Potential influence of tacrolimus and steroid avoidance on early graft function in pediatric renal transplantation

Abstract:  With the increasing adoption of steroid-sparing immunosuppression protocols in renal transplantation, it is important to evaluate any adverse effects of steroid avoidance on graft function. Early graft function, measured by CrCl was retrospectively studied in 158 consecutive pediatric renal transplant recipients from 1996 to 2005, receiving either steroid-free or steroid-based immunosuppression. Patients receiving steroid-free immunosuppression vs. steroid-based immunosuppression had no difference change in CrCl (ΔCrCl) in the first week post-transplantation (p = 0.12). When stratified by corticosteroid usage, patients with higher tacrolimus trough levels (≥14 ng/mL) had slower graft function recovery in the first week post-transplantation than those with lower tacrolimus trough levels (p = 0.008) in the steroid-free group only. Despite initial slower graft function recovery in this subgroup, there was no negative impact on graft function in the steroid-free group; in fact steroid-free patients trended towards better CrCl at six months (p = 0.047) and 12 months (p < 0.001) post-transplant than the steroid-based group. With the improved immunological outcomes with steroid avoidance, close surveillance should be performed of tacrolimus levels to avoid levels >14 ng/mL. In patients with slow recovery of early graft function, short-term perioperative steroids may be considered.     

Pharmacokinetic monitoring of intravenous cyclosporine A in pediatric stem-cell transplant recipients. The trough level is not enough

Abstract:  In order to monitor CsA serum levels after SCT, trough levels (C0) are widely used. The aim of this study was to estimate the population and individual PK parameters for patients receiving intravenous CsA after SCT. In 27 pediatric patients after SCT receiving CsA (3 mg/kg/day) every 12 h, a total of 289 CsA concentrations was obtained. To describe the PK parameters of CsA, a two-compartment model with first order elimination was used. Covariate analysis identified body weight, age, and the co-administration with itraconazole and tobramycine as factors influencing the Cl. The statistical comparison of AUC, trough level, and C2 indicates a correlation between AUC and C2, but no correlation between the AUC and C0, r = 0.24 (p = 0.146) vs. r = 0.526 (p = 0.000692), respectively. Our results underscore the fact that CsA trough levels do not reflect the drug exposure in patients receiving intravenous CsA after SCT. By contrast, CsA blood levels measured 2–6 h after CsA infusion showed a better correlation with the AUC. Our data provide new information to optimize the balancing act between GvHD-prophylaxis, graft vs. leukemia effect, and CsA side-effects after SCT.     

Clinical comparison of weight‐ and age‐based strategy of dose administration in children receiving intravenous busulfan for hematopoietic stem cell transplantation

Bu, combined with TDM‐guided dosing, is associated with fewer graft failures/relapses and lower toxicity in pediatric HSCT. We aimed this retrospective study for comparison of weight‐ and age‐based dosing in terms of clinical outcomes such as time to engraftment, early complications, EFS, OS, and toxicity profiles in children receiving iv Bu. Sixty‐one children who underwent HSCT from April 2010 to February 2013 by means of a Bu‐based conditioning regimen and completed 100 days after transplantation at Ankara Children?s Hematology and Oncology Hospital Bone Marrow Transplantation Unit were enrolled in this study. SOS and neutropenic fever occurred more frequently in the weight‐based dosing group. We found a statistically significant correlation between Bu dose and the incidence of SOS (r = 0.26, p = 0.04). Multivariate analysis showed only weight‐based dosing of Bu was a significant predictor of SOS (HR = 9.46; p = 0.009). However, no relationship was found between two groups in terms of hemorrhagic cystitis, engraftment syndrome, acute or chronic GvHD, time to engraftment, chimerism, TRM, OS, and EFS rates. Weight‐based dosing of Bu may cause higher incidence of SOS and early infectious complications at the places where TDM of Bu cannot be performed.     

