COVID-19 infection in patients with history of pediatric heart transplant in Germany, Austria, and Switzerland.

COVID-19 is a heterogenous infection-asymptomatic to fatal. While the course of pediatric COVID-19 infections is usually mild or even asymptomatic, individuals after adult heart transplantation are at high risk of a severe infection. We conducted a retrospective, multicenter survey of 16 pediatric heart transplant centers in Germany, Austria and Switzerland to evaluate the risk of a severe COVID-19 infection after pediatric heart transplantation between 02/2020 and 06/2021. Twenty-six subjects (11 male) with a median age of 9.77 years at time of transplantation and a median of 4.65 years after transplantation suffered from COVID-19 infection. The median age at time of COVID-10 infection was 17.20 years. Fourteen subjects had an asymptomatic COVID-19 infection. The most frequent symptoms were myalgia/fatigue (n = 6), cough (n = 5), rhinitis (n = 5), and loss of taste (n = 5). Only one subject showed dyspnea. Eleven individuals needed therapy in an outpatient setting, four subjects were hospitalized. One person needed oxygen supply, none of the subjects needed non-invasive or invasive mechanical ventilation. No specific signs for graft dysfunction were found by non-invasive testing. In pediatric heart transplant subjects, COVID-19 infection was mostly asymptomatic or mild. There were no SARS-CoV-2 associated myocardial dysfunction in heart transplant individuals.

Turbulence in surgical suction heads as detected by MRI.

BACKGROUND: Blood loss is common during surgical procedures, especially in open cardiac surgery. Allogenic blood transfusion is associated with increased morbidity and mortality. Blood conservation programs in cardiac surgery recommend re-transfusion of shed blood directly or after processing, as this decreases transfusion rates of allogenic blood. But aspiration of blood from the wound area is often associated with increased hemolysis, due to flow induced forces, mainly through development of turbulence. METHODS: We evaluated magnetic resonance imaging (MRI) as a qualitative tool for detection of turbulence. MRI is sensitive to flow; this study uses velocity-compensated T1-weighted 3D MRI for turbulence detection in four geometrically different cardiotomy suction heads under comparable flow conditions (0-1250 mL/min). RESULTS: Our standard control suction head Model A showed pronounced signs of turbulence at all flow rates measured, while turbulence was only detectable in our modified Models 1-3 at higher flow rates (Models 1 and 3) or not at all (Model 2). CONCLUSIONS: The comparison of flow performance of surgical suction heads with different geometries via acceleration-sensitized 3D MRI revealed significant differences in turbulence development between our standard control Model A and the modified alternatives (Models 1-3). As flow conditions during measurement have been comparable, the specific geometry of the respective suction heads must have been the main factor responsible. The underlying mechanisms and causative factors can only be speculated about, but as other investigations have shown, hemolytic activity is positively associated with degree of turbulence. The turbulence data measured in this study correlate with data from other investigations about hemolysis induced by surgical suction heads. The experimental MRI technique used showed added value for further elucidating the underlying physical phenomena causing blood damage due to non-physiological flow.

Expression and prognostic impact of DNA-PK in human lung cancer.

Among all cancer patient's lung cancer is the leading cause of death. Prognostic biomarkers continue to be investigated for the detection and stratification of lung cancer for clinical use. The DNA-dependent protein kinase is involved in mechanisms of DNA damage repair. Deregulation and overexpression of DNA-dependent protein kinase is associated with poor prognosis in various tumor entities. In this study, we investigated the expression of DNA-dependent protein kinase in relation to clinicopathological features and overall survival in patients with lung cancer. By immunohistochemistry, expression of DNA-dependent protein kinase was analyzed in 205 cases of lung cancer; 95 cases of adenocarcinoma, 83 cases of squamous cell lung carcinoma and 27 cases of small cell lung cancer and correlated with clinicopathological characteristics as well as patient's overall survival. In patients with adenocarcinoma, a significant correlation between strong expression of DNA-dependent protein kinase and worse overall survival was found. No significant association was observed in patients with squamous cell lung carcinoma and small cell lung cancer. Strong detection of DNA-dependent protein kinase expression was most evident in small cell lung cancer (81.48 %), followed by squamous cell lung carcinoma (62.65 %) and adenocarcinoma (61.05 %). In our study, expression of DNA-dependent protein kinase was associated with poor overall survival in patients with adenocarcinoma. DNA-dependent protein kinase could serve as a new prognostic biomarker.

