A newborn male born at 35 weeks’ gestation displays respiratory distress, flaccid abdominal musculature, and undescended testes. ### Prenatal History ### Birth History and Presentation ### Vital Signs

PurposeMedian survival in pediatric lung transplantation is limited by chronic rejection. Extracorporeal photopheresis (ECP) has been used to treat chronic rejection after lung transplantation in adults, but there is limited published data on the use of ECP to treat chronic rejection in pediatric lung transplant recipients.MethodsFifteen cases of chronic rejection, representing either bronchiolitis obliterans or bronchiolitis obliterans syndrome, treated with ECP, spanning April 2009 through October 2014, were reviewed and transplant outcomes were recorded. Among these cases, seven patients had pulmonary function testing (PFT) data preceding and following ECP treatment sufficient for analysis. Linear regression was used to estimate rate of change in forced expiratory volume in 1 second (FEV1) in the year prior to, and in the year following, first ECP treatment. Difference in the FEV1 rate of change (ml/day) preceding and following treatment was compared for each patient using a paired t-test.ResultsAmong the fifteen total cases of chronic rejection treated with ECP, seven patients (47%) were bridged to retransplant. Four patients (27%) were not retransplant candidates and died due to progressive respiratory failure. The remaining four patients (27%) are alive and have not been retransplanted to date. Among the seven patients with PFT data, five patients (71%) had an improvement in FEV1 decline following ECP. During the year preceding ECP patients had an average decline in FEV1 of 1.7ml/day, and in the year following treatment their decline was 0.5ml/day, a mean improvement of 1.2ml/day (95% confidence interval -0.2 to 2.7, p=0.08).ConclusionECP can be used as a bridge to retransplant in pediatric lung transplant recipients with chronic rejection. There is a trend toward improvement in FEV1 decline among patients receiving ECP therapy. Further study is necessary to compare the measured efficacy against other chronic rejection therapies, determine optimal timing of ECP in pediatric lung transplant patients, and to identify whether there are certain patients -- by underlying diagnosis, or by disease severity, for example -- who are most likely to benefit from ECP. PurposeMedian survival in pediatric lung transplantation is limited by chronic rejection. Extracorporeal photopheresis (ECP) has been used to treat chronic rejection after lung transplantation in adults, but there is limited published data on the use of ECP to treat chronic rejection in pediatric lung transplant recipients. Median survival in pediatric lung transplantation is limited by chronic rejection. Extracorporeal photopheresis (ECP) has been used to treat chronic rejection after lung transplantation in adults, but there is limited published data on the use of ECP to treat chronic rejection in pediatric lung transplant recipients. MethodsFifteen cases of chronic rejection, representing either bronchiolitis obliterans or bronchiolitis obliterans syndrome, treated with ECP, spanning April 2009 through October 2014, were reviewed and transplant outcomes were recorded. Among these cases, seven patients had pulmonary function testing (PFT) data preceding and following ECP treatment sufficient for analysis. Linear regression was used to estimate rate of change in forced expiratory volume in 1 second (FEV1) in the year prior to, and in the year following, first ECP treatment. Difference in the FEV1 rate of change (ml/day) preceding and following treatment was compared for each patient using a paired t-test. Fifteen cases of chronic rejection, representing either bronchiolitis obliterans or bronchiolitis obliterans syndrome, treated with ECP, spanning April 2009 through October 2014, were reviewed and transplant outcomes were recorded. Among these cases, seven patients had pulmonary function testing (PFT) data preceding and following ECP treatment sufficient for analysis. Linear regression was used to estimate rate of change in forced expiratory volume in 1 second (FEV1) in the year prior to, and in the year following, first ECP treatment. Difference in the FEV1 rate of change (ml/day) preceding and following treatment was compared for each patient using a paired t-test. ResultsAmong the fifteen total cases of chronic rejection treated with ECP, seven patients (47%) were bridged to retransplant. Four patients (27%) were not retransplant candidates and died due to progressive respiratory failure. The remaining four patients (27%) are alive and have not been retransplanted to date. Among the seven patients with PFT data, five patients (71%) had an improvement in FEV1 decline following ECP. During the year preceding ECP patients had an average decline in FEV1 of 1.7ml/day, and in the year following treatment their decline was 0.5ml/day, a mean improvement of 1.2ml/day (95% confidence interval -0.2 to 2.7, p=0.08). Among the fifteen total cases of chronic rejection treated with ECP, seven patients (47%) were bridged to retransplant. Four patients (27%) were not retransplant candidates and died due to progressive respiratory failure. The remaining four patients (27%) are alive and have not been retransplanted to date. Among the seven patients with PFT data, five patients (71%) had an improvement in FEV1 decline following ECP. During the year preceding ECP patients had an average decline in FEV1 of 1.7ml/day, and in the year following treatment their decline was 0.5ml/day, a mean improvement of 1.2ml/day (95% confidence interval -0.2 to 2.7, p=0.08). ConclusionECP can be used as a bridge to retransplant in pediatric lung transplant recipients with chronic rejection. There is a trend toward improvement in FEV1 decline among patients receiving ECP therapy. Further study is necessary to compare the measured efficacy against other chronic rejection therapies, determine optimal timing of ECP in pediatric lung transplant patients, and to identify whether there are certain patients -- by underlying diagnosis, or by disease severity, for example -- who are most likely to benefit from ECP. ECP can be used as a bridge to retransplant in pediatric lung transplant recipients with chronic rejection. There is a trend toward improvement in FEV1 decline among patients receiving ECP therapy. Further study is necessary to compare the measured efficacy against other chronic rejection therapies, determine optimal timing of ECP in pediatric lung transplant patients, and to identify whether there are certain patients -- by underlying diagnosis, or by disease severity, for example -- who are most likely to benefit from ECP.