Transition from brand to generic tacrolimus is associated with a decrease in trough blood concentration in pediatric heart transplant recipients

There are limited data available on the bioequivalence of generic and brand‐name tacrolimus in pediatric and heart transplant patients. We characterized changes in 12‐hour trough concentrations and clinical outcomes after transition from brand to generic tacrolimus in pediatric thoracic organ transplant recipients. Patients with a pharmacy‐confirmed date of switch between generic and brand tacrolimus were identified, as well as a matched control group that did not switch for comparison. We identified 18 patients with a confirmed date of switch, and in 12 patients that remained on the same dose, trough concentrations were 14% less than when they were on brand (p = 0.037). The average change was ?1.15 ± 1.76 ng/mL (p = 0.045). The control group did not experience a change in trough concentration and was different than the switched group (p = 0.005). There were no differences in dosage changes or kidney or liver function. In the year after switch, 24% of patients who were switched to generic experienced a rejection event vs. 18% in the patients on brand. We suggest a strategy of monitoring around the time of transition, and education of the patient/family to notify the care team when changes from brand to generic or between generics occur.     

Slow versus rapid enteral feeding advancement in preterm newborn infants 1000–1499 g: a randomized controlled trial

Aim:  To evaluate whether preterm neonates weighing 1000–1499 g at birth receiving rapid enteral feeding advancement at 30 mL/kg/day attain full feedings (180 mL/kg/day) earlier than those receiving slow enteral feeding advancement at 20 mL/kg/day without increase in the incidence of feeding intolerance or necrotizing enterocolitis.
Methods:  A total of 100 stable intramural neonates weighing between 1000 and 1499 g and gestational age less than 34 weeks were randomly allocated to enteral feeding (expressed human milk or formula) advancement of 20 mL/kg/day (n   = 50) or 30 mL/kg/day (n   = 50).
Results:  Neonates in the rapid feeding advancement group achieved full volume feedings before the slow advancement group (median 7 days vs. 9 days) (p < 0.001), had significantly fewer days of intravenous fluids (median 2 days vs. 3.4 days) (p < 0.001), shorter length of stay in hospital (median 9.5 days vs. 11 days) (p = 0.003) and regained birth weight earlier (median 16 days vs. 22 days) (p < 0.001). There were no statistical differences in the proportion of infants with apnea, feed interruption or feed intolerance.
Conclusion:  Rapid enteral feeding advancements of 30 mL/kg/day are well tolerated by stable preterm neonates weighing 1000–1499 g.     

Nutrition, anthropometry, gastrointestinal dysfunction, and circulating levels of tumour necrosis factor alpha receptor I and interleukin-1 receptor antagonist in children during stem cell transplantation

Abstract:  To evaluate anthropometry, nutrition and gastrointestinal dysfunction, and to characterize the relation between these parameters and the inflammatory activity evaluated by plasma levels of soluble tumour necrosis factor alpha receptor I (sTNFRI) and interleukin-1 receptor antagonist (IL-1Ra) levels during stem cell transplantation (SCT) in children. Clinical assessments and blood sampling were performed on days −3, 0, +7, +15 and +31 in eight children undergoing SCT. Energy intake, anthropometry, gastrointestinal dysfunction (WHO toxicity score) and sTNFRI and IL-1Ra were evaluated. The energy intake was below recommended levels. There was a loss of lean body mass (arm muscle area)(median, 2031 mm² (day -3) vs 1477 mm² (day 31); p = 0.04), and of fat mass (arm fat area) (791 mm² (day -3) vs 648 mm² (day +31); p = 0.04). sTNFRI was elevated throughout the course of transplantation, and peaked after the day of graft infusion (day 0). sTNFRI levels at day 0 predicted changes in weight SDS (r = 0.65; p = 0.05), triceps skinfold SDS (r = 0.85; p = 0.007) and gastrointestinal dysfunction (r = 0.88; p = 0.004). Likewise, IL-1Ra levels at day 0 correlated with the gastrointestinal dysfunction (r = 0.83; p = 0.01) and with the change in weight SDS (r = 0.77; p = 0.03). This study suggests that pretransplant levels of inflammatory markers are associated with posttransplant symptoms of gastrointestinal dysfunction and loss of both fat and lean body mass. Future studies should adress if the use of conditioning regimens with limited proinflammatory cytokine inducing activity, anti-inflammatory agents, or more optimised nutritional support can reduce the burden of such posttransplant complications.     

