Pekka Hämmäinen

Usefulness of extracorporeal membrane oxygenation as a bridge to lung transplantation: A descriptive study

BACKGROUND This retrospective study investigated early outcome in patients with end-stage pulmonary disease bridged with extracorporeal membrane oxygenation (ECMO) with the intention of lung transplantation (LTx) in 2 Scandinavian transplant centers. METHODS ECMO was used as a bridge to LTx in 16 patients between 2005 and 2009 at Sahlgrenska and Helsinki University Hospitals. Most patients were late referrals for LTx, and all failed to stabilize on mechanical ventilation. Thirteen patients (7 men) who were a mean age of 41 ± 8 years (range, 25-51 years) underwent LTx after a mean ECMO support of 17 days (range, 1-59 days). Mean follow-up at 25 ± 19 months was 100% complete. RESULTS Three patients died on ECMO while waiting for a donor, and 1 patient died 82 days after LTx; thus, by intention-to-treat, the success for bridging is 81% and 1-year survival is 75%. All other patients survived, and 1-year survival for transplant recipients was 92% ± 7%. Mean intensive care unit stay after LTx was 28 ± 18 days (range, 3-53 days). All patients were doing well at follow-up; however, 2 patients underwent retransplantation due to bronchiolitis obliterans syndrome at 13 and 21 months after the initial ECMO bridge to LTx procedure. Lung function was evaluated at follow-up, and mean forced expiratory volume in 1 second was 2.0 ± 0.7 l (62% ± 23% of predicted) and forced vital capacity was 3.1 ± 0.6 l (74% ± 21% of predicted). CONCLUSION ECMO used as a bridge to LTx results in excellent short-term survival in selected patients with end-stage pulmonary disease.

Tumor necrosis factor-?? in a porcine bronchial model of obliterative bronchiolitis1

Background. In posttransplant obliterative bronchiolitis (OB), the major pathologic features are inflammation, epithelial cell injury, fibrosis, and obliteration of the small airways. Tumor necrosis factor (TNF)-&agr; is a cytokine known to mediate and augment the inflammatory reaction and to enhance fibroblast proliferation. We assessed the role of TNF-&agr; in the development of OB in our heterotopic porcine bronchial transplantation model. Methods. Three groups were formed: autografts, nontreated allografts, and allografts treated with preoperative anti–TNF-&agr; monoclonal antibody (infliximab) infusion. The implants were harvested on days 2, 4, 7, 11, 14, 21, and 28 for histologic and immunohistochemical analysis. Results. TNF-&agr; inhibition reduced inflammation, rate of epithelial loss, fibrosis, and obliteration early in the development of OB. In the epithelium, the numbers of TNF-&agr;–positive epithelial and inflammatory cells and macrophages were significantly lower in treated than in nontreated allografts on day 4; furthermore, in the epithelium and in the bronchial wall, invasion of CD8+ lymphocytes was significantly decreased during the first week. Conclusions. These results indicate that TNF-&agr; promotes the development of OB, and inhibition of TNF-&agr; may prove beneficial in a clinical setting.

Autologous bone marrow mononuclear cell transplantation in ischemic heart failure: A prospective, controlled, randomized, double-blind study of cell transplantation combined with coronary bypass

BACKGROUND Bone marrow mononuclear cell (BMMC) transplantation for heart failure has shown inconsistent therapeutic efficacy. METHODS We enrolled 104 ischemic heart failure patients scheduled for coronary artery bypass surgery (CABG). After 4- to 12-week pharmacotherapy optimization, 39 patients with left ventricular ejection fraction (LVEF) of ≤45% received injections of BMMC or vehicle intra-operatively into the myocardial infarction border area in a randomized, double-blind manner. RESULTS The median number of cells injected was 8.4 × 10(8) (interquartile range [IQR]: 5.2 × 10(8) to 13.5 × 10(8)). We measured LV function and myocardial scar size by magnetic resonance imaging (MRI), and viability by positron emission tomography (PET) and single-photon emission computed tomography (SPECT), pre-operatively and after 1-year follow-up. LVEF, the pre-defined primary end-point measure, improved by a median of 5.6% in the control group (IQR 0.2 to 10.1) and by 4.8% in the BMMC group (IQR -0.5 to 8.2) (p = 0.59). Wall thickening in injected segments rose by a median of 4.5% among controls (IQR -18.1 to 23.9) and by 5.5% in the BMMC group (IQR -6.6 to 26.5) (p = 0.68). Changes in viability by PET and SPECT did not differ between groups. Myocardial scar size by MRI in injected segments rose by a median of 5.1% among controls (IQR -3.3 to 10.8), but fell by 13.1% in the BMMC group (IQR -21.4 to -6.5) (p = 0.0002). CONCLUSIONS BMMC therapy combined with CABG failed to improve LV systolic function, or viability, despite reducing myocardial scar size.

