[show abstract][hide abstract] ABSTRACT: BACKGROUND: Procalcitonin (PCT) is widely used in critically ill patients to diagnose clinically significant infection and sepsis. Aim of this study was to evaluate the prognostic value of PCT in comparison to white blood cell count (WBC) and C-reactive protein (CRP) for clinical outcome and its correlation with microbiological etiology in patients with infective endocarditis (IE). METHODS: A retrospective single-center analysis was performed from 2007 till 2009. All patients were diagnosed having IE according to Duke standard criteria. Before starting antibiotic therapy, WBC, CRP and PCT were measured and blood cultures were taken for microbiological diagnosis of the etiological pathogen. Patients were followed up during in-hospital stay for poor outcome, defined as death or serious complications due to IE. RESULTS: During the study period 50 patients (57 +/- 17 years, 72% male) fulfilling Duke criteria for IE were identified. In all patients PCT measurements before start of antibiotic therapy were available. In ROC analysis, a cut-off for PCT > 0.5 ng/mL was most accurate for the prediction of poor outcome with a sensitivity of 73% and specificity of 79%, a positive predictive value of 79% and a negative predictive value of 73%. Patients with a PCT > 0.5 ng/mL had an odds ratio of 12.8 (95% CI 2.5 -- 66.2) for finding Staphylococcus aureus in blood cultures. CONCLUSIONS: For the first time, this study shows that in IE, an initial value of PCT > 0.5 ng/mL is a useful predictor of poor outcome, i.e. death or serious infectious complications. PCT > 0.5 ng/mL should raise the suspicion of Staphylococcus aureus as the etiological pathogen, whereas PCT levels < 0.5 ng/mL make staphylococcal infection unlikely.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Extracorporeal membrane oxygenation (ECMO) can replace the lungs' gas exchange capacity in refractory lung failure. However, its limited hemocompatibility, the activation of the coagulation and complement system as well as plasma leakage and protein deposition hamper mid- to long-term use and have constrained the development of an implantable lung assist device. In a tissue engineering approach, lining the blood contact surfaces of the ECMO device with endothelial cells might overcome these limitations. As a first step towards this aim, we hypothesized that coating the oxygenator's gas exchange membrane with proteins might positively influence the attachment and proliferation of arterial endothelial cells. METHODS: Sheets of polypropylene (PP), polyoxymethylpentene (TPX) and polydimethylsiloxane (PDMS), typical material used for oxygenator gas exchange membranes, were coated with collagen, fibrinogen, gelatin or fibronectin. Tissue culture treated well plates served as controls. Endothelial cell attachment and proliferation were analyzed for a period of 4 days by microscopic examination and computer assisted cell counting. RESULTS: Endothelial cell seeding efficiency is within range of tissue culture treated controls for fibronectin treated surfaces only. Uncoated membranes as well as all other coatings lead to lower cell attachment. A confluent endothelial cell layer develops on fibronectin coated PDMS and the control surface only. CONCLUSIONS: Fibronectin increases endothelial cells' seeding efficiency on different oxygenator membrane material. PDMS coated with fibronectin shows sustained cell attachment for a period of four days in static culture conditions.
[show abstract][hide abstract] ABSTRACT: Hintergrund:Der Morbus Pompe (Glykogenose Typ II) ist eine seltene generalisierte lysosomale Speicherkrankheit aufgrund eines Mangels
der sauren α-1,4-Glucosidase (saure Maltase). Die infantile Verlaufsform geht mit einer schweren Myopathie und Kardiomegalie
einher und führt unbehandelt in den ersten 2 Lebensjahren zum Tod. Der juvenile Typ verläuft etwas milder, eine kardiale Beteiligung
findet sich mit zunehmendem Lebensalter seltener. Bei der adulten Form findet sich zumeist eine progrediente, proximal und
an den Beinen betonte Myopathie. Beeinträchtigungen der Atemmuskulatur im Verlauf sind häufig. Seit kurzem steht mit dem Präparat
Myozyme™ eine intravenöse Enzymersatztherapie zur Verfügung. Es gibt bislang aber nur wenige Daten über die Behandlung der
adulten Form des Morbus Pompe.
