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.

Intraoperative zero-heat-flux thermometry overestimates nasopharyngeal temperature by 0.39 °C: an observational study in patients undergoing congenital heart surgery.

During surgery for congenital heart disease (CHD) temperature management is crucial. Vesical (Tves) and nasopharyngeal (TNPH) temperature are usually measured. Whereas Tves slowly responds to temperature changes, TNPH carries the risk of bleeding. The zero-heat-flux (ZHF) temperature monitoring systems SpotOn™ (TSpotOn), and Tcore™ (Tcore) measure temperature non-invasively. We evaluated accuracy and precision of the non-invasive devices, and of Tves compared to TNPH for estimating temperature. In this prospective observational study in pediatric and adult patients accuracy and precision of TSpotOn, Tcore, and Tves were analyzed using the Bland-Altman method. Proportion of differences (PoD) and Lin´s concordance correlation coefficient (LCC) were calculated. Data of 47 patients resulted in sets of matched measurements: 1073 for TSpotOn vs. TNPH, 874 for Tcore vs. TNPH, and 1102 for Tves vs. TNPH. Accuracy was - 0.39 °C for TSpotOn, -0.09 °C for Tcore, and 0.07 °C for Tves. Precisison was between - 1.12 and 0.35 °C for TSpotOn, -0.88 to 0.71 °C for Tcore, and - 1.90 to 2.05 °C for Tves. PoD ≤ 0.5 °C were 71% for TSpotOn, 71% for Tcore, and 60% for Tves. LCC was 0.9455 for TSpotOn, 0.9510 for Tcore, and 0.9322 for Tves. Temperatures below 25.2 °C (TSpotOn) or 27.1 (Tcore) could not be recorded non-invasively, but only with Tves. Trial registration German Clinical Trials Register, DRKS00010720.

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.

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.

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.

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.

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.

Aortic surgery after previous procedure of congenital aortic stenosis.

Irrespective of previous procedure in congenital aortic stenosis, aortic surgery later in life may be indicated. The aim of the present study was the analysis of indications, risks, and outcomes of aortic surgery after previous aortic valve procedure. The data of patients who underwent aortic surgery after previous treatment of congenital aortic stenosis in a 10-year period (from 2000 to 2009) were retrospectively analyzed. Thirty-two patients (23 male and 9 female) underwent redo aortic surgery. The mean age at surgery was 13.5 ± 11.3 years. Seventeen patients had undergone initial aortic balloon valvuloplasty (BVP) and 15 patients open commissurotomy (COM). Nine cases had undergone the primary procedure at neonatal age and two patients had undergone cardiac surgery before the initial aortic valve procedure. Seven of the patients with previous COM (43.8%) had undergone concomitant surgery along with initial commissurotomy. A reintervention within the first year after the primary procedure was performed in seven patients (seven after BVP and none after COM; P < 0.05). The interval between the last intervention and the first redo aortic surgery was 7.5 ± 9.5 years (3.1 ± 3.5 years after BVP vs. 12.5 ± 11.7 years after COM; P < 0.05). A second redo surgery was performed in nine patients (four after initial BVP and five after COM). Congenital aortic stenosis is very often presented in combination with additional pathologies. These concomitant diseases along with the underlying disease give the indication for reoperation. Reinterventions are more often indicated after primary BVP. Long follow-up in specialized centers is mandatory.

Low-output is not the cause of death of neonatal piglets early after cardiopulmonary bypass.

The mortality rate of neonatal piglets after heart surgery is high. Searching for a possible explanation for the death of neonatal piglets early after cardiopulmonary bypass, we analyzed hemodynamic parameters regarding survival and non-survival. Initially, 10 neonatal piglets (younger than 7 days) were connected to cardiopulmonary bypass (CPB). The mean body weight was 2.98 ± 0.44 kg. Exposure of the heart was performed through a median sternotomy. After connection to the CPB, the piglets were cooled to 32°C core temperature before the ascending aorta was cross-clamped and the heart arrested (90 min). Thereafter, piglets were re-warmed to 37°C and separated from CPB. During follow-up, the piglets did not receive inotropic support or vasopressors. Piglets who survived at least 2 h after termination of CPB were included in the study for further data analysis (n = 9). Five piglets died 2.5 to 4.0 h (median: 3.5 h) after CPB; these piglets formed the non-survivors group. Four animals survived the complete follow-up of 6 h after CPB and formed the survivors group. Regarding contractility (dP/dt(max) , dP/dt(max) /P, and wall thickening) there were not statistically significant differences between the groups. Non-survivors showed prolonged decrease of mean arterial pressure of more than 20% of baseline values, corresponding with a value of below 30 mm Hg. In conclusion, the death of neonatal piglets early after cardiopulmonary bypass was not determined by low output.

The effect of cardiopulmonary bypass and hypothermic circulatory arrest on hepatic histology in newborn animals: an experimental study.

