Inferior Outcomes on the Waiting List in Low-Volume Pediatric Heart Transplant Centers.

Low case volume has been associated with poor outcomes in a wide spectrum of procedures. Our objective was to study the association of low case volume and worse outcomes in pediatric heart transplant centers, taking the novel approach of including waitlist outcomes in the analysis. We studied a cohort of 6482 candidates listed in the Organ Procurement and Transplantation Network for pediatric heart transplantation between 2002 and 2014; 4665 (72%) of the candidates underwent transplantation. Candidates were divided into groups according to the average annual transplantation volume of the listing center during the study period: more than 10, six to 10, three to five, or fewer than three transplantations. We used multivariate Cox regression analysis to identify independent risk factors for waitlist and posttransplantation mortality. Of the 6482 candidates, 24% were listed in low-volume centers (fewer than three annual transplantations). Of these listed candidates in low-volume centers, only 36% received a transplant versus 89% in high-volume centers (more than 10 annual transplantations) (p < 0.001). Listing at a low-volume center was the most significant risk factor for waitlist death (hazard ratio [HR] 4.5, 95% confidence interval [CI] 3.5-5.7 in multivariate Cox regression and HR 5.6, CI 4.4-7.3 in multivariate competing risk regression) and was significant for posttransplantation death (HR 1.27, 95% CI 1.0-1.6 in multivariate Cox regression). During the study period, one-fourth of pediatric transplant candidates were listed in low-volume transplant centers. These children had a limited transplantation rate and a much greater risk of dying while on the waitlist.

Advancing the field: the design of the Archstone Foundation Elder Abuse and Neglect Initiative.

The Archstone Foundation is a private grantmaking organization whose mission is to contribute toward the preparation of society in meeting the needs of an aging population. In 2006, the Archstone Foundation launched a 5-year $8 million Elder Abuse and Neglect Initiative (Initiative) with the goal of improving the quality and coordination of elder abuse and neglect services in the state of California. Lessons learned through the Initiative may serve to inform the field of elder abuse and the larger philanthropic community.

Vision for 2020.

This article reflects the collective thoughts of the 20 projects supported by the Archstone Foundation Elder Abuse and Neglect Initiative on offering a vision for improving the response system for elder abuse and, in turn, the lives of older adults between now and the year 2020. Five key areas were identified as critically important for advancing the field in the next ten years: (a) increased public awareness and shifting public attitudes, (b) improved identification and triage of cases, (c) increased integrated service models, (d) improved justice system response, and (e) leveraging and utilizing emerging and untapped resources. The lessons learned from the experiences of these 20 projects in California can serve as demonstration models for other communities to adopt, adapt, and improve response systems for elder abuse and neglect.

Kidney and pancreas transplantation in the United States, 1999-2008: the changing face of living donation.

The waiting list for kidney transplantation continued to grow between 1999 and 2008, from 41 177 to 76 089 candidates. However, active candidates represented the minority of this increase (36 951-50 624, a 37% change), while inactive candidates increased over 500% (4226-25 465). There were 5966 living donor (LD) and 10 551 deceased donor (DD) kidney transplants performed in 2008. The total number of pancreas transplants peaked at 1484 in 2004 and has declined to 1273. Although the number of LD transplants increased by 26% from 1999 to 2008, the total number peaked in 2004 at 6647 before declining 10% by 2008. The rate of LD transplantation continues to vary significantly as a function of demographic and geographic factors, including waiting time for DD transplant. Posttransplant survival remains excellent, and there appears to be greater use of induction agents and reduced use of corticosteroids in LD recipients. Significant changes occurred in the pediatric population, with a dramatic reduction in the use of LD organs after passage of the Share 35 rule. Many strategies have been adopted to reverse the decline in LD transplant rates for all age groups, including expansion of kidney paired donation, adoption of laparoscopic donor nephrectomy and use of incompatible LD.

Osterix enhances BMSC-associated osseointegration of implants.

