Returning to work in lung cancer survivors-a multi-center cross-sectional study in Germany.

PURPOSE: To investigate the work situation of lung cancer survivors and to identify the factors associated with their returning to work. METHODS: Descriptive analysis and logistic regression were used to evaluate study population characteristics and independent factors of subsequently returning to work. To analyze time to return to work, Cox regression was used. RESULTS: The study sample included 232 lung cancer survivors of working age from 717 enrolled participants in the multi-center cross-sectional LARIS (Quality of Life and Psychosocial Rehabilitation in Lung Cancer Survivors) study. About 67% of the survivors were not employed during the survey. More than 51% of the survivors who were employed before their illness did not return to their work. The survivors who had returned to their careers were younger, associated with higher household income, lower fatigue score, and stable relationship and vocational training. Patients who received social service counseling showed a higher chance of regaining their career. CONCLUSIONS: Lung cancer survivors were found to be associated with a high risk of unemployment and very low professional reintegration after interruption due to illness. More comprehensive studies are needed to support lung cancer survivors and targeting of patients in need of special attention in rehabilitation that would benefit from the findings in the present study.

Pitfalls of cannulation for extracorporeal life support: review of the literature and illustrative case presentation.

Extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) are an increasingly established advanced therapy for emerging severe lung and/or cardiocirculatory dysfunction or failure. Several reports have provided evidence for a potential benefit in prognosis by ECLS in cases of cardiogenic shock including cardiopulmonary resuscitation. Routine use in specialized centers reduces the incidence of negative side effects (e.g., vascular/ischemic, embolic, hemorrhagic, hemolytic and, furthermore, septic). Vascular complications like not only limb ischemia but also hypoxia proximal to the cannulation site up to complete sectorial hypoxia called "harlequin phenomenon" could refer to be a major adverse event in ECLS which, therefore, should be limited primarily to cardiocirculatory indications. Here we report on a case with "harlequin phenomenon" after ECLS implementation as a relevant complication of the mode of cannulation and review benefits and risks of commonly used variants of vascular access.

Changes of Laryngeal Mobility and Symptoms Following Thyroid Surgery: 6-Month Follow-Up.

OBJECTIVE: Swallowing disorders are frequent complaints after thyroidectomy even in the absence of recurrent laryngeal nerve palsy. The aim of this study was to assess different symptoms in relation to laryngeal mobility following thyroidectomy. MATERIALS AND METHODS: 53 patients (mean age 52.4 ± 12.5 years; 36 female) with initially benign diagnosis and intact recurrent nerve functioning were prospectively evaluated. Laryngeal movement was analyzed by ultrasound preoperatively and 1, 3, and 6 months postoperatively. In addition, a dysphagia and voice-specific quality-of-life questionnaire was used. RESULTS: Mean laryngeal movement differed between genders preoperatively and postoperatively resulting in a recovery predominantly in women (reduction of mobility at 1, 3, and 6 months postoperatively in females was 6.0, 3.7, and 1.5 mm, and in males 13.8, 11.7, and 10.3 mm, respectively). Mainly, women reported hoarseness (9 females) and cervical discomfort (7 females, 3 males) 1 month postoperatively. After 6 months, these complaints resolved (cervical discomfort 1 female). CONCLUSION: Laryngeal mobility was significantly impaired postoperatively and only females revealed a recovery close to baseline after 6 months. Although showing only a small grade of recovery of laryngeal movement, subjective clinical symptoms were found to be rare in male patients.

Quality of life in lung cancer survivors treated with tyrosine-kinase inhibitors (TKI): results from the multi-centre cross-sectional German study LARIS.

