Good outcomes after repeated pediatric liver retransplantations: A justified procedure even in times of organ shortage.

BACKGROUND: Pediatric liver transplantations generally represent advanced surgery for selected patients. In case of acute or chronic graft failure, biliary or vessel complications, a retransplantation (reLT) can be necessary. In these situations massive adhesions, critical patient condition or lack of good vessels for anastomosis often are problematic. METHODS: Between 2008 and 2021, 208 pediatric patients received a liver transplantation at our center. Retrospectively, all cases with at least one retransplantation were identified and stored in a database. Indication, intra- and postoperative course and overall survival (OS) were analyzed. RESULTS: Altogether 31 patients (14.9%) received a reLT. In 22 cases only one reLT was done, 8 patients received 2 reLTs and 1 patient needed a fourth graft. Median age for primary transplantation, first, second and third reLT was 14 (range: 1-192 months), 60.5 (range: 1-215 months), 58.5 (range: 14-131 months) and 67 months, respectively. Although biliary atresia (42%) and acute liver failure (23%) represented the main indications for the primary liver transplantation, acute and chronic graft failure (1st reLT: 36%, 2nd reLT: 38%), hepatic artery thrombosis (1st reLT: 29%, 2nd reLT: 25%, 3rd reLT: 100%) and biliary complications (1st reLT: 26%, 2nd reLT: 37%) were the most frequent indications for reLT. OS was 81.8% for patients with 1 reLT, 87.5% with 2 reLTs and 100% with 3 reLTs. CONCLUSION: Pediatric liver retransplantation is possible with a good outcome even after multiple retransplantations in specialized centers. Nevertheless, careful patient and graft selection, as well as good preoperative conditioning, are essential.

Intraoperative contrast-enhanced ultrasound has an outcome-relevant impact on surgery of primary and metastatic liver lesions.

PURPOSE: Complete resection of the affected tissue remains the best curative treatment option for liver-derived tumors and colorectal liver metastases. In addition to preoperative cross-sectional imaging, contrast-enhanced intraoperative ultrasound (CE-IOUS) plays a crucial role in the detection and localization of all liver lesions. However, its exact role is unclear. This study was designed to evaluate the clinical and oncological impact of using CE-IOUS in the surgical treatment of these diseases. MATERIALS AND METHODS: Over the three-year study period, 206 patients with primary liver tumors and hepatic metastases were enrolled in this prospective, monocentric study to evaluate the impact of CE-IOUS in liver surgery. Secondary outcomes included comparing the sensitivity and specificity of CE-IOUS with existing preoperative imaging modalities and identifying preoperative parameters that could predict a strategic impact of CE-IOUS. In addition, the oncological significance of CE-IOUS was evaluated using a case-cohort design with a minimum follow-up of 18 months. RESULTS: CE-IOUS findings led to a change in surgical strategy in 34% of cases (n=70/206). The accuracy in cases with a major change could be confirmed histopathologically in 71.4% of cases (n=25/35). The impact could not be predicted using parameters assumed to be clinically relevant. An oncological benefit of a CE-IOUS adapted surgical approach was demonstrated in patients suffering from HCC and colorectal liver metastases. CONCLUSION: CE-IOUS may significantly increase R0 resection rates and should therefore be used routinely as an additional staging method, especially in complex liver surgery.

Color Mapping using Ultrasound System-integrated Perfusion Software for Evaluation of Focal Liver Lesions: A Possible First Step for More Independent Reading.

AIMS: To assess the value of using integrated parametric ultrasound software for contrast-enhanced ultrasonography (CEUS) of liver tumors. METHODS: 107 patients with liver tumors were studied. CEUS were performed to detect focal lesions. Parametric images were based on continuous CINE LOOPs, from the early-arterial phase (15 s) to the portal-venous phase (1 min) generated by perfusion software. The evaluations of the parametric images and their dignity for liver lesions were performed independently by an experienced and a less-experienced investigator. Computed tomography, magnetic resonance imaging scans or histological analysis were used as references. RESULTS: High parametric image quality were obtained in all patients. Among the patients, 44% lesions were benign, 56% were malignant. The experienced investigator correctly classified 46 of 47 (98%) as benign, and 60 of 60 (100%) as malignant tumors based on the parametric images. The less-experienced investigator correctly classified 39 of 47 (83%) as benign, and 49 of 60 (82%) malignant tumors, acheaving a high statistical accuracy of 98% with this type of diagnostic. CONCLUSION: Parametric imaging for grading the malignant degree of tumor may be a good complement to existing ultrasound techniques and was particularly helpful for improving the assessments of the less-experienced examiner.

