Gregor Warnecke

Hannover Medical School, Hanover, Lower Saxony, Germany

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Publications (139)407.12 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    American Journal of Transplantation 07/2014; · 6.19 Impact Factor
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    ABSTRACT: 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). 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. 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). 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.
    Langenbeck s Archives of Surgery 04/2014; · 1.89 Impact Factor
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    ABSTRACT: Background Infection and rejection represent major complications following lung transplantation and are often associated with pulmonary infiltrates. The differential diagnosis of these infiltrates depends on their timing after transplantation. The aim of this study was to characterize lung transplant recipients (LTR) presenting with new pulmonary infiltrates.MethodsA retrospective analysis of all LTR and heart–lung transplant recipients attending outpatient follow-up at our institution between September 1, 2006 and October 14, 2011 was performed. All patients presenting with new pulmonary infiltrates on chest x-ray who underwent bronchoscopy were included.ResultsA total of 913 patients accounted for 13,156 attendances, with 3,912 bronchoscopies being performed. Seventy-eight patients (9%) exhibited new pulmonary infiltrates and proceeded to bronchoscopy. Infiltrates occurred at a median 15 (interquartile range [IQR] 5–39) months after transplantation. Forty-eight patients (62%) were male, and median patient age was 47 (IQR 29–57) years. Subsequent investigation revealed pneumonia to be the underlying cause in 63 patients (81%). In the remaining patients, chronic lung allograft dysfunction (CLAD) was responsible in 6 (8%), acute rejection in 5 (6%), and toxic pneumonitis in 4 (5%) patients. Overall 1-year survival in LTR presenting with new infiltrates was 97%, compared with 96% for all LTR attending our Outpatient Department.Conclusions New pulmonary infiltrates occurring after the first month in LTR are most likely due to infection. Through prompt diagnosis and treatment, early mortality appears unaffected. Late mortality remains attributable to CLAD.
    Transplant Infectious Disease 04/2014; · 1.98 Impact Factor
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    ABSTRACT: Primary graft dysfunction (PGD) is the most important cause of early morbidity and mortality in lung transplantation (LTX) with an incidence of 8% to 20%. We hypothesized that application of C1-esterase-inhibitor (C1-INH) in LTX-recipients showing early signs of severe PGD would attenuate the condition. Starting as of May 2010, all recipients showing a PaO2/FiO2 ratio of less than 100 as early sign of PGD at first measurement in the OR were immediately treated with C1-INH. Postoperative courses of C1-INH-treated recipients were compared with a subgroup of recipients that developed severe PGD (PGD3-group) within 72 hours after LTX but did not receive C1-INH. Additionally, a third group consisting of all remaining recipients was assembled. A total of 275 LTX were performed between May 2010 and September 2012 at our center. Among these, 24 patients (8.7%) revealed a first PaO2/FiO2 ratio less than 100 and were treated with C1-INH (C1-INH-group). The PGD3-group consisted of 14 patients; the control cohort consisted of 237 patients. PGD scores were significantly higher in the C1-INH-group and PGD3-group as compared with the control group at all times postoperatively. ICU stay was longest in the PGD3 cohort and prolonged in C1-INH patients compared with the control group (29 [2-70] vs. 9 [2-83] vs. 3 [1-166] days, P=0.002). One-year survival in the PGD3-cohort was 71.4%, the C1-INH-treated-group had a one-year-survival of 82.5%, the control group had the best outcome (95%) (P=0.001). Treatment of PGD with C1-INH led to acceptable outcome. Although survival in the C1-INH treated patients was lower than in the remaining collective, it was as good or better, compared with the PGD3 group and as what is internationally regarded as reasonable after LTX.