Natural course and risk factors for impaired renal function during the first year after heart transplantation

BACKGROUND Post-operative renal failure is a common and potentially hazardous complication after heart transplantation (HTx). In this study we characterized pre- and post-operative risk factors for acute renal failure requiring renal replacement therapy (RRT). METHODS Ninety-three patients underwent orthotopic HTx between 2000 and 2007. The risk factors for RRT during the early post-operative period and predictors contributing to impaired renal function within the first post-transplant year were analyzed by regression analysis. The impact of pre-operative renal failure and early post-operative RRT on renal function within 1 year were studied. RESULTS Before HTx, 55% of patients (51 of 93) had normal renal function or mild renal failure (glomerular filtration rate [GFR] >60 ml/min/1.73 m(2)). Before discharge from the hospital, 25% (23 of 93) developed acute renal failure and required RRT. Of these, 16% (8 of 51) had pre-operatively normal renal function or mild renal failure, and 36% (15 of 42) had moderate or severe renal failure (GFR <60 ml/min/1.73 m(2); p = 0.02). The prognosticators for early RRT were prolonged graft dysfunction, re-admission to the operating room due to post-operative bleeding, poor diuresis during surgery (<1,000 ml), pre-operative pacemaker implantation, intubation time >24 hours, pre-operative GFR <60 ml/min/1.73 m(2), post-operative troponin T >6 microg/liter and pre-operative use of angiotensin receptor blocker. CONCLUSIONS Pre-operative renal failure is a significant risk factor for RRT during the immediate post-operative period and requires aggressive treatment. Patients with pre-operative renal failure secondary to severe heart failure and acute post-operative renal failure requiring RRT tend to recover within the first year post-HTx.

Single lung allotransplantation in pigs : a morphologic study of tissue preservation with modified euro-collins and fluorocarbon solutions

In the present study the functional and morphologic effects of two pulmoplegic solutions are evaluated. Single left-lung allotransplantation with ligation of the right pulmonary artery was performed in 15 piglets (13-20 kg). The lungs were preserved after donor prostaglandin E-1 treatment with single pulmonary artery flush with either modified Euro-Collins solution (mECS) (9 pigs) or oxygenated fluorocarbon emulsion (FC-43) (6 pigs) and transplanted after 6-hr storage in cold Physiosol solution. Tidal volumes of 15 ml/kg x fr (18) with 40% inspired oxygen were used for ventilation during reperfusion. Function of the transplanted lung was monitored for 4 hr postoperatively by determining pa CO2 and pa O2 levels from arterial samples and by noninvasive monitoring of end-tidal CO2 values and arterial oxygen saturations. Sequential morphologic changes in pulmonary artery flow surface and lung tissue were studied after 6-hr storage and 4-hr reperfusion, using light, scanning, and transmission electron microscopy (LM, SEM, TEM). There was no mortality. After transplantation the mECS group experienced significant hypoxia and hypercarbia and had low end-tidal CO2 values as signs of defective oxygenation and gas exchange, whereas the FC-43 group was normoxic and normoventilated without disturbed elimination of carbon dioxide. After storage and reperfusion, LM showed signs of increased vascular permeability and reperfusion damage--more evident in the mECS group compared with the FC-43 group--while the lymphoid cell population was more intensely activated in the latter group. Electron microscopy after storage showed good overall preservation of structures in both groups. After reperfusion preservation of pulmonary artery flow surface and lung tissue was estimated to be moderate in the mECS group, whereas it was good-to-moderate in the FC-43 group by SEM (NS). TEM of lung tissue, however, showed significantly better-preserved alveolar epithelial lining in the FC-43 group compared with the mECS group. In conclusion, oxygenated fluorocarbon (FC-43) pulmoplegia gave better functional and morphologic preservation of lung grafts compared with modified Euro-Collins solution.