Regional transplant rates depend more on physician-dependent variables than on proximity to transplant center.

PURPOSE: The objective of this work was to uncover inequalities in access to liver transplantation in Bavaria, Germany. METHODS: For this purpose, the annual transplantation rate per 1 million inhabitants for the respective districts was determined from the aggregated postal codes of the place of residence of transplanted patients. The variables examined were proximity and travel time to the nearest transplant center, as well as the care category of the regional hospital. In addition, we assessed whether the head of gastroenterology at the regional hospital through which liver transplant candidates are referred was trained at a liver transplant center. RESULTS: We could not demonstrate a direct relationship between proximity or travel time to the nearest transplant center and access to liver transplantation. Multivariate regression analysis shows that liver transplant training (p < 0.0001) of the chief physician (gastroenterologist) of the regional hospital was the most decisive independent factor for access to liver transplantation within a district. CONCLUSION: We show that the transplant training experience of the head of gastroenterology at a regional hospital is an independent factor for the regional transplantation rate. Therefore, it appears important to maintain some liver transplant expertise outside the transplant centers in order to properly identify and assign potential transplant candidates for transplantation.

Phenotypic Characterization of Colorectal Liver Metastases: Capsule versus No Capsule and the Potential Role of Epithelial Mesenchymal Transition.

Background: Colorectal liver metastases (CRLM) can be encased in a fibrous capsule separating cancer from normal liver tissue, which correlates with increased patient survival. This study investigated the cellular and molecular components of capsule formation and the possible role of epithelial mesenchymal transition (EMT). Methods: From 222 patients with CRLM, 84 patients (37.8%) were categorized to have CRLM encased with a capsule. A total of 34 CRLM from 34 selected patients was analyzed in detail by EMT pathway-profiling and custom PCR arrays to identify differences in gene expression between CRLM with (n = 20) and without capsule (n = 14). In parallel, those 34 CRLM were used to analyze 16 gene products at the metastasis margin via immunohistochemistry. Results: Encapsulated CRLM showed an elevated expression of signal transduction pathways and effector molecules involved in EMT. E-cadherin and keratin-19 were more prevalent, and transcription as well as translation (immunohistochemistry) of pGSK-3-ß, SOX10, tomoregulin-1, and caldesmon were increased. By contrast, the loss of E-cadherin and the prevalence of snail-1 were increased in CRLM without capsule. Collagen I and III and versican were identified as capsule components with extracellular matrix fibers running concentrically around the malignant tissue and parallel to the invasive front. Caldesmon was also demonstrated as a capsule constituent. Conclusions: The fibrous capsule around CRLM can be produced by cells with mesenchymal characteristics. It functions as a protective border by both the features of fiber architecture and the inhibition of invasive growth through EMT recruiting mesenchymal cells such as myofibroblasts by transformation of surrounding epithelial or even carcinoma cells. By contrast, EMT demonstrated in non-encapsulated CRLM may lead to a more mesenchymal, mobile, and tissue-destructive carcinoma cell phenotype and facilitate malignant spread.

Diaphragmatic Injuries among Severely Injured Patients (ISS ≥ 16)-An Indicator of Injury Pattern and Severity of Abdominal Trauma.

