Abstract Objectives To characterize the effect of ultra-short glucocorticoids followed by Tocilizumab monotherapy on the intima-media thickness (IMT) in GCA. Methods Eighteen GCA patients received 500 mg for 3 consecutive days (total of 1500mg) i.v. methylprednisolone on days 0–2, followed by i.v. Tocilizumab (8 mg/kg) on day 3 and thereafter weekly s.c. Tocilizumab injections (162 mg) over 52 weeks. US of temporal (TAs), axillary (AAs) and subclavian (SAs) arteries was performed at baseline, on days 2–3, and at weeks 4, 8, 12, 24 and 52. The largest IMT of all segments and IMT at landmarks of AA/SA were recorded. IMT was scaled by mean normal values and averaged. Each segment was classified according to diagnostic cut-offs. Results Of the 18 GCA patients, 16 patients had TA and 6 had extracranial large artery involvement. The IMT showed a sharp decline on day 2/3 in the TAs and AAs/SAs. In TAs, this was followed by an increase to baseline levels at week 4 and a subsequent slow decrease, which was paralleled by decreasing symptoms and achievement of clinical remission. The AAs/SAs showed a new signal of vasculitis at week 4 in three patients, with an IMT increase up to week 8. Conclusion Glucocorticoid pulse therapy induced a transient decrease of the IMT in TAs and AAs/SAs. Tocilizumab monotherapy resulted in a slow and steady decrease in IMT of the TAs and a smaller and delayed effect on the AAs/SAs. The data strongly support a remission-inducing effect of Tocilizumab and argue the case for US having an important role in monitoring disease activity in GCA. Trial registration ClinicalTrials.gov, www.clinicaltrials.gov, NCT03745586.
1.0 Abstract The direct modification of tumor cells using cytokine genes as a strategy to enhance host immunity against cancer has been studied extensively in animal models. Results obtained showed that mice injected with IL-2-transfected cancer cells mount a tumor-specific immune response that is sufficient in magnitude to protect the animals against a challenge with a tumorigenic dose of wild-type parental cancer cells. Currently, trials are ongoing to determine the feasibility of such a treatment in patients with renal cell carcinoma, colon carcinoma and melanoma. We now propose a cancer vaccine trial for stage IV melanoma patients with no hope for cure by either chemotherapy, surgery or irradiation. The vaccine consists of irradiated, autologous melanoma cells which had been genetically engineered by means of receptor-mediated, adenovirus-augmented gene delivery (transferrinfection) to produce human IL-2. Patients receive repeated injections of two different doses of the vaccine and will be monitored for the occurrence of any adverse reactions to it. In addition, we will determine whether the administration of the vaccine induces and/or enhances tumor-specific host responses at the immunological and/or clinical level.
To investigate intra- and inter-reader agreement of ultrasonography (US) and conventional radiography (CR) for the evaluation of osteophyte presence and size within the tibiofemoral joint. In addition, to correlate these findings with arthroscopic degeneration of the articular cartilage.Forty adult patients with knee pain were enrolled in this study. Knee CR and US scanning of the medial and lateral bone margins were performed on all patients. A novel atlas for the US grading of knee osteophytes was used in the evaluation. The number and size of the osteophytes were evaluated semi-quantitatively in two rounds from both the CR images (four readers) and the US images (14 readers). The Noyes grading system was used for the evaluation of arthroscopic degeneration of the articular cartilage in 26 patients.On average, intra- and inter-reader US and CR agreement was substantial and comparable to each other (κ = 0.60-0.72). US detected more osteophytes than CR at both the medial (65% vs. 48%) and lateral (70% vs. 60%) compartments. A statistically significant correlation between CR- or US-based osteophyte and arthroscopy grades was observed only for US at the medial compartment (rs = 0.747, p < 0.001).The detection of knee osteophytes using the novel US atlas is as reproducible as reading conventional radiographs. US is more sensitive to detect knee osteophytes than CR. Furthermore, osteophytes detected with US correlate significantly with arthroscopic cartilage changes at the medial knee compartment whereas those detected by CR do not.
A report about a human embryo of about 4 weeks of age afflicted with the formation of amnion cord with a slinglike formation. The corion sac had on its surface only a sparse cover with chorion vili. The intraembryonical vascular system was not shown except of small partial spaces in the front sector. The cause for the formation of an amnion cord is seen primarily in a faulty supply of the amniotic sac with its content. The formation of an amnion cord has been interpreted for this early phase of the embryogenesis as follows: In sufficiency of nourishment led to a dehiscence of the amnion. Mesenchym entered from the extraembryonal celom and combined itself with the lateral wall of embryo which showed because of insufficient nourishment in one area of defective epithelium. The mesenchym, which surrounded the frontal trunk part did not connect with the embryo and grew because of growth pressure into a loop with collagenous fibers. Amnionepithelecells spread only secondarily over the mesenchymloop and epithelialized it.
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