PURPOSE: We aimed at exploring the quality of life (QOL) of lung cancer survivors with proven tyrosine-kinase receptor (RTK) genetic alterations and targeted tyrosine-kinase inhibitors (TKI) therapy, compared to lung cancer survivors with no-RTK alterations and no-TKI therapy. METHODS: Data were collected in a cross-sectional multi-centre study. Primary lung cancer survivors were asked about their socio-demographic and clinical information, QOL, symptom burden, and distress. QOL and symptom burden were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), and distress with the Patient Health Questionnaire-4 (PHQ-4). Demographic and clinical characteristics were reported in absolute and relative frequencies, QOL, and symptom burden using mean scores. Differences in mean scores with relative 95% confidence intervals were used for comparison. RESULTS: Three groups of survivors were defined: group A with proven RTK alterations, TKI therapy at any time during therapy, and stage IV lung cancer at diagnosis (n = 49); group B: non-TKI therapy and stage IV lung cancer (n = 121); group C: non-TKI therapy and stage I-III lung cancer (n = 495). Survivors in group A reported lower QOL (mean score difference = -11.7 vs. group B) and symptom burden for dyspnoea (difference = -11.5 vs. group C), and higher symptom burden for appetite loss (difference = + 11.4 vs. group C), diarrhoea and rash (differences = + 25.6, + 19.6 and + 13.2, + 13.0, respectively, vs. both groups). CONCLUSIONS: Our results suggest that the specific side effects of TKI therapy can impair QOL among lung cancer survivors. Therefore, specific focus towards the optimal management of these side effects should be considered.

High permeability dialysis membrane allows effective removal of myoglobin in acute kidney injury resulting from rhabdomyolysis.

OBJECTIVE: The objective of this study was to test the ability of myoglobin removal of a novel, high-permeability polysulphone dialyzer in acute kidney injury as a result of rhabdomyolysis. SETTING: Intensive care unit of a tertiary care hospital. PATIENTS: Six patients (one female; aged 24, 36, 41, 55, 63, and 65 yrs) with oligoanuric acute kidney injury resulting from rhabdomyolysis. INTERVENTIONS: Extended dialysis was performed using a single-pass batch dialysis system and a novel polysulphone high-flux dialyzer (effective surface area 1.8 m; inner lumen 220 µm; wall thickness 35 µm; allowing elimination of substances with a molecular weight of up to 30 kDa). MEASUREMENTS AND MAIN RESULTS: Samples were collected at prefilter and postfilter sites as well as from the collected spent dialysate. The dialyzer clearance was calculated from concentrations before and directly after the dialysis membrane, the blood flow, and the ultrafiltration rate. The total amount of the myoglobin removed was measured directly as the whole dialysate was preserved. A median myoglobin clearance of 90.5 mL/min (range, 52.4-126.3 mL/min) was achieved, resulting in a median myoglobin removal per treatment hour of 0.54 g (range, 0.15-2.21 g). CONCLUSIONS: Extended dialysis with a high-flux, high-permeability membrane allowed effective elimination of myoglobin with a clearance of myoglobin that surpassed all previously reported dialysis techniques. This membrane may be advantageous in preventing acute kidney injury or avoiding complete loss of kidney function in patients with rhabdomyolysis. Further studies are needed to determine whether improving renal recovery or mortality in patients with acute kidney injury resulting from rhabdomyolysis is possible.

Quality of Life in NSCLC Survivors - A Multicenter Cross-Sectional Study.

INTRODUCTION: The objective was to assess quality of life (QoL) in lung cancer survivors, compare it to the general population, and identify factors associated with global QoL, physical functioning, emotional functioning, fatigue, pain, and dyspnea. METHODS: Data from NSCLC patients who had survived 1 year or longer after diagnosis were collected cross-sectionally in a multicenter study. QoL was assessed with the European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and the lung cancer module QLQ-LC13 across different clinical subgroups and compared to age- and sex-standardized general population reference values. Multivariable linear regression analyses were performed to test the associations of patient-, tumor-, and treatment-related factors with the six primary QoL scales. RESULTS: Six hundred fifty-seven NSCLC patients participated in the study with a median time since diagnosis of 3.7 years (range, 1.0-21.2 years). Compared to the age- and sex-standardized general population, clinically meaningful differences in the QoL detriment were found on almost all domains: lung cancer survivors had clinically relevant poorer global QoL (10 points, p < 0.001). Whereas in 12 months or longer treatment-free patients this detriment was small (8.3), it was higher in patients currently in treatment (16.0). Regarding functioning and symptom scales, respective detriments were largest for dyspnea (41 points), role function (33 points), fatigue (27 points), social function (27 points), physical function (24 points), and insomnia (21 points) observed across all subgroups. The main factor associated with poorer QoL in all primary QoL scales was mental distress (ß |19-31|, all p < 0.001). Detriments in QoL across multiple primary QoL scales were also observed with current treatment (ß |8-12|, p < 0.01), respiratory comorbidity (ß |4-5|, p < 0.01), and living on a disability pension (ß |10-11|, p < 0.01). The main factor associated with better QoL in almost all primary QoL scales was higher physical activity (ß |10-20|, p < 0.001). Better QoL was also observed in patients with high income (ß |10-14|, p < 0.01). CONCLUSIONS: Lung cancer survivors experience both functional restrictions and symptoms that persist long term after active treatment ends. This substantiates the importance of providing long-term supportive care.

