Persistence of denosumab in Slovak patients with bone metastases - a prospective observational study.

BACKGROUND: An integrated analysis of phase III trials in patients with advanced solid tumors demonstrated superiority of denosumab over zoledronic acid in preventing skeletal-related events. A drug's clinical efficacy, however, depends on regular and continued administration (persistence); persistence in Slovak real-life is yet undetermined for denosumab in the oncology indication. PATIENTS AND METHODS: This was a single-arm, prospective, observational, non-interventional study in patients with bone metastases from solid tumors treated with denosumab every 4 weeks in real-world clinical practice in 5 European countries. The results of the 54 patients from Slovakia are presented here. Persistence was defined as denosumab administration at ≤ 35-day intervals over 24 or 48 weeks, respectively. RESULTS: Previous skeletal-related events were found in 5.6% of patients. 84.8% were persistent over 24 weeks and 61.4 % over 48 weeks. The median (95% confidence interval (CI)) time to non-persistence was 306.5 days (Q1 = 151.0; Q3 = 315.0). The most frequent reason for non-persistence was delayed administration of denosumab. There was a trend towards weaker analgesics over time, with > 70% of patients not requiring any analgesics. Serum calcium remained within the normal range throughout the whole study. Adjudicated osteonecrosis of the jaw was not documented in any Slovak patient. CONCLUSION: Most patients received denosumab regularly once every 4 weeks over 24 weeks of treatment. Non-persistence was mainly due to delayed administration. The incidence of adverse drug reactions was in line with expectations from previous studies, osteonecrosis of the jaw did not occur in any of the patients involved in the study.

Clinical and (31)P magnetic resonance spectroscopy characterization of patients with critical limb ischemia before and after autologous cell therapy.

Autologous cell therapy (ACT) is a new treatment method for diabetic patients with critical limb ischemia (CLI) not eligible for standard revascularization. After intramuscular injection of bone marrow-derived mononuclear cells local arteriogenesis in the ischemic tissue occurs. Studies assessing visualization of this therapeutic vasculogenesis after ACT by novel imaging techniques are lacking. The aim of our study was to assess the effect of ACT on possible metabolic changes and perfusion of critically ischemic limbs using (31)P magnetic resonance spectroscopy ( (31)P MRS) and its possible correlation with changes of transcutaneous oxygen pressure (TcPO(2)). Twenty-one patients with diabetes and no-option CLI treated by ACT in our foot clinic over 8 years were included in the study. TcPO(2) as well as rest (phosphocreatine, adenosine triphosphate and inorganic phosphate) and dynamic (mitochondrial capacity and phosphocreatine recovery time) (31)P-MRS parameters were evaluated at baseline and 3 months after cell treatment. TcPO(2) increased significantly after 3 months compared with baseline (from 22.4±8.2 to 37.6±13.3 mm Hg, p=0.0002). Rest and dynamic (31)P MRS parameters were not significantly different after ACT in comparison with baseline values. Our study showed a significant increase of TcPO(2) on the dorsum of the foot after ACT. We did not observe any changes of rest or dynamic (31)P MRS parameters in the area of the proximal calf where the cell suspension has been injected into.

Impact of severe diabetic kidney disease on the clinical outcome of autologous cell therapy in people with diabetes and critical limb ischaemia.

AIM: To assess the impact of autologous cell therapy on critical limb ischaemia in people with diabetes and diabetic kidney disease. METHODS: A total of 59 people with diabetes (type 1 or type 2) and critical limb ischaemia, persisting after standard revascularization, were treated with cell therapy in our foot clinic over 7 years; this group comprised 17 people with and 42 without severe diabetic kidney disease. The control group had the same inclusion criteria, but was treated conservatively and comprised 21 people with and 23 without severe diabetic kidney disease. Severe diabetic kidney disease was defined as chronic kidney disease stages 4-5 (GFR <30 ml/min/1.73 m²). Death and amputation-free survival were assessed during the 18-month follow-up; changes in transcutaneous oxygen pressure were evaluated at 6 and 12 months after cell therapy. RESULTS: Transcutaneous oxygen pressure increased significantly in both groups receiving cell therapy compared to baseline (both P<0.01); no significant change in either of the control groups was observed. The cell therapy severe diabetic kidney disease group had a significantly longer amputation-free survival time compared to the severe diabetic kidney disease control group (hazard ratio 0.36, 95% CI 0.14-0.91; P=0.042); there was no difference in the non-severe diabetic kidney disease groups. The severe diabetic kidney disease control group had a tendency to have higher mortality (hazard ratio 2.82, 95% CI 0.81-9.80; P=0.062) than the non-severe diabetic kidney disease control group, but there was no difference between the severe diabetic kidney disease and non-severe diabetic kidney disease cell therapy groups. CONCLUSIONS: The present study shows that autologous cell therapy in people with severe diabetic kidney disease significantly improved critical limb ischaemia and lengthened amputation-free survival in comparison with conservative treatment; however, the treatment did not influence overall survival.

Perfusion scintigraphy in the assessment of autologous cell therapy in diabetic patients with critical limb ischemia.

Perfusion scintigraphy with technetium-99-methoxy-isobutyl-isonitrile ((99m)Tc-MIBI) is often used for assessing myocardial function but the number of studies concerning lower limb perfusion is limited. The aim of our study was to assess whether (99m)Tc-MIBI was an eligible method for evaluation of the effect of cell therapy on critical limb ischemia (CLI) in diabetic patients. (99m)Tc-MIBI of calf muscles was performed before and 3 months after autologous cell therapy (ACT) in 24 diabetic patients with CLI. Scintigraphic parameters such as rest count and exercising count after a stress test were defined. These parameters and their ratios were compared between treated and untreated (control) limbs and with changes in transcutaneous oxygen pressure (TcPO(2)) that served as a reference method. The effect of ACT was confirmed by a significant increase in TcPO(2) values (p<0.001) at 3 months after ACT. We did not observe any significant changes of scintigraphic parameters both at rest and after stress 3 months after ACT, there were no differences between treated and control limbs and no association with TcPO(2) changes. Results of our study showed no significant contribution of (99m)Tc-MIBI of calf muscles to the assessment of ACT in diabetic patients with CLI over a 3-month follow-up period.

[Special contact splints in postoperative care for patients with the diabetic foot]. / Pouzití speciálních kontaktních dlah v pooperacní péci u syndromu diabetické nohy.

UNLABELLED: Adequate stabilization and off-loading of the lower limb is an integral part of postoperative care for patients with the diabetic foot. Off-loading can accelerate the healing process and reduce the number of complications and reoperations. The newly introduced method of the performance of removable contact splints (modified contact removable casts) seems to fulfil a number of requirements for stabilization and off-loading devices - the method is safe and can actually reduce the healing time and the number of reoperations in patients with the diabetic foot. KEY WORDS: diabetic foot - off-loading - splints.