Preoperative serum uric acid predicts incident acute kidney injury following cardiac surgery.

BACKGROUND: Acute kidney injury (AKI) following cardiac surgery is a frequent complication and several risk factors increasing its incidence have already been characterized. This study evaluates the influence of preoperative increased serum uric acid (SUA) levels in comparison with other known risk factors on the incidence of AKI following cardiac surgery. METHODS: During a period of 5 month, 247 patients underwent elective coronary artery bypass grafting, valve replacement/ repair or combined bypass and valve surgery. Datas were prospectively analyzed. Primary endpoint was the incidence of AKI as defined by the AKI criteria comparing patients with preoperative serum uric acid (SUA) levels below versus above the median. Multivariate logistic regression analysis was used to identify independent predictors of postoperative AKI. RESULTS: Thirty (12.1%) of the 247 patients developed postoperative AKI, 24 of 30 (80%) had preoperative SUA- levels above the median (≥373 µmol/l) (OR: 4.680, CI 95% 1.840; 11.904, p = 0.001). In the multivariate analysis SUA levels above the median (OR: 5.497, CI 95% 1.772; 17.054, p = 0.003), cardiopulmonary bypass (CPB) time > 90 min (OR: 4.595, CI 95% 1.587; 13.305, p = 0.005), cardiopulmonary bypass (CPB) > 30 kg/m2 (OR: 3.208, CI 95% 1.202; 8.562; p = 0.02), and preoperative elevated serum-creatinine levels (OR: 1.015, CI 95% 1.001; 1.029, p = 0.04) were independently associated with postoperative AKI. CONCLUSIONS: Serum uric acid is an independent risk marker for AKI after cardiac surgery. From all evaluated factors it showed the highest odds ratio.

Guidelines versus reality: is coronary stent application in three-vessel disease standard or the exception?

The national guidelines for treatment of chronic coronary heart disease (CHD) recommend surgical coronary aortic bypass grafting (CABG) rather than percutaneous coronary intervention (PCI) for patients with a coronary three-vessel disease. The epidemiology of three-vessel CHD and data about the application of different revascularisation strategies raise suspicion of deviation from the guidelines in the treatment of those patients. Claims data containing records of almost 10 million patients of the largest German statutory health insurance fund (Techniker Krankenkasse) were utilised to measure adherence to the guidelines for treatment of groups of patients with one-, two-, and three-vessel CHD, respectively. The impact of age, sex, and comorbidity on each patient's revascularisation procedure was investigated as well. There was no significant difference in the rate of PCI between the groups. In conclusion, the hypothesis that patients with a coronary three-vessel disease are not always treated according to the recommendations of the national guidelines could not be disproved by this study. Finally, the results of this study suggest that the best revascularisation strategy for each patient with two- and three-vessel disease should be decided upon by an interdisciplinary discussion between both cardiologists and cardiac surgeons.

TIMP3 is Regulated by Pericytes upon Shear Stress Detection Leading to a Modified Endothelial Cell Response.