Control of early Aspergillus mortality after lung transplantation: outcome and risk factors.

Historic treatment strategies in our institute had resulted in 10% Aspergillus mortality within the first posttransplant year. Despite nebulized amphotericin B (nAmB) prophylaxis, a significant incidence of Aspergillus infection, usually with poor outcome, is still reported. The aim of this single-center retrospective study was to evaluate the outcomes of patients receiving either standard nAmB or additional systemic caspofungin prophylaxis for selected high-risk patients. We also tried to define independent risk factors for either fungal infection or death. We followed 76 consecutive lung transplant patients performed at our center between 2002 and 2010 from the day of transplantation. The median follow-up duration was 953 days (2.6 years; range, 16-2,751 days). The endpoints were postoperative Aspergillus colonization or disease or death due to any cause. All patients received either nAmB deoxycholate (nAmBd, 15 patients) or nAmB lipid complex (nAmBLC, 61 patients). In addition, 33 patients also received short-term caspofungin prophylaxis. The overall cumulative mortality during the entire follow up was 14.5%. No clinically confirmed invasive Aspergillus infections (IPA) occurred during the first 2 postoperative years; however, there was 1 possible and 1 probable IPA. One patient died of bronchiolitis obliterans and IPA at 2 years 3 months. Twelve patients showed transient Aspergillus colonization. The antifungal prophylactic regimens were well tolerated. The risk factors for death were age >55 years and postoperative Aspergillus detection (P = .011 and P = .015, respectively). Preoperative Aspergillus colonization/disease was not a risk factor for death (P = 1.000). The strongest predictor of death was age >55 years, due to the elder probably being more susceptible to the adverse effects of immunosuppressants. Postoperative detection of Aspergillus still seems to be an indicator of a poorer outcome. Preoperative Aspergillus colonization is not necessarily a threat with prompt institution of antifungal prophylaxis.

Association between gastrointestinal symptoms and health-related quality of life after heart transplantation

BACKGROUND Heart transplantation (HTx) ameliorates the self-perceived health-related quality of life (HRQoL) of patients with terminal heart disease; gastrointestinal (GI) symptoms, due to obligatory immunosuppression, may contribute to impaired HRQoL post-HTx. METHODS In this cross-sectional, exploratory study we aimed to investigate association between GI symptoms and HRQoL. The study consisted of 167 patients who had undergone HTx between 1985 and 2006 in Finland. Short-Form 36 (SF-36) Quality of Life and Gastrointestinal Symptom Rating Scale (GSRS) questionnaires were sent to the patients at the end of 2006 for capturing data on the HRQoL of HTx recipients. RESULTS Higher or equal SF-36 scores describing the HRQoL dimensions compared with the Finnish age- and gender-matched reference population were as follows: physical functioning, 60.5%; role-physical, 67.5%; bodily pain, 62.6%; general health, 64.0%; vitality, 68.1%; social functioning, 68.1%; role-emotional, 70.0%; and mental health, 70.4%. The prevalence of troublesome GI symptoms (GSRS score >1) per GSRS dimension was 53.9% for diarrhea, 91.0% for indigestion, 60.6% for constipation, 73.4% for abdominal pain, 46.4% for reflux and 95.8% for any GI symptom. Diabetes contributed to the presence of diarrhea (odds ratio [OR]: 3.00; 95% confidence interval [CI]: 1.12 to 8.00), use of prednisolone to indigestion (OR: 3.21; 95% CI: 1.05 to 9.79) and increased age to constipation (OR: 1.04; 95% CI: 1.02 to 1.07). CONCLUSIONS HRQoL after HTx is relatively good and comparable to the age- and gender-matched reference population. HRQoL is vulnerable to side-effects caused by the obligatory post-HTx immunosuppressive regimen, where GI symptoms play a major but clearly an underestimated role.

