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We report a patient with acute respiratory syndrome coronavirus 2 infection and irreversible lung destruction who underwent successful lung transplantation after 138 days of bridging with extracorporeal membrane oxygenation support. The case exemplifies that lung transplantation might be a possibility after very long-term Coronavirus disease 2019 care, even if the patient is initially unsuitable. Patient consent was acquired before writing the case report.

We investigated early outcomes in patients with end-stage pulmonary disease bridged with extracorporeal membrane oxygenation (ECMO) with the intention to perform lung transplantation (LTx).ECMO was used as a bridge to LTx in 20 patients between 2005 and 2013. Most patients suffered from rapid progress of disease and most failed to stabilize on mechanical ventilation. Sixteen patients (10 males, median age 42 years, range 25-59) underwent LTx after ECMO support for a median of 9 (range 1-229) days. Most patients were not on the waiting list while receiving ECMO, but after being assessed were on the waiting list for a median of 6 (range 1-72) days before LTx or death occurred. Median follow-up at 535 (range 36-3074) days was 100% complete, 9 patients have been followed for1 year and 4 patients have been bridged during 2013.Four patients died on ECMO waiting for a donor and as intention-to-treat, the success for bridging was 80% (16/20) and 1-year survival was 62% (10/16, not including 4 with1-year follow-up). For those who underwent LTx, 3 patients died in-hospital after LTx on Days 0, 16 and 82, respectively, and currently, 11/16 (69%) are alive and 1-year survival for transplanted patients was 9/12 (75%). Median ICU stay before and after LTx was 9 (range 2-229) days and 20 (range 0-53) days, respectively. At follow-up, lung function was evaluated, and mean forced expiratory volume at 1 s and forced vital capacity were 56±22% of predicted and 74±24% of predicted, respectively.ECMO used as a bridge to LTx results in acceptable survival in selected patients with end-stage pulmonary disease.

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 ± 0.7l (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.

Background A large proportion of donor lungs are discarded due to known or presumed organ dysfunction. Ex vivo lung perfusion (EVLP) has proven its value as a tool for discrimination between reversible and irreversible donor lung pathology. However, the long-term outcome after transplantation of lungs after EVLP is essentially unknown. We report short-term and midterm outcomes of recipients who received transplants of EVLP-evaluated lungs. Methods Single-center results of recipients of lungs with prior EVLP were compared with consecutive recipients of non-EVLP lungs (controls) during the same period. Short-term follow-up included time to extubation, time in the intensive care unit, and the presence of primary graft dysfunction at 72 hours postoperatively. Mortality and incidence of chronic lung allograft dysfunction were monitored for up to 4 years after discharge. Results During a 4-year period, 32 pairs of initially rejected donor lungs underwent EVLP. After EVLP, 22 double lungs and 5 single lungs were subsequently transplanted. During this period, 145 patients received transplants of conventional donor lungs that did not have EVLP and constituted the control group. Median time to extubation was 7 hours in the EVLP group and 6 hours in the non-EVLP control group (p = 0.45). Median intensive care unit stay was 4 days vs. 3 days, respectively (p = 0.15). Primary graft dysfunction grade > 1 was present in 14% in the EVLP group and in 12% in the non-EVLP group at 72 hours after transplant. Survival at 1 year was 92% in the EVLP group and 79% in the non-EVLP group. Cumulative survival and freedom from retransplantation or chronic rejection were also comparable between the 2 groups (p = 0.43) when monitored up to 4 years. Conclusions Selected donor lungs rejected for transplantation can be used after EVLP. This technique is effective for selection of transplantable donor lungs. Patients who received lungs evaluated under EVLP have short-term and midterm outcomes comparable to recipients of non-EVLP donor lungs.