Investigation of impaired carbohydrate metabolism in pediatric liver transplant recipients

Abstract:  OGTT was performed in 28 liver transplants maintained with tacrolimus to investigate carbohydrate metabolism and assess risk factors for development of PTDM. None had PTDM that was detected by OGTT. Early PTDM in four cases (14.3%) resolved in follow-up. Five new cases (17.9%) demonstrated DCM (DCM  = IGT ± hyperinsulinemia). Fasting measurements were normal in two hyperinsulinemic cases. With one (20%, p > 0.05) exception none of the children with DCM were overweight or had a family history of diabetes. All five (100%) children with DCM had been given high cumulative dosage of steroids 18 (78.3%) – without DCM (p > 0.05). The median age of children with DCM was greater [4.3 (12.7–18.0) vs. 7.0 (2.3–18.0) yr, p < 0.01] and duration of follow-up longer [5.3 (2.3–7.0) vs. 2.5 (0.7–7.3) yr, p < 0.05]. Four children (80%) with DCM were pubertal (p < 0.05). However, neither age nor duration of follow-up or pubertal stage had significant effect on DCM development. Early PTDM is a transient phenomenon and is not predictive for future development of diabetes. DCM is frequently observed in liver transplanted children. Albeit the children with DCM were given high cumulative dose of steroids, were older, mostly were pubertal, and had longer duration of follow-up, we cannot draw firm conclusions on effects of the risk factors on carbohydrate metabolism because of the small sample size and relatively short duration of follow-up. Unlike fasting measurements, OGTT can detect all children with DCM.     

Physical activity and overweight in children and adolescents using intensified insulin treatment

Aim:  To describe physical activity and inactivity and parameters associated with overweight in a population-based study of children and adolescents on intensive insulin treatment.
Methods:  Physical activity and inactivity were evaluated in 723 type 1 diabetic subjects, 240 children aged 6–10 yr and 483 adolescents aged 11–19 yr, using a questionnaire that can estimate total amount of time spent on inactivity and light, moderate and vigorous activity.
Results:  Overall, 54% of the participants do not fulfil the international recommendations of 60 min of moderate-to-vigorous activity per day. Girls are less active than boys in childhood (70 vs. 88 min/d, p = 0.01) and in adolescence (47 vs. 57 min/d, p = 0.02). Furthermore, this study shows that those who are more active are also those who seldom skip meals (p < 0.001). Forty-three percent of the participants watch TV for more than 2 h a day, and TV viewing was found to be related to overweight in children and adolescents with type 1 diabetes [OR: 2.5 (1.40–4.54), p = 0.002]. No statistical differences in physical activity were noted between the different intensified insulin regimens. Patients wearing insulin pumps were not less active.
Conclusion:  To increase physical activity to recommended level and limit TV viewing should be an important issue in education of all children and adolescents with type 1 diabetes, independent of insulin regimen.     

Sirolimus pharmacokinetics in pediatric renal transplant recipients receiving calcineurin inhibitor co-therapy

We have previously reported sirolimus (SRL) pharmacokinetics (PK) in pediatric renal transplant recipients on a calcineurin inhibitor (CNI)-free protocol. We now report pediatric SRL PK in pediatric renal transplant patients receiving SRL + CNI. SRL was dosed to achieve target trough levels between 10 and 20 ng/mL. We performed 49 SRL PK profiles in pediatric renal transplant recipients receiving SRL in combination with either cyclosporine (CsA; 25 profiles), or tacrolimus (TCL; 24 profiles). Ten of the SRL + TCL profiles were obtained from children receiving SRL on a b.i.d. dosing regimen. All other SRL profiles were q.d. regimens. We calculated, the maximum concentration (C(max)), AUC, apparent clearance (aCL; dose/AUC) for dose in mg/m(2), and mean residence time (MRT). SRL levels were measured at 6 and 7 time points for b.i.d. and q.d. dosing, respectively. Regression analysis of SRL trough values vs. AUC showed good correlation in the SRL q.d. + CsA, SRL q.d. + TCL, and SRL b.i.d. + TCL groups (r(2) = 0.95, 0.68, and 0.44, respectively). SRL aCL corrected for body surface area was higher in children aged 0-5 yr receiving SRL with either CsA or TCL. SRL dosing schedule should be tailored to each patient. Higher SRL aCL may be present in younger children when administered with CNI.     