Fallbeschreibung:Eine 67-jährige Patientin mit bekanntem Morbus Pompe und schwerster Beeinträchtigung der Atemmuskulatur wurde wiederholt wegen
einer schweren respiratorischen Insuffizienz als Notfall stationär aufgenommen. Bereits wenige Wochen nach Beginn einer Enzymersatztherapie
mit Myozyme™ besserte sich die respiratorische Situation deutlich. Nach 7-monatiger Enzymersatztherapie konnten nahezu normale
Blutgase gemessen werden.
Schlussfolgerung:Kommt es im Erwachsenenalter zu einer langsam progredienten Muskelschwäche der Beckengürtel- und Oberschenkelmuskulatur mit
oder ohne Entwicklung einer respiratorischen Insuffizienz durch Befall der Atemmuskulatur, so sollte auch an die Glykogenose
Typ II gedacht werden. Neben supportiven Therapiemaßnahmen steht mit dem Enzymersatzpräparat Myozyme™ auch im Erwachsenenalter
erstmals ein vielversprechender Therapieansatz zur Verfügung.
Background:Pompe's disease, a rare, inherited deficiency of the enzyme α-1,4-glucosidase (GAA), is a lysosomal storage disorder. Early-onset
(infantile) Pompe's disease is associated with cardiomegaly and severe myopathy and, if left untreated, will inevitably lead
to death within the first 2 years of life. In juvenile Pompe's disease, progression of the disease is generally slower and
involvement of the myocardium is less likely with onset at a later age. The adult form of Pompe's disease is frequently associated
with a progressive proximal myopathy which is more marked in the lower limbs. Involvement of the respiratory system is common.
A new treatment with intravenous enzyme replacement (Myozyme™) is now available. At present, there is only limited data available
regarding its efficacy in the treatment of the adult form of Pompe's disease.
Case Report:A 67-year-old lady with Pompe's disease and known severe respiratory compromise due to involvement of the respiratory muscles
had had recurrent emergency admissions with respiratory failure. After only a few weeks of treatment with intravenous enzyme
replacement with Myozyme™, significant improvement in her respiratory function was noticed. Following a total length of treatment
of 7 months, her arterial blood gas results on room air had almost returned to normal.
Conclusion:A glycogen storage disorder (type II) should be excluded in all adult patients with a slowly progressive weakness involving
pelvic and thigh muscles even when respiratory involvement is not present. In addition to supportive treatment, a new enzyme
replacement therapy for patients with late-onset disease has now become available which shows promising results.
[show abstract][hide abstract] ABSTRACT: Ein wesentliches Problem im Management von pulmonalen Infektionen ist, dass klinische Symptome wie Husten, Auswurf, Fieber
und Dyspnoe nicht spezifisch sind für eine exakte Diagnose „respiratorische Infektion“ und vor allem nicht für die Notwendigkeit
einer antibiotischen Therapie. Ein idealer Biomarker für bakterielle pulmonale Infektionen sollte eine frühzeitige Diagnose
ermöglichen, einen prognostischen Wert haben und therapeutische Entscheidungen erleichtern. Die beiden klinisch verwendeten
Biomarker sind das C-reaktive Protein (CRP) und das Procalcitonin (PCT). Das CRP ist sehr unspezifisch und sowohl bei bakteriellen
und viralen Infektionen erhöht. PCT ist aktuell der einzige Biomarker, der für bakterielle pulmonale Infektionen spezifisch
genug ist. In mehreren Interventionsstudien konnte nachgewiesen werden, dass durch eine PCT-Steuerung Häufigkeit und Dauer
einer antibiotischen Therapie signifikant reduziert werden können bei gleicher klinischer Heilungsrate.
A problem in the management of pulmonary infections is the low specificity of clinical symptoms such as cough, sputum, fever,
and dyspnea for the exact diagnosis of “respiratory infection” and the need for antibiotic therapy. An ideal biomarker for
bacterial pulmonary infections should allow rapid diagnosis, have prognostic value, and facilitate therapeutic decision making.
