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Background: Secondary hyperparathyroidism is a common complication in children receiving hemodialysis. Active vitamin D is an effective therapy, but its use is often limited by hypercalcemia and increased calcium x phosphorus (Ca x P) product. Paricalcitol, a selective vitamin D receptor activator, causes less sustained hypercalcemia and increase in Ca x P product than calcitriol and has been used effectively in adult hemodialysis patients., Study Design: Double blind, placebo-controlled., Setting & Participants: Hemodialysis units and pediatric subjects receiving hemodialysis., Intervention: After a washout period of 2 to 6 weeks, 29 subjects aged 5 to 19 years received either paricalcitol or placebo for up to 12 weeks (0.04 mug/kg if initial intact parathyroid hormone [iPTH] level < 500 pg/mL [ng/L]; 0.08 mug/kg if initial iPTH level > 500 pg/mL [ng/L]). The dose was increased by 0.04 mug/kg every 2 weeks until there was a 30% decrease in iPTH level from baseline or calcium level greater than 11 mg/dL (>2.74 mmol/L) or Ca x P product greater than 75 mg(2)/dL(2) (>6.04 mmol(2)/L(2))., Outcomes & Measurements: Two consecutive 30% decreases from baseline in iPTH levels and safety of paricalcitol, including hypercalcemia and increase in Ca x P product., Results: 60% of the paricalcitol group had 2 consecutive 30% decreases from baseline iPTH levels compared with 21% in the placebo group (P = 0.06). The paricalcitol group had a mean decrease in iPTH level of 164 pg/mL (ng/L), whereas the placebo group had a mean increase of 238 pg/mL (ng/L; P = 0.03). There was no difference from baseline to final visit in calcium, phosphorus, or Ca x P product values in either group., Limitations: Low power to detect differences in safety between groups and a short-term study., Conclusion: Paricalcitol decreased iPTH levels in children receiving hemodialysis with no significant changes in serum calcium, phosphorus, or Ca x P product values during the course of the study.

A classification system has been proposed to standardize the definition of acute kidney injury in adults. These criteria of risk, injury, failure, loss, and end-stage renal disease were given the acronym of RIFLE. We have modified the criteria based on 150 critically ill pediatric RIFLE (pRIFLE) patients to assess acute kidney injury incidence and course along with renal and/or non-renal comorbidities. Of these children, 11 required dialysis and 24 died. Patients without acute kidney injury in the first week of intensive care admission were less likely to subsequently develop renal Injury or Failure; however, 82% of acute kidney injury occurred in this initial week. Within this group of 123 children, 60 reached pRIFLEmax for Risk, 32 reached Injury, and 31 reached Failure. Acute kidney injury during admission was an independent predictor of intensive care; hospital length of stay and an increased risk of death independent of the Pediatric Risk of Mortality (PRISM II) score (odds ratio 3.0). Our results show that a majority of critically ill children develop acute kidney injury by pRIFLE criteria and do so early in the course of intensive care. Acute kidney injury is associated with mortality and may lead to increased hospital costs. We suggest that the pRIFLE criteria serves to characterize the pattern of acute kidney injury in critically ill children.

Hemodialysis remains the only life sustaining maintenance renal replacement therapy option for children who cannot undergo expeditious renal transplantation or who are not medical candidates for peritoneal dialysis. Provision of maintenance hemodialysis to small children entails many challenges, which arise from the limited choices for appropriately sized disposable dialysis treatment components. The dialysis extracorporeal circuit volume, comprised of the blood tubing and dialyzer, should be low enough to prevent hypotension and prevent the need for repeated blood transfusions. We performed a market acceptance evaluation of the Polyflux 6H dialyzer (0.6 m2 membrane surface area; Gambro Renal Products, Lakewood, Colorado) in six pediatric patients (3 male, 3 female, mean weight 24.4+6.5 kg, mean age 10.3+3.8 yrs). We found that the Polyflux 6H Dialyzer provided a trend for improved clearance compared to Fresenius F3 and F4 dialyzers. We found that the Polyflux 6H Dialyzer provided adequate clearance for children up to 24 kg in size and is a suitable dialyzer choice for patients 13 to 26 kg in size.

Accurate dry weight assessment is difficult in pediatric hemodialysis patients but is essential to prevent chronic fluid overload, hypertension, and cardiovascular morbidity. A noninvasive monitoring (NIVM) of hematocrit-guided ultrafiltration algorithm was studied prospectively in 20 pediatric hemodialysis patients. The algorithm targeted the first 50% of total goal ultrafiltration to be removed during the first hour of dialysis with a maximum blood volume change of 8 to 12% per hour. The second 50% was removed during the remaining treatment time with a maximum blood volume change of 5% per hour. Data that were collected at baseline and 6 mo included weight, BP, number of antihypertensive medications, 24-h ambulatory BP monitoring (ABPM), echocardiogram, and ultrafiltration-associated symptoms. Sixteen of 20 enrolled patients completed the study. No difference was seen between baseline and 6-mo weight, predialysis casual BP, nighttime ABPM, or left ventricular mass index. There was a decrease in postdialysis casual systolic BP, daytime ABPM, number of antihypertensive medications prescribed, and rate of intradialytic events related to ultrafiltration (all P < or = 0.05). Adoption of a standardized NIVM-guided algorithm led to (1) improved ABPM profiles, (2) decreased antihypertensive medication burden, and (3) decreased ultrafiltration-associated symptoms. Wider use of NIVM-guided ultrafiltration may decrease cardiovascular morbidity in pediatric hemodialysis patients.

We conducted a retrospective review of the North American Renal Transplant Cooperative Study (NAPRTCS) Registry transplant and dialysis arms to assess anemia and growth patterns in children who returned to dialysis after a failed renal transplant from January 1, 1992 to February 3, 2004. Of the 1807 potential study subjects, 1451 had transplant removal data (TxIn vs. TxOut) available for analysis. Four hundred and twenty-one of 1451 patients (29%) had a transplant nephrectomy at the time of entry into the NAPRTCS Registry Dialysis arm. Anemia rates steadily decreased from 72.2% at 30 days after dialysis initiation to 59.5% at 12 months after dialysis initiation. Factors associated with anemia at 30 days after dialysis initiation included hemodialysis, lack of Epo use, and patients who comprised earlier study era cohorts. At one yr after return to dialysis, earlier study cohort era was the only factor associated with anemia status. Patients did not demonstrate significant improvement in height SDS over the course of the study (-2.17 at day 30 to -2.32 at 24 months). The high anemia, poor growth, and low recombinant human growth hormone utilization rates in a group of patients followed longitudinally as they transition from renal transplant to dialysis should cause the pediatric nephrology community to reassess the processes in place to provide optimal care to pediatric end-stage renal disease patients.