Background. Only a minority of the potential candidates for lung donation are considered suitable, using current evaluation methods. A new method for ex vivo evaluation, with the potential for reconditioning of marginal and nonacceptable lungs, has been developed. This is a report of the ex vivo evaluation of six donor lungs deemed nonacceptable (arterial oxygen pressure less than 40 kPa) by the Scandiatransplant, Eurotransplant, and UK transplant organizations. Methods. The lungs are perfused ex vivo with Steen solution, a lung evaluation-preservation solution, mixed with red blood cells to a hematocrit of 15%. This extracellular solution is designed to have an optimal colloid osmotic pressure so that physiologic pressure and flow can be maintained without development of pulmonary edema. An oxygenator connected to the extracorporeal circuit maintains a normal mixed venous blood gas level in the perfusate. The lungs are ventilated and evaluated through analyses of pulmonary vascular resistance, oxygenation capacity, and arterial carbon dioxide pressure minus end-tidal carbon dioxide difference. Results. The arterial oxygen pressure (inspired oxygen fraction, 1.0) increased from 27 kPa (range, 17 to 34 kPa) in situ in the organ donor at the referring hospital to 57 kPa (range, 39 to 66 kPa) during the ex vivo evaluation. The pulmonary vascular resistance varied from 3.2 to 5.7 Wood units, and the arterial carbon dioxide pressure minus end-tidal carbon dioxide difference was in the range of 1 to 2.5 kPa. Conclusions. The arterial oxygen pressure improves significantly in this model. This ex vivo evaluation model is a valuable addition to the armamentarium in finding acceptable lungs in a donor population with inferior arterial oxygen pressure values.

OBJECTIVES An increasing number of studies have shown that ex vivo lung perfusion (EVLP) is safe and that rejected donor lungs can be resuscitated and used for lung transplantation (LTx). Early clinical outcomes in patients transplanted with reconditioned lungs at our centre were reviewed and compared with those of contemporary non-EVLP controls. METHODS During 18 months starting January 2011, 11 pairs of donor lungs initially deemed unsuitable for transplantation underwent EVLP. Haemodynamic (pulmonary flow, vascular resistance and artery pressure) and respiratory (peak airway pressure and compliance) parameters were analysed during evaluation. Lungs that improved (n = 11) to meet International Society of Heart and Lung Transplantation criteria were transplanted and compared with patients transplanted with non-EVLP lungs (n = 47) during the same time period. RESULTS Donor lungs were initially rejected due to either inferior PaO2/FiO2 ratio (n = 9), bilateral infiltrate on chest X-ray (n = 1) or ongoing extra corporeal membrane oxygenation (n = 1). The donor lungs improved from a mean PaO2/FiO2 ratio of 27.9 kPa in the donor to a mean of 59.6 kPa at the end of the EVLP (median improvement 28.4 kPa, range 21.0-50.7 kPa). Two single lungs were deemed unsuitable and not used for LTx. Eleven recipients from the regular waiting list underwent either single (n = 3) LTx or double (n = 8) LTx with EVLP-treated lungs. The median time to extubation (12 (range, 3-912) vs 6 (range, 2-1296) h) and median intensive care unit (ICU) stay (152 (range, 40-625) vs 48 (range, 22-1632) h) were longer in the EVLP group (P = 0.05 and P = 0.01, respectively). There were no differences in length of hospital stay (median 28 (range 25-93) vs 28 (18-209), P = 0.21). Two patients in the EVLP group and 6 in the control group had primary graft dysfunction >Grade 1 at 72 h postoperatively. Three patients in the control group died before discharge. All recipients of EVLP lungs were discharged alive from hospital. CONCLUSIONS The use of EVLP seems safe and indicates that lungs otherwise refused for LTx can be recovered and subsequently used for transplantation, although time to extubation and ICU stay were longer for the EVLP group.