    Transplantation 02/2014; · 3.78 Impact Factor
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    ABSTRACT: Accurate immunosuppression is of critical importance in preventing rejection, while avoiding toxicity following lung transplantation. The mainstay immunosuppressants are calcineurin inhibitors, which require regular monitoring due to interactions with other medications and diet. Adherence to immunosuppression and patient knowledge is vital and can be improved through patient education. Education using tablet-computers was investigated. To compare tablet-PC education and conventional education in improving immunosuppression trough levels in target range 6 months after a single education. Secondary parameters were ratio of immunosuppression level measurements divided by per protocol recommended measurements, time and patient satisfaction regarding education. Single-centre, open labelled randomised controlled trial. Patients >6 months after lung-transplantation with <50% of calcineurin inhibitor trough levels in target range. Tablet-pc education versus personal, nurse-led education. Calcineurin inhibitor levels in target range 6 months after education, level variability, interval adherence, knowledge and adherence was studied. As outcome parameter, renal function was measured and adverse events registered. Sixty-four patients were 1:1 randomised for either intervention. Levels of immunosuppression 6 months after education were equal (tablet-PC 58% vs. conventional 48%, p = 0.27), both groups improved in achieving a CNI trough level within target range by either education method (delta tablet-PC 29% vs. conventional 20%). In all patients, level variability decreased (-20.4%), whereas interval adherence remained unchanged. Knowledge about immunosuppression improved by 7% and compliance tests demonstrated universal improvements with no significant difference between groups. Education is a simple, effective tool in improving adherence to immunosuppression. Tablet-PC education was non-inferior to conventional education. ClinicalTrials.gov NCT01398488 http://clinicaltrials.gov/ct2/show/NCT01398488?term=gottlieb+tablet+pc+education&rank=1.
    PLoS ONE 01/2014; 9(3):e90828. · 3.53 Impact Factor
  • The Journal of Heart and Lung Transplantation. 01/2014; 33(4):S17–S18.
  • Heart Lung &amp Circulation 01/2014; · 1.25 Impact Factor
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    ABSTRACT: Background The impact of early donor specific anti-HLA antibodies (DSA) on patient and graft survival following lung transplantation remains controversial. This study aims to analyze risk factors for DSA that developed before initial hospital discharge after lung transplantation (early DSA) and to compare mid-term outcomes in patients with or without DSA. Methods Between 01/2009 and 08/2013, 546 patients underwent lung transplantation at our institution. One hundred (18%) patients developed early DSA (Group A), 446 (82%) patients (Group B) did not. Patient records were retrospectively reviewed. Results Retransplantation (OR=2.7; 95% confidence interval [CI] 1.1 to 6.5 p=0.03), preoperative HLA antibodies (OR=2.1; 95%CI 1.2-3.4 p=0.003) and primary graft dysfunction (PGD) score grade 2-3 at 48 hours (OR=2.6; 95%CI 1.5-4.6 p=0.001) were associated with early DSA development. Overall, 1 and 3-year survival in Group A and B patients was 79±4% vs. 88±2% and 57±8% vs. 74±3%, respectively (p=0.019). Eleven Group A (11%) and 32 Group B (7%) patients died prior to hospital discharge (p=0.34). Among patients surviving beyond discharge, 1 and 3-year survival in Group A and B patients was 89±4% vs. 95±1% and 65±8% vs. 80±3% in group A and B patients, respectively (p=0.04). Multivariate analysis identified early anti-HLA class II DSA (OR=1.9; 95% CI 1.0-3.4, p=0.04) as an independent risk factor for post-discharge mortality but not for in-hospital mortality. Conclusions Preoperative HLA antibodies, re-transplantation or postoperative PGD increase the risk of developing early DSA, which were independently associated with an increased risk for mortality.
    The Journal of Heart and Lung Transplantation. 01/2014;
  • The Journal of Heart and Lung Transplantation. 01/2014; 33(4):S17.
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    ABSTRACT: To prospectively evaluate quantitative airway wall measurements of thin-section CT for the diagnosis of Bronchiolitis Obliterans Syndrome (BOS) following lung transplantation. In 141 CT examinations, bronchial wall thickness (WT), the wall area percentage (WA%) calculated as the ratio of the bronchial wall area and the total area (sum of bronchial wall area and bronchial lumen area) and the difference of the WT on inspiration and expiration (WTdiff) were automatically measured in different bronchial generations. The measurements were correlated with the lung function parameters. WT and WA% in CT examinations of patients with (n = 25) and without (n = 116) BOS, were compared using the unpaired t-test and univariate analysis of variance, while also considering the differing lung volumes. Measurements could be performed in 2,978 bronchial generations. WT, WA%, and WTdiff did not correlate with the lung function parameters (r<0.5). The WA% on inspiration was significantly greater in patients with BOS than in patients without BOS, even when considering the dependency of the lung volume on the measurements. WT on inspiration and expiration and WA% on expiration did not show significant differences between the groups. WA% on inspiration was significantly greater in patients with than in those without BOS. However, WA% measurements were significantly dependent on lung volume and showed a high variability, thus not allowing the sole use of bronchial wall measurements to differentiate patients with from those without BOS.