Introduction: Serum creatinine is a late marker of acute kidney injury (AKI). Urine neutrophil gelatinase-associated lipocalin (uNGAL) is an early marker of AKI, where the timing of kidney injury is known. It is unknown whether uNGAL predicts AKI in the general critical care setting. We assessed the ability of uNGAL to predict AKI development and severity in critically ill children., Methods: This was a prospective cohort study of critically ill children. Children aged between 1 month and 21 years who were mechanically ventilated and had a bladder catheter inserted were eligible. Patients with end-stage renal disease or who had just undergone kidney transplantation were excluded. Patients were enrolled within 24 to 48 hours of initiation of mechanical ventilation. Clinical data and serum creatinine were collected daily for up to 14 days from enrollment, and urine was collected once daily for up to 4 days for uNGAL measurement. AKI was graded using pRIFLE (pediatric modified Risk, Injury, Failure, Loss, End Stage Kidney Disease) criteria. Day 0 was defined as the day on which the AKI initially occurred, and pRIFLEmax was defined as the worst pRIFLE AKI grade recorded during the study period. The chi2 test was used to compare associations between categorical variables. Mann-Whitney and Kruskal-Wallis tests were used to compare continuous variables between groups. Diagnostic characteristics were evaluated by calculating sensitivity and specificity, and constructing receiver operating characteristic curves., Results: A total of 140 patients (54% boys, mean +/- standard deviation Pediatric Risk of Mortality II score 15.0 +/- 8.0, 23% sepsis) were included. Mean and peak uNGAL concentrations increased with worsening pRIFLEmax status (P < 0.05). uNGAL concentrations rose (at least sixfold higher than in controls) in AKI, 2 days before and after a 50% or greater rise in serum creatinine, without change in control uNGAL. The parameter uNGAL was a good diagnostic marker for AKI development (area under the receiver operating characteristic curve [AUC] 0.78, 95% confidence interval [CI] 0.62 to 0.95) and persistent AKI for 48 hours or longer (AUC 0.79, 95% CI 0.61 to 0.98), but not for AKI severity, when it was recorded after a rise in serum creatinine had occurred (AUC 0.63, 95% CI 0.44 to 0.82)., Conclusion: We found uNGAL to be a useful early AKI marker that predicted development of severe AKI in a heterogeneous group of patients with unknown timing of kidney injury.

The accurate diagnosis of acute kidney injury (AKI) is especially problematic in critically ill patients in whom renal function is in an unsteady state, rendering creatinine-based baseline assessment measures of renal function potentially inadequate. Herrero-Morin and colleagues performed a cross-sectional analysis of the ability of cystatin C and beta2 microglobulin to reflect creatinine clearance in pediatric patients with AKI. The aim of this commentary is to review the current state of AKI clinical and translational research in the light of the results presented in that study.

Currently available extracorporeal circuits in the US often require blood priming to prevent hypotension/anemia in smaller pediatric patients. The PRISMA M10 circuit, available in other countries has not received extensive study and has not been cleared for use in the US. We performed an FDA mandated study of the M10 circuit in the US for use in critically ill pediatric patients with acute kidney injury <15 kg in size. FDA guidelines allowed for maximal blood pump flow of 20 ml/min. Fifteen pts (9 M, 6 F, mean size 5.8+/-2.8 kg, range 2.6-12.5 kg, age 4 d - 13 mo, mean creatinine =1.2+/-0.7 mg/dL) were studied at 4 ppCRRT centers. Sixty-one filters (range 1-4 circuits per pt) were used (mean circuit life 28.6+/-22.5 h, range 1 to 74.5 h, 55%>24 h). No blood leaks occurred. All circuits achieved Qb 20 ml/min. Forty-two out of 61 filters clotted and mean circuit life was lower for these filters than those changed for other reasons (23+/-17 vs. 41+/-28 h, <0.005). Circuits using larger access demonstrated significantly longer survival. We conclude that the M10 filter can serve well for CRRT in small pediatric patients. Further study is needed to determine in higher blood flow rates would decrease clotting rates and increase filter life span and ultrafiltration rates.

Dialysis provides effective and safe treatment of ESRD in children, but patients who are maintained on chronic dialysis are at risk for cardiovascular disease. One major risk factor for cardiovascular disease in adult patients with ESRD is chronic inflammation. The effect of anti-inflammatory therapy with aspirin on serum cytokine concentration was studied in seven children who were receiving hemodialysis (HD) and seven who were receiving continuous cycling peritoneal dialysis (CCPD or PD). Dialysis vintage was 4.3 +/- 4.6 yr; single-pool Kt/V was 1.46 +/- 1.4, mean equilibrated Kt/V was 1.27 +/- 0.16, and PD weekly Kt/V was 2.45 +/- 0.30. Baseline proinflammatory cytokine IL-1beta, IL-6, IL-8, and TNF-alpha serum concentrations were significantly elevated, whereas serum anti-inflammatory cytokine IL-4 and IL-10 concentrations were normal. The patterns of cytokine elevation were similar for patients who were receiving HD versus PD. IL-4 and IL-6 concentrations demonstrated strong positive correlation with dialysis vintage (IL-4, P < 0.03; IL-6, P < 0.0001). Pre-aspirin serum cytokine concentrations did not vary with single-pool Kt/V or equilibrated Kt/V for HD patients or with weekly Kt/V for PD patients. Serum IL-8 and TNF-alpha concentrations were significantly reduced by aspirin treatment at 4 mo (P = 0.04 and P = 0.007, respectively). Serum IL-6 concentration decreased with aspirin treatment but not significantly (P = 0.1). Serum IL-1beta concentration remained unchanged, and IL-4 and IL-10 concentrations remained stable throughout aspirin treatment. The effect of aspirin treatment on serum cytokine concentrations was similar for HD and PD patients. In HD patients, IL-6, IL-8, and TNF-alpha remained suppressed 1 mo after discontinuation of aspirin. It is concluded that proinflammatory cytokines are elevated in pediatric HD and PD patients without counterbalance from anti-inflammatory cytokines, and aspirin therapy attenuates inflammation.

Current formulas that estimate the delivered dose of hemodialysis rely upon pre- and post-treatment blood urea nitrogen (BUN) concentrations for calculation. Single-pool kinetic modeling (spKt/V) uses a convenient 30-s post-dialysis BUN sample but does not take urea rebound into account. Double-pool modeling (eKt/V) uses an equilibrated BUN (eqBUN) and is the best reflection of the true urea mass removed by hemodialysis but is inconvenient for patients and costly to the dialysis unit to wait to obtain an eqBUN sample. We compared simple spKt/V and eKt/V estimation formulas using data obtained from the Centers for Medicare & Medicaid Services (CMS) End Stage Renal Disease (ESRD) Clinical Performance Measures (CPM) Project to determine how frequently these two results would lead to different prescription management. We set an expected difference Kt/V (spKt/V-eKt/V) of 0.20 based on results of the Hemodialysis (HEMO) Study; 1,513 paired spKt/V and estimated eKt/V results were available for comparison. For patients with an arteriovenous fistula (AVF) or arteriovenous graft (AVG) (n=720), mean spKt/V and estimated eKt/V were 1.62+/-0.30 and 1.37+/-0.26, respectively. For patients with a catheter (n=793), mean spKt/V and estimated eKt/V were 1.53+/-0.32 and 1.33+/-0.29, respectively. Examination of the different spKt/V and estimated eKt/V pairings revealed a greater adequacy discordance rate between a 0.20 difference in spKt/V and estimated eKt/V at higher Kt/V values, but Kt/V discordance rates only varied from 0.3 to 5.5% depending on the paired Kt/V values used.