Objectives Ex vivo lung perfusion (EVLP) can potentially reduce pulmonary edema. In a pig model with induced pulmonary edema, we evaluated the effect of hemofiltration (HF) during EVLP on lung function, perfusate oncotic pressure, and lung weight. Methods In anesthetized pigs (n = 14), pulmonary edema was induced by a balloon in the left atrium, combined with crystalloid infusion (20 mL/kg), for 2 hours. The lungs were harvested, stored cold for 2 hours, and randomized to EVLP, with or without a hemofilter (HF and noHF groups, respectively, n = 7 for each). EVLP was performed with cellular perfusate at a hematocrit of 10% to 15%. Oncotic pressure, lung performance, and weight were measured before and after 180 minutes of EVLP reconditioning with or without HF. Results After in vivo induction of edema, arterial oxygen tension (Pa o 2)/inspired oxygen fraction (F io 2), and compliance decreased by 63% and 16%, respectively. Pa o 2/F io 2 was considerably improved at first evaluation ex vivo in both groups. HF increased oncotic pressure by 43% and decreased lung weight by 15%. The effects were negligible in the noHF group. Compliance decreased in both groups during reconditioning, although less so in the HF group (P o 2/F io 2, shunt fraction, and oxygen saturation remained unchanged in both groups. Pulmonary flow index decreased in both groups, and was partially reversed by nitroglycerin. Dorsal atelectatic consolidations were seen in both groups. Conclusions In this lung-edema model, EVLP reconditioning with hyperoncotic solution did not affect the degree of lung edema. HF during EVLP increased perfusate oncotic pressure, decreased lung weight with beneficial effects on compliance, but did not improve lung oxygenation capacity.

The majority of patients undergoing solid organ transplantation develop hypertension, to which vasoconstriction and impaired endothelial function have been suggested to contribute. We compared basal vascular resistance and nitric oxide-mediated endothelial-dependent and independent vasoreactivity between cyclosporine-treated lung transplant recipients and healthy subjects. Forearm blood flow was measured by venous occlusion plethysmography at rest and during acetylcholine, glyceryltrinitrate and N(G)-monomethyl-L-arginine acetate (L-NMMA) infusion in 11 lung transplant recipients 3-5 years after transplantation and in eight healthy subjects. Forearm vascular resistance (FVR) was calculated. Plasma levels of endothelin-1 (ET-1) and von Willebrand factor (vWf) were analysed. Basal vascular resistance was 40% lower in transplant recipients than in healthy subjects (P = 0.021). Endothelial-dependent and independent vasodilation did not differ. Plasma levels of ET-1 and vWf were higher in transplant recipients (P = 0.009 and P < 0.001 respectively). There was a significant correlation between ET-1 levels and FVR in healthy subjects (r = 0.83, P = 0.042), but not in transplant recipients (r = -0.14, P = 0.70). The findings oppose the theory of generalized vasoconstriction and impaired endothelial function in the pathogenesis of hypertension after transplantation. Increased plasma levels of ET-1 do not cause increased FVR in lung transplant recipients.

Purpose This retrospective study investigated early and late outcome in patients with end stage pulmonary disease bridged with extracorporeal membrane oxygenation (ECMO) with the intention of lung transplantation (LTx). Methods and Materials ECMO was used as a bridge to LTx in 16 patients between 2005 and 2012. Most patients were late referrals for LTx and all failed to stabilize on mechanical ventilation. 12 patients (7 males, mean age 40±9 years, range 25-51) underwent LTx after a mean ECMO support of 16 days (range 1-59). Mean follow-up at 33±31 months was 100% complete. Results Four patients died on ECMO waiting for a donor and two patients died after LTx on day 16 and 82, respectively. As intention-to-treat the success for bridging was 75% and 1-year survival for the whole group was 63%. All other patients survived, and currently 10/12 (83%) are alive after LTx, and 1-year survival for transplanted patients was 8/10 (80%). Mean ICU-stay after LTx was 26±19 days (range, 3-63). At follow-up, lung function was evaluated and mean FEV1 and FVC were 2.2±0.9l (62%±20% of predicted) and 3.2±0.9l (78%±21% of predicted), respectively. Patient life of quality is under assessment and results will be compared to all contemporary LTx. Conclusions ECMO used as a bridge to LTx results in acceptable early and late survival in selected patients with end stage pulmonary disease.