The two biomarkers in actual clinical use are C-reactive protein (CRP) and procalcitonin (PCT). CRP is quite unspecific and
may be elevated in bacterial as well as in viral infections. Today, PCT is the only biomarker specific enough for pulmonary
infections. In several interventional studies, PCT-guided therapy has been shown to allow a significant reduction in the frequency
and duration of antibiotic therapy, with a clinical cure rate comparable to that of standard therapy.
[show abstract][hide abstract] ABSTRACT: Hintergrund:
Der Morbus Uhl ist eine seltene Erkrankung, die durch eine Aplasie des rechtsventrikulären Myokards charakterisiert ist. Die
massive Funktionseinschränkung des rechten Ventrikels mit seiner pergamentartig dünnen Wand führt zu einer massiven Rechtsherzdilatation
und bei Ausprägung des Vollbildes zum progredienten Rechtsherzversagen.
Ein 70-jähriger Patient mit progredienter Dyspnoe und massiven peripheren Ödemen stellte sich mit dem Bild einer chronischen
Rechtsherzinsuffizienz mit akuter Dekompensation vor. In einer auswärtigen Klinik waren bei Rechtsherzinsuffizienz die Verdachtsdiagnose
einer pulmonalarteriellen Hypertonie gestellt und eine Therapie mit Sildenafil eingeleitet worden. In der Echokardiographie
und der Kardio-MRT (Magnetresonanztomographie) fanden sich eine ausgeprägte Hypoplasie der freien Wand des rechten Ventrikels
sowie eine ausgeprägte Rechtsherzdilatation ohne Nachweis einer pulmonalen Hypertonie. Anhand des typischen Kardio-MRTs wurde
die Diagnose eines Morbus Uhl gestellt. Unter medikamentöser Herzinsuffizienztherapie konnte eine langsame kardiale Rekompensation
erzielt werden. Der Patient war im weiteren Verlauf medikamentös über 9 Monate kardial stabil ohne erneute akute Dekompensation.
Bei Patienten mit einer massiven Rechtsherzdilatation ohne Nachweis einer pulmonalen Hypertonie sollte auch im Erwachsenenalter
an einen Morbus Uhl gedacht werden. Wichtigster diagnostischer Hinweis ist hierfür die Hypoplasie der freien Wand des rechten
Ventrikels, die in der Echokardiographie und Kardio-MRT nachweisbar ist. Kausale Therapieoptionen bestehen nicht. Neben einer
medikamentösen Herzinsuffizienztherapie ist evtl. eine rechtsventrikuläre Kardiomyoplastie oder als Ultima Ratio eine Herztransplantation
Uhl’s disease is a rare disorder characterized by aplasia of the right ventricular myocardium leading to its parchment-like
appearance. The loss of right ventricular function causes massive dilation of the right heart with progressive right heart
failure in severe cases.
A 70-year-old patient with progressive dyspnea and massive peripheral edema presented with an acute decompensation of chronic
right heart failure. Previously, pulmonary arterial hypertension was suspected and therapy with sildenafil was initiated.
Echocardiography and cardiac MRI (magnetic resonance imaging) showed marked hypoplasia of the right ventricular free wall
and marked dilation of the right heart without pulmonary arterial hypertension. The diagnosis of Uhl’s disease was confirmed
by typical MRI morphology. A slow cardiac recompensation was achieved by medicinal treatment of heart insufficiency. Hence
the patient remained stable for 9 months with medicinal therapy without signs of further decompensation.
Uhl’s disease should be suspected in patients with massive right heart dilation without pulmonary hypertension even in the
adult. The major diagnostic clue is hypoplasia of the right ventricular free wall, which can be demonstrated by echocardiography
and cardiac MRI. There is no causal therapy for the disease. Besides medicinal therapy for heart failure, right ventricular
cardiomyoplasty and, ultimately, transplantation might be undertaken successfully.