Background and Objectives: Abdominal trauma among severely injured patients with an injury severity score (ISS) of 16 and above can lead to potentially life-threatening injuries that might need immediate surgical intervention. Traumatic injuries to the diaphragm (TID) are a challenging condition often accompanied by other injuries in the thoracoabdominal region. Materials and Methods: We retrospectively analyzed the occurrence and clinical course of TID among severely injured patients treated at our center between 2008 and 2019 and compared them to other groups of severely injured patients without TID. Results: Thirty-five patients with TID and a median ISS of 41 were treated in the period mentioned above. They were predominantly middle-aged men and mostly victims of blunt trauma as a consequence of motor vehicle accidents. A total of 70.6% had left-sided TID, and in 69.6%, the size of defect was larger than 10 cm. The diagnosis was made with computed tomography (CT) in 68.6% of the cases, while in 25.8%, it was made intraoperatively or delayed by a false-negative initial CT scan, and in 5.7%, an intraoperative diagnosis was made without preoperative CT imaging. Surgical repair was mostly conducted via laparotomy, performing a direct closure with continuous suture. A comparison to 191 patients that required laparotomy for abdominal injuries other than TID revealed significantly higher rates of concomitant injuries to several abdominal organs among patients suffering from TID. Compared to all other severely injured patients treated in the same period (n = 1377), patients suffering from TID had a significantly higher median ISS and a longer mean duration of hospital stay. Conclusions: Our findings show that TID can be seen as an indicator of particularly severe thoracoabdominal trauma that requires increased attention from the treatment team so as not to miss relevant concomitant injuries that require immediate intervention.

Semiresorbable biologic hybrid meshes for ventral abdominal hernia repair in potentially contaminated settings: lower risk of recurrence.

In case of potential contamination, implantation of synthetic meshes in hernia and abdominal wall surgery is problematic due to a higher risk of mesh infection. As an alternative, a variety of different biologic meshes have been used. However, relevant data comparing outcome after implantation of these meshes are lacking. Between January 2012 and October 2021, biologic meshes were used for reconstruction of the abdominal wall in 71 patients with preoperative or intraoperative abdominal contamination. In this retrospective study, semiresorbable biologic hybrid meshes (BHM) and completely resorbable meshes (CRM) were compared and analyzed using a Castor EDC database. In 28 patients, semiresorbable biologic hybrid meshes were used; in 43 patients, completely resorbable meshes were used. Both groups showed no difference in age, gender, BMI, operation duration, hernia size and Charlson comorbidity index. The risk degree of surgical-site occurrences was graded according to the Ventral Hernia Working Group (VHWG) classification, and the median value was 3 (range 2-4) in the BHM group and 3 (range 2-4) in the CRM group. Hernia recurrence within 24 months after hernia repair was significantly lower in the BHM group (3.6% vs. 28.9%; p = 0.03), while postoperative complication rate, with respect to seromas in need of therapy (61.4% vs. 55.5%, p = 0.43) and operative revision (28.6% vs. 16.3%, p = 0.22) was not different in either group. Biologic hybrid meshes can be used safely in case of possible contamination. BHM seems to reduce the risk of hernia recurrence compared to completely resorbable biologic meshes, but this has to be investigated further.

3D In Vivo Models for Translational Research on Pancreatic Cancer: The Chorioallantoic Membrane (CAM) Model.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with adverse outcomes that have barely improved over the last decade. About half of all patients present with metastasis at the time of diagnosis, and the 5-year overall survival rate across all stages is only 6%. Innovative in vivo research models are necessary to combat this cancer and to discover novel treatment strategies. The chorioallantoic membrane (CAM) model represents one 3D in vivo methodology that has been used in a large number of studies on different cancer types for over a century. This model is based on a membrane formed within fertilized chicken eggs that contain a dense network of blood vessels. Because of its high cost-efficiency, simplicity, and versatility, the CAM model appears to be a highly valuable research tool in the pursuit of gaining more in-depth insights into PDAC. A summary of the current literature on the usage of the CAM model for the investigation of PDAC was conducted and subdivided into angiogenesis, drug testing, modifications, personalized medicine, and further developments. On this comprehensive basis, further research should be conducted on PDAC in order to improve the abysmal prognosis of this malignant disease.

ADP-induced platelet reactivity and bleeding events in patients with acute myocardial infarction complicated by cardiogenic shock.

