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Biomedical subjects

Walter Klepetko

Publications and source records attributed to Walter Klepetko.

At least 37 records · Page 2Linked to original sources
PubMed2005

Extended donor criteria for lung transplantation--a clinical reality.

OBJECTIVE: Standard lung donor criteria have been established on opinions and individual experiences rather than on existing evidence. Since the scarcity of donor organs is one of the major limitations to lung transplantation, extension of donor lung criteria might considerably increase the donor pool. This study therefore evaluates the outcome, achieved with the use of extended donors versus standard donors and aims to redefine lung donor criteria. METHODS: We performed a retrospective analysis of 98 consecutive primary lung transplantations from 94 donors from 1/2001 to 12/2002. Donors were classified as extended if they fulfilled at least one criteria: age >55 years, PaO(2) at FiO(2)/PEEP 5 <300mmHg, tobacco history >20 pack years, inhalative drug abuse, presence of infiltration on chest X-ray or purulent secretions at bronchoscopy. Recipients were stratified in two groups according to whether they received a 'standard' or 'extended' organ. Postoperative complications, extubation time, ICU and hospital stay and survival were compared. RESULTS: Twenty-three (24.5%) donors were extended. Twenty-six recipients (26.55%) received organs from extended donors. Differences in intubation times (12+/-2 days standard vs. 14+/-5 days extended, P=0.70), ICU stay (16+/-2 days standard vs. 18+/-5 days extended, P=0.74) and hospital stay (38+/-4 days standard vs. 40+/-6 days extended, P=0.71) were not statistically significant. Postoperative bleeding rates were comparable (n=14 standard vs. n=3 extended) as well as bronchial anastomotic complications (n=7 standard vs. n=3 extended). Three months survival was 88.89% in the standard group vs. 92.31% in the extended group. One year survival is comparable as well with 81.94 vs. 84.62%, respectively. CONCLUSIONS: The use of lung donors who fail to meet standard criteria does not impair short and medium term results compared to standard lung donors. The impact on long term development of BOS has yet to be evaluated. The strict application of standard lung donor criteria excludes a considerable number of lungs potentially suitable for transplantation, thus liberalisation of donor criteria might help to overcome donor shortage.

Adult↗
PubMed2005

Quality of life after lung transplantation: a cross-sectional study.

BACKGROUND: The increase in life expectancy has raised the importance of quality of life after lung transplantation, although this issue has not yet been systematically investigated. The aim of this cross-sectional study was to provide an overview of quality of life in lung transplant patients. METHODS: Between April and July 2001, a set of 4 questionnaires were given to all adult, German-speaking lung transplant recipients (n = 108; response rate 87% [n = 94]): St. George's Respiratory Questionnaire (SGRQ), a lung-specific health status instrument; the Short Form-36 (SF-36), a general quality of life measure; the Hospital Anxiety and Depression Scale (HADS-D) and a self-reported questionnaire concerning sexual functioning, physical symptoms, adverse effects of immunosuppression and satisfaction with outcome. RESULTS: With regard to the SGRQ, all lung transplant recipients had significantly better scores, which reflected an enhanced quality of life compared with the reference value for patients with obstructive pulmonary disease (SGRQ: p < 0.001 in all sub-scales). The Hospital Anxiety and Depression Scale and the Mental Component Summary Scale of the SF-36 did not differ significantly compared with published normative data in the healthy population. However, the side effects of immunosuppression proved to be a major factor influencing the quality of life of lung transplant recipients (11% influenced strongly and 24% moderately). Seventy-six percent of lung transplant patients were highly satisfied with the transplant outcome and 92% would opt for the procedure again. Among all lung transplant recipients, those with cystic fibrosis were most satisfied (significantly) with their quality of life. CONCLUSIONS: Although lung transplant patients must cope with the side effects of immunosuppression, they report a highly satisfying quality of life with regard to physical and emotional well-being and social and sexual function.

Adult↗
PubMed2005

Broncho-alveolar lavage matrix metalloproteases as a sensitive measure of bronchiolitis obliterans.