As part of creating a pediatric ESRD-specific Health-Related Quality of Life (HRQOL) assessment instrument, we established pilot data with the PedsQL 4.0 Generic Core Scales in 96 pediatric patients with ESRD receiving hemodialysis (HD), peritoneal dialysis (PD) or with a renal transplant (TX). Patient age ranges were: 2-4 (8; PD n=3, TX n=5), 5-7 (12; HD n=9, TX n=3), 8-12 (25; HD n=5, PD n=6, TX n=14), 13-18 (51; HD n=18, PD n=10, TX n=23). PedsQL ESRD data were compared to healthy children (n=131 child report; n=145 parent report) and across HD/PD/TX. For all domains, ESRD patient HRQOL scores were significantly lower than healthy controls. Transplant patients reported better physical and psychosocial health than dialysis patients. No difference was noted between HD and PD patients for any PedsQL domain. Our data demonstrate that the PedsQL 4.0 Generic Core Scales is a useful measurement instrument to screen for HRQOL impairment in pediatric patients with ESRD. We suggest that the ESRD-specific HRQOL instrument in development is needed to help define condition-specific HRQOL differences between modalities.

Medical care advancements for children with chronic kidney disease (CKD) receiving hemodialysis, peritoneal dialysis, or with a renal transplant have resulted in relatively improved long-term patient survival compared with adult patients with CKD. Optimal care for the pediatric patient with CKD requires attention not only to medical management, but also the psychosocial and developmental factors that either will ensure or prevent a pediatric patient's successful transition into adulthood. We review the range of issues that impact pediatric CKD patients' health-related quality of life (HRQOL), the history of pediatric CKD patients' HRQOL investigation, and the instruments currently available to assess HRQOL.

Few data exist regarding the long-term sequelae of acute renal failure (ARF), and these studies are limited to a few renal conditions. We aim to assess the 3-5-year survival and incidence of renal injury in children who previously developed ARF of varying causes. We queried parents, physicians, and hospital/state vital statistics records to find patient survival in 174 children who previously had ARF and survived to hospital discharge. We assessed the following in 29 children for residual renal injury: (a) microalbuminuria, (b) glomerular filtration rate (GFR) by Schwartz formula, (c) hypertension, and (d) hematuria. The 3-5-year survival of children with ARF who survived to hospital discharge was 139/174 (79.9%). Most deaths (24/35 (68.5%)) occurred within 12 months after initial hospitalization. Combining those who died during initial hospitalization and in subsequent 3-5 years, the overall survival rate was 139/245 (56.8%). In all, 16 children progressed to end-stage renal disease; thus, renal survival was 127/173 (91%). Those with primary renal/urologic conditions had lower renal survival than others (24/35 (68.6%) vs 134/139 (96.4%); P<0.0001). Among the 29 patients assessed for long-term sequelae at 3-5 years, 17/29 (59%) subjects had at least one sign of renal injury; microalbuminuria (n=9), hyperfiltration (n=9), decreased GFR (n=4), and hypertension (n=6). A pediatric nephrologist was involved in care of only 6/17 (35%) with chronic renal injury. Patients have high risks of ongoing residual renal injury and death after ARF; therefore, periodic evaluation after the initial insult is necessary.

Degassing of the Earth's mantle through magmatism results in the irreversible loss of helium to space, and high (3)He/(4)He ratios observed in oceanic basalts have been considered the main evidence for a 'primordial' undegassed deep mantle reservoir. Here we present a new global data compilation of ocean island basalts, representing upwelling 'plumes' from the deep mantle, and show that island groups with the highest primordial signal (high (3)He/(4)He ratios) have striking chemical and isotopic similarities to mid-ocean-ridge basalts. We interpret this as indicating a common history of mantle trace element depletion through magmatism. The high (3)He/(4)He in plumes may thus reflect incomplete degassing of the deep Earth during continent and ocean crust formation. We infer that differences between plumes and the upper-mantle source of ocean-ridge basalts reflect isolation of plume sources from the convecting mantle for approximately 1-2 Gyr. An undegassed, primordial reservoir in the mantle would therefore not be required, thus reconciling a long-standing contradiction in mantle dynamics.

The Centers for Medicare & Medicaid Services' (CMS) end-stage renal disease (ESRD) Clinical Performance Measures (CPM) Project has collected data on all adolescent hemodialysis patients since 2000. Thus, by 2002 data were available on all adolescents on hemodialysis in the USA for 3 consecutive years. Possible associations between clinical parameters and linear growth in this cohort were evaluated. Ninety-four adolescents were on hemodialysis for the 3 study years. The mean height standard deviation score (ht SDS) fell from -1.97 to -2.36 over the 3 study years. Compared with patients with ht SDS > or =-1.88, patients with ht SDS <-1.88 in the 2002 study year (n =53) were more likely to be male (66% vs 44%, p <0.05), on dialysis longer (6.9+/-4.5 years vs 4.1+/-2.3 years, p <0.001), and had lower height SDS in the 2000 study year (-2.90+/-1.31 vs -0.772+/-1.10, p <0.001). Patients with a ht SDS <-1.88 had a lower mean hemoglobin (11.4+/-1.6 g/dl vs 12.0+/-1.1 g/dl, p <0.05), but there were no differences in other clinical parameters. Among patients with ht SDS <-1.88, 38.8% (n =20) were prescribed recombinant human growth hormone (rhGH) in the 2002 study year. There were no differences in demographic or clinical parameters between rhGH treated and untreated patients. Many adolescents who remain on hemodialysis have poor linear growth. Further evaluation is needed to delineate contributory factors and the possible underutilization of rhGH.

The non-invasive diagnosis of renal osteodystrophy (ROD) in patients with end-stage renal disease (ESRD) remains dependent on the determination of an accurate parathyroid hormone (PTH) level. Older assays that determine the "intact" PTH molecule are known to cross react with various PTH fragments, resulting in overestimation of PTH levels. Recently, assays that determine the whole 1-84 PTH molecule have been made available. Monthly PTH values in chronic dialysis patients at our institution were compared using the Nichols Bio-Intact PTH (BiPTH, 1-84 PTH) and the intact PTH (iPTH) assay over 3 consecutive months. One hundred twenty-four samples were obtained from 51 (29 male) pediatric dialysis patients (27 HD). The mean patient age was 14.2+/-5.6 years (1.8-25.7 years), with 12 patients<10 years and 15 patients <30 kg. The mean 1-84 PTH/iPTH ratio was 0.48+/-0.11. While BiPTH values correlated closely with iPTH values ( r =0.98, P <0.05), we observed significant intra-patient (16.4+/-15.4%; range: -73.9 to 67.7%, total % error: 47.2%) and inter-patient (17.2+/-18.9%; range: -73.9 to 129.9%, total % error: 55%) variability in the 1-84 PTH/iPTH ratio over the 3-month study period. Thus, our findings suggest that ROD management based on prior associations between iPTH levels and bone biopsy findings should not be extrapolated using the newer 1-84 PTH assay.

