STABIL-study: The Course of Therapy, Safety and Pharmacokinetic Parameters of Conversion of Prograf® to Tacrolimus HEXAL®/Crilomus® in Renal Transplant Recipients - an Observational Study in Germany.

BACKGROUND/OBJECTIVE: Tacrolimus HEXAL®/Crilomus® is an approved generic immunosuppressant for the prevention and treatment of rejection following renal transplantation. For safe and socioeconomically efficient conversion of the innovator into a generic formulation, high- -quality data are necessary, in view of the different and country-specific comorbidities and pharmacokinetics in kidney transplant recipients. PATIENTS AND METHODS: From 2014 to 2017, we enrolled 32 kidney transplant recipients, receiving newly prescribed Tacrolimus HEXAL®/Crilomus® in 5 German centers. Efficacy and safety data were collected over 6-8 months and retrospectively compared to the period prior to conversion. RESULTS: The mean tacrolimus trough level was 4.91 ng/mL Standard Deviation (SD) (SD ±1.7) before and 5.06 ng/mL (SD ±1.97) after conversion. Mean tacrolimus trough concentration-dose-ratio (+/- SD) was 187.1 ng/mL/mg/kg/day (SD 99.2) for the reference and 205.1 ng/mL/mg/kg/day (SD 133) for the generic product, resulting in a non-significant difference of 18.0 ng/mL/mg/kg/day (SD 71.8) (p=0.84, Wilcoxon V=180). Overall, dosing had to be changed in 4 (14.8%) patients. Graft function remained stable and no rejections occurred. CONCLUSION: In conclusion, conversion to the generic tacrolimus formulation can be considered safe and feasible in long-term kidney transplant recipients in Germany. As suggested by guidelines, vigilant therapeutic drug monitoring is recommended to account for possible tacrolimus concentration variability on the individual patient level.

Moderate endurance and muscle training is beneficial and safe in patients with quiescent or mildly active Crohn's disease.

BACKGROUND AND AIMS: Physical activity is beneficial in several chronic disorders including Crohn's disease, but the preferred type of exercise is unknown. Our study aimed to examine and compare the safety, feasibility and potential beneficial effects of individual moderate endurance and moderate muscle training in patients with Crohn's disease. METHODS: Quiescent or mildly active (Crohn's disease activity index <220) patients with Crohn's disease were randomly allocated to either a control, endurance, or muscle training group. Participants exercised individually for 3 months three times per week. Endpoints included dropout rate, disease activity, inflammatory parameters including faecal calprotectin, anthropometric data, quality of life, physical activity and strength. RESULTS: A total of 45 patients with Crohn's disease were randomly allocated. In the endurance group (n = 17), the dropout rate was significantly higher (47% vs. 13%) compared with the muscle group (n = 15). In both groups the maximal and average strength in the upper and lower extremities increased significantly (all P < 0.04). In the endurance group emotional function was significantly improved (P = 0.03). Statistically significant changes of disease activity and other outcome parameters were not observed in this pilot cohort. CONCLUSION: Both individual moderate endurance and muscle training can be safely performed in patients with mild or quiescent Crohn's disease. Muscle training appears more feasible and may be favoured. Both forms of exercise have beneficial effects on strength. Quality of life increased in both intervention groups, although statistical significance was only reached in one subgroup.

Low-molecular-weight iron dextran in the management of renal anaemia in patients on haemodialysis--the IDIRA Study.

BACKGROUND: Intravenous iron supplementation is a basic principle in the therapy of haemodialysis (HD) patients with renal anaemia. In the Iron Dextran in Renal Anaemia (IDIRA) study, we analysed the efficacy of a therapy with low-molecular-weight iron dextran (LMW-ID) in stable HD patients with adequate iron stores previously treated with ferric gluconate. METHODS: IDIRA was an open-label, prospective, non-randomized, observational multicenter trial over 12 months in iron-repleted HD patients. All patients were treated with intravenous LMW-ID. Measures of efficacy were changes of haemoglobin (Hb), serum ferritin, erythropoietin dose and the response to iron therapy calculated as ferritin efficacy and Hb efficacy. Statistical analysis was done by the Wilcoxon test. RESULTS: A total of 221 HD patients with a mean age 63.7 +/- 13.8 years were included. A total of 208 out of 221 patients were on erythropoietin therapy. Median time on dialysis was 2 (1-4) years. Mean Kt/V was 1.3. Of the 221 patients, 208 completed the 12-month study period. Mean Hb and serum ferritin increased without the need for higher erythropoietin doses. The mean amount of iron per week administered remained stable. Ferritin efficacy and Hb efficacy improved using LMW-ID (p < 0.01). CONCLUSIONS: We conclude that LMW-ID improves anaemia management even in iron-pretreated HD patients.

[Listeriosis in a patient with hemodialysis and iron overload]. / Listeriose bei einem Patienten mit Hämodialyse und Eisenüberladung.

A case of listeriosis in a patient undergoing long-term hemodialysis is reported. The 69-year-old man with chronic renal failure due to polycystic renal dysplasia had received hemodialysis treatment for 10 years. Renal anemia and iron overload developed within this time. In the course of a hemodialysis the patient presented with malaise, chills and fever to 38.7 degrees C. Blood culture specimens were obtained and the patient received ampicillin-sulbactam. Blood culture specimens subsequently showed growth of Listeria monocytogenes. During therapy the patient improved rapidly and was free from fever on day 5. The relation of iron overload and Listeria infection is discussed.

Transvenous treatment of carotid cavernous and dural arteriovenous fistulae: results for 31 patients and review of the literature.

OBJECTIVE: To evaluate findings for patients with carotid cavernous fistulae or dural arteriovenous fistulae (AVFs) who underwent transvenous embolization via different transvenous approaches. METHODS: Retrospective analysis of data for 31 patients (age range, 17-81 yr; mean age, 59.3 yr) with carotid cavernous fistulae (n = 6) or dural AVFs (cavernous sinus [CS], n = 11; transverse/sigmoid sinus, n = 14) was performed. The AVFs were treated with coils via different transvenous approaches, in 56 procedures. Doppler ultrasonography and time-resolved, two-dimensional, magnetic resonance projection angiography were performed to confirm the treatment. The mean clinical follow-up period was 32.5 months. RESULTS: A total of 34 transvenous procedures were performed for 17 AVFs of the CS. Eleven patients with AVFs of the CS (63%) were cured with respect to clinical symptoms, and six patients experienced improvement (37%). The approach via the internal jugular vein and inferior petrosal sinus (n = 15) was possible in 60% of cases, with complete occlusion of the fistula in 78% of cases. With the approach via the facial vein (n = 8), there was a 50% success rate. The superior ophthalmic vein approach (n = 5) was associated with a high rate of technical success (100%), with a rate of complete fistula occlusion of 80%. We encountered complications, with transient morbidity, in four cases (23.5%). For 14 dural AVFs of the transverse/sigmoid sinus, 22 transvenous procedures were performed; 12 patients were cured (85.7%) and 2 experienced improvement (14.3%). The technical success rate was 86%, with complete occlusion in 42% of cases. Minor complications occurred in six cases (42.9%) but did not lead to permanent morbidity. CONCLUSION: Transvenous treatment of CS and transverse/sigmoid sinus AVFs can be effective if all transvenous approaches, including combined surgical/endovascular approaches, are considered.