Benefits of conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in pediatric renal transplant patients with stable graft function

Abstract:  Conversion from MMF to EC-MPS may reduce GI complications and permit increased MPA dosing with a concomitant reduction in CNI dose. In a prospective trial, paediatric renal transplant patients with stable graft function were converted from MMF to EC-MPS and followed-up for 12 months. Data from 28 patients (mean age 13.9 ± 3.1 yr) were available for analysis. Mean EC-MPS dose increased significantly from conversion to month 12 (668 ± 81 mg/m²/day vs. 747 ± 98 mg/m²/day, p < 0.001). CsA-ME dose (n = 23) decreased from 5.3 ± 1.7 mg/kg/day at conversion to 4.6 ± 1.4 mg/kg/day at month 12 (p = 0.010). cGFR increased from 69.5 ± 23.3 mL/min/1.73 m² at the time of conversion to 80.7 ± 30.7 mL/min/1.73 m² at month 12 (p = 0.007). The number of patients reporting at least one GI event during six months prior to conversion was 15/28 (53.6%), declining to 8/28 (28.6%) at month 6 post-conversion and 5/28 (17.8%) at month 12. This single-arm study suggests that conversion of paediatric renal transplant patients from MMF to EC-MPS does not compromise efficacy and leads to improved GI tolerability. MPA dose increased and CsA-ME dose decreased significantly, with an associated improvement in calculated GFR. A large-scale controlled trial is required to confirm these promising findings.     

Tacrolimus and sirolimus in capillary dried blood spots allows for remote monitoring

Therapeutic drug monitoring of tacrolimus and sirolimus plays a significant role in the clinical follow‐up of transplant patients receiving IMS therapy. Success of transplant and favorable patient outcome relies on maintaining adequate therapeutic drug levels. The purpose of this research is to assess the clinical utility of remote collection of DBS for immunosuppressant monitoring and compare the IMS level in paired collections of venous whole blood and DBS. Sirolimus and tacrolimus levels were clinically correlated in capillary blood collected from a finger poke with venous whole blood from pediatric, post‐transplant patients. The participants took the dried blood spot card home with them with a pre‐addressed, postage‐paid envelope and mailed it back to the laboratory. Overall, a small but statistically significant negative bias was observed (?0.6 ng/mL, p = 0.0011). A chart review was performed to assess whether clinical management would have changed, and none of the cases revealed a clinically significant change. Sirolimus in DBS also correlated with venous levels. Overall, a small but statistically negative bias was observed (?0.8 ng/mL, p = 0.029). In summary, analysis of IMS levels in DBS is possible, and the difference noted between capillary and venous blood is within the clinically acceptable limits.     

Physical activity and health related quality of life in children following kidney transplantation

Abstract:  Participation in PA is often diminished in children with CKD. Limited research exists on exercise tolerance/capacity but no studies to date have investigated lifestyle PA and its determinants in these children. The aim of this study was to investigate level of PA and potential physiological and psychological associations in a group of pediatric KTx recipients compared with CS. Twenty KTx and 33 CS participated. PA was measured by PAQ. HRQOL (PedsQL 4.0) and CY-PSPP were also measured. BMI and WC was recorded in all subjects; GFR, BP and immunosuppressants in KTx. Body measurements indicated the two groups were similar: 25% KTx and 24% CS had BMI >85th percentile. KTx were less physically active than CS in total exercise minutes (p = 0.005). CS reported higher HRQOL than KTx (p = 0.001). Higher perceptions of HRQOL were significantly correlated with higher number of steps/day in both groups (p = 0.034). KTx showed significantly lower perceptions of sports competence (p = 0.007) and physical conditioning (p = 0.001) than CS. Higher PAQ activity scores were significantly correlated with higher perceptions of body attractiveness (p = 0.019), Sport (p = 0.003) and Conditioning (p = 0.001). These results suggest that PA may play a role in overall well-being and HRQOL in KTx.     