Expression and prognostic impact of CD49b in human lung cancer.

ABSTRACT: Lung cancer remains the worldwide leading cause of cancer-related death. Currently, prognostic biomarkers for the detection and stratification of lung cancer are being investigated for clinical use. The surface protein cluster of differentiation 49b (CD49b) plays an important role in promoting cell proliferation and invasion in different tumor entities and blocking CD49b improved the tumor immune response. Overexpression of CD49b has been associated with unfavorable survival rates in several malignant tumor entities, such as prostate cancer, gastric cancer and colon cancer. Therefore, we aimed to analyze the protein expression of CD49b in patients with different types of lung cancer and additionally to identify the influence of CD49b on clinicopathological characteristics and overall survival.Expression levels of CD49b were retrospective analyzed by immunohistochemistry in 92 cases of pulmonary adenocarcinoma (AC), 85 cases of squamous cell lung carcinoma (SQCLC) and 32 cases of small cell lung cancer (SCLC) and correlated with clinicopathological characteristics and patients' overall survival.A strong expression of CD49b was most seen in SQCLC (78%), followed by AC (48%) and SCLC (9%). All patients combined, strong expression of CD49b correlated significantly with poorer overall survival. However, an increased expression of CD49b correlated significantly with a poorer survival rate only in SQCLC. In AC and SCLC, no significant correlation could be demonstrated in this regard.In our study, CD49b expression was associated with poor overall survival in patients with SQCLC. Accordingly, CD49b could serve as a new prognostic biomarker and, moreover, be a potential new drug target in SQCLC.

Re-exploration Early after Cardiac Surgery in Adults: The Importance of Bleeding-Related Complications.

BACKGROUND: Re-explorations soon after cardiac surgery are mostly related to bleeding or unclear hemodynamic situations possibly related to heart compression resulting from pericardial hematoma. This condition has a significant impact on mortality, morbidity, and costs. The aim of this study was to analyze indications and outcomes of re-exploration for bleeding or pericardial tamponade early after cardiac surgery in adults. METHODS: The clinical data of 4790 consecutive adult patients who underwent cardiac surgery in our institution from January 2011 to May 2016 were retrospectively analyzed. RESULTS: We identified 331 re-explorations performed in 231 patients. Sixty-seven of these patients had >1 re- exploration. In most cases (88%), repeat sternotomy was performed. Most procedures (57%) were performed within the first 48 hours. In two-thirds of re-explorations, active bleeding or pericardial hematoma was verified. In the remaining cases, neither bleeding nor significant pericardial hematoma leading to tamponade was found. Among the cases with active bleeding causes, the most bleeding sites were found to be at the coronary anastomosis and the epicardial exposure harvesting site, as well as from the side branches of bypass grafts and intercostal arteries. CONCLUSIONS: The incidence of re-exploration after cardiac surgery in adults was low (4.8%). In about two-thirds of the cases, active bleeding or significant pericardial hematoma was found. The most common bleeding causes were the easiest to treat.

The effect of a novel turbulence-controlled suction system in the prevention of hemolysis and platelet dysfunction in autologous surgery blood.

BACKGROUND: Re-transfusion of autologous blood is an important aspect of intraoperative blood management. Hemolysis and platelet dysfunction due to turbulence in the blood suction system strongly impede later usage of suction blood for re-transfusion. The aim of this study was to analyze the effects of a novel surgical-blood suction system with an automatic control setup for minimization of turbulence in the blood flow. METHODS: We compared the turbulence-controlled suction system (TCSS) with a conventional suction system and untreated control blood in vitro. Blood cell counts, hemolysis levels according to free hemoglobin (fHb) and platelet function were analyzed to determine the integrity of the suction blood. RESULTS: In the conventional suction system, we found a strong increase of the fHb levels. In contrast, erythrocyte integrity was almost completely preserved when using the TCSS. We obtained similar results regarding platelet function. The expression of platelet glycoproteins, such as GP IIb/IIIa and P-selectin, native or after stimulation with ADP, were markedly impaired by the conventional system, but not by the TCSS. In addition, platelet aggregometry revealed significant platelet dysfunction in conventional suction blood, but less aggregation impairments were present in blood samples from the TCSS. CONCLUSION: Our findings on an in vitro assessment show major improvements in red blood cell integrity and platelet function of suction blood when using the TCSS compared to a conventional suction system. These results reflect a significant benefit for autologous re-transfusion. We suggest testing the TCSS in surgery for clinical evaluation.