Protein-energy malnutrition (PEM) is a significant cause of morbidity and mortality for patients receiving maintenance hemodialysis. Minimal study has evaluated therapeutic options for and biochemical marker assessment of pediatric patient PEM. In 2001, we expanded the indications for intradialytic parenteral nutrition (IDPN) treatment of PEM to all maintenance hemodialysis patients, regardless of etiology, who had a >10% weight loss and were at less than the 90th percentile of ideal body weight. Nine patients received thrice weekly IDPN from 3 to 22 months with minimal side effects. Six patients had weight and body mass index increase, 1 patient stopped losing weight, and 2 patients continued to lose weight during the initial 5 months of IDPN therapy. Cohort subanalysis showed that all patients with organic PEM responded to IDPN therapy, whereas patients with psychosocial causes of PEM did not. The normalized protein catabolic rate increased significantly for patients whose condition responded to IDPN therapy, whereas serum albumin did not change. The current study suggests that IDPN is effective treatment of organic causes of PEM in pediatric patients receiving maintenance hemodialysis and that normalized protein catabolic rate may be superior to serum albumin as a marker of nutrition status. The observation that IDPN was not sufficient to reverse PEM in patients with psychosocial PEM causes should direct caregivers to address the relevant underlying causes as well as to provide intensive nutrition therapy.

Background: Heparin (hepACG) and regional citrate anticoagulation (citACG) remain the most commonly reported continuous renal replacement therapy (CRRT) ACG methods employed. No prospective multi-centre published data exist that compare different ACG methods with respect to CRRT filter life span or patient complications., Methods: A total of 138 patients from seven US centres receiving 18 208 h of CRRT comprising a total of 442 CRRT circuits were utilized to assess filter life span and ACG-related complications in patients receiving CRRT with hepACG, citACG or no ACG (noACG)., Results: Mean circuit life was 41.2+/-30.8 h. Mean circuit survival was no different for circuits receiving hepACG (42.1+/-27.1 h) and citACG (44.7+/-35.9 h), but was significantly lower for circuits with noACG (27.2+/-21.5 h, P<0.005). Kaplan-Meier analyses revealed no survival difference between hepACG and citACG circuits, but significantly lower survival for noACG circuits (P<0.001). Log-rank analysis showed that 69% of hepACG and citACG circuits whereas only 28% of noACG were functional at 60 h. Clotting rates were similar for hepACG circuits (58 out of 230, 25%) and citACG circuits (43 out of 158, 27%), but were significantly higher for noACG circuits (27 out of 54, 50%, P < 0.001). Life-threatening bleeding complications attributable to ACG were noted in the hepACG group but were absent in the citACG group., Conclusions: The current analysis represents the largest evaluation of CRRT ACG methods to date. While the standard hepACG and citACG methods studied in the prospective paediatric CRRT registry led to similar filter life spans and were superior to noACG, our data suggest that citACG may result in less life-threatening complications.

Sea level is a sensitive index of global climate that has been linked to Earth's orbital variations, with a minimum periodicity of about 21,000 years. Although there is ample evidence for climate oscillations that are too frequent to be explained by orbital forcing, suborbital-frequency sea-level change has been difficult to resolve, primarily because of problems with uranium/thorium coral dating. Here we use a new approach that corrects coral ages for the frequently observed open-system behavior of uranium-series nuclides, substantially improving the resolution of sea-level reconstruction. This curve reveals persistent sea-level oscillations that are too frequent to be explained exclusively by orbital forcing.

Evidence from high-sedimentation-rate South Atlantic deep-sea cores indicates that global and Southern Ocean carbon budget shifts preceded thermohaline circulation changes during the last ice age initiation and termination and that these were preceded by ice-sheet growth and retreat, respectively. No consistent lead-lag relationships are observed during abrupt millennial warming events during the last ice age, allowing for the possibility that ocean circulation triggered some millenial climate changes. At the major glacial-interglacial transitions, the global carbon budget and thermohaline ocean circulation responded sequentially to the climate changes that forced the growth and decline of continental ice sheets.

Background: Critical illness leading to multi-organ dysfunction syndrome (MODS) and associated acute renal failure (ARF) is less common in children compared to adult patients. As a result, many issues plague the pediatric ARF outcome literature, including a relative lack of prospective study, a lack of modality stratification in subject populations and inconsistent controls for patient illness severity in outcome analysis., Methods: We now report data from the first multicenter study to assess the outcome of pediatric patients with MODS receiving continuous renal replacement therapy (CRRT). One hundred twenty of 157 Registry patients (63 male/57 female) experienced MODS during their course., Results: One hundred sixteen patients had complete data available for analysis. The most common causes leading to CRRT were sepsis (N= 47; 39.2%) and cardiogenic shock (N= 24; 20%). Overall survival was 51.7%. Pediatric Risk of Mortality (PRISM 2) score, central venous pressure (CVP), and% fluid overload (%FO) at CRRT initiation were significantly lower for survivors versus nonsurvivors. Multivariate analysis controlling for severity of illness using PRISM 2 at CRRT initiation revealed that%FO was still significantly lower for survivors versus nonsurvivors (P < 0.05) even for patients receiving both mechanical ventilation and vasoactive pressors. We speculate that increased fluid administration from PICU admission to CRRT initiation is an independent risk factor for mortality in pediatric patients with MODS receiving CRRT., Conclusion: We suggest that after initial resuscitative efforts, an increased emphasis should be placed on early initiation of CRRT and inotropic agent use over fluid administration to maintain acceptable blood pressure.

Background: Previous epidemiological data for pediatric patients with acute renal failure (ARF) predate current intensive care unit (ICU) technology and practice, and do not reflect newer disease therapies for bone marrow, hepatic, and cardiac transplantation and congenital heart disease surgery., Methods: We conducted a retrospective review of 254 ARF episodes in 248 children discharged from a tertiary referral center, Texas Children's Hospital (Houston, TX), between January 1998 and June 2001 to update current pediatric ARF epidemiological characteristics., Results: The most common causes of ARF were renal ischemia (21%), nephrotoxic medications (16%), and sepsis (11%). Primary renal diseases accounted for only 17 cases (7%), and hemolytic uremic syndrome accounted for only 3 cases. Overall ARF survival for the entire cohort was 176 of 254 patients (70%), whereas 110 of 185 patients (60%) requiring ICU admission and 43 of 77 patients (56%) receiving renal replacement therapy survived., Conclusion: These current pediatric ARF data show that pediatric ARF epidemiological characteristics have changed from primary renal disease to renal involvement secondary to other systemic illness. Longitudinal data from this cohort are underway to determine the long-term sequelae of pediatric ARF.