Cellular and molecular events in osseointegration at the dental implant surface remain largely unknown. We hypothesized that bone marrow stromal cells (BMSCs) participate in this process, and that osterix (Osx) promotes implant osseointegration. To prove this hypothesis, we tracked double-labeled BMSCs in implantation sites created in nude mice transplanted with these cells. We also inserted implants into the femurs of our established transgenic mice after local administration of viruses encoding Osx, to determine the osteogenic effects of Osx. Immunohistochemical results demonstrated that BMSCs can recruit from peripheral circulation and participate in wound healing and osseointegration after implantation. Microcomputed tomography (microCT) analysis revealed an increased bone density at the bone-to-implant interface in the Osx group, and histomorphometric analysis indicated an elevated level of bone-to-implant contact in the Osx group. We concluded that exogenous BMSCs participate in the osseointegration after implantation, and that Osx overexpression accelerates osseointegration.

Dredged Illinois River sediments: plant growth and metal uptake.

Sedimentation of the Illinois River in central Illinois has greatly diminished the utility and ecological value of the Peoria Lakes reach of the river. Consequently, a large dredging project has been proposed to improve its wildlife habitat and recreation potential, but disposal of the dredged sediment presents a challenge. Land placement is an attractive option. Previous work in Illinois has demonstrated that sediments are potentially capable of supporting agronomic crops due to their high natural fertility and water holding capacity. However, Illinois River sediments have elevated levels of heavy metals, which may be important if they are used as garden or agricultural soil. A greenhouse experiment was conducted to determine if these sediments could serve as a plant growth medium. A secondary objective was to determine if plants grown on sediments accumulated significant heavy metal concentrations. Our results indicated that lettuce (Lactuca sativa L.), barley (Hordeum vulgare L.), radish (Raphanus sativus L.), tomato (Lycopersicon lycopersicum L.), and snap bean (Phaseolus vulagaris L. var. humillis) grown in sediment and a reference topsoil did not show significant or consistent differences in germination or yields. In addition, there was not a consistent statistically significant difference in metal content among tomatoes grown in sediments, topsoil, or grown locally in gardens. In the other plants grown on sediments, while Cd and Cu in all cases and As in lettuce and snap bean were elevated, levels were below those considered excessive. Results indicate that properly managed, these relatively uncontaminated calcareous sediments can make productive soils and that metal uptake of plants grown in these sediments is generally not a concern.

Glomerular filtration rate in children with solid tumors: normative values and a new method for estimation.

Many chemotherapy regimens used in children are nephrotoxic. Accurate dosing of these medications requires that some estimation of glomerular filtration rate (GFR) be performed prior to initiating chemotherapy. However, few studies evaluating normal GFR in children exist. The authors report normal values for GFR for children with nonhematogenous malignancies using a highly accurate method of directly measuring GFR and an equation for estimating absolute GFR in these children. Children with nonhematogenous malignancies with no evidence of renal involvement or prior use of nephrotoxic agents had their GFR measured using an iothalamate infusion methodology. A total of 111 children (males and females) with a mean age = 7.95 years (range 2.8 months-19.5 years) were included in the study. GFR adjusted for body surface area (mL/min/1.73 m(2)) increases in the first 2 years of life and then plateaus at a level comparable to adult values. GFR adjusted for body surface area for males >2 years = 131.3 +/- 22.5, females = 126.8 +/- 24.4 mL/min/1.73 m(2) (p value not significant). Absolute GFR in mL/min can be easily estimated by a simple formula (r(2) =.97) based on the child's weight and serum creatinine: GFR (mL/min) = k sqrt[ ( (agemos+ 6)* wt) / Cr serum ] where agemos is age in months, wt is weight in kg, and k = 1.05 for males and 0.95 for females. The accurate measurement of GFR remains vitally important in the safe and effective treatment of pediatric solid tumors. This study provides a set of normal GFR values for these children and an equation for easy estimate of absolute GFR.

Successful use of Tesio catheters in pediatric patients receiving chronic hemodialysis.

Semipermanent venous catheters remain the most commonly used access for chronic hemodialysis (HD) in pediatric patients. The recent availability of Tesio catheters in 7 and 10 F has expanded available HD catheter options for children and adolescents. We report our experience with Tesio catheter survival, complications, and effect on dialysis adequacy in comparison to standard dual-lumen (DL) catheters in our pediatric HD patients. Demographic data were similar between the two groups. Overall actuarial survival was significantly longer for Tesio versus DL catheters (46% versus 0% at 1 year; P = 0.003). A comparison of smaller catheters (7 F Tesio catheter, 8 or 10 F DL catheter) showed that smaller Tesio catheters had a significantly longer survival (median survival, 244 versus 13 catheter-days; P < 0.01). Tesio 10 F catheters also survived significantly longer than the larger 11.5 and 12 F DL catheters (P < 0.02). Catheter sepsis occurred less frequently with Tesio catheters (one episode/20 catheter-months) than DL catheters (one episode/5 catheter-months) despite the longer duration of Tesio catheters. Adequate dialysis (single-pool Kt/V > 1.2) was delivered with the same frequency, but for a longer duration with Tesio catheters (76% +/- 32% over 100 monthly measurements versus DL catheter, 57% +/- 45% over 54 monthly measurements). Our clinical practice was to replace cuffed catheters when adequate dialysis could not be delivered. We conclude that Tesio catheters provide superior performance compared with DL catheters in terms of catheter survival, infection rates, and duration of adequate performance.