While previous reports showed ADP-induced platelet reactivity to be an independent predictor of bleeding after PCI in stable patients, this has never been investigated in patients with cardiogenic shock. The association of bleeding events with respect to ADP-induced platelet aggregation was investigated in patients undergoing primary PCI for acute myocardial infarction complicated by cardiogenic shock and with available on-treatment ADP-induced platelet aggregation measurements. Out of 233 patients, 74 suffered from a severe BARC3 or higher bleed. ADP-induced platelet aggregation was significantly lower in patients with BARC≥3 bleedings (p < .001). Multivariate analysis identified on-treatment ADP-induced platelet aggregation as an independent risk factor for bleeding (HR = 0.968 per AU). An optimal cutoff value of <12 AU for ADP-induced platelet aggregation to predict BARC≥3 bleedings was identified via ROC analysis. Moreover, the use of VA-ECMO (HR 1.972) or coaxial left ventricular pump (HR 2.593), first lactate (HR 1.093 per mmol/l) and thrombocyte count (HR 0.994 per G/l) were independent predictors of BARC≥3 bleedings. In conclusion, lower on-treatment ADP-induced platelet aggregation was independently associated with severe bleeding events in patients with AMI-CS. The value of platelet function testing for bleeding risk prediction and guidance of anti-thrombotic treatment in cardiogenic shock warrants further investigation.

Collateral effects of the SARS-CoV-2 pandemic on oncologic surgery in Bavaria.

BACKGROUND: The ongoing SARS-COV-2 pandemic has severe implications for people and healthcare systems everywhere. In Germany, worry about the consequences of the pandemic led to the deferral of non-emergency surgeries. Tumor surgery accounts for a large volume in the field of visceral surgery and cannot be considered purely elective. It is not known how the SARS-COV-2 pandemic has changed the surgical volume in tumor patients. METHODS: Retrospective analysis of the amount of oncological surgeries in three academic visceral surgery departments in Bavaria, Germany, in 2020. Procedures were split into subgroups: Upper Gastrointestinal (Upper GI), Colorectal, Hepato-Pancreato-Biliary (HPB), Peritoneal and Endocrine. Procedures in 2020 were compared to a reference period from January 1st, 2017 to December 31st 2019. Surgical volume was graphically merged with SARS-COV-2 incidence and the number of occupied ICU beds. RESULTS: Surgical volume decreased by 7.6% from an average of 924 oncologic surgeries from 2017 to 2019 to 854 in 2020. The decline was temporally associated with the incidence of infections and ICU capacity. Surgical volume did not uniformly increase to pre-pandemic levels in the months following the first pandemic wave with lower SARS-COV-2 incidence and varied according to local incidence levels. The decline was most pronounced in colorectal surgery where procedures declined on average by 26% following the beginning of the pandemic situation. CONCLUSION: The comparison with pre-pandemic years showed a decline in oncologic surgeries in 2020, which could have an impact on lost life years in non-COVID-19 patients. This decline was very different in subgroups which could not be solely explained by the pandemic.

How exercise can deteriorate the clinical course of an ARVC patient: a case report.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC)/dysplasia is a genetic disease characterized by fibro-adipose degeneration of ventricular myocardium. Initial clinical presentation is variable and ranges from asymptomatic cases to chronic heart failure and sudden cardiac death due to malignant arrhythmias. CASE SUMMARY: Here, a 67-year-old male patient who started extensive physical training upon retirement and presented with ventricular tachycardia and progressive heart failure as a first sign of his disease. Arrhythmogenic right ventricular cardiomyopathy diagnosis was established according to the 2010 modified Task Force Criteria and supported by HRS/EHRA consensus-based genotyping. After initial discharge on optimal medical therapy and prophylactic implantable cardioverter-defibrillator implantation according to his individual ARVC risk score, the patient reported rapid decline in physical capacity on a regular follow-up 4 months later. To better understand the aetiology of his clinical deterioration, we performed stress echocardiography, coronary angiogram, and exercise right heart catheterization, which conclusively suggest impaired left ventricular filling secondary to right ventricular failure as a main cause of global circulatory failure. DISCUSSION: The present case report focuses on relation of physical activity to disease onset and the concomitant advent of symptoms during exercise as well as a structured and guideline-aided diagnostic workup in ARVC and staged treatment options. Continuous ARVC centre-oriented re-assessment and treatment planning including lifestyle intervention, psychological support, medical, surgical, and interventional options are key elements of sustained long-term care for ARVC patients.

Health promoting behaviour of medical versus non-medical students during COVID-19 pandemic: results from the COLA cross-sectional study.

