Ralf Schiel

Low-density Lipoprotein Apheresis: An Overview

Abstract:  Atherosclerosis with myocardial infarction, stroke, and peripheral cellular disease still maintains its position at the top of morbidity and mortality statistics in industrialized nations. Established risk factors widely accepted are smoking, arterial hypertension, diabetes mellitus, and central obesity. Furthermore, there is a strong correlation between hyperlipidemia and atherosclerosis. The prognosis of patients suffering from severe hyperlipidemia, sometimes combined with elevated lipoprotein (a) (Lp(a)) levels, and coronary heart disease (CHD) refractory to diet and lipid‐lowering drugs is poor. For such patients, regular treatment with low‐density lipoprotein (LDL) apheresis is the therapeutic option. Today, there are four different LDL apheresis systems available: immunoadsorption, heparin‐induced extracorporeal LDL/fibrinogen precipitation, dextran sulfate LDL adsorption and LDL hemoperfusion. Regarding the different LDL apheresis systems used, there is no significant difference with respect to the clinical outcome or concerning total cholesterol, LDL, high‐density lipoprotein (HDL), or triglyceride concentrations. With respect to elevated Lp(a) levels, however, the immunoadsorption method seems to be the most effective. In 45 patients (25 women, 20 men) suffering from familial hypercholesterolemia resistant to diet and lipid lowering drugs, low‐density lipoprotein (LDL) apheresis was performed over 95.6 ± 44.7 months. Four different systems (Liposorber, 32 of 45, Kaneka, Osaka, Japan; Therasorb, 6 of 45, Baxter, Munich, Germany; Lipopak, 2 of 45, Pocard, Moscow, Russia; and Dali, 5 of 45, Fresenius, St. Wendel, Germany) were used. With all methods, average reductions of 57% for total cholesterol, 55.9% for LDL, 75.8% for lipoprotein (a) (Lp[a]), and 45.9% for triglycerides, and an average increase of 14.3% for HDL were reached. Severe side‐effects such as shock or allergic reactions were very rare (0.3%) in all methods. In the course of treatment, an improvement in general well‐being and increased performance were experienced by 44 of 45 patients. The present data demonstrate that treatment with LDL apheresis of patients suffering from familial hypercholesterolemia resistant to maximum conservative therapy is very effective and safe even in long‐term application.

Surface treated large bore catheters with silver based coatings versus untreated catheters for extracorporeal detoxification methods

Infection, thrombosis, and stenosis are among the most frequent complications associated with blood contacting catheters. Because these problems are usually related to surface properties of the base catheter material, surface treatment processes, such as ion implantation and ion beam assisted deposition (silver based coatings), can be used to mitigate such complications. Because these ion beam based processes affect only the near-surface region (approximately the outer 1

Structured treatment and teaching of patients with Type 2 diabetes mellitus and impaired cognitive function—the DICOF trial

mUn), there is little effect on bulk material properties. This study evaluated silver coated large bore catheters used for extracorporeal detoxification. In a 122 patient prospective study, 156 large bore catheters were inserted into the internal jugular or subclavian veins. Seventy-eight surface treated catheters (SPI-ARCENT, Spire Corporation, Bedford, MA; n = 32 acute catheters, n = 45 long-term catheters) were Bam-bauer inserted in 55 patients. Seventy-eight untreated catheters placed in 67 patients served as controls (n = 35 acute catheters, n = 43 long-term catheters). After removal, the catheters were cultured for bacterial colonization using standard microbiologic assays. They were also examined using a scanning electron microscope (SEM). Bacterial colonization was observed in 15.4% of the treated catheters compared with 44.9% of untreated catheters. The SEM investigations showed all treated catheters to possess low thrombogenicity. Results of the study indicate that ion beam based processes can be used to improve thrombus and infection resistance of blood contacting catheters. ASAIO Journal 1998; 44:303–308.

LDL-apheresis: technical and clinical aspects.

Background  Patient education is integral part of any diabetes therapy in Germany, but elderly patients are not able to follow the variety of topics comprising standard treatment and teaching programmes (TTP), primarily due to impaired neuropsychological function. This leads to deficits in diabetes knowledge and hindered ability for diabetes self‐management.

Post-transplant diabetes mellitus: risk factors, frequency of transplant rejections, and long-term prognosis

The prognosis of patients suffering from severe hyperlipidemia, sometimes combined with elevated lipoprotein (a) levels, and coronary heart disease refractory to diet and lipid-lowering drugs is poor. For such patients, regular treatment with low-density lipoprotein (LDL) apheresis is the therapeutic option. Today, there are five different LDL-apheresis systems available: cascade filtration or lipid filtration, immunoadsorption, heparin-induced LDL precipitation, dextran sulfate LDL adsorption, and the LDL hemoperfusion. There is a strong correlation between hyperlipidemia and atherosclerosis. Besides the elimination of other risk factors, in severe hyperlipidemia therapeutic strategies should focus on a drastic reduction of serum lipoproteins. Despite maximum conventional therapy with a combination of different kinds of lipid-lowering drugs, sometimes the goal of therapy cannot be reached. Hence, in such patients, treatment with LDL-apheresis is indicated. Technical and clinical aspects of these five different LDL-apheresis methods are shown here. There were no significant differences with respect to or concerning all cholesterols, or triglycerides observed. With respect to elevated lipoprotein (a) levels, however, the immunoadsorption method seems to be most effective. The different published data clearly demonstrate that treatment with LDL-apheresis in patients suffering from severe hyperlipidemia refractory to maximum conservative therapy is effective and safe in long-term application.