Bronchiolitis obliterans (BO) is a survival-limiting factor in lung transplantation. There are no common BO markers in use. Since BO is associated with extracellular matrix remodeling, we asked whether matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs) could serve as BO markers. In 72 lung transplant patients (34 BO syndrome (BOS) 0, 15 BOS 0-p, and 23 BOS 1) serum and broncho-alveolar lavage (BAL) MMP and TIMP levels were examined by ELISA. The BAL cell counts were additionally analyzed. The serum MMP-2, MMP-8, MMP-9 and TIMP-2 levels were not different in all groups. In contrast, the BAL MMP-8, -9 and TIMP-1 levels were significantly elevated in BOS 0-p (p = 0.003; p = 0.007; p = 0.0003, respectively) and BOS 1 (p = 0.003; p = 0.001; p = 0.0004, respectively) as compared to BOS 0 patients. The BAL MMP-8, -9 and TIMP-1 levels were significant predictors of BOS 0-p (p = 0.01; p = 0.01; p = 0.01, respectively) and BOS-1 (p = 0.007; p = 0.01; p = 0.006, respectively) in receiver operating characteristic analysis. Except for BAL macrophages that were significantly decreased in BOS 0-p versus BOS 0 patients; other cell counts were not different between the groups. BAL MMP-8, -9 and TIMP-1 might be useful markers to detect BO in lung transplant patients.

Adult↗
PubMed2005

Medical conditions increasing the risk of chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by organized thromboemboli that obstruct the pulmonary vascular bed. Although CTEPH is a serious complication of acute symptomatic pulmonary embolism in 4% of cases, signs, symptoms and classical risk factors for venous thromboembolism are lacking. The aim of the present study was to identify medical conditions conferring an increased risk of CTEPH. We performed a case-control-study comparing 109 consecutive CTEPH patients to 187 patients with acute pulmonary embolism that was confirmed by a high probability lung scan. Splenectomy (odds ratio=13, 95% CI 2.7-127), ventriculo-atrial (VA-) shunt for the treatment of hydrocephalus (odds ratio=13, 95% CI 2.5-129) and chronic inflammatory disorders, such as osteomyelitis and inflammatory bowel disease (IBD, odds ratio=67, 95% CI 7.9-8832) were associated with an increased risk of CTEPH.

Adult↗
PubMed2005

Bosentan therapy for inoperable chronic thromboembolic pulmonary hypertension.

BACKGROUND: Bosentan, an oral endothelin (ET)-A/ET-B receptor antagonist, is effective in the treatment of pulmonary arterial hypertension. OBJECTIVE: To investigate the safety and efficacy of bosentan therapy in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). DESIGN: Case series. SETTING: Pulmonary Hypertension Unit of the Medical University of Vienna, Austria. PATIENTS: Sixteen patients (9 women and 7 men; mean age +/- SD, 70 +/- 13 years). INTERVENTION: Off-label bosentan treatment over 6 months. MEASUREMENTS: Changes from baseline in liver enzymes, New York Heart Association (NYHA) functional class, 6-min walking distance (6-MWD), and serum amino-terminal pro-brain natriuretic peptide (proBNP). RESULTS: After 6 months, NYHA functional class improved by one class in 11 patients. Mean 6-MWDs increased from 299 +/- 131 m at baseline to 391 +/- 110 m at 6 months (p = 0.01). In parallel, proBNP decreased from 3,365 +/- 2,923 to 1,755 +/- 1,812 pg/mL (p = 0.01). Neither aspartate aminotransferase (25 +/- 2 U/L vs 25 +/- 2 U/L, p = 0.25) nor alanine aminotransferase (23 +/- 12 U/L vs 24 +/- 9 U/L, p = 0.57) changed significantly. Limitations of the study were uncontrolled design and small sample size. CONCLUSIONS: Our study suggests a beneficial effect of the oral dual ET receptor antagonist bosentan in patients with inoperable CTEPH, urging the need for a randomized, placebo-controlled trial.

Adult↗
PubMed2004

Association of cytomegalovirus DNA concentration in epithelial lining fluid and symptomatic cytomegalovirus infection in lung transplant recipients.