Efficacy and safety of non-transvenous cardioverter defibrillators in infants and young children.

BACKGROUND: Implantable cardioverter defibrillators (ICD) protect from sudden cardiac death (SCD). In infants and young children, ICD implantation and programming is challenging due to small body size, elevated heart rates, and high physical activity. PURPOSE: We report our experience applying a non-transvenous ICD (NT-ICD) system to infants and children < 12 years of age and < 45-kg body weight. METHODS: Between 07/2004 and 07/2016, NT-ICD had been implanted in 36 patients. Nine out of 36 patients (25%) had NT-ICD implantation for primary and 27/36 (75%) for secondary prevention. Underlying diseases included inherited primary electrical arrhythmogenic diseases (n = 26; 72%), cardiomyopathies (n = 8; 22%), and congenital heart defects (n = 2; 6%). The median (interquartile range) age at implantation was 6 (1.9-8.4) years, and the median body weight was 21.7 (11.2-26.8) kg. Three different NT-ICD implantation techniques had been applied over time: (1) abdominal device/subcutaneous shock coil, (2) abdominal device/pleural shock coil, and (3) subcardiac device/pleural shock coil. RESULTS: During median follow-up of 5.2 (2.7-7.2) years, appropriate ICD discharges were documented in 12 (33.3%) and inappropriate shocks in 4 patients (11.1%). In 12/36 individuals (33.3%), a total of 25 surgical revisions were required due to NT-ICD malfunction. Eighteen out of 25 (72%) surgical revisions were necessary in patients with subcutaneous shock coil/abdominal device position. Surgical revisions (3/25, 12%) were significantly reduced (p < 0.001) after modifying the implantation technique to subcardiac device/pleural shock coil. CONCLUSIONS: NT-ICD was safe and effective in infants and young children. Appropriate ICD discharges occurred in a considerable number of patients. After modifying the implantation technique, the need for surgical revision could significantly be decreased.

Activation of protein phosphatase 1 by a selective phosphatase disrupting peptide reduces sarcoplasmic reticulum Ca2+ leak in human heart failure.

BACKGROUND: Disruption of Ca2+ homeostasis is a key pathomechanism in heart failure. CaMKII-dependent hyperphosphorylation of ryanodine receptors in the sarcoplasmic reticulum (SR) increases the arrhythmogenic SR Ca2+ leak and depletes SR Ca2+ stores. The contribution of conversely acting serine/threonine phosphatases [protein phosphatase 1 (PP1) and 2A (PP2A)] is largely unknown. METHODS AND RESULTS: Human myocardium from three groups of patients was investigated: (i) healthy controls (non-failing, NF, n = 8), (ii) compensated hypertrophy (Hy, n = 16), and (iii) end-stage heart failure (HF, n = 52). Expression of PP1 was unchanged in Hy but greater in HF compared to NF while its endogenous inhibitor-1 (I-1) was markedly lower expressed in both compared to NF, suggesting increased total PP1 activity. In contrast, PP2A expression was lower in Hy and HF compared to NF. Ca2+ homeostasis was severely disturbed in HF compared to Hy signified by a higher SR Ca2+ leak, lower systolic Ca2+ transients as well as a decreased SR Ca2+ load. Inhibition of PP1/PP2A by okadaic acid increased SR Ca2+ load and systolic Ca2+ transients but severely aggravated diastolic SR Ca2+ leak and cellular arrhythmias in Hy. Conversely, selective activation of PP1 by a PP1-disrupting peptide (PDP3) in HF potently reduced SR Ca2+ leak as well as cellular arrhythmias and, importantly, did not compromise systolic Ca2+ release and SR Ca2+ load. CONCLUSION: This study is the first to functionally investigate the role of PP1/PP2A for Ca2+ homeostasis in diseased human myocardium. Our data indicate that a modulation of phosphatase activity potently impacts Ca2+ cycling properties. An activation of PP1 counteracts increased kinase activity in heart failure and successfully seals the arrhythmogenic SR Ca2+ leak. It may thus represent a promising future antiarrhythmic therapeutic approach.

