Arne K Andreassen

Oslo University Hospital, Kristiania (historical), Oslo, Norway

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Publications (101)447.47 Total impact

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    ABSTRACT: Early initiation of everolimus with calcineurin inhibitor therapy has been shown to reduce the progression of cardiac allograft vasculopathy (CAV) in de novo heart transplant recipients. The effect of de novo everolimus therapy and early total elimination of calcineurin inhibitor therapy has, however, not been investigated and is relevant given the morbidity and lack of efficacy of current protocols in preventing CAV. This 12-month multicenter Scandinavian trial randomized 115 de novo heart transplant recipients to everolimus with complete calcineurin inhibitor elimination 7-11 weeks after HTx or standard cyclosporine immunosuppression. Ninety-five (83%) patients had matched intravascular ultrasound examinations at baseline and 12 months. Mean (± SD) recipient age was 49.9 ± 13.1 years. The everolimus group (n = 47) demonstrated significantly reduced CAV progression as compared to the calcineurin inhibitor group (n = 48) (ΔMaximal Intimal Thickness 0.03 ± 0.06 and 0.08 ± 0.12 mm, ΔPercent Atheroma Volume 1.3 ± 2.3 and 4.2 ± 5.0%, ΔTotal Atheroma Volume 1.1 ± 19.2 mm(3) and 13.8 ± 28.0 mm(3) [all p-values ≤ 0.01]). Everolimus patients also had a significantly greater decline in levels of soluble tumor necrosis factor receptor-1 as compared to the calcineurin inhibitor group (p = 0.02). These preliminary results suggest that an everolimus-based CNI-free can potentially be considered in suitable de novo HTx recipients. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.
    American Journal of Transplantation 03/2015; DOI:10.1111/ajt.13214
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    ABSTRACT: Heart failure patients with reduced and preserved left ventricular (LV) ejection fraction (EF) show reduced exercise capacity. We explored the relationship between exercise capacity and systolic and diastolic myocardial function in heart failure patients. Exercise capacity, by peak oxygen uptake (VO2), was assessed in 100 patients (56 ± 12 years, NYHA functional class: 2.5 ± 0.9, EF: 42 ± 19%). LV systolic function, as EF and global longitudinal strain (GLS), and right ventricular function were assessed by echocardiography. Left atrial volume index and the ratio of peak early diastolic filling velocity (E) to early diastolic mitral annular velocity (e') were measures of diastolic function. Thirty-seven patients had heart failure with preserved EF (HFpEF), defined as EF ≥50% and echocardiographic diastolic dysfunction. LV GLS and peak pulmonary arterial systolic pressure were independently correlated to peak VO2 in the total study population and in HFpEF separately. LV GLS was superior to EF in identifying patients with impaired peak VO2 <20 mL/kg/min as shown by receiver operating characteristic analyses [areas under curves 0.93 (0.89-0.98) vs. 0.85 (0.77-0.93), P < 0.05]. In patients with HFpEF, GLS was reduced below normal (-17.5 ± 3.2%) and correlated to E/e' (R = 0.45, P = 0.005) and left atrial volume index (R = 0.48, P = 0.003), while EF did not. GLS correlated independently to peak VO2 in patients with reduced and preserved EF and was superior in identifying patients with reduced exercise capacity. In HFpEF, systolic function by GLS was impaired. There was a significant relationship between diastolic function and GLS, confirming a coupling between diastolic and longitudinal systolic function in HFpEF. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.