OBJECTIVES: Atherosclerosis is a hallmark of cardiovascular disease. Shear stress on endothelial cells has been linked to atherogenesis and to fibrous cap thinning and rupture. Pericytes reside in the sub-endothelial space of vessels and have vasoprotective effects. They are subjected to shear stress when endothelial cell integrity is disrupted. The aim was to investigate the susceptibility and response of pericytes to shear stress. METHODS: Endothelial cells and pericytes were seeded in two dimensional monocultures and co-cultures, and in a novel three dimensional co-culture system and were subjected to no, low and high shear stress (0, 10, 30 dyne/cm2) for 48 h. The morphological response to flow was assessed by histology and the expression of extracellular matrix proteins was analysed using quantitative polymerase chain reaction, immunoblotting, and ELISA. RESULTS: While endothelial cells aligned into flow direction, pericytes aligned perpendicularly (p < .001), indicating that they must be capable of sensing flow. When pericytes were embedded into a 3D matrix they showed similar alignment and pericytes built long processes towards the lumen. Under shear stress endothelial cells upregulated "a disintegrin and metalloproteinase with thrombospondin motif 1" (ADAMTS-1) (p < .01) and pericytes upregulated "tissue inhibitor of matrix metalloproteinase" (TIMP) 3 (p < .05), an inhibitor of ADAMTS-1, meanwhile differential expression of extracellular matrix (ECM) proteins could be detected in co-cultures of both cells. For TIMP3 expression direct cell-cell contact between endothelial cells and pericytes was required. CONCLUSION: The experiments highlight that pericytes are able to sense direct flow thereby regulating ECM proteins known to be involved in vascular remodelling. Furthermore, pericytes counter-regulate endothelial ADAMTS-1 by protective TIMP3 expression to prevent matrix degradation and maintain vascular stability. For this protective effect direct cell contact was necessary. This observation might represent an adaptive, protective mechanism of pericytes to counteract endothelial damage in the onset of atherosclerosis.

[Cardiac surgery in the elderly]. / Herzchirurgie im Alter.

Due to the increasing demographic changes and the fact that cardiovascular diseases are still the leading cause of death, the mean chronological age of patients undergoing cardiac surgery is steadily increasing. In 2015, 14.8% of these patients were aged 80 years and older. This meta-analysis reviewed if and under what circumstances elderly patients benefit from cardiac surgical procedures without running the risk of limitations in the quality of life and high rates of morbidity and mortality. Generally, the chronological age was not a risk factor for higher perioperative and postoperative morbidity and mortality but the biological age was the critical factor, in particular the associated comorbidities of patients and the timing of the surgical procedure in the course of the disease. The result is that elective operations resulted in a better outcome than operations in a symptomatic or decompensated stage of a disease. Compared to patients receiving conventional medicinal therapy, elderly patients undergoing cardiac surgery had an improved life expectancy. A significant increase in the quality of life could also be identified and was ultimately comparable to those of younger patients after cardiac surgery; therefore, elderly patients even those over 80 years old benefit in all aspects of cardiac surgery, as long as individually adapted operative techniques are considered.

Pulmonary metastasectomy - A retrospective comparison of surgical outcomes after laser-assisted and conventional resection.

INTRODUCTION: Indications and surgical techniques for pulmonary metastasectomy (PME) are controversially discussed issues. Laser-assisted surgery (LAS) is a recent innovation that has been advocated especially in patients with multiple pulmonary metastases (PM). However, there are hardly any studies comparing surgical outcomes after laser-assisted and conventional resection. The aim of the current study was to evaluate the value of LAS in a larger study population. MATERIALS & METHODS: A retrospective analysis was completed on 178 consecutive patients undergoing 236 PMEs at a single center between 2010 and 2015. The main endpoint was survival. Statistical analysis was performed using the Kaplan-Meier method and survival rates were compared with the log rank test. Follow-up was done with special attention to the development of recurrent PM. Local relapse was defined as a recurrent metastasis in direct relation to the previously resected area according to CT scan comparisons. RESULTS: LAS was performed on 256 metastases in 99 patients, non-laser-assisted surgery (NLAS) on 127 metastases in 79 patients. 5-year-survival rates were 69.3% in all patients, 65.7% after LAS and 73.6% after NLAS. There was no statistically significant survival difference after LAS or NLAS (p = 0.41). The rate of local relapse was 0.8% after LAS vs 3.1% after NLAS (p = 0.073). CONCLUSION: Despite a larger number of negative predictors for survival in LAS patients, overall survival (OS) was similar in the compared groups. There was also a trend for a lower risk of local relapses after LAS. Therefore, LAS should be considered a promising method for PME.

A new era of thoracic oncology? Ex-vivo stereotactic ablative radiosurgery within Ex-vivo Lung Treatment System as a hybrid therapy for unresectable locally advanced pulmonary malignancies.

