Hanns Ackermann

Paclitaxel-Coated Balloon Catheter Versus Paclitaxel-Coated Stent for the Treatment of Coronary In-Stent Restenosis

Background— Treatment of in-stent restenosis with paclitaxel-coated balloon catheter as compared with plain balloon angioplasty has shown surprisingly low late lumen loss at 6 months and fewer major adverse cardiac events up to 2 years. We compared the efficacy and safety of a paclitaxel-coated balloon with a paclitaxel-eluting stent as the current standard of care. Methods and Results— One hundred thirty-one patients with coronary in-stent restenosis were randomly assigned to treatment by a paclitaxel-coated balloon (3 &mgr;g/mm2) or a paclitaxel-eluting stent. The main inclusion criteria encompassed diameter stenosis of ≥70% and ≤22 mm in length, with a vessel diameter of 2.5 to 3.5 mm. The primary end point was angiographic in-segment late lumen loss. Quantitative coronary angiography revealed no differences in baseline parameters. At 6 months follow-up, in-segment late lumen loss was 0.38±0.61 mm in the drug-eluting stent group versus 0.17±0.42 mm (P=0.03) in the drug-coated balloon group, resulting in a binary restenosis rate of 12 of 59 (20%) versus 4 of 57 (7%; P=0.06). At 12 months, the rate of major adverse cardiac events were 22% and 9%, respectively (P=0.08). This difference was primarily due to the need for target lesion revascularization in 4 patients (6%) in the coated-balloon group, compared with 10 patients (15%) in the stent group (P=0.15). Conclusions— Treatment of coronary in-stent restenosis with the paclitaxel-coated balloon was at least as efficacious and as well tolerated as the paclitaxel-eluting stent. For the treatment of in-stent restenosis, inhibition of re-restenosis does not require a second stent implantation.

Prognostic significance of polo-like kinase (PLK) expression in non-small cell lung cancer

Our previous data indicate that the expression of the PLK gene which codes for a serine/threonine kinase is restricted to proliferating cells. In Northern blot experiments PLK mRNA expression was at the limit of detection in normal lung tissue but elevated in most samples of non-small cell lung cancer (NSCLC). A very low frequency of PLK transcripts was only found in bronchiolo-alveolar carcinomas. NSCLC patients whose tumors showed moderate PLK expression survived significantly longer (5 year survival rate=51.8%) than those with high levels of PLK transcripts (24.2%, P=0.001). No statistically significant correlation was found between PLK mRNA expression and age, sex, TNM status, histological type or degree of differentiation. Interestingly, the prognosis of patients in post-surgical stages I and II was correlated with PLK expression (5 year survival rates in stage I: 69.1% (moderate PLK)  –  43.5% (high PLK), P=0.03 or in stage II: 51.9% (moderate PLK)  –  9.9% (high PLK), P=0.006). These results suggest that PLK mRNA expression provides a new independent prognostic indicator for patients with NSCLC.

Focused echocardiographic evaluation in life support and peri-resuscitation of emergency patients: A prospective trial ,

PURPOSE OF THE STUDY Focused ultrasound is increasingly used in the emergency setting, with an ALS-compliant focused echocardiography algorithm proposed as an adjunct in peri-resuscitation care (FEEL). The purpose of this study was to evaluate the feasibility of FEEL in pre-hospital resuscitation, the incidence of potentially treatable conditions detected, and the influence on patient management. PATIENTS, MATERIALS AND METHODS A prospective observational study in a pre-hospital emergency setting in patients actively undergoing cardio-pulmonary resuscitation or in a shock state. The FEEL protocol was applied by trained emergency doctors, following which a standardised report sheet was completed, including echo findings and any echo-directed change in management. These reports were then analysed independently. RESULTS A total of 230 patients were included, with 204 undergoing a FEEL examination during ongoing cardiac arrest (100) and in a shock state (104). Images of diagnostic quality were obtained in 96%. In 35% of those with an ECG diagnosis of asystole, and 58% of those with PEA, coordinated cardiac motion was detected, and associated with increased survival. Echocardiographic findings altered management in 78% of cases. CONCLUSIONS Application of ALS-compliant echocardiography in pre-hospital care is feasible, and alters diagnosis and management in a significant number of patients. Further research into its effect on patient outcomes is warranted.