To investigate the COVID-19 pandemic related alteration of health promoting behaviour during lockdown among medical students compared to other students.In this cross-sectional study, we enrolled 1940 Bavarian students. Participants were asked to complete an online questionnaire 3 weeks after lockdown implementation, evaluating their lifestyle behaviour focusing on self-reported and objectively assessed physical activity.1154 medical (59.5%) and 786 non-medical (40.5%) students were included (median age 22.0 [IQR, 20.0-25.0], 71.5% female). Physical activity decreased in both groups after lockdown implementation. During lockdown, medical students reported higher physical activity levels compared to non-medical students. This was corroborated by daily step count data assessed by wearables (median steps per day [IQR], 6979 [5218-9348] versus 6581 [4497-8491], p = 0.02). Smoking behaviour during lockdown did not differ between medical and non-medical students (increased in 11.8% vs 13.6%, decreased in 31.9% versus 36.9%).During the COVID-19 pandemic, alteration of lifestyle behaviour among medical students was significantly different compared to non-medical students. This result suggests that medical students are more concerned about health promoting behaviour even in crisis situations.

Successful auxiliary two-staged partial resection liver transplantation (ASPIRE-LTx) for end-stage liver disease to avoid small-for-size situations.

BACKGROUND: Risks for living-liver donors are lower in case of a left liver donation, however, due to lower graft volume, the risk for small-for-size situations in the recipients increases. This study aims to prevent small-for-size situations in recipients using an auxiliary two-staged partial resection liver transplantation (LTX) of living-donated left liver lobes. CASE PRESENTATION: Two patients received a two-stage auxiliary LTX using living-donated left liver lobes after left lateral liver resection. The native extended right liver was removed in a second operation after sufficient hypertrophy of the left liver graft had occurred. Neither donor developed postoperative complications. In both recipients, the graft volume increased by an average of 105% (329 ml to 641 ml), from a graft-to-body-weight ratio of 0.54 to 1.08 within 11 days after LTX, so that the remnant native right liver could be removed. No recipient developed small-for-size syndrome; graft function and overall condition is good in both recipients after a follow-up time of 25 months. CONCLUSIONS: Auxiliary two-staged partial resection LTX using living-donor left lobes is technically feasible and can prevent small-for-size situation. This new technique can expand the potential living-donor pool and contributes to increase donor safety.

Intraoperative Characterization of Pancreatic Tumors Using Contrast-Enhanced Ultrasound and Shear Wave Elastography for Optimization of Surgical Strategies.

OBJECTIVES: To evaluate intraoperative contrast-enhanced ultrasound (IoCEUS) and intraoperative shear wave elastography (IoSWE) for characterization of focal pancreatic lesions (FPLs) in correlation with postoperative histologic results. Thereby, the impact of intraoperative ultrasound (US) on pancreas surgery was evaluated. METHODS: Intraoperative CEUS and SWE data from 54 patients, who underwent pancreas surgery between 2017 and 2019, were analyzed retrospectively. Ultrasound examinations were performed with multifrequency linear/T-shaped transducers (3-9 MHz) on a high-end US device (LOGIQ E9; GE Healthcare, Chicago, IL). To analyze FPL stiffness by SWE, regions of interest were placed to measure the shear wave speed (meters per second) and stiffness (kilopascals). After intravenous bolus injections of 2.4 to 10 mL of sulfur hexafluoride microbubbles, a dynamic analysis of FPL microvascularization from arterial to late phases was performed using IoCEUS considering hypoenhancement/irregular vascularization of macrocystic/small solid FPL malignancy criteria. Ultrasound findings were correlated with postoperative histologic results. The impact of intraoperative US on surgery was documented in each case. RESULTS: Of 54 FPLs, IoCEUS could correctly characterize 39 of 39 malignant and 6 of 15 benign FPLs; IoSWE 29 of 39 as malignant and 7 of 15 as benign. Intraoperative CEUS's sensitivity was 100%; specificity, 40%; accuracy, 83.3%; positive predictive value, 81.3%; and negative predictive value, 100% (P < .05). Applying cutoff values of 3 m/s and 28.7 kPa, SWE's sensitivity was 74.4%; specificity, 46.7%; accuracy, 66.7%; positive predictive value; 78.4%; and negative predictive value, 41.2% for cancer detection (P < .05). The combined use of both techniques showed an accuracy rate of 76%, sensitivity of 74.4%, and specificity of 33.3%. In 29.6%, US results had an immediate impact on surgery. CONCLUSIONS: Intraoperative SWE and CEUS are highly valuable techniques for intraoperative characterization of FPLs. Although IoCEUS proved to be superior to IoSWE, the combined use can be helpful in particular cases.