The addition of rosiglitazone to insulin in adolescents with type 1 diabetes and poor glycaemic control: a randomized-controlled trial

Objective:  To evaluate the effect of rosiglitazone, an insulin sensitizer, on glycaemic control and insulin resistance in adolescents with type 1 diabetes mellitus (T1DM)
Research design and methods:  Randomized, double-blind, placebo-controlled crossover trial of rosiglitazone (4 mg twice daily) vs. placebo (24 wk each, with a 4 wk washout period). Entry criteria were diabetes duration >1 yr, age 10–18 yr, puberty (≥Tanner breast stage 2 or testicular volume >4 mL), insulin dose ≥1.1 units/kg/day, and haemoglobin A1c (HbA1c) >8%. Responses to rosiglitazone were compared with placebo using paired t -tests.
Results:  Of 36 adolescents recruited (17 males), 28 completed the trial. At baseline, age was 13.6 ± 1.8 yr, HbA1c 8.9 ± 0.96%, body mass index standard deviation scores (BMI-SDS) 0.94 ± 0.74 and insulin dose 1.5 ± 0.3 units/kg/day. Compared with placebo, rosiglitazone resulted in decreased insulin dose (5.8% decrease vs. 9.4% increase, p = 0.02), increased serum adiponectin (84.8% increase vs. 26.0% decrease, p < 0.01), increased cholesterol (+0.5 mmol/L vs. no change, p = 0.02), but no significant change in HbA1c (−0.3 vs. −0.1, p = 0.57) or BMI-SDS (0.08 vs. 0.04, p = 0.31). Insulin sensitivity was highly variable in the seven subjects who consented to euglycaemic hyperinsulinaemic clamps. There were no major adverse effects attributable to rosiglitazone.
Conclusion:  The addition of rosiglitazone to insulin did not improve HbA1c in this group of normal weight adolescents with T1DM.     

Increased serum IL-10/IL-12 ratio in wheezing infants

To investigate the association between various serum markers and atopic symptoms in the first year of life, and to evaluate the prognostic value of these markers for the development of wheezing and skin rash in the second year of life. Data of 86 children on the development of wheezing and skin rash in the first 2 years of life were collected prospectively, making use of parental completed questionnaires, weekly symptom cards, structured interview and physical examination. Serum markers (IL-10, IL-12, IL-13, eotaxin, sE-selectin, sICAM-1, sIL-2R) and total and specific IgE were determined at age 1. Children who developed wheezing in the first year of life had lower serum levels of IL-12 than children without symptoms (median 40.3 pg/ml vs. 49.0 pg/ml, p = 0.01) and a higher serum IL-10/IL-12 ratio (0.41 vs. 0.31, p = 0.001) at age 1. The IL-10/IL-12 ratio increased with an increasing number of wheezing episodes. Levels of sE-selectin in children with wheezing and in children with itchy skin rash in the first year of life were higher than in symptom free children (6.1 ng/ml and 5.9 ng/ml vs. 4.9 ng/ml, p = 0.01 and p = 0.03, respectively). Children who developed wheezing in the second year of life already had increased sICAM-1 levels at age 1. Children who developed wheezing in the first year of life showed a serum cytokine response that is skewed towards a T-helper 2 profile, with lower IL-12 levels and an increased IL-10/IL-12 ratio. Children who developed wheezing in the second year of life had elevated sICAM-1 levels at age 1. Follow-up of the children is needed to evaluate the prognostic value of various serum markers for the development of allergic disease in later childhood.     

Serum concentration of macrophage-derived chemokine may be a useful inflammatory marker for assessing severity of atopic dermatitis in infants and young children

