Portal vein complications and outcomes following pediatric liver transplantation: Data from the Society of Pediatric Liver Transplantation.

Children who undergo liver transplantation are at risk for portal vein complications (PVCs) including thrombosis (PVT) and stenosis (PVS). Using multicenter data from the Society of Pediatric Liver Transplantation, we analyzed the prevalence, timing, and risk factors for PVC following a first liver transplantation, and assessed the potential impact of PVC on patient outcomes. Our cohort included 4278 patients, of whom 327 (7.6%) developed PVC. Multivariate analysis discovered several factors independently associated with PVC: younger recipient age, lower weight at time of transplantation, diagnosis of biliary atresia (BA), receiving a technical variant graft (TVG), warm ischemia time over 3 h, PVT in the recipient's pretransplantation native liver, and concurrent hepatic artery thrombosis (all p < 0.05). Subgroup analysis of those with BA found higher prevalence in patients transplanted at less than 2 years of age and those with TVGs. There was no difference in PVC prevalence among patients with BA with vs. without prior Kasai portoenterostomy. Most PVT (77.7%) presented within 90 days after transplantation. Patients with PVC had a higher risk of graft failure (23.9% vs. 8.3%; adjusted hazard ratio [HR], 3.08; p < 0.001) and a higher risk of death (16.4% vs. 8.9%; adjusted HR, 1.96; p = 0.01). Recurrence after retransplantation was similar to the overall prevalence in the cohort (8.2%). Our results recognize the common occurrence of PVC following pediatric liver transplantation, describe independently associated risk factors, and determine that patients with PVC have worse outcomes. Further studies are needed to improve PVC prevention, detection, and management strategies.

Real-world treatment drop-off among recurrent or metastatic cervical cancer patients: A US community oncology-based analysis.

OBJECTIVE: Understanding real-world treatment patterns and proportions of eligible patients in each line of treatment is imperative to inform future clinical trial designs and multi-line treatment algorithm development. METHODS: We conducted a retrospective observational cohort study of adult women who received first-line (1 L) therapy for r/mCC between 01 September 2014 and 31 December 2019, using The US Oncology Network electronic health records and chart review data. Patients were followed to 31 December 2020. Patient demographic and clinical characteristics, treatment patterns, and clinical outcomes were assessed descriptively. RESULTS: A total of 262 patients with r/mCC met study inclusion criteria (mean age = 53 years). The majority of patients in 1 L received platinum-based chemotherapy doublet plus bevacizumab (66%) or chemotherapy doublet alone (24%). Nearly half the patients (48%) completing 1 L received 2 L therapy. Among these patients, there was no consistent 2 L treatment of choice. Overall median time to treatment discontinuation was 3.5 months from 1 L treatment initiation, and median overall treatment-free interval was 2.1 months from 1 L discontinuation. Besides elevated serum creatinine, abnormal BMI indicated a directional trend for lower likelihood of receiving 2 L. Other predictors may include no prior bevacizumab, worse ECOG, and earlier disease prevention. CONCLUSIONS: >50% of the patients who initiated 1 L treatment did not receive 2 L therapy, highlighting the need for novel and effective treatment options. As the treatment landscape continues to evolve, we anticipate that more patients will live longer with more treatment options across multiple lines of therapies in the r/mCC setting.

Burden and Correlates of Mental Health Symptoms Among Young Black Gay, Bisexual, and Other Men Who Have Sex with Men Engaged in HIV Care in Atlanta.

Mental health comorbidities are prevalent among young Black gay, bisexual, and other men who have sex with men (YB-GBMSM) living with HIV and can adversely impact HIV-related outcomes. We conducted a cross-sectional survey study with 100 YB-GBMSM recruited from two HIV care centers in Atlanta, and constructed multivariable logistic and linear regression models to examine correlates of depression, anxiety, trauma symptoms, and general well-being. In adjusted models, full-time employment was associated with fewer depressive symptoms, while HIV stigma and substance use were associated with higher levels of depressive symptoms. Younger age and full-time employment were negatively associated with severe anxiety, while HIV stigma was positively associated with severe anxiety and trauma symptoms. Trust in physicians, lower HIV stigma, full-time employment, and lack of substance use were associated with higher average general well-being scores. In conclusion, we found high frequency of depressive, anxiety, and trauma-related symptoms among this sample of YB-GBMSM living with HIV. Unemployment, substance use, and HIV stigma emerged as particularly salient correlates of psychological morbidity, suggesting a need for structural and community-level interventions to address mental health in this population.

