Interventional treatment and outcome in elderly patients with stable coronary artery disease. Results from the German ALKK registry.

BACKGROUND: The number of elderly and very elderly patients undergoing percutaneous coronary interventions (PCI) is increasing. We therefore analyzed data from the German ALKK registry (Arbeitsgemeinschaft Leitende Krankenhausärzte; Working Group of Hospital Cardiologists) to determine differences in procedural features, antithrombotic treatment, and in-hospital outcome in patients with coronary artery disease (CAD) according to age in a large series of patients. METHODS AND RESULTS: The present analysis was based on the data of 35,534 consecutive patients undergoing elective PCI who were enrolled in the ALKK registry. Of these 27,145 (76.4 %) were younger than 75 years, 7,645 (21.5 %) were aged between 75 and 84 years, and 744 (2.1 %) patients were older than 85 years. Mean age was 68.5 years (60.9-74.5 years), and 25,784 patients (72.6 %) were male. Overall intraprocedural events were very low (1.1 %) and there was no significant difference between the three age groups [< 75 years (1.1 %); 75-< 85 years (1.2 %); ≥ 85 years (0.5 %) (p = not significant)]. Rates of in-hospital death, stroke and transient ischemic attack (TIA), as well as the combined endpoint in-hospital major adverse cardiac and cerebrovascular events (MACCE) were also very low (0.6 % vs. 0.9 % vs. 0.9 %; p < 0.001) but significantly higher in elderly patients with no further increase in the very elderly patient group. CONCLUSION: We found no differences in this registry in intraprocedural complications during elective PCI between younger and elderly patients. Although in-hospital MACCE were somewhat higher in the elderly, the overall event rate was low and thus elderly patients should not be deprived from this therapy because of age alone.

Impact of coronary artery disease on in-hospital mortality in patients with aortic valve disease. Results from the German ALKK registry.

OBJECTIVE: Although aortic valve disease (AVD) is frequently associated with coronary artery disease (CAD), little is known about the impact of significant coronary artery disease on mortality after diagnostic cardiac catheterization in patients with AVD. METHODS: We analyzed data of the coronary angiography registry of the "Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte" (ALKK) in Germany. The primary endpoint was in-hospital mortality. RESULTS: A total of 1427 consecutive patients with AVD (438 patients with CAD versus 989 patients without CAD) underwent diagnostic catheterization in 2006 in 42 hospitals. All cause in-hospital mortality was more than threefold higher in patients with CAD (16/438; 3.7%) as compared to patients without CAD (12/989; 1.2%; p < 0.01; OR 3.09, 95% CI 1.45-6.58). Even after adjustment for age, sex, presence of diabetes mellitus and renal insufficiency, in-hospital all cause mortality remained statistically significant different between the two groups (OR 2.4; 95% CI 1.09-5.28; p < 0.01). Several factors, such as transient ischemic attack/stroke, volume of contrast agent, and left heart catheter-associated complications could not be identified as possible causes for the increase in mortality. CONCLUSION: This analysis in patients with the leading diagnosis of AVD shows a significantly higher in-hospital mortality after diagnostic cardiac catheterization in case of an accompanying CAD. However, further studies are necessary to identify the driving force for the increase in mortality.

Use of gene expression profiling to identify candidate genes for pretherapeutic patient classification in acute appendicitis.