The concept of oligometastases is the medical rationale for a local treatment of a limited number of metastatic tumor manifestations. Patients with pulmonary oligometastases are candidates for surgery or radiotherapy, however there are a number of technical issues that limit treatment. Technical issues relating to radiotherapy include organs at risk of irradiation, chest wall toxicity and decreased precision of tumor targeting because of breathing movements. Technical issues relating to surgery include loss of lung parenchyma and unresectability. We propose the hypothesis that ex-vivo radiosurgery as new hybrid technique in thoracic oncology has the capability to overcome these technical issues and will expand the medical spectrum in thoracic oncology. The proposed - highly complex - technique consists of surgical lung explantation, followed by stereotactic radiotherapy during ex-vivo perfusion followed by surgical re-implantation.

[Pioneering surgical innovations in Germany : Part 2: public funding and origins of surgical innovations]. / Bahnbrechende chirurgische Innovationen in Deutschland : Teil 2: Öffentliche Finanzierung und Ursprünge chirurgischer Innovationen.

BACKGROUND: In recent years research that conforms with evidence-based medicine (EBM) has been demanded even in surgery. Uniform studies were carried out to prove the benefits of new procedures; however, compared to other research sectors, public third party funding for surgical research was significantly cut back. OBJECTIVE: Collation of special features in surgery with respect to external funding of surgical top level research. Examination of the benefits of a continuous promotion and of organizations involved in research. MATERIAL AND METHODS: Part one of this investigation presented the methods used to identify and analyze pioneering research in surgery. RESULTS: Out of a total of 15 revolutionary innovations only 3 projects were financed by external funding and 2 projects received indirect financial support as a result of a cooperation with the medical industry. This demonstrates that the majority of projects were neither directly nor indirectly subsidized. Apart from one instance the majority of innovations were generated by university hospitals highly active in research. DISCUSSION: In effect, the non-existing external funding for outstanding surgical innovations and hospitals suggests that a reformation of surgical research is required. To strengthen the quality of innovations in surgery a concentration of funding to institutions that are highly active in research makes sense. Institutional funding directly linked to a project should form a key component of support particularly in the early stages of development.

Everolimus Versus Mycophenolate Mofetil De Novo After Lung Transplantation: A Prospective, Randomized, Open-Label Trial.

The role of mammalian target of rapamycin (mTOR) inhibitors in de novo immunosuppression after lung transplantation is not well defined. We compared Everolimus versus mycophenolate mofetil in an investigator-initiated single-center trial in Hannover, Germany. A total of 190 patients were randomly assigned 1:1 on day 28 posttransplantation to mycophenolate mofetil (MMF) or Everolimus combined with cyclosporine A (CsA) and steroids. Patients were followed up for 2 years. The primary endpoint was freedom from bronchiolitis obliterans syndrome (BOS). The secondary endpoints were incidence of acute rejections, infections, treatment failure and kidney function. BOS-free survival in intention-to-treat (ITT) analysis was similar in both groups (p = 0.174). The study protocol was completed by 51% of enrolled patients. The per-protocol analysis shows incidence of bronchiolitis obliterans syndrome (BOS): 1/43 in the Everolimus group and 8/54 in the MMF group (p = 0.041). Less biopsy-proven acute rejection (AR) (p = 0.005), cytomegalovirus (CMV) antigenemia (p = 0.005) and lower respiratory tract infection (p = 0.003) and no leucopenia were seen in the Everolimus group. The glomerular filtration rate (GFR) decreased in both groups about 50% within 6 months. Due to a high withdrawal rate, the study was underpowered to prove a difference in BOS-free survival. The dropout rate was more pronounced in the Everolimus group. Secondary endpoints indicate potential advantages of Everolimus-based protocols but also a potentially higher rate of drug-related serious adverse events.

[Pioneering surgical innovations in Germany : Part 1: generation of medical evidence]. / Bahnbrechende chirurgische Innovationen in Deutschland : Teil 1: Generierung medizinischer Evidenz.