Randomized trial of two maintenance doses of vitamin D in children with chronic kidney disease.

BACKGROUND: Correction of nutritional vitamin deficiency is recommended in children with chronic kidney disease (CKD). The optimal daily dose of vitamin D to achieve or maintain vitamin D sufficiency is unknown. METHODS: We conducted a phase III, double-blind, randomized trial of two doses of vitamin D3 in children ≥ 9 years of age with CKD stages 3-5 or kidney transplant recipients. Patients were randomized to 1000 IU or 4000 IU of daily vitamin D3 orally. We measured 25-hydroxvitamin D (25(OH)D) levels at baseline, 3 months and 6 months. The primary efficacy outcome was the percentage of patients who were vitamin D replete (25(OH)D ≥ 30 ng/mL) at 6 months. RESULTS: Ninety-eight patients were enrolled: 49 randomized into each group. Eighty (81.6%) patients completed the study and were analyzed. Baseline plasma 25(OH)D levels were ≥ 30 ng/mL in 12 (35.3%) and 12 (27.3%) patients in the 1000 IU and 4000 IU treatment groups, respectively. At 6 months, plasma 25(OH)D levels were ≥ 30 ng/mL in 33.3% (95% CI: 18.0-51.8%) and 74.4% (95% CI: 58.8-86.5%) in the 1000 IU and 4000 IU treatment groups, respectively (p = 0.0008). None of the patients developed vitamin D toxicity or hypercalcemia. CONCLUSIONS: In children with CKD, 1000 IU of daily vitamin D3 is unlikely to achieve or maintain a plasma 25(OH)D ≥ 30 ng/mL. In children with CKD stages 3-5, a dose of vitamin D3 4000 IU daily was effective in achieving or maintaining vitamin D sufficiency. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01909115.

Evaluation of a Multifaceted Protocol in Reducing Unnecessary Telemetry Monitoring across a Large Healthcare System.

OBJECTIVES: Telemetry is frequently overused in hospitals. The goal of this study was to evaluate a telemetry protocol aimed at decreasing inappropriate telemetry utilization across four different hospitals within a large healthcare system by modifying the electronic telemetry order to incorporate the 2017 American Heart Association practice guidelines on the appropriate use of telemetry and using an electronic nursing screening task form to safely discontinue telemetry. METHODS: We performed a retrospective analysis of telemetry utilization before and after we implemented a protocol across four hospitals within a large healthcare system. We compared the average number of days of telemetry monitoring and hospital length of stay during the preintervention period with the 6-month postintervention period. RESULTS: There were a total of 23,774 encounters evaluated. There was a statistically and clinically significant 24% decrease in telemetry duration between pre- and postintervention time periods (P < 0.0001). The mean (standard error) telemetry duration was 4.11 (0.17) and 2.36 (0.13) days in pre- and postintervention periods, respectively. CONCLUSIONS: The results of our study demonstrate a statistically significant decrease in overall duration of telemetry monitoring by nearly 1.75 days across each of the four hospitals with the implementation of a multifaceted telemetry protocol that included hardwiring the American Heart Association practice guidelines into the electronic order and using a nursing-driven discontinuation protocol.

Fast track dialysis: Improving emergency department and hospital throughput for patients requiring hemodialysis.

OBJECTIVE: To describe the impact of a novel communication and triage pathway called fast track dialysis (FTD) on the length of stay (LOS), resource utilization, and charges for unscheduled hemodialysis for end stage renal disease (ESRD) patients presenting to the emergency department (ED). METHODS: Prospective and retrospective cohorts of ESRD patients meeting requirements of routine or urgent hemodialysis at a tertiary academic hospital from September 25th, 2016 to September 25th, 2018 in 1 year cohorts. Two sample t-tests were used to compare most outcomes of the cohorts with a Mann-Whitney U test used for skewed data. Nephrology group outcomes were analyzed by two-way ANOVA and Kruskal-Wallis and chi-square tests. RESULTS: There were 98 encounters in the historical cohort and 143 encounters in the fast track dialysis cohort. FTD had significantly lowered median ED LOS (4.05 h, vs 5.3 h, p < 0.001), median hospital LOS (12.8 h vs 27 h, p < 0.001), time to hemodialysis (4.78 h vs 7.29 h, p < 0.001), and median hospital charges ($26,040 vs $30,747, p < 0.016). The FTD cohort had increased 30 day ED return for each encounter compared to the historical cohort (1.85 visits vs 0.73 visits, p < 0.001), however no significant increase in 1 year ED visits (6.52 visits vs 5.80, p = 0.4589) or 1 year readmissions (5.89 readmissions vs 4.81 readmissions, p = 0.3584). Most nephrology groups had significantly lower time to hemodialysis order placement and time to start hemodialysis. CONCLUSION: A multidisciplinary approach with key stakeholders using a standard pathway can lead to improved efficiency in throughput, reduced charges, and hospital resource utilization for patients needing urgent or routine hemodialysis. A study with a dedicated geographic observation unit for protocolized short stay patients including conditions ranging from low risk chest pain to transient ischemic events that incorporates FTD patients under this protocol should be considered.