GAD autoantibodies in a selection-free population of insulin-treated diabetic patients: indicator of a high prevalence of LADA?

BackgroundEstimates of the incidence of new-onset diabetes after renal transplantation vary between 2% and 54%. It was the aim of the present trial to study the prevalence of post-transplant diabetes mellitus (DM), the risk factors, the frequency of transplant rejections, and the long-term prognosis.MethodsWe studied all consecutive patients with endstage renal disease, but without DM who received kidney transplantation at our center since 1992 (n = 253; age, 52.2 ± 12.6 years; body mass index, 22.0 ± 7.9 kg/m2). Follow up was 3.3 ± 1.6 years (range, 0.1–17.7) years.ResultsIn total, 43/253 patients (17%) developed new-onset DM after transplantation. Patients with new-onset diabetes were significantly older (58.3 ± 11.4 vs 50.9 ± 12.5 years; P < 0.01) and had a tendency to a higher body mass index (24.0 ± 8.5 vs 21.6 ± 7.8 kg/m2; P = 0.077). There were no differences between the groups in respect of blood pressure control (137.7 ± 19.0/81.8 ± 14.2 vs 137.1 ± 21.9/83.9 ± 13.1 mmHg; P = 0.89/0.39), glomerular filtration rate (58.0 ± 28.1 vs 64.1 ± 22.1 ml/min per 1.73 m2; P = 0.13), steroid dosage (4.5 ± 1.2 [n = 21] vs 4.6 ± 2.2 [n = 135] mg/day; P = 0.13), or the frequency and dosage of immunosuppressive drugs such as cyclosporine, tacrolimus, and sirolimus during the follow up. However, more patients with post-transplant diabetes received steroids (83.7% vs 64.3%; P = 0.021) and azathioprine (41.9% vs 24.3%; P = 0.030). Patients with new-onset diabetes had higher serum creatinine values (163.4 ± 67.9 vs 138.7 ± 59.5 µmol/l; P = 0.017). The mean hemoglobin (Hb)A1c in patients with DM was 6.28 ± 1.29% (Tosho HPLC; mean normal, 5.15%). In 18 patients (7.1%) transplant rejections occurred (16 patients without DM [7.6%] vs 2 patients with new-onset DM [4.7%]; P = 0.39). On performing multivariate analysis, the only parameter found to be associated with new-onset DM was the body mass index (R2 = 0.05; β = 0.23; P = 0.02), and the only factor associated with transplant rejection was fasting blood glucose (R2 = 0.07; β = 0.28; P = 0.02). None of the other parameters included in the models (age, duration after transplantation, diabetes duration, immunosuppressive therapy, HbA1c, HLA mismatches) showed any associations.ConclusionsThe prevalence of new-onset DM after renal transplantation was 17%. The most important parameter associated with new-onset diabetes was a higher body mass index, and the most important parameter associated with transplant rejection was an elevated fasting blood glucose level. To prevent transplant rejections and to improve patients’ outcome, in addition to providing optimal immunosuppressive therapy and HLA matching, good blood pressure control and HbA1c, but also near normal fasting blood glucose levels, should be achieved.

Long-term efficacy of a 5-day structured teaching and treatment programme for intensified conventional insulin therapy and risk for severe hypoglycemia

UNLABELLED Up to the present only few data have been available concerning the prevalence of diabetes-specific autoantibodies (anti-GAD, ICA, IAA, IA-2) in unselected populations, in particular in type 2 diabetic patients. Hence, the aim of the present study was to determine the prevalence of anti-GAD in a selection-free population of insulin-treated diabetic patients. Accordingly, 90% of all the insulin-treated diabetic patients (type 1, n=127, type 2, n=117) aged 16-60 years and living in the city of Jena (100242 inhabitants) were examined. In order to test sera for anti-GAD, serum samples were taken in 75% of type 1 (n=95) and in 80% of insulin-treated type 2 diabetic (n=94) patients. RESULTS In the group of type 1 diabetic patients 55% of the patients tested were positive for anti-GAD. But, interestingly, in the type 2 group, a total of 21% patients were positive. With respect to this high percentage of anti-GAD positive type 2 diabetic patients it must be suggested that the frequency of patients with latent autoimmune diabetes mellitus in adults (LADA) was underestimated in the past.

Electronic health technology for the assessment of physical activity and eating habits in children and adolescents with overweight and obesity IDA.