BACKGROUND: In recent years research which conforms to evidence-based medicine (EBM) has been required even in surgery. Prospective, randomized studies are carried out in order to provide justification for the benefits of new procedures. OBJECTIVE: The acquisition of special features in surgery with respect to the application of EBM. MATERIAL AND METHODS: The investigation period selected was from1933 to 2013; therefore, all disciplines within the German Society of Surgery were questioned on the achievement of revolutionary innovations. The investigation was carried out utilizing personal interviews and a questionnaire. Only novel methods which were developed in Germany were considered. The survey was completed by carrying out research in database files. RESULTS: During the past 80 years 15 pioneering innovations have been published in surgical research, although the prerequisites of EBM were only partly met. They appear to be based on the lowest level of evidence as these methods were mostly published as case reports or case series in journals with a low impact factor. DISCUSSION: In general, innovative surgical procedures through top level research are still being published in the form of case reports or case series. This allows a rapid distribution of research results to the surgical community. Controlled studies still do not represent an alternative for the introduction of pioneering surgical innovations.

Augmentation of Transient Donor Cell Chimerism and Alloantigen-Specific Regulation of Lung Transplants in Miniature Swine.

Donor alloantigen infusion induces T cell regulation and transplant tolerance in small animals. Here, we study donor splenocyte infusion in a large animal model of pulmonary transplantation. Major histocompatibility complex-mismatched single lung transplantation was performed in 28 minipigs followed by a 28-day course of methylprednisolone and tacrolimus. Some animals received a perioperative donor or third party splenocyte infusion, with or without low-dose irradiation (IRR) before surgery. Graft survival was significantly prolonged in animals receiving both donor splenocytes and IRR compared with controls with either donor splenocytes or IRR only. In animals with donor splenocytes and IRR, increased donor cell chimerism and CD4(+) CD25(high+) T cell frequencies were detected in peripheral blood associated with decreased interferon-γ production of leukocytes. Secondary third-party kidney transplants more than 2 years after pulmonary transplantation were acutely rejected despite maintained tolerance of the lung allografts. As a cellular control, additional animals received third-party splenocytes or donor splenocyte protein extracts. While animals treated with third-party splenocytes showed significant graft survival prolongation, the subcellular antigen infusion showed no such effect. In conclusion, minipigs conditioned with preoperative IRR and donor, or third-party, splenocyte infusions may develop long-term donor-specific pulmonary allograft survival in the presence of high levels of circulating regulatory T cells.

[Minimally invasive chest surgery. Is palpation control still necessary with modern computed tomography?]. / Minimal-invasive Thoraxchirurgie. Macht die moderne Computertomographie die Palpationskontrolle verzichtbar?

BACKGROUND: A fundamental argument against minimally invasive oncological chest surgery is the risk of overlooking pulmonary nodules due to a lack of intraoperative palpation. In the literature this risk in the treatment of primary lung cancer is given as up to 8.4 % and as more than 15 % in the surgical treatment of pulmonary metastases. OBJECTIVE: The aim of this study was to evaluate if modern computed tomography (CT) is sensitive enough to replace intraoperative palpation and justify a minimally invasive approach. PATIENTS AND METHODS: The medical records from 92 patients who underwent 95 open lung resections due to pulmonary malignancies from April 2010 through September 2011 at the Medical School Hannover were retrospectively analysed. A comparison was carried out between the lesions detected preoperatively by CT and those removed during surgery and histologically confirmed as being malignant. Patients with more than five nodules suspected of being malignant in the preoperative CT scan were excluded. RESULTS: According to the final histopathological examination 125 malignant nodules were resected and 2 of these were not detected in the preoperative CT scan, which were performed in external hospitals with a slice thickness of 5 mm and 8 mm, respectively. This represents a sensitivity of 98 % for all CT scans in terms of detection of pulmonary nodules. With thin slice CT (slice thickness up to 1.5 mm) a sensitivity of 100 % was even achieved. CONCLUSION: The results demonstrate that a high sensitivity of thin slice CT for detection of lung nodules can be achieved. Based on these results the categorical reservation with respect to thoracoscopic resection of pulmonary metastases should be reconsidered in suitable patients where a minimally invasive resection is possible. The extent of lymph node dissection is not influenced by these data. Further studies with larger sample sizes are warranted to confirm these results.