Chemokines are responsible for the trafficking of leukocytes to sites of inflammation. Serum chemokine levels were previously shown to be increased in adult patients with atopic dermatitis (AD). We tested whether serum concentrations of chemokines, including macrophage-derived chemokine (MDC), thymus and activation-regulated chemokine (TARC), eotaxin (EOX), interferon gamma inducible protein 10 (IP-10) and monocyte chemotactic protein 1 (MCP-1), are useful inflammatory markers for assessing AD severity in infants and young children. To investigate this, we assessed the severity of AD clinically using the SCORing Atopic Dermatitis (SCORAD) index system. Serum chemokine concentrations were determined by sandwich enzyme immunoassay. Twenty AD patients with a median age of 2.1 years [interquartile range (IQR): 0.6–4.2] were recruited. Their SCORAD score was 23.5 (12.5–33.5). Serum concentrations of MDC, TARC, EOX, IP-10 and MCP-1 were 2551 (1978–3935), 1469 (1125–3070), 68 (57–85), 126 (101−226) and 518 (419–614) pg/ml, respectively. Serum MDC levels correlated with SCORAD (r = 0.608, p = 0.004) and its extent (r = 0.629, p = 0.003) and intensity (r = 0.557, p = 0.011) components. Serum TARC concentration showed weaker correlation with extent (r = 0.474, p = 0.035) and intensity (r = 0.465, p = 0.039) of skin involvement but not SCORAD. The median serum levels of MDC (3131 vs. 2394 pg/ml; p = 0.031) and EOX (80 vs. 61 pg/ml; p = 0.046) were also higher in children with moderate as compared with mild AD. The other chemokines did not correlate with AD severity. In conclusion, our results suggest that serum MDC concentration may be a useful inflammatory marker for assessing AD severity in infants and young children.     

Conversion from cyclosporin A to tacrolimus in pediatric liver transplantation

The dosing regimen for conversion from cyclosporin A (CsA) to tacrolimus immunosuppression was studied in 12 pediatric liver allograft recipients. Patients were stratified according to their age. Tacrolimus was started orally at a dosage of 0.05 mg/kg b.i.d., 12 h after stopping CsA administration and increased thereafter if needed. Tacrolimus and CsA concentrations were assayed by immunoassay using, respectively, an IMx and a TDx autoanalyzer (Abbott-France). Mean CsA concentration was in the therapeutic range 12 h prior to and at the time of introduction of tacrolimus. After 72 h of tacrolimus therapy, CsA concentrations were undetectable whereas mean tacrolimus concentration was 10.4 ng/mL with a mean dose of 0.09 mg/ kg b.i.d. The decline of CsA concentration was clearly biphasic. A slower decline in CsA concentration was detected after initiation of tacrolimus therapy, suggesting an inhibition of CsA metabolism by tacrolimus. No nephrotoxicity was observed. This dosage regimen allowed effective immunosuppression while avoiding additive nephrotoxicity.     

Safety and pharmacokinetics of daclizumab in pediatric renal transplant recipients

Abstract:  This study examined the safety and pharmacokinetics/pharmacodynamics of daclizumab in combination with mycophenolate mofetil (or azathioprine), corticosteroids, and cyclosporine or tacrolimus, in 61 pediatric renal allograft recipients in three age groups: less than or equal to five yr (n = 18), 6–12 yr (n = 18), and 13–17 yr (n = 25). The dosing regimen was daclizumab 1.0 mg/kg before transplantation, followed by four biweekly doses. The pharmacokinetics of daclizumab were described using NONMEM software. Median (range) estimated trough daclizumab levels achieved on day 56 (before dose 5) were 3.88 μg/mL (2.48–8.78), 4.54 μg/mL (1.79–18.7), and 4.94 μg/mL (0.05–10.6) in the less than or equal to five yr (n = 15), 6–12 yr (n = 17), and 13–17 yr (n = 22) age groups, respectively. Steady-state median (range) daclizumab exposures were 2040 mg · h/mL (1585–3778), 2757 mg · h/mL (1873–3494) and 3297 mg · h/mL (1705–6453), respectively. Saturation of the IL-2R occurred rapidly and was maintained for greater than or equal to three months after transplantation. Daclizumab was generally well-tolerated with no acute allergic or anaphylactic reactions, deaths or malignancies during the study. The proportion of patients who developed acute rejection at six and 12 months was 8.5% and 16.7%, respectively. This study shows that adding daclizumab at 1 mg/kg to standard immunosuppressive therapy provides safe and effective IL-2R blockade.     