    European Heart Journal – Cardiovascular Imaging 12/2014; 16(2). DOI:10.1093/ehjci/jeu277
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    ABSTRACT: Elevated levels of soluble ST2 (sST2) are associated with adverse outcome in heart failure. A change in sST2 levels has also been shown to presage outcome. In vitro, ST2 expression is induced by myocardial stress and pro-inflammatory stimuli. The determinants of sST2 levels in vivo, and how they vary with clinical status over time, have not been well described. In a cohort of patients with non-ischemic heart failure, we aimed to assess the association between sST2-levels and hemodynamic parameters reflecting right and left ventricular pre- and afterload, and how these vary with time and clinical status.Methods We prospectively recruited 102 patients with a left ventricular ejection fraction of 26 ± 10% and a diagnosis of idiopathic dilated cardiomyopathy based on patient history, clinical examination, echocardiography and coronary angiography. Patients went through extensive baseline work-up and were re-examined after one year. Subsequently, heart transplantations and deaths were recorded. Determinants of sST2 were analyzed at baseline and after one year. Soluble ST2 was measured with a highly sensitive immunoassay.ResultsSoluble ST2 levels were associated with hemodynamic parameters, but these associations were attenuated with clinical improvement. Soluble ST2 was elevated in patients with severe symptoms, but did not vary with etiology, viral presence or the amount of myocardial fibrosis. Heart rate and right atrial pressure remained independent predictors of sST2 on multiple regression analysis.Conclusions Our results imply that in non-ischemic heart failure, sST2 reflects hemodynamic stress rather than pathogenic processes in the myocardium.
    International Journal of Cardiology 11/2014; 179. DOI:10.1016/j.ijcard.2014.11.003
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    ABSTRACT: In a randomized, open-label trial, everolimus was compared to cyclosporine in 115 de novo heart transplant recipients. Patients were assigned within 5 days posttransplant to low-exposure everolimus (3–6 ng/mL) with reduced-exposure cyclosporine (n = 56), or standard-exposure cyclosporine (n = 59), with both mycophenolate mofetil and corticosteroids. In the everolimus group, cyclosporine was withdrawn after 7–11 weeks and everolimus exposure increased (6–10 ng/mL). The primary efficacy end point, measured GFR at 12 months posttransplant, was significantly higher with everolimus versus cyclosporine (mean ± SD: 79.8 ± 17.7 mL/min/1.73 m2 vs. 61.5 ± 19.6 mL/min/1.73 m2; p < 0.001). Coronary intravascular ultrasound showed that the mean increase in maximal intimal thickness was smaller (0.03 mm [95% CI 0.01, 0.05 mm] vs. 0.08 mm [95% CI 0.05, 0.12 mm], p = 0.03), and the incidence of cardiac allograft vasculopathy (CAV) was lower (50.0% vs. 64.6%, p = 0.003), with everolimus versus cyclosporine at month 12. Biopsy-proven acute rejection after weeks 7–11 was more frequent with everolimus (p = 0.03). Left ventricular function was not inferior with everolimus versus cyclosporine. Cytomegalovirus infection was less common with everolimus (5.4% vs. 30.5%, p < 0.001); the incidence of bacterial infection was similar. In conclusion, everolimus-based immunosuppression with early elimination of cyclosporine markedly improved renal function after heart transplantation. Since postoperative safety was not jeopardized and development of CAV was attenuated, this strategy may benefit long-term outcome.