Investigation of the biomechanical integrity of decellularized rat abdominal aorta.

OBJECTIVES: The loss or damage of an organ or tissue is one of the most common and devastating problems in healthcare today. Tissue engineering applies the principles of engineering and biology toward the development of functional biological replacements that are able to maintain, improve, or restore the function of pathological tissues. The aim of the overall project is to study an already existing method for the decellularization of homograft vascular grafts for use in vascular surgery. MATERIALS AND METHODS: The biomechanical integrity of native and decellularized rat aortas was assessed under uniaxial tension tests. For this purpose, 36 male rats (12 Wistar and 24 Dark Agouti [DA]) were used to excise their abdominal aortas. Twelve of the aortas were tested fresh (Wistar and DA rats), within 24 hours from euthanasia, and the rest were decellularized using a modified protocol (DA rats only). Fresh and decellularized samples (n = 12) were subjected to uniaxial tensile loading to failure, and the recorded stress-strain behaviour of each specimen was assessed in terms of 6 biomechanical parameters. RESULTS: No statistically significant differences were found in any of the biomechanical parameters studied between the decellularized DA rat aorta group and both the native DA and Wistar rat aorta groups (P > .05). Also, no significant difference was shown between the native DA and native Wistar rat aorta groups. CONCLUSIONS: The results from this study have shown that the decellularization protocol did not affect the mechanical properties of the native rat aorta. In addition to this, both native Wistar and native/decellularized DA rat aorta groups shared similar mechanical properties.

A new era of ventricular assist device surgery: less invasive procedures.

As the number of patients suffering of congestive heart failure is rising worldwide, the use of mechanical circulatory support to treat these patients has also grown enormously, surpassing the number of annual heart transplants. Moreover latest generation of left ventricular assist devices (LVADs) is characterized by improved technologies. Moreover the size of new LVAD systems is considerably reduced when compared to older generation devices. Therefore, less invasive surgery is now possible for the implantation, explantation, and exchange of LVADs. Although experience with these new techniques is still limited, minimally invasive procedures are thought to improve surgical outcomes by declining the rates of operative complications such as bleeding or wound infection. The miniaturization of LVADs will continue, so that minimally invasive techniques will be used for most LVAD-related procedures in the future. In this article, we summarize and describe minimally invasive surgical techniques, with a focus on the most common LVAD systems in adults.

Paclitaxel-coated balloons in refractory nonanastomostic airway stenosis following lung transplantation.

Airway stenosis represents the commonest airway complication following lung transplantation, affecting between 7% and 18% of patients. Existing treatment options offer limited efficacy and can cause additional patient morbidity. Paclitaxel-coated balloons (PCB) have proved effective in managing postinterventional coronary artery re-stenosis. In a first-in-man study, we evaluated similar PCBs in refractory nonanastomotic airway stenosis in 12 patients. Following a single application, luminal patency was maintained in 50% at 270 days. No significant peri-interventional or early postinterventional complications occurred. Given these encouraging initial findings, further studies appear warranted.

Optimal timing of pulmonary metastasectomy--is a delayed operation beneficial or counterproductive?