Predicting Breakthrough Urinary Tract Infection: Comparative Analysis of Vesicoureteral Reflux Index, Reflux Grade and Ureteral Diameter Ratio.

PURPOSE: The vesicoureteral reflux index is a simple, validated tool for predicting resolution of reflux. Along with likelihood of spontaneous resolution identification of children at risk for febrile urinary tract infection impacts management. We evaluated the usefulness of the vesicoureteral reflux index as a predictive factor for breakthrough febrile urinary tract infection compared to reflux grade and distal ureteral diameter ratio. MATERIALS AND METHODS: Children with primary vesicoureteral reflux and detailed voiding cystourethrogram data were identified. A 1 to 6-point index was assigned, and ureteral diameter ratio was computed by measuring largest ureteral diameter within the pelvis and dividing by the distance between L1 to L3 vertebral bodies. Random forest modeling and logistic multivariable regression were employed to estimate the predictive ability of grade, ureteral diameter ratio and vesicoureteral reflux index with regard to breakthrough febrile urinary tract infection. RESULTS: We analyzed 94 girls and 45 boys with a mean±SD age of 5.4±4.7 months at diagnosis. Mean±SD length of followup was 32.1±24.5 months. A total of 13 children (9.4%) experienced breakthrough febrile urinary tract infection. On univariate analysis ureteral diameter ratio (p=0.01) and vesicoureteral reflux index (p=0.0005) were associated with breakthrough urinary tract infection, while grade (p=0.09) did not reach significance. Area under the curve was generated as a measure of accuracy for each variable and was 0.77 for the vesicoureteral reflux index, 0.71 for ureteral diameter ratio and 0.68 for grade, indicating superiority of the vesicoureteral reflux index for predicting breakthrough febrile urinary tract infection. CONCLUSIONS: Children with higher vesicoureteral reflux index are at increased risk for breakthrough febrile urinary tract infection independent of reflux grade. The vesicoureteral reflux index provides valuable prognostic information about infection risk, facilitating improved clinical decision making.

Correction to: Geographic surveillance of community associated MRSA infections in children using electronic health record data.

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Geographic surveillance of community associated MRSA infections in children using electronic health record data.

BACKGROUND: Community- associated methicillin resistant Staphylococcus aureus (CA-MRSA) cause serious infections and rates continue to rise worldwide. Use of geocoded electronic health record (EHR) data to prevent spread of disease is limited in health service research. We demonstrate how geocoded EHR and spatial analyses can be used to identify risks for CA-MRSA in children, which are tied to place-based determinants and would not be uncovered using traditional EHR data analyses. METHODS: An epidemiology study was conducted on children from January 1, 2002 through December 31, 2010 who were treated for Staphylococcus aureus infections. A generalized estimated equations (GEE) model was developed and crude and adjusted odds ratios were based on S. aureus risks. We measured the risk of S. aureus as standardized incidence ratios (SIR) calculated within aggregated US 2010 Census tracts called spatially adaptive filters, and then created maps that differentiate the geographic patterns of antibiotic resistant and non-resistant forms of S. aureus. RESULTS: CA-MRSA rates increased at higher rates compared to non-resistant forms, p = 0.01. Children with no or public health insurance had higher odds of CA-MRSA infection. Black children were almost 1.5 times as likely as white children to have CA-MRSA infections (aOR 95% CI 1.44,1.75, p < 0.0001); this finding persisted at the block group level (p < 0.001) along with household crowding (p < 0.001). The youngest category of age (< 4 years) also had increased risk for CA-MRSA (aOR 1.65, 95%CI 1.48, 1.83, p < 0.0001). CA-MRSA encompasses larger areas with higher SIRs compared to non-resistant forms and were found in block groups with higher proportion of blacks (r = 0.517, p < 0.001), younger age (r = 0.137, p < 0.001), and crowding (r = 0.320, p < 0.001). CONCLUSIONS: In the Atlanta MSA, the risk for CA-MRSA is associated with neighborhood-level measures of racial composition, household crowding, and age of children. Neighborhoods which have higher proportion of blacks, household crowding, and children < 4 years of age are at greatest risk. Understanding spatial relationship at a community level and how it relates to risks for antibiotic resistant infections is important to combat the growing numbers and spread of such infections like CA-MRSA.