Cardiovascular disease (CVD) is a common cause of morbidity and mortality after solid-organ transplantation. Both pre-existing cardiovascular risk factors in recipients and immunosuppressive drug toxicity may contribute to CVD. We sought to describe the prevalence of new-onset hypertension, hypercholesterolemia and diabetes mellitus in lung transplant recipients and to identify predisposing factors.One hundred twenty-six patients without pre-transplant hypertension, hypercholesterolemia or diabetes were included in a retrospective descriptive study. All patients were initially on cyclosporine-based triple immunosuppression. Cumulative prevalence of new-onset hypertension, hypercholesterolemia and diabetes were calculated. A multivariate Cox regression model was used to identify independent pre-operative predictors.By 3 years after transplantation, 90% of patients had developed at least 1 cardiovascular risk factor and 40% developedor = 2 risk factors. The cumulative prevalence of new-onset hypertension at 1, 3, 5 and 7 years was 45%, 65%, 67% and 72%, respectively. The corresponding prevalence for hypercholesterolemia was 16%, 33%, 48% and 58%, and for diabetes 6%, 7%, 7% and 10%, respectively. The independent pre-transplant predictors were: for hypertension, diastolic blood pressure (odds ratio: 2.1 per 10 mm Hg [95% confidence interval: 1.3 to 3.5], p = 0.005); for hypercholesterolemia, serum cholesterol level (OR: 1.8 per mmol/liter [95% CI: 1.3 to 2.5], p0.001); and, for diabetes, cystic fibrosis diagnosis (OR: 7.4 [95% CI: 1.6 to 35.6], p = 0.01) and blood glucose level (OR 2.2 per mmol/liter [95% CI 1.1 to 4.5], p = 0.02).The majority of cyclosporine-treated lung transplant recipients develop new-onset hypertension or hypercholesterolemia early after transplantation. Pre-transplant blood pressure, serum cholesterol levels and blood glucose levels are independent predictors of post-transplant hypertension, hypercholesterolemia and diabetes, respectively.

Background: The majority of patients undergoing solid organ transplantation develop hypertension, to which cyclosporine (CsA)-induced peripheral vasoconstriction may contribute. We hypothesized that CsA-treated transplant recipients have an increased basal vascular tone and an altered response to nitric oxide. To test this hypothesis arterial resistance, non-endothelial dependent relaxation and arterial stiffness were investigated in CsA-treated lung transplant recipients within 18 months after transplantation. Methods: In study 1, forearm blood flow (FBF) was measured by venous occlusion plethysmography at baseline and during glyceryl trinitrate (GTN) and N(G)-monomethyl-l-arginine acetate (l-NMMA) infusion in seven lung transplant recipients and nine healthy subjects. In study 2, arterial stiffness in carotid (CCA) and radial artery (RA) was measured by ultrasound (echo-tracking) in 10 lung transplant recipients, 12 healthy subjects and six patients waiting for lung transplantation. Results: Basal FBF (3.1 ± 0.2 vs. 3.0 ± 0.3 mL/min, p = 0.79) and forearm arterial resistance (36 ± 3 vs. 33 ± 3 mmHg/mL/min, p = 0.60) did not differ between transplant recipients and controls. GTN infusion increased and l-NMMA decreased blood flow equally in both groups. Transplant recipients had increased arterial stiffness compared to both pre-transplant patients and healthy subjects (CCA stiffness index 11.7 ± 1.1 vs. 8.5 ± 0.2 and 8.6 ± 0.6, p