Heart-lung and lung transplantation in grown-up congenital heart disease: long-term single centre experience.

OBJECTIVE: Because of considerable progress in paediatric cardiac surgery life expectancy of patients with congenital heart disease (CHD) has improved significantly over the years. There are a growing number of adults with CHD presenting with progressive decline of cardiopulmonary function and Eisenmenger's syndrome. We analysed our experience with heart-lung and lung transplantation in this patient group. METHODS: Since 1988, a total of 46 heart-lung transplantations and 5 double lung transplantations have been performed in adults with CHD at our institution. Underlying diagnoses were: ventricular septal defect, atrial septal defect, persistent ductus arteriosus and others. Pulmonary hypertension was present in all patients. Twelve patients had undergone previous cardiac procedures. All patients were included in this retrospective analysis. Mean follow up was 5.1+/-4.7 years. Patient survival was estimated with the Kaplan-Meier method and analysed using the log-rank test. RESULTS: Thirty-day mortality was 11.8% (n=6). Survival was 80% at 1 year, 69% at 5 years and 53% at 10 years. Major causes of death were infection and sepsis, chronic rejection, initial graft failure and acute rejection. Compared to the overall mortality after lung and heart-lung transplantation for other indications at our institution there was no significant difference (1 year, 5 years, 10 years: 76%; 60%; 45%), but a tendency towards a better long-time survival of the CHD patients. CONCLUSIONS: Lung and heart-lung transplantation can be performed with an acceptable risk and a favourable long-term outcome in patients with grown-up CHD. Careful patient selection and planning of the surgical strategy is essential in this high-risk patient population.

Retrograde in situ versus antegrade pulmonary preservation in clinical lung transplantation: a single-centre experience.

OBJECTIVE: Experimental and clinical studies have indicated a beneficial effect of retrograde lung preservation on post-transplant results. Accordingly, we conducted a non-randomized trial. METHODS: A total of 209 consecutive recipients transplanted with low-potassium dextrane (LPD)-preserved lungs were eligible for analysis. Antegrade lung preservation (AP) was performed in 173 patients and retrograde in situ perfusion (RP) in 36 patients using low-potassium dextrane solution in all cases. The prostacycline was added to preservation solution. RESULTS: The main donor, graft and recipient characteristics did not differ significantly between groups. There was a beneficial trend toward improved oxygenation indices in the RP cohort within the initial 48 post-transplant hours. The incidence of severe primary graft dysfunction was comparable up to 48 h post-transplant and was significantly increased in the RP cohort 72 h post-transplant (2.2% AP vs 14.8% RP, P = 0.016). Fatal bronchial dehiscences occurred more often in RP recipients (5.6% RP vs 0.6% AP, P = 0.067). The occurrence of bronchial stenoses revealed a slightly improved trend in the RP group (24.9% AP vs 13.9% RP, P = 0.218). Survival (P = 0.927) and bronchiolitis obliterans syndrome-free survival (P = 0.337) were comparable between groups. CONCLUSION: In our clinical survey, this analysis does not confirm the beneficial results of retrograde lung preservation alone, as was previously observed in experimental studies.