Long-term treatment of focal segmental glomerulosclerosis in children with cyclosporine given as a single daily dose.

Cyclosporine (CsA) has been successfully used for treatment of children with focal segmental glomerulosclerosis (FSGS) and nephrotic syndrome (NS) for the last decade. Response rates of 50% to 100% have been reported using twice-daily dosing of 5 to 32 mg/kg/d, achieving trough blood levels of 70 to 500 ng/mL. Treatment has been associated with a high incidence of side effects, including nephrotoxicity, hypertension, gingival hyperplasia, and hirsutism. To determine whether once-daily low-dose CsA could minimize side effects and still induce remission, 21 children with biopsy-proven FSGS and NS, each treated with CsA, 4.6 +/- 0.8 mg/kg/d, with no predetermined target trough blood levels, were studied. Eleven of 21 children (52%) attained complete remission and 5 of 21 children (24%) attained partial remission, for a total response rate of 76%. Mean time to response was 2.8 +/- 0.8 months, and mean duration of therapy was 20.6 +/- 13.7 months. CsA dosage was tapered or stopped in 9 responders; 3 of these patients maintained remission at last follow-up 6 to 13 months later, and 6 patients relapsed at 1.5 to 18.7 months (mean, 8.7 months). Five of these 6 patients responded again when CsA therapy was restarted or the dosage was increased. Twelve of 16 responders were still being administered CsA at last follow-up 11 to 60 months (mean, 24.6 months) later. Five of 21 patients (24%) had no response to CsA during 2 to 27 months of therapy; 4 of these 5 patients developed end-stage renal disease after CsA therapy was stopped. Side effects of CsA therapy were minimal: 1 patient each developed new-onset hypertension or gingival hyperplasia, and no patient had hirsutism or nephrotoxicity. Single daily low-dose CsA appears to be effective for long-term treatment of children with FSGS and NS, with fewer side effects than twice-daily dosing.

Outcome in children receiving continuous venovenous hemofiltration.

OBJECTIVE: Continuous venovenous hemofiltration (CVVH) alone or with dialysis (D) has become an important supportive therapy for critically ill children with acute renal failure. Previous reports of pediatric patient outcome either mix CVVH/D with other renal replacement modalities or do not examine severity of illness. The current study examines only outcomes of children receiving CVVH/D using Pediatric Risk of Mortality (PRISM) scores to control for severity of illness. PATIENTS: Twenty-one patients (mean age: 8.8 +/- 6.3 years; mean weight: 28.3 +/- 20.8 kg) received 22 courses of CVVH/D. OUTCOMES: Nine (42.8%) of 21 patients survived. Nine (75%) of 12 deaths occurred within 25 days of pediatric intensive care unit (PICU) admission. Mean PRISM score at PICU admission and CVVH initiation were 13.1 +/- 5.8 and 15.4 +/- 8.9, respectively. Mean patient weight, age, PRISM score at PICU admission and at CVVH/D initiation, maximum pressor number, estimated glomerular filtration rate at CVVH/D initiation and change in mean airway pressure did not differ between survivors and nonsurvivors. The degree of fluid overload at CVVH/D initiation was significantly lower in survivors (16.4% +/- 13.8%) compared with nonsurvivors (34.0% +/- 21.0%), even when controlled for severity of illness by PRISM score. Mean cost of providing CVVH/D accounted for only 1% of total PICU cost per patient. CONCLUSIONS: The pattern of early multiorgan system failure and death, minimal relative cost of CVVH/D provision, and potential for improved outcome with initiation of CVVH/D at lesser degrees of fluid overload are factors that may support early initiation of CVVH/D in critically ill children with acute renal failure.