[show abstract][hide abstract] ABSTRACT: A relevant problem in the management of pulmonary infections is the low specificity of clinical symptoms for the exact diagnosis and the need of antibiotic therapy. An ideal biomarker for bacterial pulmonary infections should allow a rapid diagnosis, have a prognostic value and facilitate therapeutic decision making. The two biomarkers currently needed in clinical use are C-reactive protein and procalcitonin. C-reactive protein is very unspecific and elevated in bacterial as well as viral infections. Today, procalcitonin is the best validated biomarker for pulmonary infections. In several interventional studies procalcitonin-guided therapy has proven to allow a significant reduction of duration and frequency of antibiotic therapy. However, for the evaluation of prognosis in community-acquired pneumonia, new cardiovascular biomarkers are superior compared with inflammatory markers, especially for the determination of long-term mortality. The combination of several biomarkers reflecting different pathophysiological pathways has the potential to improve the management of community-acquired pneumonia in the future.
Expert Review of Respiratory Medicine 04/2012; 6(2):203-14.
[show abstract][hide abstract] ABSTRACT: Fibrin gel has proven a valuable scaffold for tissue engineering. Complex geometries can be produced by injection molding; it offers effective cell seeding and can be produced autologous. In order to evaluate its suitability for respiratory tissue engineering, we examined proliferation, functionality, and differentiation of respiratory epithelial cells on fibrin gel in comparison to culture on collagen-coated, microporous membranes. Respiratory epithelial cells formed a confluent layer by day 4, and proliferation showed no significant difference with respect to surface. Measurement of the transepithelial electrical resistance reflected the development of a confluent epithelial cell layer and the subsequent initiation of adequate ion-transfer processes. Appearance of ciliae could be detected at similar time points, and ciliary beating could be observed for cells on both surfaces. Histology and immunohistochemistry of cells grown on fibrin gel revealed the onset of adequate differentiation. As no significant differences in respiratory epithelial cells' proliferation, function, and differentiation could be observed between cells grown on fibrin gel compared to cells on a collagen-coated, microporous surface, we concluded that fibrin gel might prove a suitable scaffold for respiratory tissue engineering and merits further investigation to overcome the limitations associated with scaffolds currently in use.
Annals of biomedical engineering 03/2012; 40(3):679-87. · 2.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: Interventional radiological procedures for the treatment of primary and secondary pulmonary malignancies have become increasingly important. In addition to thermally ablative treatment, selective chemoembolisation by a vascular access allows localised therapy. These treatments are considered to be palliative for patients in a reduced general condition which does not allow systemic chemotherapy. In functionally inoperable patients especially the ablative procedures are potentially curative alternatives to surgery. This article provides an overview of the currently used interventional radiological procedures in lung oncology and assesses their importance. Further studies are needed to show whether interventional radiological procedures, which are promising due to their favourable risk-benefit ratio, may represent an alternative to radiotherapy or be effective in multimodal approaches.
[show abstract][hide abstract] ABSTRACT: The aim was to correlate dynamic magnetic resonance imaging perfusion parameters of pulmonary tumors with histological tumor classification. Eighty-six patients with lung cancer were examined. A differentiation of non-small cell lung cancer vs. small cell lung cancer was possible with the parameters tumor necrosis, maximum contrast upslope, and the time until the maximum contrast upslope was reached. The beginning of a relevant contrast uptake, the mean time to peak and the time until the maximum contrast upslope was reached allowed a differentiation between squamous cell carcinoma and adenocarcinoma.
[show abstract][hide abstract] ABSTRACT: There is almost no data about the influence of antimicrobial pre-treatment (APT) on levels of inflammatory markers in community acquired pneumonia (CAP). The aim of this study was to investigate the influence of APT on inflammatory markers in CAP.
991 hospitalized patients (64.3±17.6 years, 61% male) with CAP were enrolled. In all patients procalcitonin (PCT), C-reactive protein (CRP), and leukocyte count (WBC) were determined. Patients were followed-up for 28 days for survival.