Achieving dry weight during hemodialysis (HD) while minimizing symptoms is critical for optimizing patient outcome by preventing chronic fluid overload, hypertension, and cardiomyopathy. Dry weight changes frequently in children because of growth and development and waxing and waning of appetite. We have previously shown non-invasive hematocrit monitoring (NIVM) helps to decrease intradialytic symptoms, while still achieving target dry weights in children receiving chronic HD. In the current study, we prospectively evaluated an NIVM-guided ultrafiltration (UF) management algorithm to determine target dry weight in nine pediatric patients (mean age 16.6+/-2.8 years, mean weight 41.6+/-11.1 kg). Use of NIVM could potentially lead to overly aggressive UF with increased interdialytic symptoms, post treatment thirst, and interdialytic weight gain (IDWG). To evaluate the effectiveness of our NIVM UF algorithm, we studied the effect of three different NIVM-guided UF models (100%, 90%, and 80% UF models) on intradialytic and interdialytic symptoms, pre-/post-treatment blood pressure (BP), and percentage IDWG. To assess interdialytic symptoms, patients completed two questionnaires, one for each day between treatments. No statistically significant difference was seen between the three UF models with respect to intradialytic or interdialytic symptoms, pre-/post-HD BP, or percentage IDWG. Only one of nine patients received non-ACEI chronic antihypertensive medication, yet all patients had pre- and post-HD BP <95th percentile for age and height. The current study suggests that routine determination of target dry weight using NIVM and aiming for 100% UF helps to achieve the target dry weight, reduces both the risk of chronic fluid overload and the need for antihypertensive medication, and does not lead to increased intra- or interdialytic symptomatology in pediatric patients treated with chronic HD.

Carbamazepine intoxication is common in the pediatric population. Highly protein-bound, carbamazepine is not removed efficiently through conventional hemodialysis. We describe the use of albumin-enhanced continuous venovenous hemodialysis (CVVHD) in a 10-year-old girl who developed coma and respiratory depression due to an intentional carbamazepine overdose (peak drug level of 44.8 microg/ml; therapeutic range: 8-12 microg/ml). Without intervention, the half-life of drug elimination is 25 to 60 hours in patients who are naive to carbamazepine and 12 to 20 hours in children on chronic carbamazepine therapy. In contrast, with albumin-enhanced CVVHD, we observed a half-life of 7 to 8 hours. The patient recovered rapidly and was discharged from hospital <4 days from the time of ingestion with no complications or neurologic impairment. Because the cost-benefit analysis was also favorable relative to other therapeutic options, albumin-enhanced CVVHD may be the optimal treatment of toxic-level ingestion of carbamazepine.

Acute renal failure (ARF) with fluid overload (FO) occurs often in stem cell transplant (SCT) recipients. We have previously demonstrated that an increased percentage of FO prior to the initiation of continuous renal replacement therapy (CRRT) is associated with mortality in children with ARF. Based on these data, we devised a protocol for the prevention of FO in SCT patients with ARF. SCT patients with ARF and 5% FO were started on furosemide and low-dose dopamine. To allow for nutrition, medication, and blood product administration, RRT was initiated for patients with > or =10% FO. There were 272 patients who received allogeneic SCT from 1999 to 2002. Of these, medical records of 26 SCT patients with a first episode of oliguric ARF were reviewed. The mean patient age was 13+/-5 years (range 2-23.5 years). Mean days to ARF after SCT were 28+/-29 days (range 2-90 days). Of the 26 patients, 11 (42%) survived an initial ARF episode. All 11 survivors either maintained <10% FO during their course or re-attained <10% FO with RRT treatment. Of the 15 non-survivors, 6 had <10% FO at the time of death. Of 14 patients who received RRT, 4 (29%) survived. Mechanical ventilation and pediatric risk of mortality score > or =10 at the time of admission to the intensive care unit were associated with lower survival ( P<0.05). The use of one or more pressors, the presence of graft-versus-host disease, and septic shock were not correlated with survival. Our data demonstrate that maintenance of euvolemia ( <10% FO) is critical but not sufficient for survival in SCT patients with ARF, as all non-euvolemic patients died. We suggest that aggressive use of diuretics and early initiation of RRT to prevent worsening of FO may improve the survival of SCT patients.

Many issues plague the pediatric ARF outcome literature, which include data only from single center sources, a relative lack of prospective study, mixture within studies of renal replacement therapy modality without stratification and inconsistent use of methods to control for patient illness severity in outcome analysis. Since January 2001, the Prospective Pediatric CRRT (ppCRRT) Registry Group has been collecting data from multiple United States pediatric centers to obtain demographic data regarding pediatric patients who receive CRRT, assess the effect of different CRRT prescriptions on circuit function and evaluate the impact of clinical variables on patient outcome. The aim of the current paper is to describe the ppCRRT Registry design, review the decision process and rationale for the options chosen for the ppCRRT format and discuss the analysis plan and future projects envisioned for the ppCRRT Registry.

Background: Although many surgeons use absorbable sutures for skin closure of 5-mm trocar sites, effective alternative materials exist. We compared 5-mm trocar site closures using a vicryl suture (VS), cyanoacrylate tissue adhesive (CTA), or skin tape (ST)., Methods: Patients rated wound pain and appearance at 1 and 6 weeks after surgery. Seven surgeons masked to the closure method rated wound photographs at these time points using the Hollander wound evaluation scale. Logistic regression analysis was used to evaluate the ratings of each closure group., Results: The 137 wounds of 48 patients undergoing laparoscopic procedures were randomized among three closure method groups. Patient demographics and procedure type were similar for all groups. Long closure times (>30 seconds) was significantly higher for VS compared with CTA and ST. Patients favored VS over ST and CTA at 1 week with respect to pain and wound appearance (P = 0.04 and P = 0.02, respectively). They rated CTA closures more likely to have pain and poor wound appearance at 6 weeks (P = 0.05 and P = 0.03, respectively). Surgeons rated VS less likely (P = 0.02) and CTA more likely (P = 0.003) to show moderate to severe scar formation. Vicryl suture was less likely to have wound separation and edge inversion (P = 0.017 and P = 0.006, respectively). Cyanoacrylate tissue adhesive was more likely to yield step-off (P = 0.03), contour irregularities (P = 0.005), separation (P = 0.004), excessive distortion (P = 0.001), and edge inversion (P = 0.03)., Conclusions: Although VS closure time of 5-mm trocar sites takes longer than CTA and ST, VS scar formation and comfort is superior to CTA and ST. Cyanoacrylate tissue adhesive yields poor results with respect to both wound healing and pain.