INTRODUCTION: Pulmonary metastasectomy represents an established approach in the treatment of lung metastases related to several solid malignant tumors, promising the chance of long term survival. Regarding the proper timing of metastasectomy both operation promptly after diagnosis and delayed operation after an interval of 3 months are common practice. MATERIALS AND METHODS: A systematic Medline search addressing the optimal timing of metastasectomy was performed. Since the search query "timing of metastasectomy" yields only a limited number of articles, the Medline search was expanded to include the main arguments for prompt metastasectomy ("metastases of metastasis", "growth rate of pulmonary metastases") and for delayed metastasectomy. RESULTS: Based on the data available to date, there is no necessity to expedite the timing of the operation. On the other hand, there is no evidence that a delayed operation, for example after re-staging following an interval of 3 months, provides a benefit. CONCLUSION: Therefore the timing of metastasectomy should only depend on the patient's requirements, such as general state of health and oncologic considerations, such as promising multimodal therapy concepts, extrathoracal tumor manifestations or oncologic type of the primary tumor. A delayed operation seems justified if the indication for resection is questionable due to a high risk of early multilocal recurrence.

The impact of abdominal complications on the outcome after thoracic transplantation--a single center experience.

BACKGROUND: Abdominal complications after thoracic transplantation (Tx) are potentially associated with an increased risk of mortality. We recently reported about the severe outcome after bowel perforation in patients following lung transplantation (LuTx). The aim of the present study was to likewise identify the risk factors with an impact on patient survival following heart transplantation (HTx). METHODS: A retrospective analysis for the frequency and outcome of abdominal interventions following HTx was performed in 342 patients, and these data thereafter compared to a re-evaluated pool of 1,074 patients following LuTx. All patients were transplanted at Hanover Medical School, Germany, between January 2000 and October 2011. RESULTS: The incidence for abdominal surgery was comparable between patients following HTx (n = 33; 9.6 %) and LuTx (n = 90; 8.4 %). Elective operations were more frequently performed in patients after HTx (8.5 vs. 5.1 %). In contrast, the incidence of emergency interventions was higher after LuTx (5.3 %) than that following HTx (2.3 %). Herewith associated was the mortality observed in these transplant recipients (15.3 and 9.9 % for LuTx and HTx, respectively). Leading diagnosis for emergency surgery was bowel perforation (n = 18, regarding all cases). In 11 of these patients, perforation occurred within the first 6 months after Tx and eight of them died in the course of this complication (one patient after HTx and seven patients after LuTx). CONCLUSIONS: Abdominal complications after HTx are less frequently than after LuTx but equally correlate with a high mortality rate. In finding or even reasonable suspicion of an acute abdomen after thoracic Tx, a broad practice for extended diagnostics and a low barrier for an early explorative laparotomy thus are recommended.

Phenotyping established chronic lung allograft dysfunction predicts extracorporeal photopheresis response in lung transplant patients.

Chronic lung allograft dysfunction (CLAD) remains the leading cause of mortality in lung transplant recipients after the first year. Treatment remains limited and unpredictable. Existing data suggests extracorporeal photopheresis (ECP) may be beneficial. This study aimed to identify factors predicting treatment response and the prognostic implications. A single center retrospective analysis of all patients commencing ECP for CLAD between November 1, 2007 and September 1, 2011 was performed. In total 65 patients were included, 64 of whom had deteriorated under azithromycin. Median follow-up after commencing ECP was 503 days. Upon commencing ECP, all patients were classified using proposed criteria for emerging clinical phenotypes, including "restrictive allograft syndrome (RAS)", "neutrophilic CLAD (nCLAD)" and "rapid decliners". At follow-up, 8 patients demonstrated ≥10% improvement in FEV1 , 27 patients had stabilized and 30 patients exhibited ≥10% decline in FEV1 . Patients fulfilling criteria for "rapid decliners" (n=21, p=0.005), RAS (n=22, p=0.002) and those not exhibiting neutrophilia in bronchoalveolar lavage (n=44, p=0.01) exhibited poorer outcomes. ECP appears an effective second line treatment in CLAD patients progressing under azithromycin. ECP responders demonstrated improved progression-free survival (median 401 vs. 133 days). Proposed CLAD phenotypes require refinement, but appear to predict the likelihood of ECP response.