Glutathione improves the function of porcine pulmonary grafts stored for twenty-four hours in low-potassium dextran solution.

BACKGROUND: Flush perfusion with low-potassium dextran is the standard strategy in clinical lung preservation. Despite improved outcome, endothelial cell injury and surfactant dysfunction remain a significant problem after lung transplantation. The radical scavenger glutathione has been shown to be responsible for the efficacy of Celsior solution in lung preservation. We tested the hypothesis that the addition of glutathione to low-potassium dextran might further improve graft function by ameliorating ischemia-reperfusion injury. METHODS: In 12 domestic pigs, lungs were flush preserved with either low-potassium dextran (n = 6) or low-potassium dextran supplemented by 5 mmol glutathione (n = 6). Left single lung transplantation was performed after 24-hour storage in low-potassium dextran at 8 degrees C. After 15 minutes of reperfusion the right main bronchus and pulmonary artery were crossclamped. Hemodynamic and respiratory measures were recorded in 30-minute intervals for a total observation period of 7 hours. Bronchoalveolar lavage fluid was obtained from the native lung and 2 hours after reperfusion from the graft. Bronchoalveolar lavage fluid and surfactant composition, and surfactant function analyses were performed. Neutrophil sequestration was assessed by myeloperoxidase activity assay. Tissue water content was calculated from wet/dry weight ratios at the end of the experiment. RESULTS: In the low-potassium dextran group, 2 animals died during reperfusion. After reperfusion, pulmonary vascular resistance (P = .01) and pulmonary artery pressure remained lower in the glutathione/low-potassium dextran group, which was associated with a higher cardiac output (P = .05) in this group. Also, the oxygenation index at the end of the observation period was higher in the glutathione/low-potassium dextran group compared with the low-potassium dextran group (430 +/- 130 vs 338 +/- 184, respectively; P < .05). The graft water content representing postreperfusion lung edema was not different between the 2 study groups. Alteration of surfactant was less in the glutathione/low-potassium dextran group with a significantly decreased small to large aggregate ratio (P = .03) versus low-potassium dextran group. Myeloperoxidase activity was twice as high in the low-potassium dextran group when compared with the glutathione/low-potassium dextran group (glutathione/low-potassium dextran: 134 +/- 110 mU/g vs low-potassium dextran: 274 +/- 168 mU/g, P = .07). CONCLUSION: The addition of glutathione to low-potassium dextran preservation solution reveals beneficial effects on vascular function and surfactant composition in transplanted lungs. Therefore, glutathione ameliorates ischemia-reperfusion injury in a preclinical model of lung transplantation. Future studies are needed to evaluate this promising modification in clinical lung transplantation.

Iloprost to improve surfactant function in porcine pulmonary grafts stored for twenty-four hours in low-potassium dextran solution.

OBJECTIVES: The optimal strategy for pulmonary graft preservation remains elusive. Experimental work and initial clinical experience support low-potassium dextran solutions as lung perfusates. We have previously shown a protective effect of prostaglandin E 1 on ischemia-reperfusion injury in lung transplantation by a shift from proinflammatory to anti-inflammatory cytokines in a rat lung transplantation model. In this study, we tested the hypothesis that the addition of a prostacyclin analog (iloprost) to low-potassium dextran might lead to improved surfactant and ultimately graft function. METHODS: In a randomized, blinded study with a porcine left single-lung transplantation model, donor lungs were flushed with 1 L of either low-potassium dextran solution or low-potassium dextran solution modified by the addition of 250 microg iloprost (n = 6 in each group). Grafts were stored at 4 degrees C for 24 hours. After transplantation, the right bronchus and pulmonary artery were clamped, and the animals remained dependent on the graft. Posttransplantation graft function was assessed throughout a 7-hour observation period by measuring oxygenation (30-minute intervals), different pulmonary and systemic hemodynamic parameters, and wet/dry lung weight ratios. Bronchoalveolar lavage fluid was obtained before and 2 hours after reperfusion. Surfactant function was measured from bronchoalveolar lavage fluid with a pulsating bubble surfactometer. Neutrophil sequestration was assessed by a myeloperoxidase assay performed on lung tissue specimens taken at the end of the observation period. RESULTS: Pulmonary vascular resistance remained lower in the iloprost group than in the control group (P < .05). Tissue water content after 7 hours of reperfusion remained lower in the iloprost group (P < .05). In addition, significantly reduced myeloperoxidase tissue activity was observed in the iloprost group (P < .05). Although there was no difference in degradation of surface active surfactant large aggregates to small aggregates, the surface tension measured at minimal bubble diameter was lower in the iloprost group (P < .05). CONCLUSIONS: Modification of low-potassium dextran solution with the prostacyclin analog iloprost resulted in a significant amelioration of ischemia-reperfusion injury and improved preservation of surfactant function in transplanted lungs. This intriguing approach merits further evaluation with respect to the mechanisms involved and, ultimately, potential introduction into clinical lung transplantation.