BACKGROUND: Phlegmonous and gangrenous appendicitis represent independent pathophysiological entities with different clinical courses ranging from spontaneous resolution to septic disease. However, reliable predictive methods for these clinical phenotypes have not yet been established. In an attempt to provide pathophysiological insights into the matter, a genomewide gene expression analysis was undertaken in patients with acute appendicitis. METHODS: Peripheral blood mononuclear cells were isolated and, after histological confirmation of PA or GA, analysed for genomewide gene expression profiling using RNA microarray technology and subsequent pathway analysis. RESULTS: Samples from 29 patients aged 7-17 years were included. Genomewide gene expression analysis was performed on 13 samples of phlegmonous and 16 of gangrenous appendicitis. From a total of 56 666 genes, 3594 were significantly differently expressed. Distinct interaction between T and B cells in the phlegmonous appendicitis group was suggested by overexpression of T cell receptor α and ß subunits, CD2, CD3, MHC II, CD40L, and the B cell markers CD72 and CD79, indicating an antiviral mechanism. In the gangrenous appendicitis group, expression of genes delineating antibacterial mechanisms was found. CONCLUSION: These results provide evidence for different and independent gene expression in phlegmonous and gangrenous appendicitis in general, but also suggest distinct immunological patterns for the respective entities. In particular, the findings are compatible with previous evidence of spontaneous resolution in phlegmonous and progressive disease in gangrenous appendicitis.

Diagnosis and treatment of post-transplantation lymphoproliferative disorder in pediatric heart transplant patients.

PTLD is a severe complication in transplant recipients. Detection of increased EBV load in the peripheral blood acts as a surrogate marker for increased risk of PTLD development. We analyzed the time course of the disease, its severity, the organs involved, and mortality rates in our institutional experience of pediatric heart transplantation. This paper identifies risk factors for PTLD and describes the different ways of diagnosing and treating the disease. PTLD was screened for in 146 pediatric heart transplant patients using a retrospective analysis in patients who received transplantation before 1998. Prospective determination was performed in 72/146 patients transplanted after 1998 within the post-transplant follow-up. The occurrence of PTLD with all interventions, including tapering of immunosuppression, surgery, viral monitoring, and antiviral interventions, was recorded. PTLD was diagnosed in 12/147 (8.2%) children at a mean age of 7.2 +/- 3.3 yr after a mean post-transplant period of 3.2 +/- 2.2 yr. PTLD manifested in: lymph nodes (n = 4), intestine (n = 3), tonsils and adenoids (n = 2), eye (n = 2), and lung (n = 1). It was diagnosed in 7/12 as a monomorphic B-cell lymphoma and in four patients as a monomorphic Burkitt lymphoma, a polymorphic B-cell lymphoma, a T-cell rich or angiocentric lymphoma (Liebow) and as reactive plasmacytic hyperplasia (early lesion), respectively. Histology was not possible in one patient with ocular manifestation. EBV association was 83%. Risk factors in the comparison with patients without PTLD were age at time of Tx, primary EBV infection after Tx, use of Azathioprine and >or=3 doses of ATG. CMV mismatch and CMV infection, rejection episodes and steroids were not risk factors. Despite reduction of immunosuppression, treatment consisted of surgical procedures to remove tumor masses (n = 6), Rituximab (n = 5), polychemotherapy (n = 3), antiviral (n = 1) and autologous T-cell therapy (n = 1). All patients demonstrated full remission without death related to PTLD or treatment at 3.9 (1.3-6.2) yr median follow-up time. The manifestation of PTLD in pediatric heart transplant recipients is associated with EBV infection and is predominantly in the form of a B-cell lymphoma. A tight and specific follow-up including early assessment of immunity status and specific therapeutic intervention to improve cellular immunity is warranted and may contribute to a significant reduction of PTLD-related morbidity and mortality.

[Musculoskeletal tumors: significance of morphological diagnostics]. / Tumoren des Bewegungsapparats: Bedeutung der morphologischen Diagnostik.

Musculoskeletal tumors, particularly bone neoplasms, are very rare. Diagnosis and treatment require an interdisciplinary concept as well as wide experience of all physicians involved. The final histopathologic diagnosis should not be confirmed without information regarding the patient's age, exact localization, and radiological findings. The requirements of additional diagnostic procedures (molecular pathology) have to be taken into consideration when planning a biopsy.

[Differential diagnosis of intramedullary osteosarcomas]. / Differenzialdiagnose intramedullärer Osteosarkome.