ABCB1 Genotype of the Donor but Not of the Recipient Is a Major Risk Factor for Cyclosporine-Related Nephrotoxicity after Renal Transplantation

Cyclosporine (CsA) nephrotoxicity is a severe complication in organ transplantation because it leads to impaired renal function and chronic allograft nephropathy, which is a major predictor of graft loss. Animal models and in vivo studies indicate that the transmembrane efflux pump P-glycoprotein contributes substantially to CsA nephrotoxicity. It was hypothesized that the TT genotype at the ABCB1 3435C-->T polymorphism, which is associated with decreased expression of P-glycoprotein in renal tissue, is a risk factor for developing CsA nephrotoxicity. In a case-control study, 18 of 97 patients developed CsA nephrotoxicity and showed complete recovery of renal function in all cases when switched to a calcineurin inhibitor-free regimen. Both recipients and donors were genotyped for ABCB1 polymorphisms at the positions 3435C-->T and 2677G-->T/A. For controlling for population stratification, two additional polymorphisms, CYP2D6*4 and CYP3A5*3, with intermediate allelic frequencies were studied. The P-glycoprotein low expressor genotype 3435TT only of renal organ donors but not of the recipients was overrepresented in patients with CsA nephrotoxicity as compared with patients without toxicity (chi2 = 10.5; P = 0.005). CsA dosage, trough levels, and the concentration per dose ratio were not different between the patient groups. In a multivariate model that included several other nongenetic covariates, only the donors ABCB1 3435TT genotype was strongly associated with CsA nephrotoxicity (odds ratio, 13.4; 95% confidence interval, 1.2 to 148; P = 0.034). A dominant role of the donors ABCB1 genotype was identified for development of CsA nephrotoxicity. This suggests that P-glycoprotein is an important factor in CsA nephrotoxicity.

Psoriasis patients show signs of insulin resistance

Background  Recent observations suggest that psoriasis is a risk factor for the development of coronary artery calcification which in turn represents an indicator for atherosclerosis.

Venoarterial extracorporeal membrane oxygenation for treatment of cardiogenic shock: Clinical experiences in 45 adult patients

OBJECTIVE Venoarterial extracorporeal membrane oxygenation is an established treatment option in patients with cardiogenic shock. This report reviews our 3-year experience with this support system with respect to early and midterm outcome, as well as predictors of survival. METHODS From January 2003 until November 2006, 45 (0.8%) of 5750 patients undergoing cardiac surgery procedures required the following: temporary extracorporeal membrane oxygenation support coronary artery bypass grafting, n = 20; implantation of a left ventricular assist device, n = 5; heart transplantation, n = 1; heart and lung transplantation, n = 1; coronary artery bypass grafting plus repair of postinfarction ventricular septal defect, n = 3; coronary artery bypass grafting plus mitral valve repair, n = 5; aortic valve replacement, n = 2; coronary artery bypass grafting plus aortic valve replacement, n = 3; and other procedures, n = 5. Extracorporeal membrane oxygenation implantation was performed through the femoral vessels or axillary artery or through the right atrium and ascending aorta. Additional intra-aortic balloon pumps were used in 30 patients. RESULTS Average patient age was 60.1 +/- 13.6 years. There were 35 male patients. Average duration of extracorporeal membrane oxygenation was 6.4 +/- 4.5 days. Twenty-five patients could be successfully weaned from extracorporeal membrane oxygenation. The 30-day mortality was 53% (24/45 patients). The in-hospital mortality was 71% (32/45 patients). Thirteen (29%) patients could be successfully discharged. After a follow-up period of up to 3 years, 10 (22%) patients were still alive. CONCLUSIONS Extracorporeal membrane oxygenation offers sufficient cardiopulmonary support in adults with similar hospital and midterm survival rates to those of other mechanical support systems. Early indication, alternative peripheral cannulation techniques, and reduced anticoagulation to avoid perioperative bleeding could improve our results with increasing experience.