Lung transplantation with lungs from donors fifty years of age and older.

BACKGROUND: A shortage of donors has led to the progressive expansion of criteria for donor selection in lung transplantation. The outcome of recipients of lungs from donors aged 50 years or older is analyzed systematically. METHODS: From March 1998 to June 2003, 49 recipients received lungs from donors aged 50 years or older (range 50-64 years, mean 54 +/- 3 years). This group of recipients was compared with 244 patients receiving lungs from donors aged less than 50 years (range 7-49 years, mean 32 +/- 11 years). This study was undertaken on all 293 patients at our institution who received Perfadex-preserved lungs (Vitrolife, Goteborg, Sweden). RESULTS: Recipient age, sex, and indications for transplant did not differ significantly between groups. Also, the percentage of the different types of transplants (bilateral or single lung transplantation) performed was equal in both cohorts. Donor Pa(O2) /F(IO2) ratios before lung retrieval (415 +/- 91 vs 439 +/- 113, respectively) and length of ischemic time (347 +/- 67 minutes vs 351 +/- 84 minutes, respectively) did not differ significantly between the older and younger donor groups. The following posttransplant parameters were also not statistically different: first Pa(O2)/F(IO2) at intensive care unit arrival (274 +/- 125 in the older donor group vs 253 +/- 119 in the younger donor group, respectively), mechanical ventilation time (328 +/- 427 hours vs 269 +/- 425 hours, respectively), and length of stay in the intensive care unit (16 +/- 18 days vs 14 +/- 18 days, respectively). Recipient survival in the older and younger donor groups at 30 days, 3, 6, 12, 24, and 60 months was 77% +/- 6%, 75% +/- 6%, 73% +/- 7%, 73% +/- 7%, 68% +/- 5%, and 68% +/- 4% versus 86% +/- 2%, 83% +/- 3%, 80% +/- 3%, 78% +/- 3%, 71% +/- 4%, and 66% +/- 4%, respectively. CONCLUSIONS: Lung grafts from elderly donors have been considered as marginal organs for transplantation. However, this study indicates that transplantation of lungs from carefully selected donors aged 50 years or more may lead to similar short- and long-term outcomes compared with lungs from younger donors. The use of lungs from elderly donors may help to increase the number of donor organs in lung transplantation.

Lung Preservation With Perfadex or Celsior in Clinical Transplantation: A Retrospective Single-Center Analysis of Outcomes.