Intramedullary high-grade osteosarcomas are aggressive tumors with a high metastatic capacity. The many subtypes and variants of these tumors often make the differential diagnosis difficult. Therefore, a critical review of both radiology and histomorphology is mandatory. Low-grade central osteosarcomas are a completely different tumor group. Due to their strong similarity to benign bone tumors they are frequently misdiagnosed as such. The correct diagnosis followed by radical surgery, however, is essential to reduce the high risk of local recurrences, typically seen for of these lesions. Unlike conventional high grade osteosarcomas, distant metastases are much less frequent than in low grade osteosarcomas.

Multicenter evaluation of a self-expanding carotid stent system with distal protection in the treatment of carotid stenosis.

PURPOSE: Carotid artery stent placement may be limited by the embolization of atheromatous material. We evaluated the safety and feasibility of the Medtronic Self-Expanding Carotid Stent (Exponent) in combination with the Medtronic Interceptor Carotid Filter System for the treatment of carotid stenosis among patients at high risk for carotid endarterectomy. METHODS: Patients at high risk for carotid endarterectomy but amenable to percutaneous treatment with stent placement were enrolled. Clinical follow-up was performed at 30 days and 6 and 12 months postprocedure. The National Institutes of Health Stroke Scale was assessed before and within 3 days postprocedure and at 30 days and 6 months postprocedure. Angiography was performed pre- and postprocedure, and carotid duplex scans were performed at baseline and at 30 days and 6 months. RESULTS: Fifty-two carotid procedures were performed in 51 patients (mean age, 69 years; 84% of patients were men). The major adverse event (MAE) rate (death, stroke, and myocardial infarction [MI]) at 30 days was 5.9%: 2 strokes and a single death from periprocedural MI. MAE rates after 6 and 12 months were 5.9% and 11.8%, respectively. The delivery success rate was 94.2% (49/52) for the Interceptor Filter System and 95.9% (47/49) for the Exponent Stent. The mean diameter stenosis of the target lesion was reduced from 62.4% preprocedure to 21.2% postprocedure. CONCLUSION: High delivery success rates were achieved with a low rate of MAE (death, stroke, or MI) in a high-risk population. Treatment of carotid artery disease with the Exponent Carotid Stent combined with distal protection from the Interceptor Filter System is effective and safe.

Primary percutaneous transluminal coronary angioplasty for acute myocardial infarction in patients not included in randomized studies. Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) Study Group.

Patients with acute myocardial infarction included in randomized trials comparing primary percutaneous transluminal coronary angioplasty (pPTCA) with thrombolysis represent a special subgroup of patients with a low event rate. Patients excluded from these trials represent a variety of different subgroups, with different patient characteristics and possibly different clinical event rates. Primary PTCA was performed in 491 consecutive patients with acute myocardial infarction in the prospective multicenter observational Maximal Individual Therapy in Acute Myocardial Infarction trial. They were divided into the following groups: group I, patients fulfilling the inclusion criteria of the randomized trials (284 of 491, 58%); group II, patients not included in these trials (207 of 491, 42%). Of group II the following subgroups were defined: group IIa, patients in cardiogenic shock (20 of 491, 4.1%); group IIb, patients with a left bundle branch block (12 of 491, 2,4%); group IIc, patients with contraindications for thrombolysis (42 of 491, 8.6%); group IId, patients with a nondiagnostic first electrocardiogram (95 of 491, 19.3%); group IIe, patients with a prehospital delay of > 12 hours (72 of 491, 14.7%); group IIf, patients with an unknown prehospital delay (30 of 491, 6.1%). A comparison of groups I and II showed similar baseline characteristics but a higher clinical event rate during hospitalization was seen in group II: combined end point of death, reinfarction, heart failure equal to or greater than NYHA class III, any stroke or postinfarction angina, 26.6% versus 18%; p = 0.022. Hospital deaths were nearly twice as high in these patients, without reaching statistical significance (10.6% vs 6%; p = 0.06). The subgroups of group II showed quite different rates of clinical events. In-hospital death rates were: IIa, 40% (8 of 20); IIb, 8% (1 of 12); IIc, 12% (5 of 42); IId, 5% (5 of 95); IIe, 6% (4 of 72); and IIf, 13% (4 of 30). The incidence of the combined end point was 60% (12 of 20) in IIa, 33% (4 of 12) in IIb, 29% (12 of 42) in IIc, 16% (15 of 95) in IId, 26% (19 of 72) in IIe, and 33% (10 of 30) in IIf. Thus, in clinical practice, about half of the patients treated with pPTCA would not have been included in randomized trials comparing pPTCA with thrombolysis. These patients represent a population at higher risk for in hospital clinical events. However, they do represent very different nonhomogenous subgroups with different clinical event rates.