    PLoS ONE 01/2014; 9(4):e93783. · 3.53 Impact Factor
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    ABSTRACT: Bronchoscopy represents an important diagnostic and therapeutic tool in the management of lung transplant (LTx) recipients. Outpatient bronchoscopy reduces health costs and may improve quality of life amongst these patients. This retrospective study assessed the safety and efficacy of outpatient bronchoscopy including trans-bronchial biopsy.
    Transplantation research. 01/2014; 3:11.
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    ABSTRACT: The long-term success of human lung transplantation is limited by the development of bronchiolitis obliterans syndrome. Acute rejection episodes and infections are important risk factors and seem to play major pathogenic roles. We established a relevant experimental model that mimics important aspects of human bronchiolitis obliterans syndrome. The Fischer 344-to-Lewis rat strain combination was used for orthotopic left lung transplantation. Isogeneic transplantations were performed in the Lewis rat. Recipients were treated with ciclosporin for 10 days. Lipopolysaccharide or vehicle was instilled into the airways 28 days after transplantation. Grafts were monitored by computed tomography, and recipients were euthanized on Days 28-90. The messenger RNA expression of selected chemokines and their receptors was measured on Days 28, 29, 33, 40 after transplantation. Graft histopathology on Day 90 was compared with lungs from patients who underwent re-transplantation due to end-stage allograft dysfunction. Lung allografts treated with ciclosporin and vehicle only sporadically displayed tissue remodeling. In contrast, lipopolysaccharide treatment induced severe inflammation. In the long-term, severe vascular remodeling, lung fibrosis, and fibroproliferative remodeling of airways were found that closely resemble the histopathologic changes in grafts from human patients with bronchiolitis obliterans syndrome. Chronic damage was virtually absent from pulmonary isografts and native right lungs. Chemokine (C-C motif) ligand 5 and chemokine (C-X-C motif) ligand 9-11, and their receptors, were over-expressed in allografts. Our experimental model mirrors key aspects of human bronchiolitis obliterans syndrome. It will be useful to elucidate its pathogenesis and to develop therapeutic approaches improving the long-term outcome of human lung transplantation.
    The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 09/2013; · 3.54 Impact Factor
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    ABSTRACT: Paraquat is a highly toxic herbicide, which not only leads to acute organ damage, but also to pulmonary fibrosis. There are only anecdotal reports of rescue lung transplantation, as paraquat is stored and only slowly released from different tissues. Bridging the time to complete depletion of paraquat from the body could render this exceptional therapy strategy possible, but not much is known on the time interval after which transplantation can safely be performed. We report on a case of accidental paraquat poisoning in a 23 years old Caucasian man, who developed respiratory failure due to pulmonary fibrosis. The patient was listed for high urgency lung transplantion, and extracorporeal membrane oxygenation was implemented to bridge the time to transplantation. The patient died 32 days after paraquat ingestion, before a suitable donor organ was found. In postmortem tissue specimen, no paraquat was detectable anymore. This case report indicates that complete elimination of paraquat after oral ingestion of a lethal dose is achievable. The determined time frame for this complete elimination might be relevant for patients, in which lung transplantation is considered.
    BMC pharmacology & toxicology. 09/2013; 14(1):45.
