[Pain reduction by radiosynoviorthesis in rheumatism-induced synovitis of the elbow : Results of a retrospective multicenter data analysis]. / Schmerzreduktion durch Radiosynoviorthese bei rheumatisch bedingter Synovialitis des Ellenbogens : Ergebnisse einer retrospektiven, multizentrischen Datenanalyse.

BACKGROUND: Radiosynoviorthesis (RSO) is a nuclear medical local treatment modality for inflammatory joint diseases. It is indicated in patients with rheumatoid arthritis (RA) in joints with persistent synovitis despite adequate pharmacotherapy. Arthritis of the elbow joint occurs in up to 2/3 of patients with RA. Intra-articular radiotherapy using the beta emitter [186Re] rhenium sulfide leads to sclerosis of the inflamed synovial membrane with subsequent pain alleviation. The clinical efficacy in cubital arthritis, however, has so far only been described in small monocentric studies. OBJECTIVE: The degree of pain alleviation by RSO was analyzed in patients with rheumatoid cubital arthritis, treated in several nuclear medical practices specialized in RSO. MATERIAL AND METHODS: The subjective pain intensity before and after RSO was documented in a total of 107 patients with rheumatic cubital arthritis using a 10-step numeric rating scale (NRS). A difference of ≥ -2 is rated as a significant improvement. Follow-up examinations were done after a mean interval of 14 months after RSO (at least 3 months, maximum 50 months). RESULTS: The mean NRS value was 7.3 ± 2.1 before RSO and 2.8 ± 2.2 after RSO. A significant pain alleviation was seen in 78.5% of all patients treated. The subgroup analysis also showed a significant improvement in the pain symptoms in all groups depending on the time interval between the RSO and the control examination. A significant pain progression was not observed. The degree of pain relief was independent of the time of follow-up. CONCLUSION: Using RSO for local treatment of rheumatoid cubital arthritis leads to a significant and long-lasting pain relief in more than ¾ of the treated patients.

Spray Pattern and Plume Geometry Testing and Methodology: An IPAC-RS Working Group Overview.

Plume characterization for orally inhaled and nasal drug products (OINDP) provides valuable information during OINDP development. Spray pattern and plume geometry techniques, methods, and technology have evolved over the past 20 years since the publication of the original 1998 FDA MDI DPI draft guidance. The International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS) discusses the historical context and background to plume geometry and spray pattern characterization studies; provides an analysis of the current regulatory context; addresses results from its industry surveys on application and value of such testing; and presents case studies and best practices-seeking to provide insights to regulatory bodies and other stakeholders. Assessment and consideration of published studies and industry experience note the value of plume geometry and spray pattern in development, and that further data is needed regarding their use in assessing formulation characteristics. Continued dialogue between industry and regulatory bodies is needed to establish the optimum use of these techniques.

[The Baker's cyst - a blunt sword of Damokles in radiosynoviorthesis (RSO)?] / Die Bakerzyste ­ das stumpfe Damoklesschwert bei der Radiosynoviorthese (RSO)?

The existence of a popliteal Baker's cyst was regarded as a contraindication for radiosynoviorthesis of the knee joint since decades. A so-called "ventile mechanism" was discussed leading to a significant concentration of the intraarticularly applied, high energy beta emitting radiopharmaceutical yttrium-90-colloid in the cyst. This cyst arises from a bursa beneath the tendon of the medial head of the gastrocnemius muscle, normally communicating with the knee joint space. Since the cyst wall is much thinner than the knee joint capsule, a radiogenic rupture of the cyst was feared, leading to severe radiogenic necroses of the surrounding soft tissue. Due to this potential hazard, knee joint ultrasound is mandatory prior to radiosynoviorthesis to check for any popliteal cysts. New studies however decline the risk of a radiogenic cyst rupture after an appropriately performed radiosynoviorthesis of the knee joint.In case of a preexistent cyst rupture, the risk of a radiogenic tissue damage remains an issue and magnetic resonance imaging (MRI) is the method of choice to exclude this potential hazard. However, MRI sometimes leads to equivocal results. Scintigraphy of the knee joint after intraarticular application of Tc-99m-nanocolloid offers the possibility to check for the integrity of the Baker's cyst in these patients to be sure that radiosynoviorthesis will not lead to a relevant extraarticular leakage with soft tissue necroses. This study describes the procedure of intracavitary distribution scintigraphy by means of representative case reports.

[RSO in clinical practice: Status in Germany 2020]. / RSO im klinischen Alltag: Statuserfassung in Deutschland 2020.