Telomerase activity in benign bone tumors and tumor-like lesions.

To assess the role and status of telomerase activity in benign bone tumors and tumor-like lesions, we performed telomerase assays in four giant cell tumors of bone, four fibrous dysplasias, three osteochondromas, three aneurysmal bone cysts, two osteoblastomas, one juvenile bone cyst and one myositis ossificans. A very sensitive non-radioactive TRAP assay was applied. Low level activity was detected in 7 of 18 tumor samples (38.9%), and high level activity was not detected in any of the cases. Telomerase activity was observed in all patients with osteochondromas, in two of the three aneurysmal bone cysts, in one of the four giant cell tumors of bone and in one of the four fibrous dysplasias, but not in osteoblastomas, juvenile bone cyst and myositis ossificans. Although the origin of this enzyme is still unclear, it might play a role in precancerous immortalization of benign bone tumors. Other possible reasons explaining the occurrence of telomerase activity, such as migrating lymphocytes or contamination of immortalized non-tumor cells, should not be ruled out. Telomerase activity, however, does exist in those samples having no malignant phenotype, for which reason telomerase assays are not always useful for the clinical and diagnostic approach in benign bone tumors. Determination of the telomerase status in benign lesions may contribute to a better understanding of the regulation mechanism of telomerase activity during progression of bone tumors.

Primary angioplasty in acute myocardial infarction: differences between referred patients and those treated in hospitals with on-site facilities?

BACKGROUND: Primary angioplasty for acute myocardial infarction (AMI) can only be performed in a limited number of centers. Therefore, some patients will be referred for this procedure. DESIGN: We analyzed the data of the prospective observational MITRA trial, which took place at 54 hospitals in southwest Germany, to describe current practices and outcomes in referred patients compared to patients treated on-site. RESULTS: Out of 491 patients treated with primary angioplasty, 63 (12.8%) were referred. Out of 46 hospitals without facilities to perform primary angioplasty, 29 (63%) never referred patients. Referred patients were less often male (60.3% versus 75.9%; p = 0.013), suffered more often from anterior wall infarction (62.9% versus 45.8%; p = 0.014), and more often had absolute contraindications against thrombolysis (11.1% versus 2.8%; p = 0.006). In-hospital time to treatment was 80 minutes in patients treated on-site compared to 190 minutes in referred patients (p = 0.001). There was a non-significant difference of in-hospital mortality between the two groups (11.1% for referred versus 7.5% on-site; p = 0.319). Referred patients had a higher hospital morbidity as expressed by a higher proportion of post-infarction angina (28.6% versus 4.2%; p = 0.001), a more frequent need for urgent revascularization (43.8% versus 16.4%; p = 0.001) and a higher proportion of advanced heart failure (11.1% versus 4.4%; p = 0.062). CONCLUSIONS: Referral of patients with AMI for primary angioplasty is used only in a minority of hospitals. The referred patients represent a selected, more ill subgroup, resulting in a higher hospital morbidity compared to patients treated on-site. Continuous efforts should be undertaken to decrease the time delay from admission at the initial hospital to the beginning of revascularization.