BACKGROUND: Despite improvement of lung preservation by the introduction of low-potassium dextran (LPD) solution, ischemia-reperfusion injury remains a major contributor to early post-lung transplant graft dysfunction and mortality. After favorable experimental data, Celsior solution was used in our clinical lung transplant program. Data were compared with our historic LPD cohort. METHODS: Between January 2002 and January 2005, 209 consecutive lung transplantations were performed with LPD. These were compared to 208 transplants between February 2005 and September 2007 with Celsior. Endpoints included posttransplant PaO2/FiO2 ratio at different timepoints after intensive care unit (ICU) admission, posttransplant ventilation time, ICU stay and 30-day mortality, follow-up survival, and bronchiolitis obliterans syndrome-free survival. RESULTS: Ratios of sex, urgency status, type of procedure, length of posttransplant ICU stay, and age did not show significant differences between the 2 groups. Mean ischemia times were significantly longer in the Celsior group (LPD, 355 ± 105 minutes vs Celsior, 436 ± 139 minutes, P < 0.001). Overall 3-year-survival (LPD, 66.5% vs Celsior, 72.0%; P = 0.25) was nonsignificantly improved in the Celsior cohort. CONCLUSIONS: A trend toward better survival (P = 0.09) and increased freedom from bronchiolitis obliterans syndrome (P = 0.03) was observed in the Celsior group despite prolonged ischemic times compared with LPD. Lung preservation with Celsior is safe and effective and may carry advantages.

Evidence and consensus based guideline for the management of delirium, analgesia, and sedation in intensive care medicine. Revision 2015 (DAS-Guideline 2015) - short version.

In 2010, under the guidance of the DGAI (German Society of Anaesthesiology and Intensive Care Medicine) and DIVI (German Interdisciplinary Association for Intensive Care and Emergency Medicine), twelve German medical societies published the "Evidence- and Consensus-based Guidelines on the Management of Analgesia, Sedation and Delirium in Intensive Care". Since then, several new studies and publications have considerably increased the body of evidence, including the new recommendations from the American College of Critical Care Medicine (ACCM) in conjunction with Society of Critical Care Medicine (SCCM) and American Society of Health-System Pharmacists (ASHP) from 2013. For this update, a major restructuring and extension of the guidelines were needed in order to cover new aspects of treatment, such as sleep and anxiety management. The literature was systematically searched and evaluated using the criteria of the Oxford Center of Evidence Based Medicine. The body of evidence used to formulate these recommendations was reviewed and approved by representatives of 17 national societies. Three grades of recommendation were used as follows: Grade "A" (strong recommendation), Grade "B" (recommendation) and Grade "0" (open recommendation). The result is a comprehensive, interdisciplinary, evidence and consensus-based set of level 3 guidelines. This publication was designed for all ICU professionals, and takes into account all critically ill patient populations. It represents a guide to symptom-oriented prevention, diagnosis, and treatment of delirium, anxiety, stress, and protocol-based analgesia, sedation, and sleep-management in intensive care medicine.

Pulmonary preservation with LPD and celsior solution in porcine lung transplantation after 24 h of cold ischemia.

OBJECTIVE: Pulmonary preservation for transplantation is associated with ischemia reperfusion injury resulting in endothelial cell and surfactant dysfunction. The purpose of the study was to compare two extracellular type solutions, low potassium dextrane (LPD) and Celsior in their ability of ameliorating lung ischemia reperfusion injury. METHODS: In 12 donor pigs, the left lung was perfused with either LPD (n = 6) or Celsior (n = 6) solution. After 24 h cold storage, the lungs were transplanted into 12 recipient animals. After reperfusion of the left lung, the right pulmonary artery and bronchus were clamped. Bronchoalveolar lavage fluid (BALF) was obtained before the surgical procedure and 2 h after reperfusion. Surfactant activity was measured from BALF using a pulsating bubble surfactometer. Hemodynamic and respiratory parameters were assessed in 30-min intervals for 7 post-operative hours. RESULTS: In both study groups two of six animals died from severe ischemia reperfusion injury, thus survival did not differ between groups. Rise of pulmonary vascular resistance index (P = 0.01) and sequestration of neutrophiles (P = 0.08) was less pronounced in Celsior group when compared to LPD animals. A difference in surfactant activity between both groups was not evident after 2 h of reperfusion. CONCLUSIONS: Both solutions might provide safe pulmonary preservation for 24 h of cold ischemia. While surfactant activity was affected to the same extent in both groups, Celsior solution provided slightly superior endothelial preservation.

Lung transplantation: a treatment option in end-stage lung disease.