Comparative Effectiveness of a Web-Based Patient Decision Aid for Therapeutic Options for Sickle Cell Disease: Randomized Controlled Trial.

BACKGROUND: Hydroxyurea, chronic blood transfusions, and bone marrow transplantation are efficacious, disease-modifying therapies for sickle cell disease but involve complex risk-benefit trade-offs and decisional dilemma compounded by the lack of comparative studies. A patient decision aid can inform patients about their treatment options, the associated risks and benefits, help them clarify their values, and allow them to participate in medical decision making. OBJECTIVE: The objective of this study was to develop a literacy-sensitive Web-based patient decision aid based on the Ottawa decision support framework, and through a randomized clinical trial estimate the effectiveness of the patient decision aid in improving patient knowledge and their involvement in decision making. METHODS: We conducted population decisional needs assessments in a nationwide sample of patients, caregivers, community advocates, policy makers, and health care providers using qualitative interviews to identify decisional conflict, knowledge and expectations, values, support and resources, decision types, timing, stages and learning, and personal clinical characteristics. Interview transcripts were coded using QSR NVivo 10. Alpha testing of the patient decision aid prototype was done to establish usability and the accuracy of the information it conveyed, and then was followed by iterative cycles of beta testing. We conducted a randomized clinical trial of adults and of caregivers of pediatric patients to evaluate the efficacy of the patient decision aid. RESULTS: In a decisional needs assessment, 223 stakeholders described their preferences, helping to guide the development of the patient decision aid, which then underwent alpha testing by 30 patients and 38 health care providers and iterative cycles of beta testing by 87 stakeholders. In a randomized clinical trial, 120 participants were assigned to either the patient decision aid or standard care (SC) arm. Qualitative interviews revealed high levels of usability, acceptability, and utility of the patient decision aid in education, values clarification, and preparation for decision making. On the acceptability survey, 72% (86/120) of participants rated the patient decision aid as good or excellent. Participants on the patient decision aid arm compared to the SC arm demonstrated a statistically significant improvement in decisional self-efficacy (P=.05) and a reduction in the informed sub-score of decisional conflict (P=.003) at 3 months, with an improvement in preparation for decision making (P<.001) at 6 months. However, there was no improvement in terms of the change in knowledge, the total or other domain scores of decisional conflicts, or decisional self-efficacies at 6 months. The large amount of missing data from survey completion limited our ability to draw conclusions about the effectiveness of the patient decision aid. The patient decision aid met 61 of 62 benchmarks of the international patient decision aid collaboration standards for content, development process, and efficacy. CONCLUSIONS: We have developed a patient decision aid for sickle cell disease with extensive input from stakeholders and in a randomized clinical trial demonstrated its acceptability and utility in education and decision making. We were unable to demonstrate its effectiveness in improving patient knowledge and involvement in decision making. TRIAL REGISTRATION: ClinicalTrials.gov NCT03224429; https://clinicaltrials.gov/ct2/show/NCT03224429 and ClinicalTrials.gov NCT02326597; https://clinicaltrials.gov/ct2/show/NCT02326597.

Hemoglobin A clearance in children with sickle cell anemia on chronic transfusion therapy.

BACKGROUND: Chronic transfusion therapy for sickle cell anemia reduces disease complications by diluting sickle-erythrocytes with hemoglobin A (HbA)-containing erythrocytes and suppressing erythropoiesis. Minor antigen mismatches may result in alloimmunization, but it is unknown if antigen mismatches or recipient characteristics influence HbA clearance posttransfusion. STUDY DESIGN AND METHODS: Children with sickle cell anemia on chronic transfusion therapy were followed prospectively for 12 months. All patients received units serologically matched for C/c, E/e, and K; patients with prior red blood cell (RBC) antibodies had additional matching for Fya , Jkb , and any previous alloantibodies. Patients' RBC antigen genotypes, determined by multiplexed molecular assays (PreciseType Human Erythrocyte Antigen, and RHCE and RHD BeadChip, Immucor) were compared to genotypes of transfused RBC units to assess for antigen mismatches. Decline in hbA (ΔHbA) from posttransfusion to the next transfusion was calculated for each transfusion episode. RESULTS: Sixty patients received 789 transfusions, 740 with ΔHbA estimations, and 630 with donor Human Erythrocyte Antigen genotyping. In univariate mixed-model analysis, ΔHbA was higher in patients with past RBC antibodies or splenomegaly and lower in patients with splenectomy. RBC antigen mismatches were not associated with ΔHbA. In multivariate linear mixed-effects modeling, ΔHbA was associated with RBC antibodies (2.70 vs. 2.45 g/dL/28 d, p = 0.0028), splenomegaly (2.87 vs. 2.28 g/dL/28 d, p = 0.019), and negatively associated with splenectomy (2.46 vs. 2.70 g/dL/28 d, p = 0.011). CONCLUSIONS: HbA decline was increased among patients with sickle cell anemia with prior immunologic response to RBC antigens and decreased among those with prior splenectomy, demonstrating that recipient immunologic characteristics influenced the clearance of transfused RBCs.