    American Journal of Transplantation 07/2014; DOI:10.1111/ajt.12809
  • The Journal of Heart and Lung Transplantation 04/2014; 33(4):S154. DOI:10.1016/j.healun.2014.01.412
  • The Journal of Heart and Lung Transplantation 04/2014; 33(4):S281. DOI:10.1016/j.healun.2014.01.748
  • The Journal of Heart and Lung Transplantation 04/2014; 33(4):S134. DOI:10.1016/j.healun.2014.01.361
  • The Journal of Heart and Lung Transplantation 04/2014; 33(4):S173-S174. DOI:10.1016/j.healun.2014.01.469
  • The Journal of Heart and Lung Transplantation 04/2014; 33(4):S128. DOI:10.1016/j.healun.2014.01.343
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    ABSTRACT: To examine the effect of balloon pulmonary angioplasty (BPA) on chronic thromboembolic pulmonary hypertension (CTEPH) in patients with inoperable disease or persistent pulmonary hypertension after pulmonary endarterectomy. Observational cohort study. Referred patients with inoperable or persistent CTEPH. Twenty consecutive CTEPH patients (10 females), aged 60±10 years. Right heart catheterisation, functional capacity (cardiopulmonary exercise testing (CPET) and NYHA class) and blood sampled biomarkers N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin T examined at the time of diagnosis and repeated in all patients 3 months after the last BPA. Seventy-three catheterisations were performed with 18.6±6.1 BPAs per patient on segmental and subsegmental arteries. Two deaths occurred following the first BPA, with an overall 10% periprocedural death rate. Reperfusion oedema complicated seven procedures. Comparisons before and after BPA showed significant haemodynamic improvements, including decreased mean pulmonary artery pressure (mPAP) (45±11 mm Hg vs 33±10 mm Hg; p<0.001) and increased cardiac output (4.9±1.6 L/min vs 5.4±1.9 L/min; p=0.011). Reduced right ventricular strain was indicated by significantly lower plasma levels of NT-proBNP and troponin T. Significant improvement in functional capacity was evident as assessed by NYHA class (3.0±0.5 vs 2.0±0.5; p<0.001) and CPET (13.6±5.6 mL/kg/min vs 17.0±6.5 mL/kg/min; p<0.001). Seventeen patients (85%) were alive after 51±30 months of follow-up. BPA may offer an alternative form of treatment in selected CTEPH patients. While prognostic markers such as haemodynamics, functional capacity and biomarkers improve, significant periprocedural complications must be recognised. Randomised trials are warranted.
    Heart (British Cardiac Society) 07/2013; 99(19). DOI:10.1136/heartjnl-2012-303549
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    ABSTRACT: OBJECTIVES: Due to the need for suitable donors for heart transplantation (HTx), older grafts and grafts with prolonged graft ischaemic time (GIT) are accepted. The impact of GIT and donor age on post-transplant cardiac function has not been examined with either newer echocardiographic techniques (tissue Doppler imaging, TDI) or cardiopulmonary exercise testing (CPET). Thus, we studied the influence of GIT and donor age on post-transplant cardiac function and exercise capacity. METHODS: Fifty-two stable recipients underwent echocardiography with colour TDI and CPET at a median of 4 years after HTx. Left ventricular (LV) systolic (s') and early diastolic (e') mitral annular velocities, right ventricular (RV) s', RVe' as well as LV ejection fraction (EF) and VO2peak were analysed. RESULTS: HTx recipients with GIT ≥ median value (200 min) had significantly lower septal LVs' (15%, P = 0.005), LVEF (9%, P = 0.015), RVs' (21%, P = 0.007), septal LVe' (22%, P = 0.001) and RVe' velocities (23%, P = 0.011), and slightly lower VO2peak (P = 0.098). Recipients with grafts from donor ≥median age (37 years) had significantly lower LVe' velocities (septal LVe' P = 0.047 and lateral LVe' P = 0.010), but not LV systolic or RV parameters. CONCLUSIONS: Prolonged GIT impairs both systolic and diastolic function at the interventricular septum and RV free wall, while increasing donor age impairs LV diastolic function. The duration of graft ischaemia and donor age should be taken into account when evaluating for cardiac dysfunction in HTx recipients.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 05/2013; 44(2). DOI:10.1093/ejcts/ezt233
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    ABSTRACT: Background In the early phases following heart transplantation a main challenge is to reduce the impact of acute rejections. Previous studies indicate that intracellular ciclosporin A (CsA) concentration may be a sensitive acute rejection marker in renal transplant recipients. The aims of this study were to evaluate the relationships between CsA concentrations at different target sites as potential therapeutic drug monitoring (TDM) tools in heart transplant recipients. Methods Ten heart transplant recipients (8 men, 2 women) on CsA-based immunosuppression were enrolled in this prospective single-center pilot study. Blood samples were obtained once to twice weekly up to 12 weeks post-transplant. One of the routine biopsies was allocated to this study at each sampling time. Whole blood, intralymphocyte, and endomyocardial CsA concentrations were determined with validated HPLC-MS/MS-methods. Mann–Whitney U test was used when evaluating parameters between the two groups of patients. To correlate whole blood, intralymphocyte, and endomyocardial CsA concentrations linear regression analysis was used. Results Three patients experienced mild rejections. In the study period, the mean (range) intralymphocyte CsA trough concentrations were 10.1 (1.5 to 39) and 8.1 (1.3 to 25) ng/106 cells in the rejection and no-rejection group, respectively (P=0.21). Corresponding whole blood CsA concentrations were 316 (153 to 564) and 301 (152 to 513) ng/mL (P=0.33). There were no correlations between whole blood, intralymphocyte, or endomyocardial concentrations of CsA (P >0.11). Conclusions The study did not support an association between decreasing intralymphocyte CsA concentrations and acute rejections. Further, there were no association between blood concentrations and concentrations at sites of action, potentially challenging TDM in these patients.