In the DCCT, intensification of insulin therapy led to a threefold increase in the risk of severe hypoglycemia (defined as the need for third party assistance). The reasons for this strong exponential relationship appears to be unclear to date. The present trial, a long-term evaluation of a 5-day structured teaching and treatment programme (5-DTTP) for intensified conventional insulin therapy (ICT), was performed to elucidate factors determining HbA1c and the incidence of severe hypoglycemia. A total of 71 patients were examined at baseline and 45.5 +/- 4.2 months following participation in a 5-DTTP. Comparing the data at follow-up examination with baseline measurements. HbA1c improved (8.52 +/- 2.29% vs. 8.0 +/- 1.43%, P = 0.04), the frequency of daily insulin injections (3.1 +/- 1.6 vs. 4.8 +/- 0.8, P < 0.001) and weekly blood-glucose self-tests (5.2 +/- 8.9 vs. 25.5 +/- 9.6, P < 0.001) increased, and the incidence of severe hypoglycemia (glucose i.v., glucagon injection) remained stable (0.18 vs. 0.17, P = 0.99). But, comparing the 21 patients who suffered from severe hypoglycemia during the follow-up period with the 50 patients without hypoglycemia, no differences between the two groups were found with respect to metabolic control (7.70 +/- 1.48% vs. 8.21 +/- 1.43%, P = 0.17), quality of life or treatment satisfaction. However differences arose with respect to diabetes knowledge. In the group of 21 patients with severe hypoglycemia we identified certain crucial gaps in diabetes knowledge: insulin self-adjustment; dietary aspects; hypo- and hyperglycemia. Performing multiple regression analysis, strong correlations were found between HbA1c and diabetes knowledge (r = -0.58. P = 0.002 for 50 patients without hypoglycemia and r = -0.63, P = 0.05 for 21 patients with hypoglycemia). In the total group, the most important factors determining HbA1c, were diabetes knowledge (r = -0.055, P = 0.007) and daily insulin dosage/kg body weight (r = 2.13, P = 0.0008, R2 = 0.26). Intervention like education of patients on a continuous basis and modifications of the DTTPs with more information and training in the recognition and treatment of hypoglycemic episodes seems to be essential to prevent hypoglycemia and to improve the efficacy of DTTPs over longer periods of time.

Long-term treatment of obese children and adolescents using a telemedicine support programme.

OBJECTIVE It was the goal of the trial to study the impact of electronic healthcare technology into treatment. METHODS One hundred and twenty-four children/adolescents (females 56%, age 13.5±2.8 years, height 1.64±0.13 m, weight 85.4±23.0 kg, body-mass index (BMI) 31.3±5.2 kg/m(2), BMI-standard deviation score (SDS) 2.50±0.5) were included. To assess physical activity and eating habits, a mobile motion sensor integrated into a mobile phone with digital camera was used. RESULTS The children/adolescents had a significant weight reduction of 7.1±3.0 kg. BMI/BMI-SDS decreased (p<0.01). Intensity (14.1±6.4 activity units) and duration of physical activity (290.4±92.6 min/day) were assessed with sensors. Time walking: median 45.5 (range, 2.5-206.5), running 8.0 (range, 0-39.5), cycling 27.7 (range, 0-72.5), car driving 23.7 (range, 0-83.0) min/day. Comparing self-reported physical activity (walking 292.9 (range, 9.6-496.1), running 84.8 (range, 8.4-130.2) min/day) with assessment with sensors there were significant differences (p<0.01). Duration of physical activity documented by children/adolescents was higher than the assessment with motion sensors (walking 292.9 vs 45.5 min, p<0.01, running 84.8 vs 8.0 min, p<0.01). Sensor derived energy intake was higher than recommended (469.14±88.75 kcal vs 489.03±108.25 kcal, p=0.09). Performing multivariate analysis the following parameters showed associations with weight reduction (R-square=0.75): body weight (β=-0.95, p<0.01), C-reactive protein (CRP, β=0.15, p=0.07), physical activity, time spent in activities measured with sensors (β=-0.18, p=0.04), stress management (β=0.16, p=0.06), body fat mass at onset of the trial (β=0.45, p<0.01) and body shape (β=-0.25, p=0.01). CONCLUSION The innovative mobile movement detection system is highly accepted by children and adolescents. The system is able to augment existing weight reduction and stabilization strategies.

Impact of Information Technology on the Therapy of Type-1 Diabetes: A Case Study of Children and Adolescents in Germany

Summary A total of 140 obese patients (mean age 14 years) participated in a structured treatment and teaching programme (STTP) in hospital, with the aim of weight reduction. At both the start and finish of the STTP, patients underwent clinical and psychological examination. During an average hospital stay of 35 days, their mean bodyweight decreased from 82.4 kg to 76.0 kg (P < 0.001). Patients were then followed up with a telemedicine support programme. During the next 12 months, the acceptance of the telemedicine support programme declined from 93% to 46%. The body mass index was 30.5 kg/m2 at admission and 27.7 kg/m2 at 12-month follow-up (P < 0.05). In parallel, wellbeing and treatment satisfaction increased, and there was a positive effect on eating behaviour and exercise. Intervention was needed in up to 64% of the children and adolescents who participated in the programme, most frequently due to poor results in exercise. Telemedical follow-up care and counselling seemed to be highly effective, and allowed not only an initial weight reduction, but long-term stabilization as well.