Distal Ureteral Diameter Ratio is Predictive of Breakthrough Febrile Urinary Tract Infection.

PURPOSE: Distal ureteral diameter ratio is an objective measure that is prognostic of spontaneous resolution of vesicoureteral reflux. Along with likelihood of resolution, improved identification of children at risk for recurrent febrile urinary tract infections may impact management decisions. We evaluated the usefulness of ureteral diameter ratio as a predictive factor for breakthrough febrile urinary tract infections. MATERIALS AND METHODS: Children with primary vesicoureteral reflux and detailed voiding cystourethrogram were identified. Ureteral diameter ratio was computed by measuring largest ureteral diameter within the pelvis and dividing by the distance between L1 and L3 vertebral bodies. Demographics, vesicoureteral reflux grade, laterality, presence/absence of bladder-bowel dysfunction, and ureteral diameter ratio were tested in univariate and multivariable analyses. Primary outcome was breakthrough febrile urinary tract infections. RESULTS: We analyzed 112 girls and 28 boys with a mean ± SD age of 2.5 ± 2.3 years at diagnosis. Vesicoureteral reflux was grade 1 to 2 in 64 patients (45.7%), grade 3 in 50 (35.7%), grade 4 in 16 (11.4%) and grade 5 in 10 (7.2%). Mean ± SD followup was 3.2 ± 2.7 years. A total of 40 children (28.6%) experienced breakthrough febrile urinary tract infections. Ureteral diameter ratio was significantly greater in children with (0.36) vs without (0.25) breakthrough febrile infections (p = 0.004). Controlling for vesicoureteral reflux grade, every 0.1 U increase in ureteral diameter ratio resulted in 1.7 times increased odds of breakthrough infection (95% CI 1.24 to 2.26, p <0.0001). CONCLUSIONS: Children with increased distal ureteral diameter ratio are at greater risk for breakthrough febrile urinary tract infections independent of reflux grade. Ureteral diameter ratio provides valuable prognostic information about risk of recurrent pyelonephritis and may assist with clinical decision-making.

Red blood cell minor antigen mismatches during chronic transfusion therapy for sickle cell anemia.

BACKGROUND: Red blood cell (RBC) alloimmunization occurs at a high frequency in sickle cell anemia (SCA) despite serologic matching for Rh (C/c, E/e) and K antigens. RBC minor antigen genotyping allows for prediction of antigens and RH variants that may lead to alloimmunization. STUDY DESIGN AND METHODS: RBC antigen genotyping was performed on chronically transfused pediatric SCA patients, using PreciseType human erythrocyte antigen (HEA), RHCE, and RHD BeadChip arrays. All patients received C/c, E/e, and K serologically matched units (Category 1); patients with prior RBC antibodies were also matched for Fya , Jkb , and any antibodies (Category 2). The RBC genotypes of all leukoreduced (LR) units transfused over a 12-month period were determined by the prototype HEA-LR BeadChip assay. RESULTS: There were 2320 RBC units transfused to 90 patients in 1135 transfusion episodes. Thirty-five (38.9%) patients had homozygous or compound heterozygous RH variants. Seven new alloantibodies were detected, with alloantibody incidence of 0.706 in 100 units for Category 2 transfusions and 0.068 in 100 units for Category 1 (p = 0.02). Three patients on Category 2 transfusions formed new anti-Jsa and had a higher rate of exposure to Jsa than those who did not form anti-Jsa (20.4 vs. 8.33 exposures/100 units, p = 0.02). The most frequent mismatches were S (43.9%), Doa (43.9%), Fya (29.2%), M (28.4%), and Jkb (28.1%). CONCLUSIONS: Alloimmunization incidence was higher in those with prior RBC antibodies, suggesting that past immunologic responders are at higher risk for future alloimmunization and therefore may benefit from more extensive antigen matching beyond C/c, E/e, K, Fya , and Jkb .

