Addition of FFRct in the diagnostic pathway of patients with stable chest pain to reduce unnecessary invasive coronary angiography (FUSION) : Rationale and design for the multicentre, randomised, controlled FUSION trial.

BACKGROUND: Coronary computed tomography angiography (CCTA) is widely used in the diagnostic work-up of patients with stable chest pain. CCTA has an excellent negative predictive value, but a moderate positive predictive value for detecting coronary stenosis. Computed tomography-derived fractional flow reserve (FFRct) is a non-invasive, well-validated technique that provides functional assessment of coronary stenosis, improving the positive predictive value of CCTA. However, to determine the value of FFRct in routine clinical practice, a pragmatic randomised, controlled trial (RCT) is required. We will conduct an RCT to investigate the impact of adding FFRct analysis in the diagnostic pathway of patients with a coronary stenosis on CCTA on the rate of unnecessary invasive coronary angiography, cost-effectiveness, quality of life and clinical outcome. METHODS: The FUSION trial is a prospective, multicentre RCT that will randomise 528 patients with stable chest pain and anatomical stenosis of ≥ 50% but < 90% in at least one coronary artery of ≥ 2 mm on CCTA, to FFRct-guided care or usual care in a 1:1 ratio. Follow-up will be 1 year. The primary endpoint is the rate of unnecessary invasive coronary angiography within 90 days. CONCLUSION: The FUSION trial will evaluate the use of FFRct in stable chest pain patients from the Dutch perspective. The trial is funded by the Dutch National Health Care Institute as part of the research programme 'Potentially Promising Care' and the results will be used to assess if FFRct reimbursement should be included in the standard health care package.

Cardiovascular molecular imaging of apoptosis.

INTRODUCTION: Molecular imaging strives to visualise processes at the molecular and cellular level in vivo. Understanding these processes supports diagnosis and evaluation of therapeutic efficacy on an individual basis and thereby makes personalised medicine possible. APOPTOSIS AND MOLECULAR IMAGING: Apoptosis is a well-organised mode of cell suicide that plays a role in cardiovascular diseases (CVD). Apoptosis is associated with loss of cardiomyocytes following myocardial infarction, atherosclerotic plaque instability, congestive heart failure and allograft rejection of the transplanted heart. Thus, apoptosis constitutes an attractive target for molecular imaging of CVD. Our current knowledge about the molecular players and mechanisms underlying apoptosis offers a rich palette of potential molecular targets for molecular imaging. However, only a few have been successfully developed so far. AIMS: This review highlights aspects of the molecular machinery and biochemistry of apoptosis relevant to the development of molecular imaging probes. It surveys the role of apoptosis in four major areas of CVD and portrays the importance and future perspectives of apoptosis imaging. The annexin A5 imaging protocol is emphasised since it is the most advanced protocol to measure apoptosis in both preclinical and clinical studies.

Enteral long-term nutrition via percutaneous endoscopic gastrostomy (PEG) in 210 patients: a four-year prospective study.

After PEG placement at the Medical Department of the University Hospital in Kiel, 210 patients (mean age 61.3 years; 137 men, 73 women) were prospectively followed-up for 133+/-181 days. Close-meshed evaluations of the development of nutritional status, long-term outcome, complications, subjective acceptability, patient care after discharge from the hospital, survival, and nutritional long-term problems were performed. The PEG procedure (duration 13.3+/-4.2 min) was carried out for neurological (42%), ear-nose-throat (28%), and internal medical (30%) indications. Procedure-related mortality was 0%, while altogether 3.8% severe and 20.0% mild complications were observed. Body weight decreased by a mean of 11.4+/-1.5 kg in the three months before and increased by 3.5+/-1.7 kg one year after PEG placement with no significant differences between malignant or benign underlying diseases. Individual subjective acceptability was excellent in 83%, sufficient in 15%, and poor in 2% of patients only. One-year survival rate was 34.3%. The various results of the present prospective study demonstrate that long-term enteral feeding via PEG is a safe, effective, easy-to-practice, and highly acceptable method with excellent long-term results and distinct improvement of nutritional status. Individual decisions for PEG placement should be considered much earlier and more frequently in appropriate patients.

Thrombopoietin in patients with congenital thrombocytopenia and absent radii: elevated serum levels, normal receptor expression, but defective reactivity to thrombopoietin.