BACKGROUND: Lung transplantation is the final treatment option in the end stage of certain lung diseases, once all possible conservative treatments have been exhausted. Depending on the indication for which lung transplantation is performed, it can improve the patient's quality of life (e.g., in emphysema) and/ or prolong life expectancy (e.g., in cystic fibrosis, pulmonary fibrosis, and pulmonary arterial hypertension). The main selection criteria for transplant candidates, aside from the underlying pulmonary or cardiopulmonary disease, are age, degree of mobility, nutritional and muscular condition, and concurrent extrapulmonary disease. The pool of willing organ donors is shrinking, and every sixth candidate for lung transplantation now dies while on the waiting list. METHOD: We reviewed pertinent articles (up to October 2013) retrieved by a selective search in Medline and other German and international databases, including those of the International Society for Heart and Lung Transplantation (ISHLT), Eurotransplant, the German Institute for Applied Quality Promotion and Research in Health-Care (Institut für angewandte Qualitätsförderung und Forschung im Gesundheitswesen, AQUA-Institut), and the German Foundation for Organ Transplantation (Deutsche Stiftung Organtransplantation, DSO). RESULTS: The short- and long-term results have markedly improved in recent years: the 1-year survival rate has risen from 70.9% to 82.9%, and the 5-year survival rate from 46.9% to 59.6%. The 90-day mortality is 10.0%. The postoperative complications include acute (3.4%) and chronic (29.0%) transplant rejection, infections (38.0%), transplant failure (24.7%), airway complications (15.0%), malignant tumors (15.0%), cardiovascular events (10.9%), and other secondary extrapulmonary diseases (29.8%). Bilateral lung transplantation is superior to unilateral transplantation (5-year survival rate 57.3% versus 47.4%). CONCLUSION: Seamless integration of the various components of treatment will be essential for further improvements in outcome. In particular, the follow-up care of transplant recipients should always be provided in close cooperation with the transplant center.

Initial topical cooling followed by backtable Celsior flush perfusion provides excellent early graft function in porcine single lung transplantation after 24 hours of cold ischemia.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Glutathione preconditioning ameliorates mitochondria dysfunction during warm pulmonary ischemia-reperfusion injury.

OBJECTIVES: Reduced glutathione (GSH) has been shown to improve pulmonary graft preservation. Mitochondrial dysfunction is regarded to be the motor of ischemia-reperfusion injury (IR) in solid organs. We have shown previously that IR induces pulmonary mitochondrial damage. This study elucidates the impact of GSH preconditioning on the integrity and function of pulmonary mitochondria in the setting of warm pulmonary IR. METHODS: Wistar rats were subjected to control, sham, and to two-study-group conditions (IR30/60 and GSH-IR30/60) receiving IR with or without GSH preconditioning. Rats were anesthetized and received mechanical ventilation. Pulmonary in situ clamping followed by reperfusion generated IR. Mitochondria were isolated from pulmonary tissue. Respiratory chain complexes activities (I-IV) were analyzed by polarography. Mitochondrial viability (Ca2+-induced swelling) and membrane integrity (citrate synthase assay) were determined. Subcellular-fractional cytochrome C-content (Cyt C) was quantified by enzyme-linked immunosorbent assay (ELISA). Mitochondrial membrane potential (ΔΨm) was analyzed by fluorescence-activated cell sorting (FACS) after energizing and uncoupling. Inflammatory activation was determined by myeloperoxidase activity (MPO), matrix-metalloproteinase 9 (MMP-9) activity by gel zymography. RESULTS: Pulmonary IR significantly reduced mitochondrial viability in combination with ΔΨm hyper-polarization. GSH preconditioning improved mitochondrial viability and normalized ΔΨm. Cyt C was reduced after IR; GSH protected from Cyt C liberation. Respiratory chain complex activities (I, II, III) declined during IR; GSH protected complex II function. GSH also protected from MMP-9 and neutrophil sequestration (P>.05). CONCLUSIONS: GSH preconditioning is effective to prevent mitochondrial death and improves complex II function during IR, but not mitochondrial membrane stability. GSH-mediated amelioration of ΔΨm hyper-polarization appears to be the key factor of mitochondrial protection.