Rotavirus vaccination rate disparities seen among infants with acute gastroenteritis in Georgia.

OBJECTIVE: Rotavirus (RV) is one of the most common diarrheal diseases affecting children less than 5 years of age. RV vaccines have greatly reduced this burden in the United States. The purpose of this study was to determine possible disparities and socio-economic differences in RV vaccination rates. DESIGN: Children with acute gastroenteritis were enrolled. Stool was tested for presence of rotavirus using an enzyme immunoassay kit. Vaccination records were abstracted from the state immunization registry and healthcare providers to examine complete and incomplete vaccination status. Cases were identified as children receiving a complete RV dose series and controls were identified as children with incomplete RV doses. A logistic regression model was used to determine disparities seen amongst children with incomplete vaccination status. RESULTS: Racial differences between Black and white infants for RV vaccination rates were not significant when controlling for covariates (OR 1.15, 95% CI 0.74-1.78); however ethnicity (p-value .0230), age at onset of illness (p-value .0004), birth year (p-value < .0001), and DTaP vaccination status (p-value < .0001) were all significant in determining vaccination status for children. CONCLUSIONS: Racial disparities and socio-economic differences are not determinants in rotavirus vaccination rates; however, age and ethnicity have an effect on RV vaccine status.

Efficacy and Safety of Glutamine-supplemented Parenteral Nutrition in Surgical ICU Patients: An American Multicenter Randomized Controlled Trial.

OBJECTIVE: To determine whether glutamine (GLN)-supplemented parenteral nutrition (PN) improves clinical outcomes in surgical intensive care unit (SICU) patients. SUMMARY BACKGROUND DATA: GLN requirements may increase with critical illness. GLN-supplemented PN may improve clinical outcomes in SICU patients. METHODS: A parallel-group, multicenter, double-blind, randomized, controlled clinical trial in 150 adults after gastrointestinal, vascular, or cardiac surgery requiring PN and SICU care. Patients were without significant renal or hepatic failure or shock at entry. All received isonitrogenous, isocaloric PN [1.5 g/kg/d amino acids (AAs) and energy at 1.3× estimated basal energy expenditure]. Controls (n = 75) received standard GLN-free PN (STD-PN); the GLN group (n = 75) received PN containing alanyl-GLN dipeptide (0.5 g/kg/d), proportionally replacing AA in PN (GLN-PN). Enteral nutrition (EN) was advanced and PN weaned as indicated. Hospital mortality and infections were primary endpoints. RESULTS: Baseline characteristics, days on study PN and daily macronutrient intakes via PN and EN, were similar between groups. There were 11 hospital deaths (14.7%) in the GLN-PN group and 13 deaths in the STD-PN group (17.3%; difference, -2.6%; 95% confidence interval, -14.6% to 9.3%; P = 0.66). The 6-month cumulative mortality was 31.4% in the GLN-PN group and 29.7% in the STD-PN group (P = 0.88). Incident bloodstream infection rate was 9.6 and 8.4 per 1000 hospital days in the GLN-PN and STD-PN groups, respectively (P = 0.73). Other clinical outcomes and adverse events were similar. CONCLUSIONS: PN supplemented with GLN dipeptide was safe, but did not alter clinical outcomes among SICU patients.

Vesicoureteral Reflux Index: 2-Institution Analysis and Validation.