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    ABSTRACT: Despite the scarcity of donor lungs, most potential donor organs are not offered by organ procurement organizations or are turned down by transplant centers because no suitable recipient is found according to regular allocation. Although extended criteria donors (ECDs) have recently been considered by many programs, the lung utilization rate remains <30% in most countries. The allocation policy of Eurotransplant for donor lungs that have been turned down for donor-related medical reasons by 3 centers is to attempt a rescue offer, for which centers choose the recipients themselves. At Hannover Medical School we systematically divert these organs to more stable recipients to avoid adverse transplant outcomes. We follow up on these transplants and compare them with those following regular allocation. This study is an analysis of all organ offers and corresponding recipients at our center during the period from January 2010 to August 2011. A total of 183 lung transplantations were performed, 111 regular donor lung offers were accepted for their intended recipient, whereas a total of 72 rescue lung offers, including all extended criteria donors, were accepted for recipients selected by our center. Donor characteristics differed between the 2 groups accordingly. Median age of ECD organ donors was significantly higher than that of regular donors (46.0 [IQR 21] vs 40.0 [IQR 22] years, p = 0.02). Donor mechanical ventilation time did not differ (3.5 ± 4.8 vs 3.0 ± 4.0 days, p = 0.33, not statistically significant [NS]). Donor oxygenation ratio (PaO2:FIO2) at time of organ offer was significantly lower (398.3 ± 110.3 vs 423.0 ± 97.6 mm Hg, p = 0.02). Recipients of rescue allocation organs were older than regularly selected recipients (53.7 ± 11.7 vs 46.7 ± 15.4 years, p = 0.0003), needed a shorter time for mechanical ventilation post-operatively (19.5 ± 306.6 vs 68.5 ± 718.8 hours, p = 0.02), and had shorter hospital stays (24.0 ± 23.4 vs 47.0 ± 43.4 days, p > 0.0001). Intensive care stay length did not differ significantly (2.0 ± 14.5 vs 5.0 ± 23.7 days, p = 0.21 [NS]). Post-operative survival up to 27 months after transplantation was not worse in recipients receiving rescue allocation when compared with standard allocation lung offers (81.62% vs 80.76%, p = 0.89 [NS]). The pre-operative status of the 2 recipient cohorts differed considerably, as indicated by the standard allocation group consisting of 65.8% "high-urgency" (HU)-listed patients, whereas the rescue offers were used for only 11.1% of HU-listed recipients, reflecting our center's policy. Rescue allocation donor lungs can be used safely for transplantation and therefore salvaged for the donor pool. The data support our policy of accepting marginal donor lungs for stable recipients. This practice leads to very good overall survival.
    The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 08/2013; · 3.54 Impact Factor
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    European Journal of Intensive Care Medicine 08/2013; · 5.17 Impact Factor
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    ABSTRACT: Topical in situ cooling of the donor lungs is a prerequisite for procurement of non-heart-beating donor lungs and may be of interest for living related lung donation. Twenty-four single lung transplants were performed in 4 groups of Landrace pigs (6 per group). Control LPD, control Celsior and topical cooling in situ, followed by LPD (exLPD) or Celsior (exCel) ex situ flush, were employed. All lungs were perfused antegrade with 1 liter of solution at 4°C. Lungs were stored immersed in preservation solution for 24 hours at 4°C. After transplantation of the left lung, the right recipient bronchus and pulmonary artery were clamped. Four of 6 animals each in the LPD and Celsior groups and all 6 animals in both the exLPD and the exCel groups survived the 7-hour reperfusion. The mean oxygenation index was favorably preserved in the exCel group at 7 hours after reperfusion (417 ± 81) over all other groups (LPD 341 ± 133, Celsior 387 ± 86, exLPD 327 ± 76; p < 0.0001). Pulmonary vascular resistance showed significantly lower values in the Celsior and exCel groups (LPD 1,310 ± 620, Celsior 584 ± 194, exLPD 1,035 ± 361, exCel 650 ± 116 dyn/s/cm(5) at 7 hours after reperfusion; p < 0.0001). Consistently, the wet-to-dry lung weight ratio also indicated beneficial graft protection in the exCel group (LPD 8.1 ± 0.8, Celsior 8.4 ± 0.8, exLPD 7.5 ± 1.0, exCel 3.1 ± 0.9; p < 0.0001). Initial topical cooling followed by backtable perfusion is a sufficient technique for pulmonary graft preservation providing excellent post-transplant function. Celsior subsequent to in-situ topical cooling revealed the most beneficial results in this setting. This combined technique could advance non-heart-beating, living related lung lobe donation and, potentially, regular heart-beating lung donation.
    The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 08/2013; 32(8):832-8. · 3.54 Impact Factor
  • European Respiratory Journal 08/2013; 42(2):542-4. · 6.36 Impact Factor
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    ABSTRACT: Different types of endothelial cells (EC) fulfill distinct tasks depending on their microenvironment. ECs are therefore difficult to genetically manipulate ex vivo for functional studies or gene therapy. We assessed lentiviral vectors (LVs) targeted to the EC surface marker CD105 for in vivo gene delivery. The mouse CD105-specific vector, mCD105-LV, transduced only CD105-positive cells in primary liver cell cultures. Upon systemic injection, strong reporter gene expression was detected in liver where mCD105-LV specifically transduced liver sinusoidal ECs (LSECs), but not Kupffer cells which were mainly transduced by non-targeted LVs. Tumor ECs were specifically targeted upon intratumoral vector injection. Delivery of the erythropoietin gene with mCD105-LV resulted in substantially increased erythropoietin and hematocrit levels. The human CD105-specific vector (huCD105-LV) transduced exclusively human LSECs in mice transplanted with human liver ECs. Interestingly, when applied at higher dose and in absence of target cells in the liver, huCD105-LV transduced ECs of a human artery transplanted into the descending mouse aorta. The data demonstrate for the first time targeted gene delivery to specialized endothelial cells upon systemic vector administration. This strategy offers novel options to better understand the physiological functions of endothelial cells and to treat genetic diseases such as those affecting blood factors.