Still little is known about the effect of cardiac surgery on neonatal hepatic tissue. We examined the effect of cardiopulmonary bypass (CPB) and the effect of deep hypothermic circulatory arrest (DHCA) on neonatal hepatic tissue. Liver biopsies of neonatal piglets were taken after CPB (n = 4), after DHCA (n = 5), and after surgery without CPB (non-CPB; n = 3). Additionally, findings were compared to those of control piglets (n = 9). The liver specimens were fixed, stained with hematoxylin and eosin, and scored regarding inflammatory reaction, hepatocellular edema, and apoptosis. Inflammation score of treated groups was higher than in control; CPB 2.5 ± 0.5, DHCA 1.6 ± 0.4, non-CPB 1.2 ± 0.6, control 0.4 ± 0.3 (P < 0.001 CPB and DHCA vs. control; P < 0.05 non-CPB vs. control). Hepatic cell edema was more evident after DHCA (score 2.0 ± 0.4 vs. 0.2 ± 0.3 in control and 0.6 ± 0.5 after CPB; P < 0.001 and P < 0.05, respectively). The highest apoptotic cell count was in the non-CPB group (22.3 ± 6.3 vs. 11.4 ± 3.6 in control and 8.9 ± 5.4 after CPB; P < 0.05). The present study showed that (i) surgical trauma induces hepatic cell apoptosis; (ii) CPB increases hepatic inflammatory reaction; and (iii) DHCA amplifies hepatic cell edema.

Carotid Doppler flow after cardiopulmonary bypass and mild hypothermia in neonatal piglets.

Although the mechanisms of neurological disorders after cardiac surgery in neonates are still not fully understood, alterations in blood flow after cardiopulmonary bypass (CPB) may lead to cerebral injury. The aim of the study was the analysis of flow changes in the carotid artery of neonatal piglets after CPB. Ten neonatal piglets (younger than 7 days) were connected to the CPB and further management underwent three steps: (i) cooling to 32°C core temperature within 30 min; (ii) cardiac arrest under cardioplegic myocardial protection for 90 min; and (iii) rewarming to 37°C after cross-clamp release (60 min of reperfusion). In summary, piglets were separated from CPB after a total duration time of 180 min. The blood flow was measured in the left carotid artery by an ultrasonic flow probe before CPB (baseline), immediately after CPB, 30 min, and 60 min after CPB. Additionally, the pulsatility index and the resistance index were calculated and compared. Finally, the relation of the carotid artery flow data with the corresponding pressure data at each time point was compared. After termination of CPB, the carotid artery mean flow was reduced from 28.34 ± 13.79 mL/min at baseline to 20.91 ± 10.61 mL/min and remained reduced 30 and 60 min after CPB termination (19.71 ± 11.11 and 17.64 ± 15.31 mL/min, respectively). Both the pulsatility and the resistance index were reduced immediately after CPB termination and increased thereafter. Nevertheless, values did not reach statistical significance. In conclusion, the carotid Doppler flow immediately after CPB and mild hypothermia in neonatal piglets was lower than before CPB due to reduced vascular resistance. Additionally, the pressure-flow relation revealed that immediately after CPB, a higher pressure is required to obtain adequate flow.

A new device for intraoperative renal blood flow measurement during open-heart surgery: an experimental study and the clinical pilot study.

Renal blood flow (RBF) may vary during cardiopulmonary bypass and low flow may cause insufficient blood supply of the kidney triggering renal failure postoperatively. Still, a valid intraoperative method of continuous RBF measurement is not available. A new catheter combining thermodilution and intravascular Doppler was developed, first calibrated in an in vitro model, and the catheter specific constant was determined. Then, application of the device was evaluated in a pilot study in an adult cardiovascular population. The data of the clinical pilot study revealed high correlation between the flow velocities detected by intravascular Doppler and the RBF measured by thermodilution (Pearson's correlation range: 0.78 to 0.97). In conclusion, the RBF can be measured excellently in real time using the new catheter, even under cardiopulmonary bypass.

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.

Myocardial contractility and relaxation after deep hypothermic circulatory arrest in a neonatal piglet model.

Cooling before circulatory arrest or ischemic arrest has been reported to influence myocardial performance in isolated neonatal hearts. The aim of the present study was to analyze indices of myocardial contractility and relaxation in an in vivo neonatal model after deep hypothermic circulatory arrest (DHCA). DHCA (18°C; DHCA group; n = 8) or mild hypothermic cardiopulmonary bypass ([MH-CPB] 32°C; MH-CPB group; n = 10) was applied in newborn piglets. After reperfusion (60 and 120 min), left ventricular dP/dt(max) increased in DHCA and MH-CPB, while-dP/dt(max) decreased slightly in DHCA and increased in MH-CPB. Nevertheless, the differences between the two groups did not reach statistical significance. In conclusion, left ventricular contractility remained stable after reperfusion following DHCA, to some degree at the expense of the diastolic function.

Double inferior vena cava.

Venous anomalies involving the inferior vena cava are very rare. The case of a 74-year-old man with coronary artery disease is presented. Interestingly, a double inferior vena cava was incidentally discovered during coronary artery bypass grafting. Persistence of the left hepatic segment vein appeared as a left inferior vena cava-a very rare condition.

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.

Cardiopulmonary bypass and its direct effects on neonatal piglet kidney morphology.

Renal failure after open heart surgery is a serious complication even in the pediatric population. The aim of the present study was to analyze morphological changes after cardiopulmonary bypass (CPB) surgery in a neonatal piglet model. The kidneys of newborn piglets sacrificed 6 h after CPB were examined (CPB; n = 4) regarding tubular dilatation, vacuole formation, leukocytic infiltration, epithelial destruction, and interstitial edema. Thereafter, the findings were compared with the morphology of normal (untreated) neonatal piglet kidneys (control; n = 4). All changes but the interstitial edema were statistically significant if compared with the normal renal tissue: tubular dilatation (CPB vs. control P < 0.05), vacuole formation (CPB vs. control P < .05), leukocytic infiltration (CPB vs. control P < 0.05), and epithelial destruction (CPB vs. control P < 0.001). In conclusion, CPB induces significant changes in the morphology of the neonatal piglet kidneys.