BACKGROUND: The authors have investigated the effectiveness of virus detection from bronchoalveolar lavage (BAL) samples for the identification of symptomatic cytomegalovirus (CMV) infection in lung transplant recipients. METHODS: Thus, 275 BAL samples taken from 105 lung transplant recipients during follow-up were analyzed by quantitative polymerase chain reaction (PCR) and virus isolation. RESULTS: Quantitative PCR detected virus in all 24 BAL samples taken at onset of symptomatic disease, and virus culture in only 7 samples (29.2%). Twenty-three of 251 BAL samples (9.2%) were positive by PCR, although they were obtained in an asymptomatic phase. Quantitation of CMV DNA from BAL allowed no discrimination between symptomatic and asymptomatic infection in individual cases. However, when the urea dilution method was used to recalculate the CMV DNA concentration for the epithelial lining fluid (ELF) diluted in the BAL, a CMV DNA level of more than 10 copies/mL ELF was clearly associated with symptomatic disease. CONCLUSION: The CMV DNA level in ELF may be a marker for symptomatic CMV infection.

Bronchoalveolar Lavage Fluid↗
PubMed2004

Interventional and surgical modalities of treatment for pulmonary arterial hypertension.

Beyond medical therapy, different interventional and surgical approaches exist for treatment of pulmonary arterial hypertension (PAH). Atrial septostomy has been applied in patients with lack of response to medical therapy in the absence of other surgical treatment options. With growing experience, procedure-related death rates have been reduced to 5.4%, and the most suitable patient group has been identified among patients with a mean right atrial pressure between 10 and 20 mm Hg. Pulmonary endarterectomy is the accepted form of treatment for patients with chronic thromboembolic pulmonary hypertension. Establishing the diagnosis and the classification of the type of lesions by pulmonary angiography is crucial for optimal patient selection. Perioperative mortality rates have been reduced to <10% in experienced centers, and the hemodynamic improvement is dramatic and sustained. Lung and heart-lung transplantation remains the procedure of choice for patients unsuitable for other treatment modalities. Timing of the procedure is difficult because waiting times vary between centers and usually are in a high range. Early referral of patients unresponsive to other treatment forms is therefore of importance to avoid transplantation of patients with established significant comorbidity. The survival rate during the first five years after transplantation for PAH is intermediate among the lung diseases, lower than chronic obstructive pulmonary disease but higher than idiopathic pulmonary fibrosis.

Catheterization↗
PubMed2004

Cystic fibrosis and lung transplantation--determination of the survival benefit.

INTRODUCTION: Cystic fibrosis is a well acknowledged indication for lung transplantation; however, the optimal timing for transplantation remains debatable. Liou et al. described a score for calculating 5-year probability of survival for patients with cystic fibrosis and concluded that only patients with a probability of survival < 30% gained a survival benefit from transplantation; those between 30% and 50% had equivocal survival effects from transplantation and those > 50% suffered negative effects. The aim of the present study was to determine the validity and applicability of this model. METHODS: Data from patients with cystic fibrosis transplanted between January 1995 and July 2001 were retrospectively reviewed. Survival score according to Liou was calculated from data collected before transplantation. Patients were classified according to 5-year probability of survival (group 1: < 30%, group 2: 30%-50%, groups 3-5: > 50%). Actuarial survival rates were calculated separately for each group and compared with the predicted probability of survival. RESULTS: During the observation period 27 patients were transplanted for cystic fibrosis. Three patients had to be excluded from further analysis because of incomplete pretransplant data. Fifteen patients were classified as group 1 and nine patients as group 2. No patients were eligible for groups 3 to 5. There were nine female patients and six males in group 1, mean age 22.1 +/- 4.9 years. Mean survival time was 918 +/- 787 days; 1-, 3- and 5-year survival rates were 66.6%. Three male patients and six females were classified as group 2, mean age 26.2 +/- 12.2 years. Mean survival time for this group was 701 +/- 617 days, and 1-, 3- and 5-year survival rates were 66.6%. CONCLUSION: We found that only patients with a 5-year probability of survival < 50% had been transplanted. For patients in groups 1 and 2 we report identical 5-year survival rates of 66.6%. According to our experience, cystic fibrosis patients with a 5-year probability of survival < 30% and also those between 30% and 50% gain a clear survival benefit from bilateral lung transplantation.

