2. Result of agarose gel electrophoresis after qualitative Ebola virus RT-PCR (5) with original plasma and prediluted plasma from a patient with acute Ebola fever. The dilution factor is depicted above each gel lane. No amplification was possible when the ... Inhibition of RT-PCR in plasma samples has been reported to occur at a frequency of 0.34 to 2.1% of tests (patients infected with human immunodeficiency virus type 1 or hepatitis C virus, respectively [6, 9]). It can usually be circumvented by using standard ETDA sampling tubes (as done in both cases described here) and preparation procedures based on silica column purification (7, 8, 11). Furthermore, at least with plasma, inhibition is usually reversible upon repetition of extraction of nucleic acids from the same sample (6, 9). In these cases, however, the concentration in plasma of substances interfering with PCR appeared to be extraordinarily high: amplification was repeatedly inhibited in a second extraction, even though a reliable silica column purification method (viral RNA kit; Qiagen, Hilden, Germany) was applied. Moreover, partial inhibition occurred even in 1:10-diluted material. Two important consequences can be drawn from these observations. (i) False-negative RT-PCR results are likely to occur for patients with severe viral hemorrhagic fevers, especially in the acute phase of the disease where a rapid confirmation is required. Their plasma may contain large amounts of RT-PCR inhibitors, probably resulting from the decay of tissue. These inhibitors can be detected by control reactions with spiked samples (low copy numbers of control RNA, 1 log10 above detection limit of the PCR) (5). Control reactions to detect inhibitors of RT-PCR are mandatory for a safe diagnosis for patients with suspected VHF. (ii) When PCR is used for diagnosis of viral hemorrhagic fevers, dilutions of the test sample should be tested in parallel with the original sample. The high viral RNA concentration in samples from acute VHF cases is likely to facilitate the diagnosis in spite of the dilution factor.

We tested the feasibility of a reduced-intensity conditioning regimen for hematopoietic stem cell transplantation (HSCT) perspectively allowing an adapted conditioning for performance and disease status. Treatment consisted of 2–4 Gy total body irradiation (TBI), 120mg/m2 fludarabine, 120mg/kg cyclophosphamide, 0–40 mg/kg anti-thymocyte globulin (ATG) and immunosuppression by ciclosporin-A and mycophenolate mofetil. Up to date, 10 patients (median age 59 years) ineligible for conventional conditioning due to age (>50 years), concomitant disease or previous toxicities have been transplanted on an observational basis after obtaining written informed consent. 2 patients received grafts from related donors, 1 patient an unrelated graft with HLA-C mismatch in GvHD vector and all others unrelated matched grafts. 9 patients (90%) received 2 Gy TBI and ≥30mg/kg ATG. 1 patient received 4 Gy TBI and no ATG since presenting with progressiv disease at time of HSCT and receiving an related graft. Median pre-transplant adapted Charlson index was 2,5 (range 0–6), number of previous chemotherapy protocols 2 (range 1–5). No obvious graft rejection occurred. Of the patients evaluable beyond day +30 (N = 8) 8 patients (100%) achieved consistent neutrophil counts >500/μl and 6 (75%) consistent platelet counts of >25,000/μl. Median duration for neutropenia was 25 days (range 15 – 44 days) and for thrombocytopenia 23 days (range 7–55 days). 14 units (range 2–58) packed red cells and of 7 units (range 1–62) platelets had to be given. Median hospital stay was 49 days (range 34–66 days). Of 8 patients with a follow up beyond day +30, 6 (75%) showed a chimerism of >90% around day +30. 1 patient showed a chimerism of 50% due to parallel relapse while 1 patient was not evaluable due to sepsis. All patients evaluable for toxicity (N=8) had CTC grade 4 hematological toxicity. 6 patients (75%) experienced toxicities CTC ≥3, mainly infections. Two patients (25%) died of treatment-related infections. No gastrointestinal toxicity CTC ≥3° and no case of veno-occlusive disease was observed. Hemorrhagic cystitis CTC 2° was observed in 1 patient (10%). Of the patients with a Charlson index ≥3 (N=5), 2 (40%) died of infections and 3 (60%) experienced only toxicities of ≤3. Of the evaluable patients with neutrophil recovery (N=8), 1 (12,5%) presented with acute GvHD of the skin 2° and 2 (25%) respectively with acute GvHD 1° of the skin or gut. 4 patients (50%) showed no signs of acute GvHD. Of the 2 patients evaluable for day >+100, one has chronic limited GvHD. All cases of GvHD required no therapy. Of the three patients evaluable day +100, one suffered from relapse and two are alive in complete remission. Of the patients evaluable day +30 (N=8) two (25%) presented with relapse or progressive disease around day +30, 1 (12,5%) respectively showed stable disease or further remission and 4 patients (50%) showed persisting complete remission. We conclude that the presented regimen is applicable to patients not elegibile for conventional regimens due to its tolerable overall toxicity and particularly low gastrointestinal side effects. Moreover, due to the use of 3 cytotoxic agents and 3 immunosuppressive substances it offers the option for a conditioning adapted to commorbidity, disease status and graft characteristics. A respective stratification will be presented at the meeting.