    04/2013; 2(1):5. DOI:10.1186/2047-1440-2-5
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    ABSTRACT: Calcineurin inhibitors (CNIs) remain the mainstay of immunosuppression following heart transplantation (HTx) but are associated with significant complications such as nephrotoxicity. We therefore designed a randomized trial to assess whether early introduction of everolimus (Evr) followed by withdrawal of cyclosporine (CsA) would lead to superior renal function and less chronic allograft vasculopathy (CAV) in de novo HTx recipients compared to a standard protocol of CsA-based immunosuppression.Methods and MaterialsA 12 months’ prospective, multicenter, parallell group, open-labeled study with randomization within 5 days post-HTx to CsA, mycophenolate mofetil (MMF) and corticosteroids (CS) (Group A) or to low dose Evr and reduced dose CsA, MMF and CS, with CsA withdrawal and full-dose Evr after 7-11 weeks (Group B).ResultsThe primary objective was to compare renal function assessed by measured glomerual filtration rate (mGFR) 12 months after HTx. Secondary objectives included differences in progression of CAV assessed by IVUS, renal function evaluated by change of mGFR between weeks 7-11 to month 12, renal function estimated by calculated GFR (cGFR) at each follow-up visit, number of rejections and occurence of treatment failures up to 12 months (graft loss, death, loss to follw-up or discontinuation due to lack of efficacy or toxicity), proteinuria, lipid profile, left ventricular function, safety and tolerability). Altogether 116 patients were recruited and randomized to Group A (n = 59) and Group B (n = 57) with mean (SD) age of 51.5 (12.4) and 51.1 (12.8), respectively, from 1. of December 2009 to 31. of December 2011. The last patient will complete the study in December 2012.Conclusions To be presented at the meeting.
    The Journal of Heart and Lung Transplantation 04/2013; 32(4):S134. DOI:10.1016/j.healun.2013.01.298
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    ABSTRACT: Cancer is a major cause of death after heart transplantation (HTx).Methods and MaterialsIn our national HTx center we linked our HTx database to the Norwegian Cancer Registry and examined risk factors for developing cancer post-HTx using logistic regression. Standard incidence ratios (SIR) for HTx compared to the general population were estimated. Cancer survival of HTx recipients was compared to a matched non-HTx control group, consisting of 10 cancer patients per HTx recipient.ResultsOf 650 HTx recipients (1983-2009) in our non-induction center, 143 recipients developed 240 cancers (130 skin, 22 lymfoproliferative and 88 solid cancers). Risk factors for developing cancer were increasing age at HTx, male sex, immunosuppressive burden (azathioprine and cyclosporine dose and use of cytotoxic rejection treatment) and smoking-years post-HTx. Independent risk factors were older age at HTx [OR=1.08 (1.02-1.13), p<0.005], azathioprine dose [OR=1.01 (1.01-1.02), p<0.001] and smoking years post-HTx [OR=1.14 (1.03-1.25), p<0.010]. SIR analysis revealed that the cancer risk was 3.6 (3.1-4.1) for men and 2.3 (1.4-3.5) for females in the HTx group compared to the general population. Highest SIR [27.8 (23.9-34.0)] was for males developing skin cancer. The risk of dying of cancer was higher among HTx-cancer patients;HR 2.04 (1.36-3.06), p<0.001. [figure 1]Conclusions In the Norwegian cohort, increasing age, azathioprine dose and smoking-years post-HTx are independent predictors of cancer post-HTx. Cancer is twice as common in females and tree times more frequent in male recipients than in the general population. Cancer related deaths are twice as common as among non-HTx cancer patients.