Actuarial Analysis↗
PubMed2004

Prediction of lung-transplant rejection by hepatocyte growth factor.

BACKGROUND: Graft rejection is a major complication of lung transplantation. No serological marker of rejection is in common use. Hepatocyte growth factor (HGF) is highly expressed in the lung and produced after acute lung injury; serum concentrations increase in inflammatory lung diseases. We investigated whether HGF could be an accurate marker for prediction of lung-graft rejection. METHODS: Serum concentrations of HGF were measured by ELISA in 109 patients who had undergone lung transplantation (65 for chronic obstructive pulmonary disease; 23 for cystic fibrosis; 21 for idiopathic lung fibrosis), comparing those who had no subsequent events and those with episodes of infection or rejection, as well as in 12 healthy controls. FINDINGS: The mean baseline serum HGF concentration was 645 ng/L (SD 259) in controls and 1358 ng/L (603) in the patients before transplantation. After transplantation the mean concentration in patients with no events was 1147 ng/L (510) compared with 1559 ng/L (323) in patients with infection (p=0.001 vs controls; change from pretransplant value not significant). Patients with rejection had significantly higher concentrations than all other groups (3972 ng/L [1463], p<0.0001). Logistic regression identified HGF as a predictor for lung graft rejection (p=0.012). After steroid treatment, HGF concentrations returned almost to the preoperative values within 3 days. INTERPRETATION: HGF might be a marker for graft rejection in lung transplantation. A potential link between viral infection, mainly cytomegalovirus, and HGF, however, remains to be investigated.

Acute Disease↗
PubMed2004

Sealing of the mediastinum with a local hemostyptic agent reduces chest tube duration after complete mediastinal lymph node dissection for stage I and II non-small cell lung carcinoma.

BACKGROUND: We assessed the impact of coverage of the mediastinum with a local hemostyptic agent as well as the impact of perioperative thromboembolic prophylaxis on cumulative chest drain volume and on the duration of chest tubes after surgical resection with complete mediastinal lymph node dissection for stage I or II non-small cell lung cancer. METHODS: In a prospective, randomized two-by-two factorial design, 80 patients with clinical stage I or II non-small cell lung cancer were allocated to one of two surgical therapy arms (TachoComb or conventional surgical hemostasis) and one of two anticoagulation arms (enoxaparin 4,000 IU or dalteparin 5,000 IU). Primary end point was cumulative chest drain volume; secondary end point was duration of chest tubes. Additionally clinical data were obtained. RESULTS: Comparison of the surgical arms revealed significantly lower cumulative chest drain volumes and thereby an earlier chest tube removal in the TachoComb group (p = 0.045). With regard to thromboembolic prophylaxis, a significantly earlier chest tube removal was found for patients treated with dalteparin (p = 0.039). Analysis of the interaction of surgical and anticoagulation treatment revealed the combined use of TachoComb and dalteparin was superior to other combinations (cumulative chest drain volumes 498 +/- 67 mL versus 1,000 +/- 88 mL, 924 +/- 87 mL, and 895 +/- 118 mL; p = 0.008; mean duration of chest tubes 1.78 +/- 0.15 days versus 2.96 +/- 0.21 days, 2.93 +/- 0.17 days, and 3.06 +/- 0.27 days; p = 0.019). CONCLUSIONS: The combined use of a local hemostyptic agent and dalteparin seems superior as compared with other regimens of hemostasis and thromboembolic prophylaxis in patients undergoing surgical resection and complete mediastinal lymph node dissection for stage I and II non-small cell lung cancer with regard to cumulative chest drain volume as well as duration of chest tubes.

Adult↗
PubMed2004

Upregulated hypoxia-inducible factor-1 DNA binding activity to the vascular endothelial growth factor-A promoter mediates increased vascular permeability in donor lung grafts.