BACKGROUND: Radiosynoviorthesis (RSO) is a local radionuclide therapy of inflammatory joint diseases, successfully performed since several decades mainly as an outpatient-protocol in ambulatory health care centers or nuclear medicine practices. Despite of long-term experience in some centers, only very few valuable or comparable data about the procedure itself and/or the clinical results of this treatment are available. OBJECTIVES: The aim of this online survey is to assess reliable data of the current status in Germany. MATERIALS AND METHODS: A web-based questionnaire was designed to evaluate the status of RSO in Germany including demographic data, training, pretherapeutic diagnostics, clinical procedures, and follow-up. The survey was distributed via the supplier of RSO-nuclides, national nuclear medicine societies, and personal networks. It was available for 28 days and closed on November 30, 2020. RESULTS: A total of 78 specialists in nuclear medicine answered the questionnaire, which corresponds to a response rate of 23 %. Several differences and concordances in pre-therapeutic diagnostics, in the procedure of RSO itself, and follow-up were documented in this survey for the first time. Most important, less than 70 nuclear medicine specialists in Germany perform more than 75 % of all RSO-procedures and most of them are older than 50 years of age. This implies the urgent need of a dedicated advancement of young academics in nuclear medicine and a professional advanced training in RSO to offer this beneficial treatment to future patients. CONCLUSIONS: To achieve these goals, an association of RSO experts would be useful, through which, among other things, an RSO training curriculum is developed and theoretical and practical trainings are organized. Moreover, possible cooperation agreements between ambulant and inpatient institutions would foster the education of young nuclear medicine specialists interested in RSO.

Exenatide Delays Gastric Emptying in Patients with Type 2 Diabetes Mellitus but not in Those with Gastroparetic Conditions.

The effect of the treatment with glucagon-like peptide (GLP)-1 receptor agonists on gastric emptying in patients with diabetes with and without gastroparesis is analysed. Patients with type 2 diabetes mellitus subjected to GLP-1 receptor agonist therapy with exenatide were examined before and shortly after initiation of treatment. Gastric half-emptying time was determined by 13C-octanoic breath test; routine laboratory parameter as well as active GLP-1, ghrelin, leptin, insulin, proinsulin and C-peptide levels were determined in fasting state as well as postprandial secretion within 1 h after a standardised meal. Thirty patients' data sets were available for evaluation, of those 20 patients had no gastroparesis and 10 patients showed pathological results following the breath test. Gastric half-emptying time was prolonged in nearly all patients who presented without gastroparesis at initiation of treatment with GLP-1 receptor agonists, only 2 patients with pre-existing mild gastroparesis had worsening of gastric emptying. No effect was detected on leptin and ghrelin levels. Postprandial GLP-1 concentrations measured as AUC after meal decreased significantly. Fasting insulin and C-peptide levels increased significantly without effect on postprandial levels. Proinsulin levels - fasting as well as AUC - decreased non-significantly. Patients reported comparable perception of therapeutic effects. Treatment with GLP-1 receptor agonists may be applied in patients with pre-existing gastroparesis; no effect in terms of worsening of symptoms compared to those without gastroparesis was detected. Patients reported outcome was independent from underlying gastroparesis. Negative effects on gastric emptying were only detected in patients without or with mild gastroparesis.

Radiosynoviorthesis of acromioclavicular joint using 169Er-citrate: prospective evaluation of efficacy.

BACKGROUND: There is a clinical need for therapeutic alternative in patients with persisting painful arthritis of AC-joint and failure of previous treatments. However, no radiopharmaceutical is currently explicitly approved for radiosynoviorthesis of acromioclavicular joint. The aim of our study was to prospectively assess the efficacy and safety of radiosynoviorthesis of acromioclavicular joint using erbium-169 citrate. MATERIAL AND METHODS: Radiosynoviorthesis of acromioclavicular joint was performed in 51 consecutive patients (18 males, 33 females) mean age 64.3 (range 43.8-82.6, median 63.6) years with clinically confirmed arthritis of 85 acromioclavicular joints. The efficacy of RSO was reported by patients according to 10-step visual analogue scale of pain (VAS) (0 = no pain, 10 = most severe pain) at 6 months after radiosynoviorthesis and by ranking the global therapeutic effect of RSO in 4 categories (1 = the best effect, 4 = no change). To assess the variation of blood perfusion in treated joints, the efficacy of RSO was also evaluated by variation of target (acromioclavicular joint)/non-target (soft tissue) uptake ratio (T/NTR) of metylendiphosphonate (99mTc) measured as number of counts over region of interest on blood pool phase of two-phase bone scintigraphy performed before and 6 months after RSO. RESULTS: Radiosynoviorthesis was followed by significant decrease in VAS, mean - 3.1 (-47%). Excellent, good, moderate and bad response was observed in 57 (67%), 25 (29%), 1 (1%) and in 2 (2%) of acromioclavicular joints respectively. A significant correlation between decrease of T/NTR and variation of VAS in % (ρ = 0.532, p < 0.0001) and between T/NTR and subjective evaluation of therapeutic effect in scale 1-4 (ρ = 0.388, p = 0.0002) was observed. However, it was not possible to identify the cut-off value of relative decrease in T/NTR showing sufficient sensitivity and specificity to detect the therapeutic response. CONCLUSION: Results of this prospective study permit to conclude a good efficacy and safety of radiosynoviorthesis using erbium-169 citrate in a series of patients with arthritis of acromioclavicular joint in whom previous line(s) of treatment did not lead to satisfactory pain relief.

A Multi-laboratory in Vitro Study to Compare Data from Abbreviated and Pharmacopeial Impactor Measurements for Orally Inhaled Products: a Report of the European Aerosol Group (EPAG).