Purpose An increasing number of studies have shown that rejected donor lungs can be resuscitated during ex vivo lung perfusion (EVLP) and used for lung transplantation (LTx). Early clinical outcome in patients transplanted with reconditioned lungs at our centre were reviewed and compared to contemporary controls. Methods and Materials During 18 months starting January 2011, eleven pairs of donor lungs initially deemed unsuitable for transplantation underwent EVLP. Lungs witch improved to acceptable function were transplanted. Early clinical outcome was compared to 47 consecutive patients transplanted with lungs without prior EVLP during the same period. Results Donor lungs were initially rejected due to inferior PaO2/FiO2 ratio (n=9), bilateral infiltrate on chest x-ray (n=1) or on going ECMO (n=1). The donor lungs improved from a mean PaO2/FiO2 ratio of 27.9 kPa in the donor to a mean of 59.6 kPa during EVLP (median improvement 28.4 kPa, range 21.0 – 50.7 kPa). Hemodynamic (pulmonary vascular resistance and artery pressure) and respiratory (peak airway pressure, compliance) parameters were evaluated. Two single lungs were deemed unsuitable for LTx. Eleven recipients from the regular waiting list underwent single (n=3) or double (n=8) LTx with EVLP-treated lungs. There was no difference in occurrence of primary graft dysfunction at 72 hours between groups. Median time to extubation (12 (range, 3-912) vs 6 (range, 2-1296) hours) and median ICU stay (152 (range, 40-625) vs 48 (range, 22-1632) hours) were longer in the EVLP group (p=0.05 and p=0.01, respectively). There was no difference in length of hospital stay (p= 0.21). Three patients in the control group died before discharge. All recipients of EVLP lungs were discharged alive from hospital. Conclusions Lungs otherwise refused for LTx can be recovered and subsequently used for transplantation although time to extubation and ICU stay are longer for the EVLP group. Early results are not only acceptable but seem also in most aspects comparable to recipients of non-EVLP lungs.

condition of the patient. High blood pressure complicated 2 pregnancies with a good control by medical therapy. No preeclampsia occurred. One severe pulmonary infection occurred during the last 3 months of pregnancy. Delivery occurred at 38 6 1(range : 37-39) week’s gestation, never by caesarean section. Mean birth weight was 3143 6 757 g (range : 2270-3990). Mother FEV1(%) before,during (6th month) and after (1 year) pregnancy was repectively : 87 6 18, 87 6 22, 88 6 17 (ns). After delivery, lung biopsies never showed any rejection. Conclusion : Pregnancy after HL Transplantation is feasible and can be successful with good outcome for mother and child. However, pregnancy should be planned at least 2 years after transplantation to recover from transplantation, when cardiac and respiratory conditions are stabilized ,and when immunosuppressive therapy is the lowest.

ObjectiveEx vivo lung perfusion has the potential to increase the number of patients treated with lung transplantation. Our initial clinical experience with ex vivo lung perfusion is reviewed as well as early clinical outcome in patients transplanted with reconditioned lungs.MethodsSix pairs of donor lungs deemed unsuitable for transplantation underwent ex vivo lung perfusion with Steen solution mixed with red blood cells to a hematocrit of 10% to 15%. After reconditioning, lung function was evaluated and acceptable lungs were transplanted. Technical experience with ex vivo lung perfusion as well as clinical outcome for patients transplanted with ex vivo lung perfusion-treated lungs were evaluated.ResultsDonor lungs initially rejected either as a result of an inferior partial pressure of arterial oxygen/ fraction of inspired oxygen (n = 5; mean, 20.5 kPa; range, 9.1-29.9 kPa) or infiltrate on chest radiograph (n = 1) improved their oxygenation capacity to a mean partial pressure of arterial oxygen/fraction of inspired oxygen of 57 ± 10 kPa during the ex vivo lung perfusion (mean improvement, 33.6 kPa; range, 21-51 kPa; P

Mycobacterium abscessus lung disease is difficult to treat and has been considered a strong relative contraindication to lung transplantation. We performed double lung transplantation in three cystic fibrosis patients with ongoing, and a fourth with recent treatment for Mycobacterium abscessus lung infection. Despite prolonged antibiotic courses and adjustment of immunosuppressive therapy the first three patients developed skin infection and abscesses. At follow-up after 1, 3, 5 and 7years respectively no patient had evidence of M abscessus infection and all had stable lung function. Lung transplantation in patients with M abscessus lung infection is feasible but may involve severe complications.