Objectives: To assess chronic and acute inflammation in children receiving maintenance hemodialysis., Study Design: To assess markers of acute inflammation, serum levels (ELISA) of the cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-10, and IL-6, 3 to 5 mL of serum was obtained from 13 pediatric patients (mean patient weight, 37.0+/-15.2 kg; mean age, 14.6+/-4.6 years) before and 30 minutes and 24 hours after a routine midweek hemodialysis treatment session. Chronic inflammation was assessed by serum C-reactive protein (CRP) levels., Results: Early-response cytokines TNF-alpha at 30 minutes (5.84+/-0.94 to 9.67+/-0.92 pg/mL; P=.002) and 24 hours (5.84+/-0.94 to 9.54+/-1.05 pg/mL; P=.008) and IL-1beta at 30 minutes (17.19+/-2.00 to 26.17+/-1.12 pg/mL; P=.001) and 24 hours (17.19+/-2.00 to 23.01+/-1.13 pg/mL; P=.02) increased significantly after hemodialysis. Later-response cytokines IL-10 and IL-6 activation was not significant. CRP levels were elevated in 10 of 13 patients (mean, 14.7+/-9.5mg/L; range, 7.2-38.8 mg/L) and correlated with dialysis vintage. Baseline IL-6 and IL-10 levels correlated with dialysis vintage and correlated negatively with eqKt/V., Conclusions: We observed a chronic inflammatory state in pediatric hemodialysis patients not related to the hemodialysis treatment but rather dialysis vintage and hemodialysis adequacy. We suggest that either more frequent dialysis or enhanced cytokine clearance may ameliorate the chronic inflammatory state observed in pediatric patients receiving hemodialysis.

The disease spectrum leading to pediatric renal replacement therapy (RRT) provision has broadened over the last decade. In the 1980s, intrinsic renal disease and burns constituted the most common pediatric acute renal failure etiologies. More recent data demonstrate that pediatric acute renal failure (ARF) most often results from complications of other systemic diseases, resulting from advancements in congenital heart surgery, neonatal care, and bone marrow and solid organ transplantation. In addition, RRT modality preferences to treat critically ill children have shifted from peritoneal dialysis to continuous renal replacement therapy (CRRT) as a result of improvements in CRRT technologies. Currently, multicenter prospective outcome studies for critically ill children with ARF are sorely lacking. The aims of this article are to review the pediatric specific causes necessitating renal replacement therapy provision, with an emphasis on emerging practice patterns with respect to modality and the timing of treatment, and to focus upon the application of the different renal replacement therapy modalities and assessment of the outcome of children with ARF who receive renal replacement therapy.

Results from the National Oral Health Surveillance System (NOHSS) provide an overview (at the state and national levels) of the burden of oral disease and the use of oral health services. Compared to national averages, Massachusetts residents are doing very well in terms of some broad measures, but (1) only average in the rate of edentulism, (2) below average in the rank of states with regard to its population on public water supply systems with fluoridation, and (3) marked by wide variations between the many in-state population groups.

Cardiovascular disease is a major cause of morbidity and mortality in adult patients with end-stage renal disease receiving maintenance dialysis. Coronary artery calcifications (CAC) contribute to the high prevalence of cardiac disease and are associated with hyperphosphatemia, an elevated calcium-phosphorus product (CaxP), and prolonged time on dialysis. Chronic inflammation and malnutrition are also associated with an increased risk for development of cardiac calcifications. Young adults receiving maintenance dialysis develop cardiac calcifications at a degree out of proportion to healthy adults of the same age and gender. Many of these young adults initiated dialysis as children or teenagers. Risk factors associated with the development of CAC are also seen in the pediatric dialysis population. To date, reports of cardiac calcifications in pediatric patients receiving maintenance dialysis are limited to post-mortem studies. We present two pediatric patients with ANCA-positive vasculitis diagnosed with cardiac calcifications while receiving maintenance dialysis. Hyperphosphatemia and an elevated CaxP product were seen in both patients and probably contributed to the development of extraskeletal calcifications. In addition, both patients had an underlying systemic inflammatory disease and significant weight loss/malnutrition that may have contributed to the early and rapid onset of cardiac calcifications.

Minimal pediatric data describe hospitalization causes and associated costs for children who receive maintenance hemodialysis, and no data exist to evaluate methods to decrease hospitalization. In 1999, two common causes of hemodialysis patient hospitalization at Texas Children's Hospital were fluid overload/hypertension (FO/HTN) and vascular access thrombosis (VAT). Evaluated is the effect of two noninvasive monitoring programs, monitoring of hematocrit-guided ultrafiltration algorithm and vascular access flow using ultrasound dilution vascular access flow technology, on FO/HTN and VAT in the pediatric maintenance hemodialysis population. This prospective observational study reviewed all hospitalization data for all 51 patients who received maintenance hemodialysis from January 1999 through December 2001 obtained from unit monthly performance improvement meeting records. Hospitalization rates and related costs for FO/HTN and VAT were tracked before and after institution of the noninvasive monitoring programs. Application of the noninvasive monitoring of hematocrit-guided ultrafiltration algorithm since January 2000 significantly decreased hospitalization for FO/HTN (64 total days in 1999, 4 total days in 2000 and 2001 combined) while maintaining acceptable patient BP control and minimizing antihypertensive medication requirements. The vascular access monitoring program using ultrasound dilution vascular access flow technology to direct referral for angioplasty instituted in January 2001 led to a significant decrease in hospitalization for VAT (45 d in 2000 and 21 d in 2001). It is suggested that application of noninvasive technologies to assess patient target dry weight and access flow can significantly decrease pediatric maintenance dialysis patient morbidity and health care cost.

A high-resolution mapping and sampling study of the Gakkel ridge was accomplished during an international ice-breaker expedition to the high Arctic and North Pole in summer 2001. For this slowest-spreading endmember of the global mid-ocean-ridge system, predictions were that magmatism should progressively diminish as the spreading rate decreases along the ridge, and that hydrothermal activity should be rare. Instead, it was found that magmatic variations are irregular, and that hydrothermal activity is abundant. A 300-kilometre-long central amagmatic zone, where mantle peridotites are emplaced directly in the ridge axis, lies between abundant, continuous volcanism in the west, and large, widely spaced volcanic centres in the east. These observations demonstrate that the extent of mantle melting is not a simple function of spreading rate: mantle temperatures at depth or mantle chemistry (or both) must vary significantly along-axis. Highly punctuated volcanism in the absence of ridge offsets suggests that first-order ridge segmentation is controlled by mantle processes of melting and melt segregation. The strong focusing of magmatic activity coupled with faulting may account for the unexpectedly high levels of hydrothermal activity observed.

The 2000 Census data on the numbers of children with disabilities in Massachusetts are presented in each community in the state. There are numerous difficulties associated with the delivery of dental care to these youngsters with special needs. The 2002 Kids Count Census Data Online, developed by The Annie E. Casey Foundation (using Census Bureau 2000 data), provides an extended detailed numeric picture of noninstitutionalized United States children between the ages of 5 and 15 at the state, county, city, New England town, and metropolitan area levels. In addition to standard demographic characteristics, the report provides a detailed review of the prevalence of children with one or more disabilities (including long-term sensory, physical, mental, and self-care limitations.