Cystatin C (CyC) concentration has been suggested as a marker of middle-molecule accumulation, hemodialysis (HD) adequacy and for estimating residual renal function (RRF), but it has not been studied in pediatric HD. High CyC is associated with increased cardiovascular disease (CVD). We investigated CyC kinetics and the effect of RRF on CyC in a pediatric HD population.

Middle-molecules (MM) are not monitored in children on hemodialysis (HD), but are accumulated and increase the risk of cardiovascular disease and mortality. Molecular properties of Cystatin C (CyC), 13 kDa, potentially make it a preferred MM marker over Beta-2-Microglobulin (B2M), 12 kDa. We compared CyC and B2M kinetics to investigate if CyC can be used as preferred MM marker. CyC (mg/L) and B2M (μg/mL) were measured in 21 low-flux HD sessions in seven children. Blood samples were taken at HD start (pre), 1 and 2 hours into HD and at end of HD (post) for all sessions and 60 minutes after the first HD (Eq). PreCyC (9.85 ± 2.15) did not differ (P > 0.05) from postCyC (10.04 ± 2.83). PostB2M (38.87 ± 7.12) was higher (P < 0.05) than preHD B2M (33.27 ± 7.41). There was no change in CyC at 1 and 2 hours into HD, while B2M progressively increased. CyC or B2M changes did not significantly correlate with spKt/V (2.09 ± 0.86), ultrafiltration (4.61 ± 1.98%) or HD duration (218 ± 20 minutes). EqCyC was not different from postCyC (11.07 ± 3.14 vs. 10.71 ± 2.85, P > 0.05), while EqB2M was lower than postB2M (36.48 ± 7.68 vs. 41.09 ± 8.99, P < 0.05). MMs as represented by B2M and CyC are elevated in children on standard HD. Intensified HD modalities would be needed for their removal. B2M is affected by the dialytic process with a rise during HD independent of ultrafiltration and decrease 1 hour after, while CyC remains unchanged. We suggest that CyC be used as preferred marker of MM removal and as a marker of adequacy of intensified HD regimens.

OBJECTIVES:To determine if interventions during the pre-hemolytic uremic syndrome (HUS) diarrhea phase are associated with maintenance of urine output during HUS. DESIGN:Prospective observational cohort study. SETTINGS:Eleven pediatric hospitals in the United States and Scotland. PARTICIPANTS:Children younger than 18 years with diarrhea-associated HUS (hematocrit level <30% with smear evidence of intravascular erythrocyte destruction), thrombocytopenia (platelet count <150 × 10³/mm³), and impaired renal function (serum creatinine concentration > upper limit of reference range for age). INTERVENTIONS:Intravenous fluid was given within the first 4 days of the onset of diarrhea. OUTCOME MEASURE:Presence or absence of oligoanuria (urine output ≤ 0.5 mL/kg/h for >1 day). RESULTS:The overall oligoanuric rate of the 50 participants was 68%, but was 84% among those who received no intravenous fluids in the first 4 days of illness. The relative risk of oligoanuria when fluids were not given in this interval was 1.6 (95% confidence interval, 1.1-2.4; P = .02). Children with oligoanuric HUS were given less total intravenous fluid (r = -0.32; P = .02) and sodium (r = -0.27; P = .05) in the first 4 days of illness than those without oligoanuria. In multivariable analysis, the most significant covariate was volume infused, but volume and sodium strongly covaried. CONCLUSIONS:Intravenous volume expansion is an underused intervention that could decrease the frequency of oligoanuric renal failure in patients at risk of HUS.