Risk and Outcome after Simultaneous Carotid Surgery and Cardiac Surgery: Single Centre Experience.

OBJECTIVE: Carotid artery stenosis in patients undergoing open-heart surgery may increase risk and deteriorate outcome. The aim of the study was the analysis of risks and outcome after simultaneous carotid and cardiac surgery. METHODS: We retrospectively reviewed the medical records of 100 consecutive patients who underwent simultaneous carotid surgery and open-heart surgery during a 5-year period (from 2006 to 2010). Seventy patients were male and 30 female; the mean age was 70.9±7.9 years (median: 71.8 years). Seventy-three patients underwent coronary bypass grafting (CABG), 18 patients combined CABG and valve procedures, 7 patients CABG combined with other procedures, and 3 patients isolated valve surgery. More than half of patients had had bilateral carotid artery pathology (n=51) including contralateral carotid artery occlusion in 12 cases. RESULTS: Carotid artery patch plasty was performed in 71 patients and eversion technique in 29. In 75 cases an intraluminal shunt was used. Thirty-day mortality rate was 7% due to cardiac complications (n=5), metabolic disturbance (n=1), and diffuse cerebral embolism (n=1). There were no carotid surgery-related deaths. Postoperatively, transient cerebral ischemia occurred in one patient and stroke with mild permanent neurological deficit (Rankin level 2) in another patient. CONCLUSION: Simultaneous carotid artery surgery and open-heart surgery have low risk. The underlying cardiac disease influences outcome.

Heart Transplantation in a Toddler with Cardiac Kawasaki Disease.

Kawasaki disease is very rare in Western Europe. The disease may involve coronary arteries. A 2-year-old boy diagnosed with Kawasaki disease had had seizure-like symptoms. Further evaluation revealed recurrent myocardial ischemia and myocardial infarction. Due to extraordinary extension of the coronary disease, myocardial revascularization was not feasible and the toddler underwent successful heart transplantation after 97 days on waiting list.

NGAL expression during cardiopulmonary bypass does not predict severity of postoperative acute kidney injury.

BACKGROUND: Renal injury is a serious complication after cardiac surgery and therefore, early detection and much more prediction of postoperative kidney injury is desirable. Neutrophil gelatinase-associated lipocalin (NGAL) is a predictive biomarker of acute kidney injury and may increase after cardiopulmonary bypass (CPB). However, time correlation of NGAL expression and severity of renal injury is still unclear. The aim of our study was to investigate CPB-related urine NGAL (uNGAL) secretion in correlation to postoperative renal function. METHODS: Data of NGAL expression along with clinical data of 81 patients (52 male and 29 female) were included in this study. Mean age of the patients was 66.8 ± 12.8 years. Urine NGAL was measured at seven time points (T0: baseline; T1: start CPB, T2: 40 min on CPB; T3: 80 min on CPB; T4: 120 min on CPB; Tp1: 15 min after CPB; Tp2: 4 h after admission to the intensive care unit) and renal function in the postoperative period was classified daily according to Acute Kidney Injury Network (Ronco et al, Int J Artif Organs 30(5): 373-6) criteria (AKIN). RESULTS: Expression of uNGAL increased at T4 (120 min on CPB) and post-CPB (Tp1 and Tp2; p < 0.01 vs. baseline) but there was no correlation between uNGAL level and duration of CPB nor between uNGAL expression and occurrence of postoperative kidney injury. The renal function over 10 days after surgery remained normal in 50 patients (AKIN level 0), 18 patients (22%) developed mild and insignificant renal injury (AKIN level 1), eight patients (10%) developed moderate renal failure (AKIN level 2), and five patients (6%) severe kidney failure (AKIN level 3). Twenty-four out of 31 patients developed renal failure within the first 48 h after surgery. However, there was no correlation between uNGAL expression and severity of acute renal failure. CONCLUSION: Although uNGAL expression increased after CPB, the peak values neither predict acute postoperative kidney injury, nor severity of the injury.