The pathophysiology of thrombocytopenia in the syndrome of thrombocytopenia with absent radii (TAR) is not yet understood. We examined thrombopoietin (TPO) serum levels and the in vitro reactivity of platelets to TPO in five patients affected with TAR syndrome. We found elevated TPO serum levels in all patients tested, excluding a TPO production defect as cause for thrombocytopenia in TAR syndrome. In addition, we found similar expression of the TPO receptor c-Mpl on the surface of platelets from TAR patients (5 of 5) and a similar molecular weight of the receptor as compared with healthy controls (4 of 4). Platelet response to adenosine diphosphate or thrombin receptor agonist peptide SFLLRN (TRAP) was normal in TAR patients. However, in contrast to results with healthy controls we could show absence of in vitro reactivity of platelets from TAR patients to recombinant TPO as measured by testing TPO synergism to adenine diphosphate and TRAP in platelet activation. TPO induced tyrosine phosphorylation of platelet proteins was completely absent (3 of 4) or markedly decreased (1 of 4). Our results indicate that defective megakaryocytopoiesis/thrombocytopoiesis in TAR syndrome is not caused by a defect in TPO production but a lack of response to TPO in the signal transduction pathway of c-Mpl.

[Does para-cervical block offer additional advantages in abortion induction with gemeprost in the 2nd trimester?]. / Bietet die Parazervikalblockade zusätzliche Vorteile bei der Abortinduktion mit Gemeprost im II. Trimenon?

UNLABELLED: Uterus-specific synthetic Prostaglandin analogues (gemeprost, sulproston etc.) have been widely employed for termination of pregnancy in the second trimester. Since paracervical anaesthesia may be useful during this procedure, we investigated in this prospective randomised study its impact on the clinical course of abortion and pain especially in the late first and second stage of labour. PATIENTS AND METHODS: 20 women scheduled for elective abortion (fetal reasons) between the 16th and 23rd week of gestation were to be given 1 mg gemeprost vaginally every 6 hours. They were allocated at random: 10 women received only Pethidin intravenously and Butylscopolamine rectally, another 10 women were additionally treated by paracervical anaesthesia (2 x 10 ml 0.5% Bupivacain solution) at a cervical dilatation of 2-3 cm. RESULTS: A median of 3 gemeprost applications were administered in both groups. In the group without paracervical anaesthesia the median induction to abortion interval was 20 hours (range: 8-44 hours), 13 hours (range: 8-36 hours, NS) resulting for the paracervical anaesthesia group. The intervals from the last application of prostaglandin until abortion and from 3 cm cervical dilatation to abortion were slightly, but not significantly shorter in the paracervical anaesthesia group. The requirement of Butylscopolamine was higher in the latter group (p < 0.05). The requirement of Pethidin and the intensity of pain (measured by pain scale according to Huskisson) especially in the late first stage of labour were not statistically different between both groups. Side effects of paracervical anaesthesia did not occur. CONCLUSION: Paracervical anaesthesia is a method for analgesia during second trimester abortion with a low rate of side effects. It can shorten the duration of last period of second trimester abortion in some cases but has no impact on the perception of pain nor requirement of analgesics and so with only limited benefit in second trimester abortion with vaginal gemeprost.

[18F-fluorodeoxyglucose PET in ovarian carcinoma: methodology and preliminary results]. / 18F-Fluordeoxyglukose PET beim Ovarialkarzinom: Methodik und erste Ergebnisse.

AIM: Of the present study was to evaluate 18FDG PET as a diagnostic tool in primary and recurrent ovarian cancer. METHODS: PET of the abdomen and the pelvis was performed in 26 patients suspected for primary (n = 17) or recurrent (n = 9) ovarian cancer with an ECAT 953/15 scanner 45 min after intravenous administration of 245 MBq 18F-FDG (mean). PET findings were validated by surgery, histology and/or cytology. RESULTS: Ovarian malignancies or recurrent ovarian cancer were demonstrated by PET in 16 out of 19 cases. Malignancy was excluded in six out of seven cases. False negative findings were obtained in two cases of low malignant potential tumors (LMP) and in one case of low grade serous/mucinous ovarian cystadenocarcinoma. PET yielded one false positive result in a case of salpingoophoritis. Quantitative analysis revealed a mean SUV of 6.8 +/- 2.3 in primary ovarian carcinoma vs. 2.6 +/- 1.2 in benign masses (p < 0.05). CONCLUSION: These preliminary data show 18FDG PET to be useful in diagnosis of recurrent ovarian cancer. PET is of limited use in differentiating LMP from benign tumors and ovarian cancer from inflammatory processes. Concerning this differentiation, quantitative analysis does not improve diagnostic accuracy.

Soft palate reflex: technical requirements and first results.

The present study describes technical prerequisites for soft palate reflex measurements and first results. Reflex measurements can be done using standard electromyographic methods. The data-processing system that records and processes the electromyographic signals was activated when the soft palate was stimulated by a newly developed device. The first results of objective soft palate reflex measurements in 15 healthy subjects show that the musculus levator veli palatini reacts to a mechanical stimulation of the soft palate with a contraction that can be measured electromyographically. The response latencies were constant in the individual subjects. In 12 subjects a minimum of 30 ms and a maximum of 61 ms was recorded. In one healthy subject, the reflex was activated only after 167 ms. No reflex could be evoked in two subjects. The stimulus was always supraliminal. Reaction time was longer following surface anesthesia of the oral mucosa.