BACKGROUND: Transplantation-induced hypoxia results in enhanced vascular permeability and tissue vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) overexpression in donor lung grafts. Promoter studies have uncovered a hypoxia-inducible factor (HIF)-1 binding site (HBS) in 5'-flanking region of VEGF gene that regulates the hypoxia-induced expression of VEGF; and ET-1 potently stimulates VEGF-A production. We hypothesized that HIF-1 regulates VEGF-mediated vascular permeability in lung grafts. METHODS: We studied the mRNA and protein expression of HIF-1 and its protein-binding capacity to the HBS of the VEGF gene in biopsies of preserved donor and control lungs, using real-time reverse transcription-polymerase chain reaction, Western blotting, and electrophoretic mobility shift assay. Wet-to-dry lung weight ratio was measured in donor and control lungs. RESULTS: While HIF-1 alpha mRNA expression was unchanged, HIF-1 beta was downregulated (p < 0.05) in donor versus control lungs. Protein expression of both, HIF-1 alpha and -beta was significantly upregulated in donor lung grafts. HIF-1 binding to the HBS of the VEGF promoter as well as tissue fluid content were increased in donor lung biopsies versus controls (p < 0.05). CONCLUSIONS: These data indicate that upregulated HIF-1 DNA binding activity to the HBS of VEGF-A most likely contributes to elevated VEGF levels in preserved lung grafts. Unchanged HIF-1 alpha mRNA expression did not affect HIF-1 alpha protein levels. Endothelin-1 increases HIF-1 alpha accumulation and activates HIF-1 transcription complex in vitro. Therefore, ET-1-mediated increased HIF-1 alpha protein stability most likely leads to transcriptional activation of VEGF during lung graft preservation. Targeting HIF might be of benefit to counteract edema formation in preserved lung grafts.

Aryl Hydrocarbon Receptor Nuclear Translocator↗
PubMed2004

Lung wedge resection improves outcome in stage I primary spontaneous pneumothorax.

BACKGROUND: To evaluate the role of apical lung wedge resection in patients with recurrent primary spontaneous pneumothorax with no endoscopic abnormalities at surgery as compared with simple apical pleurectomy. METHODS: We performed a retrospective analysis on 126 consecutive video-assisted thoracoscopic surgery (VATS) procedures in 113 patients treated for stage I recurrent PSP between January 1994 and December 2001. Two surgical strategies were applied: simple apical pleurectomy (57 procedures, 45.2%: group A) and apical pleurectomy together with an apical lung wedge resection (69 procedures, 54.8%: group B). RESULTS: Mean duration of chest tubes was 1.4 days (range, 1 to 7), mean hospital stay was 2.4 days. Three patients (2.4%) required redo VATS, 2 in group A (3.5%) for persistent air leak and 1 (1.4%) in group B for apical hematothorax. Mean follow-up was 38.7 months. Overall recurrence rate was 3.2%. Four patients in group A (7%) experienced recurrent ipsilateral pneumothoraces 4 to 73 weeks (mean, 30.2) after surgery. No recurrences were observed in group B (p = 0.009). CONCLUSIONS: In this selected group of patients without endoscopical abnormalities, VATS offers low recurrence rates. However, these data suggest that apical pleurectomy should be accompanied by apical lung wedge resection even for this favorable category of patients.

Adolescent↗
PubMed2004

Treatment of severe acute lung allograft rejection with OKT3 and temporary extracorporeal membrane oxygenation bridging.