Chronic endothelin-1 blockade reduces sympathetic nerve activity in rabbits with heart failure.

Endothelin-1 (ET-1) is elevated in chronic heart failure (CHF). In this study, we determined the effects of chronic ET-1 blockade on renal sympathetic nerve activity (RSNA) in conscious rabbits with pacing-induced CHF. Rabbits were chronically paced at 320--340 beats/min for 3--4 wk until clinical and hemodynamic signs of CHF were present. Resting RSNA and arterial baroreflex control of RSNA were determined. Responses were determined before and after the ET-1 antagonist L-754,142 (a combined ET(A) and ET(B) receptor antagonist, n = 5) was administered by osmotic minipump infusion (0.5 mg. kg(-1) x h(-1) for 48 h). In addition, five rabbits with CHF were treated with the specific ET(A) receptor antagonist BQ-123. Baseline RSNA (expressed as a percentage of the maximum nerve activity during sodium nitroprusside infusion) was significantly higher (58.3 +/- 4.9 vs. 27.0 +/- 1.0, P < 0.001), whereas baroreflex sensitivity was significantly lower in rabbits with CHF compared with control (3.09 +/- 0.19 vs. 6.04 +/- 0.73, P < 0.001). L-754,142 caused a time-dependent reduction in arterial pressure and RSNA in rabbits with CHF. In addition, BQ-123 caused a reduction in resting RSNA. For both compounds, RSNA returned to near control levels 24 h after removal of the minipump. These data suggest that ET-1 contributes to sympathoexcitation in the CHF state. Enhancement of arterial baroreflex sensitivity may further contribute to sympathoinhibition after ET-1 blockade in heart failure.

Non-invasive intravascular monitoring in the pediatric hemodialysis population.

Assessment of dry weight in pediatric hemodialysis (HD) patients is difficult, since small fluid shifts may result in dialysis-associated morbidity (DAM) and children may not verbalize complaints. Achieving dry weight is critical since chronic fluid overload can result in hypertension and left ventricular hypertrophy. To determine if non-invasive monitoring of hematocrit (NIVM) is useful in preventing DAM in pediatric HD patients, we reviewed 200 HD treatments performed with or without NIVM (no NIVM). DAM was defined as an "event" (e.g., hypotension, headache, cramping) that required nursing intervention. Patient age, weight, and gender were similar in both groups. Desired ultrafiltration was obtained in both groups. The event rate was lower in NIVM than no NIVM for all treatments (0.22 vs. 0.3, P = 0.07) and significantly lower in patients < 35 kg (0.25 vs. 0.47, P = 0.01). The second event rate (fraction of treatments with one event that had a subsequent event occurring at least 15 min later) was lower with NIVM (P < 0.01). For the NIVM group, events in the first 90 min occurred when blood volume changed > 8% per hour; 71% of events (43/60) at 90-240 min occurred when blood volume changed > 4% per hour. NIVM decreases DAM in pediatric HD patients, especially those < 35 kg. Ultrafiltration with blood volume change < 8% per hour is safe in the 1st h and < 4% after 1 h reduces DAM in children.

A survey of pediatric nephrologists on adolescent sexual health.

Chronic renal disease often has an adverse effect on adolescent physiologic and psychosocial development. The severity of the disease may necessitate that the pediatric nephrologist be the adolescent's main medical provider and the most available physician to screen for adolescent health risk behaviors. The purpose of this study was to determine pediatric nephrologists' practices of sexual history taking and diagnosis and treatment of sexually transmitted infections in their adolescent patients. A survey was performed on a convenience sample of 66 pediatric nephrologists attending an educational seminar on adolescent care at the 1997 national meeting of the American Society of Pediatric Nephrology. The outcome measures included physicians' reports of interviewing adolescents alone and screening for sexually transmitted infections. Fifty-six percent reported interviewing adolescents alone, 55% routinely ask female adolescents about sexual intercourse (53% ask males) and 10% routinely perform pelvic exams. Current practice in this selected sample of pediatric nephrologists, who by their attendance at the seminar may represent those most motivated to do screening, still leaves adolescents with chronic renal disease potentially at risk for sexually transmitted infections and pregnancy. Educational efforts should be directed at increasing routine confidential sexual history taking for adolescents with chronic renal disease.

Vascular C3 deposits on renal biopsy in pediatric patients with hematuria.