Ceramide synthases and ceramide levels are increased in breast cancer tissue

Several in vitro studies have correlated dysfunction of the sphingolipid-signaling pathway with promotion of tumor cell growth as well as progression and resistance of tumors to chemotherapeutic agents. As ceramides (Cer) constitute the structural backbones of all sphingolipids, we investigated the endogenous ceramide levels in 43 malignant breast tumors and 21 benign breast biopsies and compared them with those of normal tissues using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The total ceramide levels in malignant tumor tissue samples were statistically significantly elevated when compared with normal tissue samples. Upregulation of the total ceramide level averaged 12-fold and 4-fold higher than normal tissue samples, for malignant tumors and benign tissues, respectively. Specifically, the levels of C(16:0)-Cer, C(24:1)-Cer and C(24:0)-Cer were significantly raised in malignant tumors as compared with benign and normal tissue. The augmentation of the various ceramides could be assigned to an increase of the messenger RNA levels of ceramide synthases (CerS) LASS2 (longevity assurance), LASS4 and LASS6. Notably, elevated levels of C(16:0)-Cer were associated with a positive lymph node status, indicating a metastatic potential for this ceramide. Moreover, the levels of C(18:0)-Cer and C(20:0)-Cer were significantly higher in estrogen receptor (ER) positive tumor tissues as compared with ER negative tumor tissues. In conclusion, progression in breast cancer is associated with increased ceramide levels due to an upregulation of specific LASS genes.

High-Dose-Rate Interstitial Brachytherapy as Monotherapy for Clinically Localized Prostate Cancer: Treatment Evolution and Mature Results

PURPOSE To report the clinical outcome of high-dose-rate (HDR) interstitial (IRT) brachytherapy (BRT) as sole treatment (monotherapy) for clinically localized prostate cancer. METHODS AND MATERIALS Between January 2002 and December 2009, 718 consecutive patients with clinically localized prostate cancer were treated with transrectal ultrasound (TRUS)-guided HDR monotherapy. Three treatment protocols were applied; 141 patients received 38.0 Gy using one implant in 4 fractions of 9.5 Gy with computed tomography-based treatment planning; 351 patients received 38.0 Gy in 4 fractions of 9.5 Gy, using 2 implants (2 weeks apart) and intraoperative TRUS real-time treatment planning; and 226 patients received 34.5 Gy, using 3 single-fraction implants of 11.5 Gy (3 weeks apart) and intraoperative TRUS real-time treatment planning. Biochemical failure was defined according to the Phoenix consensus, and toxicity was evaluated using Common Toxicity Criteria for Adverse Events version 3. RESULTS The median follow-up time was 52.8 months. The 36-, 60-, and 96-month biochemical control and metastasis-free survival rates for the entire cohort were 97%, 94%, and 90% and 99%, 98%, and 97%, respectively. Toxicity was scored per event, with 5.4% acute grade 3 genitourinary and 0.2% acute grade 3 gastrointestinal toxicity. Late grade 3 genitourinary and gastrointestinal toxicities were 3.5% and 1.6%, respectively. Two patients developed grade 4 incontinence. No other instance of grade 4 or greater acute or late toxicity was reported. CONCLUSION Our results confirm IRT-HDR-BRT is safe and effective as monotherapy for clinically localized prostate cancer.