Surgical Site Infections and their economic significance in hepatopancreatobiliary surgery: A retrospective incidence, cost, and reimbursement analysis in a German centre of the highest level of care.

Surgical site infections (SSI) in open Hepatopancreatobiliary (HPB) surgery are common complications. They worsen patients' outcomes and prolong hospital stays. Their economic significance in the German diagnosis related groups (DRG) system is mostly unknown. To investigate their economic importance, we evaluated all cases for SSIs as well as clinical and financial parameters undergoing surgery in our centre from 2015 and 2016. Subsequently, we carried out a cost-revenue calculation by assessing our billing data and the cost matrix of the InEK (German Institute for the Payment System in Hospitals). A total of 13.5% of the patients developed a superficial, 9% a deep incisional, and 2.4% of the patients an organ space SSI. Compared with Patients without SSI, Patients with SSI had more comorbidities, were older, and their average length of stay was extended by 19 days (P < .001). The financial loss per SSI-case was €-7035.65 despite increased reimbursement, which resulted in a calculated total loss for the hospital of €-802 064.62 in 2015 and 2016. Surgical site infections are common complications of open HPB surgery, which lead to a significant increase in the cost per case. Further prevention strategies need to be developed. Besides, an adjustment of revenues must be demanded.

Large potassium shifts during dialysis enhance cardiac repolarization instability.

BACKGROUND: Patients with end-stage kidney disease are at high risk for the development of arrhythmias and sudden cardiac death (SCD). This has been especially attributed to large potassium shifts during hemodialysis (HD), and malignant arrhythmias are closely linked to dysfunction of the autonomic nervous system. Nevertheless, there is still a lack of methods for risk stratification in these patients. METHODS: In the present pilot study we investigated changes of the novel ECG-based biomarker periodic repolarization dynamics (PRD) mirroring the effect of efferent sympathetic nervous activity on the ventricular myocardium in 18 patients undergoing routine hemodialysis. High-resolution ECGs were recorded throughout the dialysis and PRD values were calculated out of 30 min intervals at the start and the end of dialysis. RESULTS: We detected a clear correlation between the intradialytic potassium shift and the increase in PRD levels (Spearman correlation coefficient R = 0.62, p = 0.006). Patients with a potassium shift > 1 mmol/l showed significantly increased levels of PRD at the end of dialysis when compared to patients with potassium shifts ≤ 1.0 mmol/l [delta PRD 2.82 (IQR 2.13) vs. - 2.08 (IQR 3.60), p = 0.006]. Spearman analysis showed no significant correlation between PRD changes and fluid removal (R = - 0.23, p = 0.36). CONCLUSIONS: We provide evidence that large potassium shifts during HD enhance sympathetic activity-associated repolarization instability. This could facilitate the occurrence of malignant arrhythmias, and PRD measurements might serve as a non-invasive monitoring tool in HD patients in future.

Negative pressure wound therapy (NPWT) on closed incisions to prevent surgical site infection in high-risk patients in hepatopancreatobiliary surgery: study protocol for a randomized controlled trial-the NP-SSI trial.