PURPOSE: The vesicoureteral reflux index is a novel tool designed to predict spontaneous reflux resolution in infants younger than 2 years. We performed a multi-institutional validation study to confirm the discriminatory power of the vesicoureteral reflux index to predict the vesicoureteral reflux resolution rate in young children. MATERIALS AND METHODS: We identified patients diagnosed with primary vesicoureteral reflux before age 24 months who had 2 or more voiding cystourethrograms available. Demographics, vesicoureteral reflux grade and timing, ureteral anomalies and radiographic outcomes were evaluated. The C-index was estimated for time to event model assessment. RESULTS: A total of 219 girls and 150 boys met study inclusion criteria. Mean ± SD age at diagnosis was 4.7 ± 4.9 months. Of the patients 101 (27.4%) had early to mid filling, 214 (58%) had late filling and 54 (14.6%) had voiding only vesicoureteral reflux. High grade reflux was present in 87 patients (23.6%) and ureteral anomalies were observed in 50 (13.6%). A vesicoureteral reflux index of 1, 2, 3, 4 and 5 or greater showed an improvement/resolution rate of 88.2%, 77.3%, 62.3%, 32.1% and 14.3%, respectively. On time to event analysis children with filling phase vesicoureteral reflux (p <0.001), grade 4-5 reflux (p <0.001) and ureteral anomalies (p = 0.003) had significantly longer median time to resolution. Median time to spontaneous resolution was 12.6, 12.7, 15.1, 25.6 and 31 months or greater for a vesicoureteral reflux index of 1, 2, 3, 4 and 5 or greater, respectively (C-index 0.305, 95% CI 0.252-0.357). During the study period 65 patients (17.6%) underwent surgical intervention. CONCLUSIONS: The vesicoureteral reflux index is a simple tool that reliably predicts significant improvement and spontaneous resolution of primary reflux in patients diagnosed at younger than 2 years. The index provides valuable prognostic information, facilitating individualized patient care.

Effectiveness of red blood cell exchange, partial manual exchange, and simple transfusion concurrently with iron chelation therapy in reducing iron overload in chronically transfused sickle cell anemia patients.

BACKGROUND: Chronic transfusion therapy (CTT) is indicated for stroke prevention in children with sickle cell anemia (SCA) and is complicated by iron overload and alloimmunization. CTT is performed by simple transfusion (ST), partial manual exchange (PME), or erythrocytapheresis (RCE). Although small case series have demonstrated RCE in combination with iron chelation therapy stabilizes and/or decreases ferritin, there are no reports comparing the effect of ST, PME, and RCE on liver iron concentration (LIC). CTT modality effect on serum ferritin and LIC were compared in SCA patients on iron chelation, with hemoglobin (Hb)S goal of 30%. STUDY DESIGN AND METHODS: Medical records of SCA patients on CTT and deferasirox (≥25 mg/kg/day) were retrospectively reviewed. Mean HbS%, change in ferritin and LIC, and alloimmunization rate were determined for each CTT group. RESULTS: Twenty-eight patients were included; six crossed over (one from ST to PME, one from ST to PME then to RCE, three from ST to RCE, and one from PME to RCE) to include 36 transfusion modality intervals. Median pretransfusion HbS% levels were 32.7% (ST), 36.2% (PME), and 34.7% (RCE; p = 0.732). Median ferritin changes were +15 (-17 to +45), +38 (+24 to +105), and -91 (-141 to -48) ng/mL/month (p = 0.003), and median LIC changes (available in 22 patient transfusion modality intervals) were +1.3 (-1.6 to +4.3), +2.3 (-6.5 to +8.9), and -5.7 (-10.7 to -0.5) mg/g/year (p = 0.024) in ST, PME, and RCE, respectively. There was no significant difference in alloimmunization rate between ST/PME and RCE groups. CONCLUSION: We recommend RCE plus chelation as an effective method for reducing iron overload, while maintaining HbS at 30% to 35%.

Optimizing Thrombin Generation with 4-Factor Prothrombin Complex Concentrates in Neonatal Plasma After Cardiopulmonary Bypass.