Pulmonary Retransplantation in the Nordic Countries

BACKGROUND The increasing demand for pulmonary retransplantation (re-LTx) raises ethical issues on the correct allocation of the scarce donor pool. Thus, we performed a thorough review of the current results for re-LTx in the Nordic countries. METHODS Seventy-five patients with a median age of 50 years (range, 22 to 64 years) underwent re-LTx from 1992 until June 2013, of which 53 had single re-LTx, 21 had double re-LTx, and 1 patient underwent a heart-lung retransplantation. Primary graft dysfunction (PGD) was the primary indication in 9 cases, bronchiolitis obliterans syndrome (BOS) in 62 cases, and airway complications in 4 cases. RESULTS Patients who underwent re-LTx in the period 1992 to 1999 (n = 16) had a 1-year survival of 37.5% (95% confidence interval [CI], 19.9 to 70.6), whereas patients who underwent re-LTx in the period 2000 to 2013 (n = 64) had a 1-year survival of 81.0% (95% CI, 71.5 to 91.8). Corresponding 5-year survival was 25.0% (95% CI, 10.7 to 58.4) in the early era group (1992 to 1999) and 57.2% (95% CI, 44.3 to 73.7) in the more recent era group (2000 to 2013; p = 0.0151). Patients with BOS who underwent re-LTx in the period 1992 to 1999 (n = 13) had a 1-year survival of 38.5% (95% CI, 19.3 to 76.5), whereas patients with BOS who underwent re-LTx in the period 2000 to 2013 (n = 49) had a 1-year survival of 85.4% (95% CI, 75.9 to 96.0). Corresponding 5-year survival was 23.1% (95% CI, 8.6 to 62.3) in the early era group (1992 to 1999) and 56.1% (95% CI, 41.9 to 75.2) in the more recent era group (2000 to 2013; p = 0.0199). The cumulative incidence among patients who underwent re-LTx because of BOS and developed BOS again after re-LTX was analyzed. The cumulative incidence curves for time periods 1992 to 1999 and 2000 to 2013 are not statistically different for repeat BOS (p = 0.5087), but they are highly significant for time periods among patients who died (p = 0.02381). CONCLUSIONS Results for re-LTx have improved over time, especially when BOS is the primary indication. The cumulative incidence among patients who underwent re-LTx because of BOS and developed repeat BOS after re-LTX showed equal risk between 1992 to 1999 and 2000 to 2013 in the aspect of developing repeat BOS, but in the later era the patients had a significantly higher chance of surviving.

Dichotomy in pulmonary graft-versus-host disease evident among allogeneic stem-cell transplant recipients undergoing lung transplantation

Allogeneic haematopoietic stem-cell transplantation (HSCT) has become a life-saving treatment option for numerous benign and malignant diseases, with more than 14 500 procedures being performed annually in Europe alone [1]. Late-onset noninfectious pulmonary complications (NIPCs) have emerged as the main hurdle to long-term survival, affecting up to 26% of HSCT recipients and conferring 2- and 5-year survival rates of 44% and 13%, respectively [2, 3]. Interstitial lung disease is a common, largely unrecognised feature of pulmonary GvHD after stem cell transplant http://ow.ly/DWP4307mO3i

Decreased maximum clot firmness in rotational thromboelastometry (ROTEM®) is associated with bleeding during extracorporeal mechanical circulatory support

Background: We aimed to characterize the coagulation disturbances which may increase the risk of bleeding, thrombosis or death shortly after implantation of an extracorporeal membrane oxygenation (ECMO) or ventricular assist (VAD) device. Methods: Antithrombotic treatment was started in 23 VAD and 24 ECMO patients according to the hospital protocol. Additionally, conventional laboratory testing, rotational thromboelastometry (ROTEM®) and platelet function analysis (Multiplate®) were performed at predetermined intervals. Results: Four out of twenty-four (16.7%) of ECMO patients and 6/23 (26.1%) of VAD patients had severe bleeding after the procedure. When all the patients were analyzed together, low maximum clot firmness (MCF) in ExTEM and FibTEM analyses was associated with severe bleeding (p<0.05) and low MCF in FibTEM with 30-day mortality. Low platelet count and hematocrit levels were also associated with severe bleeding. When VAD and ECMO patients were separated into different groups, the association between ROTEM® parameters, bleeding and survival was found only in limited time points. Four patients with VAD had cerebral ischemia indicative of thromboembolism. However, this had no significant correlation with ROTEM® or Multiplate® parameters. Conclusion: Hypocoagulation shown by ROTEM® was associated with bleeding complications in patients with mechanical circulatory support. In contrast, hypercoagulation did not correlate with clinical thrombosis.