    Blood 07/2013; · 9.78 Impact Factor
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    ABSTRACT: BACKGROUND: Short-term posttransplantation survival and health-related quality of life (HRQoL) is exceptionally high for all patients after organ transplantation; however, predictors of the HRQoL outcome are not well understood. Trajectories of patients' perceived benefit/burden ratio associated with the transplant procedure may differ when taking the organ type for transplantation into account. METHODS: A prospective, single-center cohort study assessed the trajectories of 354 patients after kidney (n=165), liver (n=53), heart (n=24), and lung (n=112) transplantation at 2, 6, 12, and 24 months with respect to psychosocial outcomes (HRQoL, anxiety, depression, social support, and work performance). RESULTS: Mean age was 50±13 years, and 61.6% were male in the overall sample. Demographics differed with respect to organ type. HRQoL measured by the mean SF-36 Physical Component Scale was 36.8 (95% confidence interval, 35.7-37.8) and 48.9 (95% confidence interval, 47.2-49.7) for the Psychosocial Component Scale for the entire sample at 2 months and showed a marginal decrease until 24 months after transplantation. Overall, HRQoL increased for all organ types with differing trajectories. Liver patients reported the lowest HRQoL benefit for the majority of the physical (P≤0.01) and psychosocial (P≤0.01) SF-36 subscales. Anxiety (17.4%) and depression (13.8%) were prevalent in the overall sample. Depression symptoms impaired HRQoL outcomes in both SF-36 components and unemployment impacted the SF-36 psychosocial outcomes. CONCLUSIONS: HRQoL improved after transplantation for all four types of transplant, but the trajectories were different. Regular screening for depression symptoms may diminish psychologic disorders and distress after transplantation and thus may further improve outcomes.
    Transplantation 05/2013; · 3.78 Impact Factor
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    ABSTRACT: BACKGROUND: Advanced chronic lung allograft dysfunction limits survival after lung transplantation. We hypothesize that patients with chronic lung allograft dysfunction can be subdivided by exercise tolerance in two groups, and quality of life (QOL) and survival differ between the groups. METHODS: A single-center, cross-sectional, partly prospective, study was performed in our outpatient clinic between July and November 2011, including all patients with a forced expiratory volume in 1 s <50% baseline. Respiratory parameters, 6-min walk test, and QOL were measured. Patients with low exercise capacity were defined as 6-min walk test <50% predicted or use of rollator or wheelchair. RESULTS: Fifty-two patients consented to participating in the study and 22 demonstrated low exercise capacity. These patients had pathologic respiratory muscle function (P=0.005) and decreased inspiratory capacity (IC; P=0.001). QOL was significantly reduced. Multivariate analysis proved that low IC (hazard ratio, 17.9; 95% confidence interval, 2.8-111; P=0.002) and increased P0.1/Pimax (hazard ratio, 7.1; 95% confidence interval, 1.4-35.8; P=0.016) were independently associated with decrease exercise capacity. CONCLUSION: Heterogeneity of patients with advanced lung allograft dysfunction regarding exercise tolerance might result from altered IC and impaired respiratory muscle function.
    Transplantation 04/2013; 95(8):1045-1050. · 3.78 Impact Factor

Publication Stats

738 Citations
407.12 Total Impact Points

Institutions

  • 2000–2014
    • Hannover Medical School
      • • Department of Cardiothoracic, Transplantation and Vascular Surgery (HTTG)
      • • Department of Cardiology and Angiology
      Hanover, Lower Saxony, Germany
  • 2013
    • Johannes Gutenberg-Universität Mainz
      Mayence, Rheinland-Pfalz, Germany
  • 2007–2010
    • Oxford University Hospitals NHS Trust
      • Nuffield Department of Surgery
      Oxford, England, United Kingdom
  • 2003
    • Klinikum Braunschweig
      Brunswyck, Lower Saxony, Germany