Gross hematuria, graft pain, and rising serum creatinine are classic signs of acute rejection, obstruction, or bacterial pyelonephritis for patients with renal transplants. This presentation often prompts percutaneous renal allograft biopsy. If subsequent evaluation fails to show evidence of acute rejection, obstruction, or bacterial infection, viral etiologies should be considered. We report a 14-year-old Hispanic female with a living-related renal transplant who had gross hematuria, graft tenderness, and increased serum creatinine, but did not have evidence of acute rejection, obstruction, or bacterial pyelonephritis. To our knowledge, this is the first report of adenovirus pyelonephritis in a transplanted kidney of a pediatric patient, with isolation of adenovirus in the urine and in the allograft using immunocytochemical techniques.

Background: There is growing use of continuous renal replacement therapy (CRRT) for pediatric patients, but no large studies reporting CRRT use and outcome in young children. We describe a cohort of patients weighing 10 kg or less who underwent CRRT at five US children's hospitals between 1993 and 2001., Methods: We reviewed records of 85 patients weighing 10 kg or less who underwent at least 24 hours of CRRT. We evaluated weight, diagnosis, pressor number, CRRT characteristics, days on CRRT, and outcome (survival to leave intensive care unit versus death)., Results: Patients weighed 1.5 to 10 kg (mean, 5.3 +/- 2.8 kg; 16 patients < or = 3 kg). Sixty-nine percent of patients were being administered pressors at the time of CRRT initiation, 88% of patients were administered heparin, and the others were administered citrate or no anticoagulation. Mean blood flow was 48 +/- 24 mL/min (range, 15 to 106 mL/min) or 9.5 +/- 4.2 mL/min/kg. Six hundred fifty-five patient-days of therapy were studied (mean, 7.6 +/- 8.6 d/patient; range, 1 to 46 d/patient). Thirty-two patients (38%) survived; 4 of 16 patients (25%) weighing 3 kg or less survived. The smallest survivor weighed 2.3 kg. Overall, survivors and nonsurvivors showed no significant difference in weight, days on CRRT, or pressor number. However, for patients weighing more than 3 kg, 28 of 69 patients (41%) survived, and mean pressor number was lower for survivors versus nonsurvivors (0.96 +/- 1.1 versus 1.6 +/- 1.0 pressors; P < 0.03)., Conclusion: CRRT is feasible and useful in children weighing 10 kg or less. Hemodynamic instability requiring pressor support neither precludes successful CRRT nor adversely affects survival. After CRRT, the survival rate in children who weigh 3 to 10 kg is similar to that in older children and adolescents.

Background: Transplantation is the optimal therapy for pediatric end-stage renal disease (ESRD) patients, but in a subset of patients with peritoneal membrane failure, failed transplants or poor social situations, chronic hemodialysis (HD) remains the only option. Long-term survival of arteriovenous fistulas (AVFs) and arteriovenous grafts (AVGs) in pediatric patients has not been well described., Methods: We studied the survival of permanent vascular access in 34 pediatric ESRD patients treated with chronic HD at our institution between 1/1/89 and 12/1/95 and followed to 12/31/2000., Results: Twenty-four AVFs and 28 AVGs were created in 19 and 23 patients, respectively. Mean age and weight at insertion were 15.1 years (range 7.1 to 20.9) and 46 kg (18 to 81) for AVFs and 13.3 years (3.8 to 21.1) and 41.5 kg (10.5 to 145) for AVGs. Fifteen patients weighed <35 kg at the time of access creation (7 AVFs in 5 patients, 14 AVGs in 13 patients). Excluding primary failures, one-year, three-year and five-year patency rates for AVFs (74%, 59%, 59%) and AVGs (96%, 69%, 40%) were not significantly different. Patency did not correlate with patient weight or age at access creation. Primary access failure occurred more often (P < 0.01) in AVFs (8/24) compared to AVGs (1/28). Access thrombosis, stenosis and infection occurred more frequently in AVG (P = 0.02)., Conclusions: Both AVF and AVG function well even in small pediatric patients and have survival rates equivalent to adult series and longer than cuffed venous catheters in pediatric patients. Both AVFs and AVGs are preferable for long-term HD access in pediatrics.

Very few pediatric studies have monitored nutritional status using normalized protein catabolic rate (nPCR) or treating protein-energy malnutrition (PEM) with intradialytic parenteral nutrition (IDPN). The current study compares nPCR with serum albumin as a marker for nutritional status and examines the effectiveness of IDPN treatment in three malnourished adolescent patients receiving chronic hemodialysis in a pediatric dialysis unit. All patients demonstrated reversal of weight loss and initiation of weight gain within 6 weeks of IDPN initiation. Mean values of monthly percentage weight and percentage body mass index (BMI) change were significantly lower in the pre-IDPN era (-0.61+/-2.70 and -1.3+/-2.7) versus the IDPN treatment period (1.8+/-2.1 and 1.3+/-2.1) ( P<0.02). Two patients attained ideal body weight and IDPN was discontinued after 5 months. Patients required 150% recommended daily allowance to achieve weight and BMI gain. While mean monthly nPCR was significantly lower in the pre-IDPN period versus the IDPN period (1.05+/-0.36 versus 1.35+/-0.37, P<0.05), monthly serum albumin levels were no different before and after IDPN was initiated (3.7+/-0.8 versus 3.8+/-0.6). The current study demonstrates IDPN to be effective therapy for adolescent hemodialysis patients with PEM not correctable by enteral supplementation. nPCR was superior to serum albumin as a nutritional status marker in these malnourished pediatric patients receiving hemodialysis.

Background: Hemodialysis vascular access thrombosis (VAT) is a significant cause of morbidity for hemodialysis patients and results, in part, from decreased access flow potentially caused by venous outflow stenosis. We have previously shown ultrasound dilution (UD) to be a practical and reliable predictor of venous outflow in children receiving hemodialysis., Methods: The current study is the first to our knowledge to assess the impact of a proactive UD monitoring program upon VAT in pediatric patients. Nine patients experienced 18 VAT over the two-year study. Mean values for variables potentially associated with VAT were compared to values from a size-matched seven patient group without VAT during the study period. VAT rates were compared between the year-before (pre-UD era) and year-after (UD era) UD was initiated. During the latter half of the UD era (rapid referral period), patients with VA flow rate (QAcorr) <650 mL/min/1.73 m2 were referred for balloon angioplasty within 48 hours., Results: Mean QAcorr was lower for patients with subsequent VAT (562 +/- 290 mL/min/1.73 m2) versus patients without VAT (1005 +/- 372 mL/min/1.73 m2; P = 0.02). The VAT rate was significantly lower in the UD era (4.1 VAT/100 patient-months) versus the pre-UD era (11.0 VAT/100 patient-months; P = 0.03). The decrease in VAT rates was caused predominantly in the rapid referral period, where the VAT rate dropped to 0.96 VAT/100 patient-months (P < 0.001). Cost of vascular access management was 65% higher ($1264 vs. $765/patient-month) in the pre-UD era, reflecting the increased cost for treatment of VAT., Conclusions: Monthly QAcorr <650 mL/min/1.73 m2 is predictive of imminent VAT in children receiving hemodialysis. Prompt referral for angioplasty of VA with QAcorr <650 mL/min/1.73 m2 leads to decreased VAT rates in children.