    The Journal of Heart and Lung Transplantation 04/2013; 32(4):S253. DOI:10.1016/j.healun.2013.01.655
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    ABSTRACT: Objectives. The aim of this study was to assess the overall prevalence of pulmonary hypertension (PH) in an unselected MCTD cohort and review the current knowledge with a systematic database search.Methods. A nationwide multicentre cohort of 147 adult MCTD patients were initially screened for PH by echocardiography, high-resolution computed tomography (HRCT), pulmonary function tests and N-terminal pro-brain natriuretic peptide (NT-proBNP) and then followed up for a mean of 5.6 years. Right-sided heart catheterization was performed when estimated pulmonary artery systolic pressure was >40 mmHg on echocardiography. PH was diagnosed according to the 2009 European Society of Cardiology and European Respiratory Society guidelines.Results. At inclusion, 2.0% (3/147) had established PH. Two additional PH patients were identified during follow-up, giving a total PH frequency in the cohort of 3.4% (5/147). All five had elevated serum NT-proBNP. Two had isolated pulmonary arterial hypertension (PAH) and three PH associated with interstitial lung disease (PH-ILD). Three PH patients died during follow-up. Nine other patients in the cohort also died, but none of them had echocardiographic signs of PH prior to death.Conclusion. The data from the current unselected MCTD cohort suggest that the prevalence of PH is much lower than expected from previous studies but confirm the seriousness of the disease complication.
    Rheumatology (Oxford, England) 02/2013; 52(7). DOI:10.1093/rheumatology/kes430
  • Arne K Andreassen
    Tidsskrift for den Norske laegeforening 06/2012; 132(12-13):1469-70. DOI:10.4045/tidsskr.12.0436
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    ABSTRACT: Left ventricular (LV) function can be accurately assessed using two-dimensional speckle-tracking echocardiography. The association between reduced LV global longitudinal strain (LVGLS) magnitude and risk for mortality in heart transplant recipients is unclear. The aim of this study was to test the hypothesis that LVGLS could predict 1-year mortality in heart transplant recipients. A total of 176 consecutive adult primary single-organ orthotopic heart transplant recipients were retrospectively evaluated. Of these, 167 had acceptable echocardiographic image quality and were included in the study. N-terminal pro-B-type natriuretic peptide, creatinine, C-reactive protein, and invasive hemodynamic parameters were measured, and echocardiography was performed 1 to 3 weeks after heart transplantation. LVGLS was averaged from regional strain in 16 LV segments. During the first year, 15 patients (9%) died 86 ± 72 days after heart transplantation. LVGLS and LV ejection fraction were decreased in magnitude in nonsurvivors (P < .05). They were older and had higher donor ages. Mean pulmonary capillary wedge pressures were similar in the two groups, while all other hemodynamic parameters were increased in nonsurvivors (P < .05). LVGLS was the only significant (P = .02) noninvasive independent predictor, with a hazard ratio of 1.42 (95% confidence interval, 1.07-1.88; P = .02) per 1% decrease in strain magnitude, while pulmonary vascular resistance was a significant (P < .001) invasive predictor, with a hazard ratio of 3.98 (95% confidence interval, 2.01-7.87) of 1-year mortality in multivariate Cox regression analysis. Reduced LV function and increased pulmonary vascular resistance are related to poor prognosis in heart transplant recipients. Early assessment of LVGLS might be a noninvasive predictor of 1-year mortality in these patients.
    Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography 06/2012; 25(9):1007-14. DOI:10.1016/j.echo.2012.05.010
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    ABSTRACT: Pathophysiological interactions between heart and lungs in heart failure (HF) are well recognized. We investigated whether expression of different factors known to be increased in the myocardium and/or the circulation in HF is also increased in alveolar macrophages in HF. Lung function, hemodynamic parameters, gene expression in alveolar macrophages, and plasma levels in the pulmonary and femoral arteries of HF patients (n = 20) were compared to control subjects (n = 16). Our principal findings were: (1) Lung function was significantly lower in HF patients compared to controls (P<0.05). (2) mRNA levels of ET-1, tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) were increased in alveolar macrophages from HF patients. (3) Plasma levels of ET-1, TNFα, IL-6 and MCP-1 were significantly increased in HF patients, whereas our data indicate a net pulmonary release of MCP-1 into the circulation in HF. Several important cytokines and ET-1 are induced in alveolar macrophages in human HF. Further studies should clarify whether increased synthesis of these factors affects pulmonary remodeling and, directly or indirectly, adversely affects the failing myocardium.
    PLoS ONE 05/2012; 7(5):e36815. DOI:10.1371/journal.pone.0036815
  • Arne K Andreassen, Einar Gude, Ole Geir Solberg, Thor Ueland
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    ABSTRACT: In the past 5-10 years, drug treatment of idiopathic pulmonary arterial hypertension has evolved considerably. Experience and results from use of such updated treatment in Norway has not been reported. 32 patients newly diagnosed with idiopathic pulmonary arterial hypertension, were consecutively assessed with respect to hemodynamics and physical capacity. The results after three months were compared with those after 12 months. Observed survival was compared with estimated survival from the time when only conventional treatment was available. The patients (78% women) were 42 ± 14 years, had dyspnea in NYHA class 2.9 ± 0.4 and a maximal oxygen uptake of 12.0 ± 3.9 ml/kg/min (37 ± 13% of the expected). Updated treatment led to significantly improved hemodynamics and physical capacity, which persisted during follow-up. During 43 ± 31 months follow-up, seven patients died while two underwent bilateral lung transplantation. Observed transplantation-free survival was 81% after one, two and three years, while that for estimated transplantation-free survival was 70%, 58% and 49% respectively. Treatment of idiopathic pulmonary arterial hypertension with updated treatment improves hemodynamics and thereby symptoms. Mortality remains high, but is probably lower than it was when only conventional treatment was available.
    Tidsskrift for den Norske laegeforening 07/2011; 131(13-14):1285-8. DOI:10.4045/tidsskr.10.0053
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    ABSTRACT: Although malignancy is a major threat to long-term survival of heart transplant (HT) recipients, clear strategies to manage immunosuppression in these patients are lacking. Several lines of evidences support the hypothesis of an anticancer effect of proliferation signal inhibitors (PSIs: mammalian target of rapamycin [mTOR] inhibitors) in HT recipients. This property may arise from PSI's ability to replace immunosuppressive therapies that promote cancer progression, such as calcineurin inhibitors or azathioprine, and/or through their direct biological actions in preventing tumor development and progression. Given the lack of randomized studies specifically exploring these issues in the transplant setting, a collaborative group reviewed current literature and personal clinical experience to reach a consensus aimed to provide practical guidance for the clinical conduct in HT recipients with malignancy, or at high risk of malignancy, with a special focus on advice relevant to potential role of PSIs.
    Clinical Transplantation 05/2011; 25(5):E475-86. DOI:10.1111/j.1399-0012.2011.01476.x

Publication Stats

2k Citations
447.47 Total Impact Points

Institutions

  • 1999–2015
    • Oslo University Hospital
      • • Department of Cardiology
      • • Department of Infectious Diseases
      Kristiania (historical), Oslo, Norway
  • 1998–2014
    • University of Oslo
      • • Department of Cardiology
      • • Research Institute for Internal Medicine (IIM)
      • • Division of Medicine
      Kristiania (historical), Oslo, Norway
  • 2007–2013
    • Diakonhjemmet Hospital (Norway)
      Kristiania (historical), Oslo, Norway
    • Harbor-UCLA Medical Center
      • Department of Pediatrics
      Torrance, California, United States
  • 2008
    • Cleveland Clinic
      • Department of Infectious Disease
      Cleveland, Ohio, United States