Differences in patients with acute myocardial infarction treated with primary angioplasty or thrombolytic therapy. Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) Study Group.

BACKGROUND: Little is known about the differences in patients with acute myocardial infarction (AMI) treated with primary angioplasty or intravenous thrombolysis in clinical practice. METHODS: In all, 5,906 patients with AMI were registered by the Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) study. Of these, 491 (8.3%) patients were treated with primary angioplasty and 2,817 (47.7%) with intravenous thrombolysis. RESULTS: There were only minor differences in baseline characteristics between the two groups. Prehospital delay time (median) was longer in the angioplasty group than in the thrombolysis group (161 vs. 120, p = 0.001), as was door-to-treatment time (88 vs. 30 min; p = 0.001). Patients treated with primary angioplasty more often had contraindications for thrombolytic therapy (12.9 vs. 6%, p = 0.001) and received beta blockers (65 vs. 58.1%, p = 0.004), heparin (98.2 vs. 91.6%, p = 0.001), angiotensin-converting enzyme (ACE) inhibitors (64.8 vs. 50%, p = 0.001) and "optimal" concomitant medication (56.4 vs. 42.9%, p = 0.001) more often. Univariate analysis showed a significant lower incidence of heart failure (5.3 vs. 16.5%, p = 0.001), postinfarct angina (7.3 vs. 16.4%, p = 0.001), in-hospital death (7.9 vs. 11.7%, p = 0.015) and the combined end point (21.6 vs. 40.3%, p = 0.001) in these patients. Stepwise logistic regression analysis revealed optimal concomitant medication [odds ratio (OR) = 0.94, 95% confidence interval (CI): 0.89-0.98) and the type of revascularization (OR = 0.65, 95% CI: 0.58-0.73) to be associated with a significant reduction in the incidence of the combined end point. Similar results were obtained in all predefined subgroups. CONCLUSIONS: In clinical practice, patients treated with primary angioplasty are more often treated with beta blockers and ACE inhibitors than patients treated with intravenous thrombolysis. Thus, the selection of patients and the type of revascularization contributes to the reduction in mortality, overt heart failure, and postinfarct angina in these patients.

[Unusual presentation of a Langerhans cell histiocytosis]. / Ungewöhnliche Präsentation einer Langerhans-Zell-Histiozytose.

A 16-month-old male infant was presented with swelling of the left upper eye lid 4 weeks after a blunt orbital trauma. A prolonged hematoma was suspected and the child was discharged with an appointment 4 weeks later. However, the child was presented again with progressive swelling of the lid 10 days later. Magnetic resonance imaging (MRI) showed a tumor extending from the frontal bone to the anterior cranial fossa and into the orbit. An incisional biopsy led to the diagnosis of orbital Langerhans cell histiocytosis and systemic therapy led to complete remission of the tumor. Prolonged periorbital swelling must always prompt further diagnostics even when patients present with a history of trauma.

Interim PET response criteria in paediatric non-Hodgkin's lymphoma. Results from a retrospective multicenter reading.

AIM: To evaluate the use and reliability of the PET-based response criteria for interim PET (iPET) in terms of interobserver variability in pediatric and adolescent patients suffering from non-Hodgkin´s lymphoma (NHL). Particular attention was given to the identification of visual cutoff to separate patients with a favourable outcome. PATIENTS, METHODS: Retrospective analysis of PET-datasets of 18 children and adolescents suffering from NHL who underwent iPET after two cycles of chemotherapy for response assessment. Datasets were evaluated and rated in three independent review centers (RC) (blinded-read, intra-center consensus) using a visual 5-point response scale. Ratings were compared to clinical outcome. Pairwise interobserver agreement was analysed with Cohen's kappa-test (κ). Overall agreement (between attended RCs) was assessed with Fleiss' κ-test. RESULTS: Four patients suffered relapse (early, n = 2; late, n = 2). Per region analyses on interobserver variability revealed a "substantial" agreement (Fleiss' κ = 0.618). Per patient analyses revealed concordant iPET-ratings in eight patients: iPET-negative (iPET-), n = 5; iPET-positive (iPET+), n = 2; iPET-inconclusive (iPET±), n = 1. Discordant ratings were found in the remaining patients. Patients with early relapse were concordantly identified using mediastinal blood pool structures (MBPS, score ≥ 3) as visual cutoff between iPET+ or iPET-, respectively. However, patients with late relapse were not concordantly identified taking the MBPS as visual cutoff. CONCLUSION: The iPET interpretation using a dedicated PET-based response scale assured a low interobserver variability in per-region but not in per-patient analyses in a multicenter read. Using a sensitive read out (iPET+, score ≥ 3) a reliable identification of patients suffering relapse was limited to those with early relapse.