232 patients (23.4%) had APT, 759 had no APT. Patients without APT had significantly higher levels of PCT and WBC but not of CRP compared to those with APT. In patients without APT, survivors compared to non-survivors had lower values of PCT (0.20 ng/mL; 0.02-169.10 vs. 0.83 ng/mL; 0.04-516.30, p<0.0001), WBC (12.4×10(9)/L; 1.3-49.9 vs. 14.9×10(9)/L; 3.7-34.5, p=0.047) and CRP (107.0mg/mL; 0.3-567.0 vs. 143.5mg/mL; 5.0-589.0, p=0.006). However, in patients with APT, the values of PCT, WBC and CRP were not significantly different in survivors and non-survivors. Cox regression analysis confirmed that PCT, CRP and WBC were predictive for 28 day mortality in patients without APT but not in those with APT.
PCT and WBC but not CRP levels are higher in patients without APT compared to those with APT. PCT, CRP and WBC are predictive for 28 days mortality exclusively in patients without APT. Interpretation of inflammatory parameters has to take into account possible APT.
Clinica chimica acta; international journal of clinical chemistry 12/2010; 411(23-24):1929-34. · 2.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: Several new biomarkers are related to mortality in community-acquired pneumonia (CAP).
Aim of this study was to compare new biomarkers for the prediction of short- and long-term all-cause mortality in CAP.
We enrolled 728 patients (59.0 ± 18.2 yr) with CAP. Midregional proadrenomedullin (MR-proADM), midregional proatrial natriuretic peptide (MR-proANP), proarginin-vasopressin (copeptin), proendothelin-1 (CT-proET-1), procalcitonin (PCT), C-reactive protein, white blood cell (WBC) count, and clinical confusion, respiratory rate, blood pressure, and age over 65 years (CRB-65) score were determined on admission. Patients were followed up for 180 days.
In patients who died of any cause within 28 and 180 days (2.5 and 5.1%, respectively), MR-proADM, MR-proANP, copeptin, CT-proET-1 and PCT as well as CRB-65 were significantly higher compared with survivors. MR-proADM had the best performance for 28 days (HR 3.67) and 180 days (HR 2.84) survival. The C index of MR-proADM for 28-day survival (0.85) was superior to MR-proANP (0.81), copeptin (0.78), CT-proET-1 (0.79), and CRB-65 (0.72) for the prediction of mortality. For prediction of mortality at 180 days, the C index of MR-proADM (0.78) was higher than that for MR-proANP (0.74), copeptin (0.73), CT-proET-1 (0.76), PCT, C-reactive protein, and white blood cells. MR-proADM was independent of CRB-65, and added prognostic information for short- and long-term mortality. MR-proADM was an independent and strong predictor of short- and long-term mortality.
All new biomarkers were good predictors of short- and long-term all-cause mortality, superior to inflammatory markers, and at least comparable to CRB-65 score. MR-proADM showed the best performance. A combination of CRB-65 with MR-proADM might be the best predictor for mortality.
American Journal of Respiratory and Critical Care Medicine 12/2010; 182(11):1426-34. · 11.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: FDG-PET/CT is increasingly used in staging of lung cancer as single "one stop shop" method. AIM, PATIENTS, METHODS: We prospectively included 104 neurological asymptomatic patients (65 years, 26% women) with primary diagnosis of lung cancer. In all patients PET/CT including cerebral imaging and cerebral MRI were performed.
Diagnosis of brain metastases (BM) was made by PET/CT in 8 patients only (7.7%), by MRI in 22 (21.2%). In 80 patients both PET/CT and MRI showed no BM. In 6 patients (5.8%) BM were detectable on PET/CT as well as on MRI. Exclusive diagnosis of BM by MRI with negative finding on PET/CT was present in 16 patients (15.4%). 2 patients (1.9%) had findings typical for BM on PET/CT but were negative on MRI. With MRI overall 100 BM were detected, with PET/CT only 17 BM (p < 0.01). For the diagnosis of BM PET/CT showed a sensitivity of 27.3%, specificity of 97.6%, positive predictive value of 75% and negative predictive value of 83.3%. BM diameter on PET/CT and MRI were consistent in 43%, in 57% BM were measured larger on MRI.
Compared to the gold standard of MRI for cerebral staging a considerable number of patients are falsely diagnosed as free from BM by PET/CT. MRI is more accurate than PET/CT for detecting multiple and smaller BM.
In patients with a curative option MRI should be performed additionally to PET/CT for definitive exclusion of brain metastases.