BACKGROUND: Bleeding is a serious complication after pediatric cardiopulmonary bypass (CPB) that is associated with an increase in perioperative morbidity and mortality. Four-factor prothrombin complex concentrates (4F-PCCs) have been used off-label to supplement transfusion protocols for bleeding after CPB in adults; however, data on their use in neonates are limited. In this study, we hypothesized that 4F-PCCs administered ex vivo to neonatal plasma after CPB will increase thrombin generation. METHODS: Fifteen neonates undergoing complex cardiac repairs requiring CPB were enrolled in this prospective study. Arterial blood was obtained after anesthesia induction but before CPB (baseline), after CPB following heparin reversal, and after our standardized transfusion of a quarter of a platelet apheresis unit (approximately 20 mL·kg) and 3 units of cryoprecipitate. Kcentra (CSL Behring), a 4F-PCC with nonactivated factor VII (FVII), and factor 8 inhibitor bypassing activity (FEIBA; Baxter Healthcare Corporation), a 4F-PCC with activated FVII, were added ex vivo to plasma obtained after CPB to yield concentrations of 0.1 and 0.3 IU·mL. Calibrated automated thrombography was used to determine thrombin generation for each sample. RESULTS: The addition of Kcentra to plasma obtained after CPB resulted in a dose-dependent increase in the median (99% confidence interval) peak amount of thrombin generation (42.0 [28.7-50.7] nM for Kcentra 0.1 IU·mL and 113.9 [99.0-142.1] nM for Kcentra 0.3 IU·mL). The rate of thrombin generation was also increased (15.4 [6.5-24.6] nM·min for Kcentra 0.1 IU·mL and 48.6 [29.9-66.6] nM·min for Kcentra 0.3 IU·mL). The same was true for FEIBA (increase in peak: 39.8 [27.5-49.2] nM for FEIBA 0.1 IU·mL and 104.6 [92.7-124.4] nM for FEIBA 0.3 IU·mL; increase in rate: 17.4 [7.4-28.8] nM·min FEIBA 0.1 IU·mL and 50.5 [26.7- 63.1] nM·min FEIBA 0.3 IU·mL). In the posttransfusion samples, there was a significant increase with Kcentra in the median (99% confidence interval) peak amount (41.1 [21.0-59.7] nM for Kcentra 0.1 IU·mL and 126.8 [106.6- 137.9] nM for Kcentra 0.3 IU·mL) and rate (18.1 [-6.2 to 29.2] nM·min for Kcentra 0.1 IU·mL and 53.2 [28.2-83.1] nM·min for Kcentra 0.3 IU·mL) of thrombin generation. Again, the results were similar for FEIBA (increase in peak: 43.0 [36.4-56.7] nM for FEIBA 0.1 IU·mL and 109.2 [90.3-136.1] nM for FEIBA 0.3 IU·mL; increase in rate: 25.0 [9.1-32.6] nM·min for FEIBA 0.1 IU·mL and 59.7 [38.5-68.7] nM·min for FEIBA 0.3 IU·mL). However, FEIBA produced in a greater median reduction in lag time of thrombin generation versus Kcentra in samples obtained after CPB (P = 0.003 and P = 0.0002 for FEIBA versus Kcentra at 0.1 and 0.3 IU·mL, respectively) and in samples obtained after transfusion (P < 0.0001 for FEIBA versus Kcentra at 0.1 and 0.3 IU·mL). CONCLUSIONS: After CPB, thrombin generation in neonatal plasma was augmented by the addition of 4F-PCCs. The peak amount and rate of thrombin generation were enhanced in all conditions, whereas the lag time was shortened more with FEIBA. Our findings suggest that the use of 4F-PCCs containing activated FVII may be an effective adjunct to the initial transfusion of platelets and cryoprecipitate to augment coagulation and control bleeding in neonates after CPB.

Early effect of American Academy of Pediatrics Urinary Tract Infection Guidelines on radiographic imaging and diagnosis of vesicoureteral reflux in the emergency room setting.

PURPOSE: In 2011 the AAP revised practice parameters on febrile urinary tract infection in infants and children 2 to 24 months old. New imaging recommendations invigorated the ongoing debate regarding the diagnosis and management of vesicoureteral reflux. We compared evaluations in these patients with febrile urinary tract infection before and after guideline publication. MATERIALS AND METHODS: During 2 separate 6-month periods 350 patients 2 to 24 months old were evaluated in the emergency room setting. Demographics, urine culture, renal-bladder ultrasound, voiding cystourethrogram and admission status were assessed. RESULTS: A total of 172 patients presented with initial febrile urinary tract infection in 2011, of whom 47 (27.3%) required hospitalization, while 42 of 178 (23.6%) were admitted in 2012. Admission by year did not significantly differ (p = 0.423). After guideline revision 41.2% fewer voiding cystourethrograms were done (72.1% of cases in 2011 vs 30.9% in 2012, p <0.001). A 17.2% decrease in renal-bladder ultrasound was noted (75.6% in 2011 vs 58.4% in 2012, p <0.001). Of 55 voiding cystourethrograms 21 (38.2%) were positive in 2012 compared to 36.3% in 2011 (p = 0.809). Mean ± SD maximum vesicoureteral reflux grade was unchanged in 2011 and 2012 (2.9 ± 1.2 and 2.5 ± 0.93, respectively, p = 0.109). There was no association between abnormal renal-bladder ultrasound and voiding cystourethrogram positivity (p = 0.116). CONCLUSIONS: AAP guidelines impacted the treatment of infants and young children with febrile urinary tract infection. We found no relationship between renal-bladder ultrasound and abnormal voiding cystourethrogram, consistent with previous findings that call ultrasound into question as the determinant for additional imaging. Whether forgoing routine voiding cystourethrogram results in increased morbidity is the subject of ongoing study.