A published article ‘‘Contaminated heparin associated with adverse clinical events and activation of the contact system,’’ Kishimoto et al, New England Journal of Medicine, 2008; 358:2457-2467, demonstrated that contaminated heparin induced contact system activation. To better understand why only subpopulations of patients experienced contaminated heparin-induced anaphylactic reactions, we systematically examined the contact system proteins from 6 hemodialysis patient plasmas obtained from St Louis Children’s Hospital where contaminated heparin-induced anaphylactic reactions were initially established. We discovered that plasma from patients affected by contaminated heparin already showed an activated contact system. Therefore, the contaminated heparin-induced bradykinin production and the subsequent bradykinin-induced hypotension-associated adverse events revealed by an animal model and normal human plasma studies might not be the same molecular mechanism manifested by the affected patients. Heparin is the most highly sulfated naturally occurring glycosaminoglycan (GAG). Heparin is enriched in porcine, ovine, bovine intestines, or bovine lung entrails along with less sulfated GAGs, including heparan sulfate, dermatan sulfate, and chondroitin sulfate. These GAGs are made by all animal cells and are present in all tissues. Pharmaceutical grade heparin is prepared from crude heparin by the removal of the less sulfated GAGs, the so-called heparin by-product, from heparin. The highly charged heparin has much higher anticoagulation activities compared to the less sulfated heparin byproduct. In 2007 and 2008, hundreds of anaphylactic reactions and at least 149 deaths were associated with contaminated heparin. Published reports have suggested that the contaminants in heparin include an impurity, specifically dermatan sulfate, and a contaminant, oversulfated chondroitin sulfate (OSCS) presumed to derive from animal cartilage. We identified heparin contaminants as chemically oversulfated or chemically sulfated/desulfated heparin by-products. We further observed that treatment of normal human plasmas with several species of oversulfated GAGs, including OSCS, oversulfated heparan sulfate, oversulfated dermatan sulfate, and oversulfated heparin by-product (OS-HB), induced not only contact system activation (as indicated by the generation of kallikrein-like activity) but also thrombin-like activity. These observations suggest that the molecular mechanism underlying the contaminated heparin-associated adverse events might be more complex than the established model. To understand the contaminated heparininduced anaphylactic reactions, we systematically examined the contact system proteins from 6 hemodialysis patient plasmas. Patients H1 and H4 had typical anaphylactic reactions and patient H2 had delayed anaphylactic reactions induced by contaminated heparin during hemodialysis. The plasmas were obtained 4 and 5 months after the anaphylactic From the Departments of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA (YQ, JP, XZ, PW, HL, AMB, LZ); and Pfizer Inc. Chesterfield MO, USA (FFS).

Five Missouri patients infected with Escherichia coli O157:H7 were studied for an epidemiologically plausible association. Case isolates, case interviews, and pathogen and meat XbaI pulsed field electrophoresis patterns were consistent with the common source being contaminated, fermented deer sausage, a previously unrecognized mode of transmission for Escherichia coli O157:H7.

Identification and treatment of hypertension should be an important focus of physicians caring for children. Ultimately, a link between hypertension in children and the risk of cardiovascular disease will be established. Further long-term studies are likely to show that morbidity and mortality will be decreased by the institution of treatment of hypertension in children. Additional risk factors such as obesity and lipid disorders should be sought and targeted for treatment as well. Lifestyle modifications are advised for all patients and can be tried solely for those with blood pressures between the 95th and 99th percentiles. Drug therapy is indicated in children with blood pressures greater than the 99th percentile, secondary hypertension, coexisting diabetes, left ventricular hypertrophy, or those who fail a trial of nonpharmacologic treatment. Children with white coat hypertension should not be treated with drugs. Children with renal artery stenosis and drug-refractory hypertension should be considered for percutaneous angioplasty or surgery depending on the anatomy of the lesion and operator experience. Children requiring multiple drug classes for control of blood pressure and older adolescents on one drug with renal artery lesions amenable to a percutaneous procedure may elect intervention in an attempt to reduce or eliminate drug therapy. Infants and children with hypertension due to native coarctation of the aorta should undergo surgical repair. Older children and adolescents with native coarctation should have surgical repair or percutaneous angioplasty/stenting. Hypertension secondary to recurrent coarctation is usually treated with a percutaneous intervention.

The effect of prophylactic antibiotics on the occurrence of peritonitis in the 14 days following surgical peritoneal dialysis catheter placement was evaluated. Medical records from 73 pediatric patients who had 89 Tenckhoff catheters inserted over 6 years were reviewed. Twelve catheter procedures were excluded for rapid catheter loss, unavailable charts, eosinophilic peritonitis, and antibiotic administration >3 h postoperatively. Chi-squared analysis for non-continuous variables compared factors at the time of catheter placement with outcome (peritonitis). Thirteen patients developed postoperative peritonitis when 77 catheter insertions were analyzed (17%). Peritonitis was significantly more common in patients who did not receive perioperative antibiotics (7 of 16 catheter placements) (λ2 = 12.48, P≤0.001). The reduced incidence of peritonitis was not specific to any one antibiotic class. Using step-wise logistic regression analysis, no association was found between peritonitis incidence and nephrotic syndrome, immunosuppression, recent surgery (<14 days), acute versus chronic use, year of catheter placement, surgeon, or patient age. Catheter type, implantation technique, exit site care, and operative wound care did not vary. These results indicate that perioperative peritonitis episodes can be significantly reduced by the use of prophylactic antibiotics prior to or at the time of surgery.