Is there a correlation between late re-exploration after cardiac surgery and removal of epicardial pacemaker wires?

BACKGROUND: Re-exploration for bleeding accounts for increased morbidity and mortality after major cardiac operations. The use of temporary epicardial pacemaker wires is a common procedure at many departments. The removal of these wires postoperatively can potentially lead to a serious bleeding necessitating intervention. METHODS: From Jan 2011 till Dec 2015 a total of 4244 major cardiac procedures were carried out at our department. We used temporary epicardial pacemaker wires in all cases. We collected all re-explorations for bleeding and pericardial tamponade from our surgical database and then we focused on the late re-explorations, meaning on the 4th postoperative day and thereafter, trying to identify the removal of the temporary pacemaker wires as the definite cause of bleeding. Patients' records and medication were examined. RESULTS: Thirty-nine late re-explorations for bleeding, consisting of repeat sternotomies, thoracotomies and subxiphoid pericardial drainages, were gathered. Eight patients had an acute bleeding incidence after removal of the temporary wires (0.18%). In four of these patients, a pericardial drainage was inserted, whereas the remaining patients were re-explorated through a repeat sternotomy. Two patients died of the acute pericardial tamponade, three had a blood transfusion and one had a wound infection. Seven out of eight patients were either on dual antiplatelet therapy or on combination of aspirin and vitamin K antagonist. CONCLUSIONS: A need for re-exploration due to removal of the temporary pacemaker wires is a very rare complication, which however increases morbidity and mortality. Adjustment of the postoperative anticoagulation therapy at the time of removal of the wires could further minimize or even prevent this serious complication.

Myocardial histology and outcome after cardiopulmonary bypass of neonatal piglets.

BACKGROUND: Early after neonatal cardiac surgery hemodynamic dysfunction may be evident. However, still is not clear if dysfunction and outcome is related to visible myocardial alterations. The aim of the present study was the histological analysis of myocardial tissue of neonatal piglets after cardiopulmonary bypass (CPB) and cardioplegic arrest. METHODS: Neonatal piglets (younger than 7 days) were connected to CPB for 180 min, including 90 min of cardioplegic heart arrest at 32 °C. After termination of CPB the piglets were observed up to 6 h. During this observational period animals did not receive any inotropic support. Some piglets died within this period and formed the non-survivors group (CPB-NS group) and the remaining animals formed the CPB-6 h group. Myocardial biopsies (stained with H&E) were scored from 0 to 3 regarding histological alterations. Then, the histological data were evaluated and compared to the probes of animals handled comparable to previous piglets but without CPB (non-CPB group; n = 3) and to sibling piglets without specific treatment (control; n = 5). RESULTS: In the first hours after CPB six piglets out of 10 died (median 3.3 h). The animals of CPB-6 h group (n = 4) were sacrificed at the end of experiments (6 h after CPB). Although the myocardial histological score of CPB-6 h group and CPB-NS group were higher than non-CPB group (2.0 ± 0.8, 1.5 ± 0.9, and 0.8 ± 0.3 respectively), these differences were statistically not significant. But compared to control animals (score 0.3 ± 0.5) the scores of CPB-6 h and CPB-NS groups were significantly higher (p < 0.05). Between the left and the right ventricular tissue there were no significant differences. CONCLUSIONS: Myocardial tissue alterations in newborn piglets are related to the surgical trauma and potentiated by cardiopulmonary bypass and ischemia. However, outcome is not related to the degree of tissue alteration.

Long term biventricular support with Berlin Heart Excor in a Septuagenarian with giant-cell myocarditis.

Giant-cell myocarditis (GCM) is known as a rare, rapidly progressive, and frequently fatal myocardial disease in young and middle-aged adults. We report about a 76 year old male patient who underwent implantation with a biventricular Berlin Heart Excor system at the age of 74 due to acute biventricular heart failure caused by giant-cell myocarditis. The implantation was without any surgical problems; however, a difficulty was the immunosuppressive therapy after implantation. Meanwhile the patient is 76 years old and lives with circulatory support for about 3 years without major adverse events. Also, in terms of mobility in old age there are no major limitations. It seems that in even selected elderly patients an implantation of a long term support with the biventricular Berlin Heart Excor is a useful therapeutic option with an acceptable outcome.