Volume-outcome relation for contemporary percutaneous coronary interventions (PCI) in daily clinical practice: is it limited to high-risk patients? Results from the Registry of Percutaneous Coronary Interventions of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausarzte (ALKK).

OBJECTIVE: The formerly observed volume-outcome relation for percutaneous coronary interventions (PCIs) has recently been questioned. DESIGN: We analysed data of the PCI registry of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte. PATIENTS: In 2003 a total of 27 965 patients at 67 hospitals were included. RESULTS: The median PCI volume per hospital was 327. In-hospital mortality was 1.85% in hospitals belonging to the lowest PCI volume quartile and 1.21% in the highest quartile (p for trend <0.001). Two groups of patients were then compared according to their treatment at hospitals with either <325 PCIs (n = 5754) or >325 PCIs (n = 22 211) per year. Logistic regression analysis showed that a PCI performed at hospitals with a volume of >325 PCI/year was independently associated with a lower hospital mortality (OR = 0.67, 95% CI: 0.52 to 0.87; p = 0.002). If PCI was performed in patients with acute myocardial infarction there was a significant decline in mortality with increasing volume (p for trend = 0.004); however, there was no association in patients without a myocardial infarction. CONCLUSIONS: This analysis of contemporary PCI in clinical practice shows a small but significant volume-outcome relation for in-hospital mortality. However, this relation was only apparent in high-risk subgroups, such as patients presenting with acute myocardial infarction.

The safety and efficacy of an extravascular, water-soluble sealant for vascular closure: initial clinical results for Mynx.

OBJECTIVE: The purpose of this study was to evaluate the hemostatic efficacy and safety of the Mynx extravascular sealant for femoral artery closure. BACKGROUND: The Mynx device is an extra-arterial vascular closure technology utilizing a water-soluble, porous, polyethylene glycol matrix that immediately seals the arteriotomy by rapidly absorbing subcutaneous fluids and expanding in the tissue tract and then, resorbs within 30 days. METHODS: The Mynx study was a prospective, multicenter, single-arm clinical investigation conducted at five European centers. The safety and effectiveness of the Mynx device was evaluated in patients following diagnostic or interventional endovascular procedures performed through 5 Fr, 6 Fr, or 7 Fr introducer sheaths in the common femoral artery. The primary safety endpoint was the combined rate of major complications within 30 days (+/-7 days). The primary efficacy endpoints were time to hemostasis and time to ambulation. RESULTS: Patient enrollment included 190 patients with 50% having undergone diagnostic catheterization and 50% interventional procedures with a mean activated clotting time of 221 sec. One (0.5%) major vascular complication (transfusion) occurred in one patient. No device-precipitated complications associated with serious clinical sequelae were reported. Mean (+/- standard deviation) times to hemostasis and ambulation were 1.3 +/- 2.3 min and 2.6 +/- 2.6 hr, respectively. There was no significant difference in median times to hemostasis between diagnostic and interventional patients (0.5 vs. 0.6 min). CONCLUSIONS: The initial experience with the extra-arterial Mynx closure technology supports hemostatic safety and efficacy in patients undergoing diagnostic and interventional catheterization procedures.