Fine particle dose (FPD) is a critical quality attribute for orally inhaled products (OIPs). The abbreviated impactor measurement (AIM) concept simplifies its measurement, provided there is a validated understanding of the relationship with the full resolution pharmacopoeial impactor (PIM) data for a given product. This multi-center study compared fine particle dose determined using AIM and PIM for five dry powder inhaler (DPIs) and two pressurized metered-dose inhaler (pMDI) products, one of which included a valved holding chamber (VHC). Reference measurements of FPDPIM were made by each organization using either the full-resolution Andersen 8-stage non-viable impactor (ACI) or Next Generation Impactor (NGI). FPDAIM was determined for the same OIP(s) with their choice of abbreviated impactor (fast screening impactor (FSI), fast screening Andersen (FSA), or reduced NGI (rNGI)). Each organization used its validated assay method(s) for the active pharmaceutical ingredient(s) (APIs) involved. Ten replicate measurements were made by each procedure. The upper size limit for FPDAIM varied from 4.4 to 5.0 µm aerodynamic diameter, depending upon flow rate and AIM apparatus; the corresponding size limit for FPDPIM was fixed at 5 µm in accordance with the European Pharmacopoeia. The 90% confidence interval for the ratio [FPDAIM/FPDPIM], expressed as a percentage, was contained in the predetermined 85-118% acceptance interval for nine of the ten comparisons of FPD. The average value of this ratio was 105% across all OIPs and apparatuses. The findings from this investigation support the equivalence of AIM and PIM for determination of FPD across a wide range of OIP platforms and measurement techniques.

Radionuclide Therapy of Bone Metastases.

The skeleton is a potential metastatic target of many malignant tumors. Up to 85% of prostate and breast cancer patients may develop bone metastases causing severe pain syndromes in many of them. In patients suffering from multilocular, mainly osteoblastic lesions and pain syndrome, radionuclide therapy is recommended for pain palliation. Low-energy beta-emitting radionuclides ((153)samarium-ethylenediaminetetrameth-ylenephosphonate (EDTMP) and (89)strontium) deliver high radiation doses to bone metastases and micrometastases in the bone marrow, but only negligible doses to the hematopoietic marrow. The response rate regarding pain syndrome is about 75%; about 25% of the patients may even become pain free. The therapy is repeatable, depending on cell counts. Concomitant treatment with modern bisphosphonates does not interfere with the treatment effects. Clinical trials using a new, not yet approved nuclide ((223)Radium) and/or combinations of chemotherapy and radionuclides are aiming at a more curative approach.

Disentangling phylogeography, polyploid evolution and taxonomy of a woodland herb (Veronica chamaedrys group, Plantaginaceae s.l.) in southeastern Europe.

Southeastern Europe is a centre of European biodiversity, but very little is known about factors causing the observed richness. Here, we contribute to fill this gap by reconstructing the spatio-temporal diversification of the cytologically variable and taxonomically intricate complex of Veronica chamaedrys (Plantaginaceae s.l.), growing in open forests, forest edges and grasslands, with flow cytometry, molecular markers (AFLPs, plastid DNA sequences) and morphometry. Our results show that both diploid and tetraploid cytotypes are widespread, but diploids predominate on the southern Balkan Peninsula. Plastid sequences suggest a first split into three main lineages in the mid-Pleistocene and a continuous diversification during the last 0.4 my. Two of the identified plastid lineages coincide with geographically distinct AFLP clusters. Altogether, the genetic data suggest forest refugia on the southern-most Balkan Peninsula (Greece), in Bulgaria, Istria (Croatia and Slovenia) and maybe the southeastern Carpathians (Romania). Morphometric and genetic data show little congruence with current taxonomy.

EANM procedure guideline for radio-immunotherapy for B-cell lymphoma with 90Y-radiolabelled ibritumomab tiuxetan (Zevalin).

BACKGROUND: In January 2004, EMEA approved 90Y-radiolabelled ibritumomab tiuxetan, Zevalin, in Europe for the treatment of adult patients with rituximab-relapsed or -refractory CD20+ follicular B-cell non-Hodgkin's lymphoma. The number of European nuclear medicine departments using Zevalin is continuously increasing, since the therapy is often considered successful. The Therapy, Oncology and Dosimetry Committees have worked together in order to define some EANM guidelines on the use of Zevalin, paying particular attention to the problems related to nuclear medicine. PURPOSE: The purpose of this guideline is to assist the nuclear medicine physician in treating and managing patients who may be candidates for radio-immunotherapy. The guideline also stresses the need for close collaboration with the physician(s) treating the patient for the underlying disease.

Radionuclide therapy of inflammatory joint diseases.

Inflammatory joint diseases as well as arthropathy are common joint diseases. Many of them may be treated by synovectomy to stop disease progression and to improve joint function. Radiosynoviorthesis as one therapeutic procedure of rheumatoid arthritis, other inflammatory joint diseases, persistent synovial perfusion, and other joint diseases is widely used in many countries in Europe. Using Y-90 for the knee joint, Re-186 for middle sized joints and Er-169 for small joints an improvement of symptoms and function may be observed in about 60-80% of patients.