OBJECTIVES: The use of OKT3 for treatment of advanced high-grade acute rejection episodes eventually can result in cytokine release and consecutive pulmonary edema. Temporary extracorporeal membrane oxygenation (ECMO) bridging can be used to overcome this crucial period before the beneficial effects of OKT3 can be observed. METHODS: We summarize our experience with three patients, who underwent lung transplantation and presented with severe acute rejection episodes. OKT3 had to be initiated due to insufficient response to standard rejection therapy with corticosteroids. Upon initiation of OKT3 treatment, a massive life-threatening deterioration of lung function in spite of heavily invasive respirator treatment was seen and temporary ECMO support was imperative to support graft function. Results of this treatment were retrospectively reviewed. RESULTS: In all cases femoro-femoral veno-arterial ECMO was used for support of the impaired graft and after a period of 4-5 days led to a massive improvement of graft function. In the further course two patients could be discharged from hospital and are still alive 30 and 36 months, respectively, after the described incident. One patient died 4 months later due to liver failure. CONCLUSIONS: We conclude that the use of ECMO support in patients experiencing significant side effects from OKT3 therapy is a useful and effective therapeutic tool to overcome the initial critical period until the lung has sufficiently recovered.

Acute Disease↗
PubMed2004

Lobar transplantation, split lung transplantation and peripheral segmental resection--reliable procedures for downsizing donor lungs.

OBJECTIVES: The increasing scarcity of donor lungs, especially for small and pediatric recipients has stimulated the development of new operative techniques, which allow larger lungs to be downsized for use in smaller recipients. This approach has only recently gained widespread use-especially for highly urgent recipients-however, it is still not considered a standard procedure. METHODS: This report reviews the Vienna University experience with cadaveric split lung transplantation, lobar transplantation and by means of peripheral resection size reduced lung transplantation within the years 2001-2002. Peri-operative complications and outcome of those patients were retrospectively analysed and compared to the patients undergoing standard single or double lung transplantation during the observation period. RESULTS: During the observation period 98 primary lung transplantations were performed, of which 27 (27.6%) were size reduced transplantations. Size reduction was achieved by lobar transplantation (n=9), split lung transplantation (n=2) or peripheral segmental resection (n=16). There was no statistically significant difference between the size reduced and standard lung transplantation group with regard to the rate of bronchial healing problems (n=3/7; P=0.85) and the rate of post-operative bleeding (n=5/12; P=0.85). No other major thoracic surgical complications were observed. Three months survival rate was 85.2% in the size reduced group, compared to 92.9% in the standard group (P=0.13). CONCLUSIONS: Size reduced lung transplantation, including split lung transplantation, lobar transplantation and peripheral segmental resection, is a reliable procedure providing equal results compared to standard lung transplantation.

Adolescent↗
PubMed2004

Efficacy and safety of topical application of human fibrinogen/thrombin-coated collagen patch (TachoComb) for treatment of air leakage after standard lobectomy.

OBJECTIVES: Persisting air leakage after pulmonary resection remains a significant problem. The aim of the study was to evaluate the incidence of air leakage after standard lobectomy and test the efficacy and safety of TachoComb (TC). METHODS: A total of 189 patients undergoing lobectomy were enrolled in a multi-centre, open, randomised, and prospective study to test the efficacy and safety of TachoComb (TC) for air leakage treatment. Air leakage was assessed by water submersion test, and scored as grades 0 if no, 1 if countable, 2 if a stream of and 3 if coalescent bubbles have been observed. Any sites with grade 3 air leakage received further stapling or limited suturing until grade 0, 1 or 2 was obtained. Treatment of air leakage was done with TC or suturing according to randomisation. Air leakage was assessed by further submersion tests. Postoperative air leakage was assessed using the Pleur-Evac system. RESULTS: Overall incidence of air leakage 48+/-6 h after surgery was 34% for TC and 37% for standard treatment (P=0.76). The reduction of intra-operative air leak intensity in the subgroup with grades 1-2 was significantly higher for the TC group (P=0.015). Postoperative air leakage intensity in the subgroup with air leakage grades 1-2 was lower for TC than standard treatment (P=0.047). The mean duration of postoperative air leakage in the subgroup with grades 1-2 was shorter for the TC group than for standard treatment, i.e. 1.9+/-1.4 vs. 2.7+/-2.2 days (P=0.015). CONCLUSIONS: TC could be proven as well-tolerated and safe. In the subgroup of patients with established air leakage, TC showed superior potential in reduction of intra-operative air leakage as well as in reduction of intensity and duration of postoperative air leakage.

Aged↗