Effect of Carelink, an internet-based insulin pump monitoring system, on glycemic control in rural and urban children with type 1 diabetes mellitus

Objective:  To determine whether use of the internet-based insulin pump monitoring system, Carelink, improved glycemic control in rural and urban children treated with insulin pump therapy.
Research design:  We reviewed records of 94 children treated with insulin pump therapy between the years 2004 and 2007 and compared glycemic control, diabetes self-care measures, frequency of clinic visits, and geographic location associated with Carelink use.
Results:  Carelink users showed improvement in hemoglobin A1c (HbA1c) levels [8.0 ± 0.1 (SE) vs. 7.7 ± 0.1 (SE), p = 0.002]. Carelink users uploaded pump and glucometer data 2.2 ± 1.8 (SD) times per month over 0.8 ± 0.4 (SD) yr. Patients who had no access to carelink software and were followed in a conventional manner showed no change in HbA1c levels [8.0 ± 0.2 (SE) vs. 8.1 ± 0.2 (SE), p = 0.17] during the study period. Carelink non-users, defined as patients who had Carelink access but did not use it, had a higher HbA1c level at the start of the study and did not change over the study period [8.9 ± 0.2 (SE) vs. 9.0 ± 0.3 (SE), p = 0.82]. Rural Carelink users showed improvement in HbA1c levels following Carelink use [7.9 ± 0.2 (SE) vs. 7.4 ± 0.2 (SE), p = 0.001], yet had significantly fewer clinic visits per year compared with urban patients [2.8 ± 0.2 (SE) vs. 3.5 ± 0.1 (SE), p = 0.001].
Conclusion:  Use of the Carelink system was associated with improved glycemic control in children with type 1 diabetes on insulin pump therapy.     

Double apheresis of peripheral blood stem cells in a single day in children mobilized by granulocyte colony-stimulating factor for transplantation

Abstract:  Due to the movement of hematopoietic stem cells through the bone marrow environment, it may be possible to effectively harvest peripheral blood stem cells in a second apheresis within a few hours after a first apheresis. In a retrospective analysis, 107 aphereses were performed in consecutive 33 pediatric and six healthy pediatric donors who received granulocyte-colony stimulating factor at 10 μg/kg/day or 400 μg/m²/day for five days. The median age and weight of cases were seven yr (range 1–19) and 20 kg (range 8–87). The toxicities related to apheresis procedure were minimal in both aphereses. In 22 double aphereses, the average number of CD34-positive cells per body weight (kg) collected was 5.3 ± 4.2 (range 0.6–16.6) and 4.7 ± 3.1 (range 0.2–10.9) × 10⁶ in the first and second aphereses, respectively (p = 0.569). Multivariate analysis showed that number of CD34-positive cells collected in the first apheresis (p = 0.008) was an independent factor of increased CD34-positive cells in the second apheresis. Double apheresis in a single day was feasible and this procedure may be able to lessen the burden of apheresis compared to two consecutive-day apheresis.     

Correlation of nitrites in breath condensates and lung function in asthmatic children

We aimed to evaluate the value of exhaled breath condensates in monitoring airway inflammation in childhood asthma before and after high altitude climate therapy.
Forty-eight asthmatic children on regular anti-asthma treatment with a normal FEV₁ and positive skin prick test for house dust mites were recruited. All children had been referred to an alpine clinic for high altitude climate therapy, because of persistent asthmatic symptoms despite use of daily anti-inflammatory treatment. Subjects were assessed on their arrival and before departure from the alpine clinic. Spirometry, bronchial provocation tests and measurements of nitrites in breath condensates were performed.
Median levels of nitrites were significantly higher before than after high altitude climate therapy (1.27 vs. 0.93 μ m ; p = 0.008). In addition, MEF₅₀ improved significantly (p < 0.0005). There was a significant correlation between nitrites in breath condensates and MEF₅₀ (r = −0.63, p < 0.0001), symptoms (r = 0.47, p = 0.0007) and airway hyper-reactivity (AHR) (r = −0.41, p = 0.004).
In summary, we found a reduction in nitrites in breath condensates after a high altitude climate therapy. Significant correlations were found between nitrites and MEF₅₀, AHR and symptoms. We conclude that the measurement of nitrites may be feasible to objectively assess airway inflammation in asthmatic children in order to detect ongoing inflammation in children with normal FEV₁ but persistent symptoms.