Background and Purpose: The extent of lateral spread of tissue injury is important in the success of a primary anastomosis. We compared the injury produced by the Laparo-sonic Coagulation Shears and the Ligasure system., Materials and Methods: Ureters were harvested from domestic farm pigs and ligated with the Laparo-sonic (N = 13) or Ligasure (N = 9) system. The tissues were then fixed, stained, and examined by two pathologists without knowledge of the type of treatment., Results: The mean length of thermal damage from the Ligasure was 2.11 mm (range 1.0-4.0 mm) whereas it was 1.92 (range 0.5-4.25 mm) from the Laparo-sonic system. The difference is not statistically significant., Conclusion: Debridement of as much as 5 mm of each cut end produced by the Laparo-sonic or Ligasure system may be beneficial in reducing stricture and leak.

The emergence of multi-drug-resistant bacteria is of great concern to the care of pediatric end-stage renal disease (ESRD) patients who receive either hemodialysis or peritoneal dialysis via a catheter. Infections with gram-negative organisms, especially Pseudomonas aeruginosa, are difficult to eradicate and often necessitate catheter removal. Meropenem, a broad-spectrum antibiotic of the carbapenem class of beta-lactams, is effective against most gram-positive and gram-negative bacteria and has enhanced activity against P. aeruginosa. We studied the pharmacokinetics of meropenem during and between hemodialysis treatments in seven pediatric patients. Meropenem was given as a single dose of 20 mg/kg (maximum 500 mg) before and after two separate hemodialysis treatments. Meropenem administration was tolerated without any adverse effects. Hemodialysis effectively cleared meropenem in a manner that correlated with percent urea reduction. Median drug half-life was 7.3 h off dialysis (range 4.9-11.7 h). The dose of 20 mg/kg was not sufficient to produce an acceptable interdialytic pharmacodynamic profile of 70% duration with a meropenem concentration >4 microg/ml, the MIC90 of meropenem for P. aeruginosa. Dosing simulations revealed that a daily dose of 25 mg/kg or an alternate day dose of 40 mg/kg would result in an acceptable pharmacodynamic profile. Both simulated doses achieved acceptable peak concentrations.

Background: Traditional management of symptomatic paraesophageal herniation involves hernia reduction, hiatal closure, and an antireflux procedure or gastropexy. Patients with significant comorbidities may not tolerate operative repair. A new technique, laparoscopic-assisted endoscopic reduction and fixation of the stomach, may provide a minimally invasive treatment alternative., Methods: Eleven elderly patients with symptomatic paraesophageal herniation were managed with flexible endoscopy and double percutaneous endoscopic gastrostomy (PEG) tube insertion with or without laparoscopic assistance., Results: All patients presented with a symptomatic paraesophageal hernia. Mean age was 78.3 years (range 72 to 84). Each was deemed at high risk for definitive repair due to preexisting coronary artery disease as well as at least two other serious comorbidities. Hernia reduction and intra-abdominal fixation of the stomach was achieved in each case using flexible endoscopy and double PEG insertion. Laparoscopic assistance for reduction and gastropexy was utilized in 9 cases. Mean operative time was 61 minutes (range 28 to 104). Average length of stay was 2.8 days (range 0 to 12). One minor and three major postoperative complications occurred. Over a mean follow-up of 4.1 months (range 2 to 7), all patients have resumed oral intake and achieved weight gain., Conclusions: Patients with symptomatic paraesophageal herniation require intervention to alleviate symptoms and avoid the complications of gastric incarceration. For the high-risk patient, endoscopic reduction and PEG with laparoscopic assistance appears to provide effective treatment.

Achalasia is an esophageal motility disorder characterized by the failure of lower esophageal sphincter relaxation and the absence of esophageal peristalsis. The purpose of this study was to evaluate the clinical outcomes of patients undergoing laparoscopic esophageal myotomy and Toupet fundoplication for achalasia. A 9-cm myotomy was performed in most cases extending 7 cm above and 2 cm below the gastroesophageal junction. Severity of dysphagia, heartburn, chest pain, and regurgitation was graded preoperatively and postoperatively using a five-point symptomatic scale (0-4). Patients also graded their outcomes as excellent, good, fair, or poor. Between December 1995 and November 2000 a total of 49 patients (23 male, 26 female) with a mean age of 44.3 years (range 23-71 years) were diagnosed with achalasia. Mean duration of symptoms was 40.2 months (range 4-240 months). Thirty-seven patients (76%) had had a previous nonsurgical intervention or combinations of nonsurgical interventions [pneumatic dilation (23), bougie dilation (five), and botulinum toxin (19)], and two patients had failed esophageal myotomies. Forty-five patients underwent laparoscopic esophageal myotomy and Toupet fundoplication. Two patients received laparoscopic esophageal myotomies without an antireflux procedure, and two were converted to open surgery. One patient presented 10 hours after a pneumatically induced perforation and underwent a successful laparoscopic esophageal myotomy and partial fundoplication. Mean operative time was 180.5 minutes (range 145-264 minutes). Mean length of stay was 1.98 days (range 1-18 days). There were five (10%) perioperative complications but no esophageal leaks. There was a significant difference (P < 0.05) between the preoperative and postoperative dysphagia, chest pain, and regurgitation symptom scores. All patients stated that they were improved postoperatively. Eighty-six per cent rated their outcome as excellent, 10 per cent as good, and 4 per cent as fair. Laparoscopic anterior esophageal myotomy and Toupet fundoplication effectively alleviates dysphagia, regurgitation, and chest pain accompanying achalasia and is associated with high patient satisfaction, a rapid hospital discharge, and few complications.

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.

Background: In the past, prior abdominal surgery was often felt to be a contraindication to laparoscopic cholecystectomy. The presence of adhesions precludes using a simple paraumbilical open approach for insufflation and initial trocar insertion because of an increased risk of bowel perforation and the difficulty in obtaining adequate exposure., Patients and Methods: We report 32 consecutive patients with previous upper midline incisions who underwent laparoscopic cholecystectomy with cholangiography and describe the technique and lateral positioning to facilitate this approach., Results: In our series, there were no complications. The mean length of hospital stay was 1.3 days, and the conversion rate to an open procedure was 3%: one patient who had had 22 previous abdominal operations., Conclusion: Laparoscopic cholecystectomy performed with the patient in the lateral position is safe and effective for patients who have had previous midline incisions.