Daptomycin and Its Immunomodulatory Effect: Consequences for Antibiotic Treatment of Methicillin-Resistant Staphylococcus aureus Wound Infections after Heart Surgery.

Infections by methicillin-resistant Staphylococcus aureus (MRSA) play an increasing role in the postoperative course. Although wound infections after cardiac surgery are rare, the outcome is limited by the prolonged treatment with high mortality. Not only surgical debridement is crucial, but also antibiotic support. Next to vancomycin and linezolid, daptomycin gains increasing importance. Although clinical evidence is limited, daptomycin has immunomodulatory properties, resulting in the suppression of cytokine expression after host immune response stimulation by MRSA. Experimental studies showed an improved efficacy of daptomycin in combination with administration of vitamin E before infecting wounds by MRSA.

Carotid artery Doppler flow pattern after deep hypothermic circulatory arrest in neonatal piglets.

The mechanisms of cerebral injury after cardiac surgery in neonates are not clear. The aim of the study was the analysis of flow changes in the carotid artery of neonatal piglets after deep hypothermic circulatory arrest (DHCA). Eight neonatal piglets were connected to cardiopulmonary bypass (CPB) and underwent (i) cooling to 18°C core temperature within 30 min, (ii) DHCA for 90 min, and finally (iii) rewarming to 37°C after cross-clamp release (60 min of reperfusion). The blood flow was measured in the left carotid artery by an ultrasonic flow probe before CPB (baseline; T0 ), immediately after termination of reperfusion on CPB (T1 ), 30 min later (T2 ), and 60 min later (T3 ). Additionally, the pulsatility index and the resistance index were calculated and compared. Finally, the relationship between the carotid artery flow and the corresponding pressure at each time-point was compared. After termination of CPB (T1 ), the mean carotid artery flow was reduced from 45.26 ± 2.58 mL/min at baseline to 23.29 ± 2.58 mL/min (P < 0.001) and remained reduced 30 and 60 min later (P < 0.001 vs. baseline). Both the pulsatility index and the resistance index were increased after termination of reperfusion, with the maximum occurring 30 min after CPB end. In conclusion, the carotid artery Doppler flow in neonatal piglets was reduced after DHCA, while the indices of pulsatility and resistance increased.

Ca2+/calmodulin-dependent protein kinase II and protein kinase A differentially regulate sarcoplasmic reticulum Ca2+ leak in human cardiac pathology.

BACKGROUND: Sarcoplasmic reticulum (SR) Ca(2+) leak through ryanodine receptor type 2 (RyR2) dysfunction is of major pathophysiological relevance in human heart failure (HF); however, mechanisms underlying progressive RyR2 dysregulation from cardiac hypertrophy to HF are still controversial. METHODS AND RESULTS: We investigated healthy control myocardium (n=5) and myocardium from patients with compensated hypertrophy (n=25) and HF (n=32). In hypertrophy, Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and protein kinase A (PKA) both phosphorylated RyR2 at levels that were not different from healthy myocardium. Accordingly, inhibitors of these kinases reduced the SR Ca(2+) leak. In HF, however, the SR Ca(2+) leak was nearly doubled compared with hypertrophy, which led to reduced systolic Ca(2+) transients, a depletion of SR Ca(2+) storage and elevated diastolic Ca(2+) levels. This was accompanied by a significantly increased CaMKII-dependent phosphorylation of RyR2. In contrast, PKA-dependent RyR2 phosphorylation was not increased in HF and was independent of previous ß-blocker treatment. In HF, CaMKII inhibition but not inhibition of PKA yielded a reduction of the SR Ca(2+) leak. Moreover, PKA inhibition further reduced SR Ca(2+) load and systolic Ca(2+) transients. CONCLUSIONS: In human hypertrophy, both CaMKII and PKA functionally regulate RyR2 and may induce SR Ca(2+) leak. In the transition from hypertrophy to HF, the diastolic Ca(2+) leak increases and disturbed Ca(2+) cycling occurs. This is associated with an increase in CaMKII- but not PKA-dependent RyR2 phosphorylation. CaMKII inhibition may thus reflect a promising therapeutic target for the treatment of arrhythmias and contractile dysfunction.