Prediction of Acute Renal Allograft Rejection by Urinary Monokine Induced by IFN-γ (MIG)

Early diagnosis of acute allograft rejection (AR) is still decisive for long-term renal allograft survival. The aim of this study was to define the role of the chemokine monokine induced by IFN-γ (MIG) (CXCL9) and IFN-γ–inducible protein 10 (IP-10) (CXCL10) as early markers of AR in renal transplantation (NTX). In a prospective study, 69 de novo renal transplant recipients were monitored and urine samples were collected after NTX for a median of 29 d. In pH-adjusted urine, MIG and IP-10 were determined by modified ELISA. AR was clinically diagnosed in 15 of 69 recipients and confirmed by biopsy in 14 of 15 AR patients (Banff classification). Corresponding to CXCR3-positive infiltrates in renal tissue, urinary MIG was elevated in 14 of 15 AR patients with a median of 2809 pg/ml (quartile 25% and 75% = 870 and 13,000; n = 15), being significantly ( P P P

Radiation therapy for painful heel spurs: results of a prospective randomized study.

Purpose:To evaluate the efficacy of two different dose-fractionation schedules for radiation therapy (RT) in patients with painful heel spurs.Patients and Methods:130 patients were randomized into two groups: the low-dose (LD) group (n = 65 heels) received a total dose of 3.0 Gy given in two weekly fractions of 0.5 Gy; in the high-dose (HD) group (n = 65 heels), two weekly fractions of 1.0 Gy were applied over 3 weeks (total dose 6.0 Gy). In 24 sites of the HD group and 17 sites of the LD group, a second RT course was given. The results were assessed using a five-level function score which was documented before RT, at the end of each RT course, and at 6 weeks and 6 months thereafter.Results:At 6-month follow-up, RT led to a highly significant reduction of symptoms in both groups. In the HD group, 31 sites were classified as excellent (score: 90–100), 13 as good (score: 70–85), twelve as moderate (score: 45–65), and nine as poor (score: 0–40). In the LD group, 35 sites were classified as excellent, eight as good, ten as moderate, and twelve as poor. The comparison of the difference of the sum score and the single criteria before RT and at 6 months after RT using the Wilcoxon-Mann-Whitney U-test revealed no statistically significant difference of response to RT between both groups.Conclusion:RT is an effective treatment option for the management of inflammatory heel spurs. The dose for an RT course should not exceed 3.0 Gy.Ziel:Prospektiv-randomisierte Untersuchung der Effektivität zweier verschiedener Dosisregime für die Strahlentherapie von Patienten mit schmerzhaften Fersenspornen.Patienten und Methodik:130 Patienten wurden in zwei Gruppen randomisiert: Die Gruppe mit niedriger Dosis (LD-Gruppe, n = 65) wurde mit 2 × 0,5 Gy pro Woche bis zu einer Gesamtdosis von 3,0 Gy pro Serie bestrahlt, die Gruppe mit höherer Dosis (HD-Gruppe, n = 65) erhielt zwei wöchentliche Fraktionen à 1,0 Gy bis zu einer Gesamtdosis von 6,0 Gy/Serie. 24 Fälle der HD-Gruppe und 17 der LD-Gruppe erhielten eine zweite Bestrahlungsserie. Die Evaluierung der Ergebnisse erfolgte anhand eines Funktionsscores vor Bestrahlungsbeginn, am Ende jeder Serie sowie 6 Wochen und 6 Monate nach der Therapie.Ergebnisse:6 Monate nach der Bestrahlung fand sich in beiden Gruppen eine hochsignifikante Verbesserung des Scores. In der HD-Gruppe wurden 31 Patienten als exzellent (Score: 90–100), 13 als gut (Score: 70–85), zwölf als zufriedenstellend (Score: 45–65) und neun als schlecht (Score: 0–40) eingestuft. In der LD-Gruppe wurden 35 Patienten als exzellent, acht als gut, 10 als zufriedenstellend und 12 als schlecht bewertet. Der Vergleich des Summenscores und Einzelkriterien mittels des Wilcoxon-Mann-Whitney-U-Tests zeigte keinen statistisch signifikanten Unterschied zwischen beiden Gruppen.Schlussfolgerung:Die Strahlentherapie ist eine effektive Therapieoption für die Behandlung entzündlicher Fersensporne. Die Gesamtdosis von 3,0 Gy pro Serie erwies sich als ausreichend.