Isolated deposition of the third component of complement (C3) in the renal arterioles has been noted on biopsy specimens in patients with hematuria. This entity is of little known significance and reports of this finding in pediatric patients with hematuria are rare. We reviewed the clinical histories and biopsies of 17 children with hematuria and vascular C3 deposition on biopsy at Texas Children's Hospital over an 14-year period. The mean age of presentation was 10.8 (range 4.5-16.6) years with a male preponderance (71%). Family history for hematuria was positive in 6 of 17 patients (35%). Light microscopy was normal or showed only minor abnormalities. Immunofluorescence was negative for IgA and IgG in all patients. Seven patients (41.1%) were noted to have diffuse or focally thin basement membranes on electron microscopy in addition to positive C3 immunofluorescence. The mean follow-up time was 23.8 months, during which 2 of 17 patients (12%) developed worsening proteinuria. The etiopathogenesis of this condition remains unclear, but an underlying immunological process cannot be ruled out. It is possible that this condition represents a stage of an acute glomerulonephritis. Clinical follow-up of these patients is warranted, as the long-term prognosis remains unclear.

Logarithmic extrapolation of a 15-minute postdialysis BUN to predict equilibrated BUN and calculate double-pool Kt/V in the pediatric hemodialysis population.

Blood urea nitrogen (BUN) concentration rebounds logarithmically for 1 hour after a hemodialysis treatment. We have previously devised and evaluated an equilibrated Kt/V (eqKt/V) estimation method using logarithmic extrapolation of the BUN increase from 30 seconds to 15 minutes postdialysis in six pediatric hemodialysis patients. The current study evaluates logarithmic extrapolation in 15 additional pediatric patients. Mean measured equilibrated BUN (eqBUN) and estimated BUN at equilibrium (estBUN) using logarithmic extrapolation were 23.1 +/- 9.2 and 23.0 +/- 9.4 mg/dL, respectively. The mean absolute difference between estBUN and eqBUN was 0.7 +/- 0. 4 mg/dL (range, 0.1 to 1.55 mg/dL). All treatments had an absolute difference less than the SD of the laboratory measurement itself. The mean absolute percentage of difference between eqKt/V using eqBUN and estimated double-pool equilibrated Kt/V (estKt/V) using estBUN from logarithmic extrapolation was 3.4% +/- 2.3% and did not vary as a function of patient size, urea generation rate, dialyzer urea clearance, Kd/V, or ultrafiltration fraction. Mean absolute percentages of difference between eqKt/V and Kt/V estimated by the Tattersall, Daugirdas, or Maduell formulas were 4.5% +/- 3.9%, 4.4% +/- 3.7%, and 6.7% +/- 8.3%, respectively. Total percentages of error (absolute mean percentage of error + 2 SD) between eqKt/V and estKt/V by logarithmic extrapolation or the Tattersall, Daugirdas, or Maduell formulas were 8.0%, 12.3%, 11.8%, and 22.3%, respectively. The greater accuracy of logarithmic extrapolation compared with other methods of double-pool Kt/V estimation held true for patients weighing less than 35 kg. We have validated the use of an easy and accurate method requiring only an additional 15-minute posttreatment BUN level to estimate double-pool Kt/V in children.

Acyclovir prophylaxis of varicella in children with renal disease receiving steroids.

Varicella, or chickenpox, is very communicable and has been shown to be transmitted to nearly 90% of household contacts. Severe varicella infections with fatal complications have been noted in children receiving corticosteroids despite the administration of varicella-zoster immune globulin (VZIG). The use of post-exposure acyclovir prophylaxis in immunocompetent children exposed to a household contact with varicella has been shown to decrease the transmission rate of varicella significantly. We studied the safety and efficacy of acyclovir prophylaxis as an adjunctive preventive measure in 8 children (10 separate exposures) receiving corticosteroids for renal disease. Four children (6 separate exposures) served as controls. No adverse reactions were reported with the acyclovir prophylaxis. The maximum change between pre- and study serum creatinine levels was 0.1 mg/dl. None of the 8 patients who received acyclovir prophylaxis developed chickenpox. One of these 8 patients developed humoral immunity to varicella despite the absence of clinical infection. One of 4 patients who received VZIG prophylaxis alone developed chickenpox. These data support the use of acyclovir prophylaxis as an adjunctive measure to VZIG for the prevention of potentially serious varicella infection in children receiving steroids.