BACKGROUND: Incisional surgical site infections (iSSI) in hepatopancreatobiliary (HPB) surgery usually lead to prolonged hospital stays, consume valuable resources, and impact on patients' outcome. Prophylactic closed incision negative pressure wound therapy (ciNPWT) to decrease wound complications has become available. Owing to an increasing number of studies, evidence for superiority in many indication areas has accumulated; however, in general surgery, there are a few data and those have shown contradictory results. METHODS: In this monocentric, prospective, randomized, controlled, two-armed study, the influence of ciNPWT on incisional surgical site infection rates after HPB operations will be investigated. A total of 222 patients will be randomized 1:1 to an interventional group (7-day treatment with ciNPWT) or a control group (treated with gauze dressing). The primary parameter to evaluate efficacy is the rate of incisional SSIs within 30 days after surgery. Additionally, several clinically relevant secondary outcomes will be assessed. DISCUSSION: A reduction in the rate of incisional SSIs would not only lead to a significant cost reduction and shorter postoperative length of stay, but may also improve postoperative quality of life for patients. While earlier publications have shown advantages for ciNPWT, recent studies did not confirm a positive effect regarding iSSI rate. Even if iSSI rate is not reduced, findings obtained from the secondary endpoints may be of clinical relevance, such as reduction of wound complication rates. TRIAL REGISTRATION: This trial has been registered in the German Clinical Trials Register, DRKS 00015136 . Registered on 19 February 2019 and has been approved by the local ethics committee of the University of Regensburg: 18-1225-101.

Cardioprotective Potential of Human Endothelial-Colony Forming Cells from Diabetic and Nondiabetic Donors.

OBJECTIVE: The potential therapeutic role of endothelial progenitor cells (EPCs) in ischemic heart disease for myocardial repair and regeneration is subject to intense investigation. The aim of the study was to investigate the proregenerative potential of human endothelial colony-forming cells (huECFCs), a very homogenous and highly proliferative endothelial progenitor cell subpopulation, in a myocardial infarction (MI) model of severe combined immunodeficiency (SCID) mice. METHODS: CD34+ peripheral blood mononuclear cells were isolated from patient blood samples using immunomagnetic beads. For generating ECFCs, CD34+ cells were plated on fibronectin-coated dishes and were expanded by culture in endothelial-specific cell medium. Either huECFCs (5 × 105) or control medium were injected into the peri-infarct region after surgical MI induction in SCID/beige mice. Hemodynamic function was assessed invasively by conductance micromanometry 30 days post-MI. Hearts of sacrificed animals were analyzed by immunohistochemistry to assess cell fate, infarct size, and neovascularization (huECFCs n = 15 vs. control n = 10). Flow-cytometric analysis of enzymatically digested whole heart tissue was used to analyze different subsets of migrated CD34+ /CD45+ peripheral mononuclear cells as well as CD34-/CD45- cardiac-resident stem cells two days post-MI (huECFCs n = 10 vs. control n = 6). RESULTS: Transplantation of human ECFCs after MI improved left ventricular (LV) function at day 30 post-MI (LVEF: 30.43 ± 1.20% vs. 22.61 ± 1.73%, p < 0.001; ΔP/ΔTmax 5202.28 ± 316.68 mmHg/s vs. 3896.24 ± 534.95 mmHg/s, p < 0.05) when compared to controls. In addition, a significantly reduced infarct size (50.3 ± 4.5% vs. 66.1 ± 4.3%, p < 0.05) was seen in huECFC treated animals compared to controls. Immunohistochemistry failed to show integration and survival of transplanted cells. However, anti-CD31 immunohistochemistry demonstrated an increased vascular density within the infarct border zone (8.6 ± 0.4 CD31+ capillaries per HPF vs. 6.2 ± 0.5 CD31+ capillaries per HPF, p < 0.001). Flow cytometry at day two post-MI showed a trend towards increased myocardial homing of CD45+ /CD34+ mononuclear cells (1.1 ± 0.3% vs. 0.7 ± 0.1%, p = 0.2). Interestingly, we detected a significant increase in the population of CD34-/CD45-/Sca1+ cardiac resident stem cells (11.7 ± 1.7% vs. 4.7 ± 1.7%, p < 0.01). In a subgroup analysis no significant differences were seen in the cardioprotective effects of huECFCs derived from diabetic or nondiabetic patients. CONCLUSIONS: In a murine model of myocardial infarction in SCID mice, transplantation of huECFCs ameliorated myocardial function by attenuation of adverse post-MI remodeling, presumably through paracrine effects. Cardiac repair is enhanced by increasing myocardial neovascularization and the pool of Sca1+ cardiac resident stem cells. The use of huECFCs for treating ischemic heart disease warrants further investigation.