Streptococcus pneumoniae associated hemolytic uremic syndrome in children.

Introduction: Previous small-scale, single-center investigations of Streptococcus pneumoniae associated hemolytic uremic syndrome (SpHUS) have shown increased disease severity among SpHUS relative to non-SpHUS patients. Our study compares the impact of S. pneumoniae on patient outcomes between SpHUS cases and non-SpHUS controls using the national, multicenter retrospective Pediatric Health Information Systems (PHIS) Database. Methods: Children <18 years of age with a diagnosis of HUS were included. Univariate analyses and multivariable linear and logistic regressions were utilized to assess the impact of S. pneumoniae on mortality, length of stay (LOS), intensive care unit admission (ICU), and mechanical ventilation use. Models were adjusted for demographic and clinical characteristics, including cardiac, neurologic, pulmonary, gastrointestinal, immunologic and renal clinical complications. Results: Of 3,952 index HUS hospitalizations, 231 (5.8%) were due to SpHUS. SpHUS patients had worse outcomes, including longer hospital stays, increased rate of ICU admission, and increased use of mechanical ventilation (p < 0.001 for all). There was a strong positive relationship between clinical complications and adverse outcomes. After adjusting for covariates, SpHUS was associated with an increase in hospital LOS by 3.47 days (p = 0.009) and overall ICU-LOS by 4.21 days (p < 0.001). SpHUS was also associated with increased likelihood of mechanical ventilation (OR: 3.08; p < 0.001), with no increase in ICU admission (p = 0.070) and in-hospital mortality (p = 0.3874). Discussion: Our study highlights that SpHUS patients are at increased risk of multiple adverse outcomes likely due to the summative impact of pneumococcal infection and HUS as well as more frequent clinical complications.

Preparing for kidney replacement therapy in pediatric advanced CKD: a review of literature and defining a multi-disciplinary clinical approach to patient-caregiver education.

Pediatric patients with progressive chronic kidney disease (CKD) approaching kidney replacement therapy (KRT) make up a small population but carry significant morbidity and mortality. Patients and caregivers require comprehensive kidney failure education to ensure a smooth start to KRT. Choice of KRT modality can be influenced by medical comorbidities, patient/caregiver comprehension, and comfort with a particular modality, social and economic factors, and/or implicit bias of the health care team. As KRT modality can influence morbidity, mortality, and quality of life, we created a pediatric advanced CKD clinic to provide comprehensive KRT education and to promote informed decision-making for our advanced CKD patients and their caregivers.

Renal oximetry for early acute kidney injury detection in neonates with hypoxic ischemic encephalopathy receiving therapeutic hypothermia.

BACKGROUND: Neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia are at high risk of acute kidney injury (AKI). METHODS: We performed a two-site prospective observational study from 2018 to 2019 to evaluate the utility of renal near-infrared spectroscopy (NIRS) in detecting AKI in 38 neonates with HIE receiving therapeutic hypothermia. AKI was defined by a delayed rate of serum creatinine decline (< 33% on day 3 of life, < 40% on day 5, and < 46% on day 7). Renal saturation (Rsat) and systemic oxygen saturation (SpO2) were continuously measured for the first 96 h of life (HOL). Renal fractional tissue oxygen extraction (RFTOE) was calculated as (SpO2 - Rsat)/(SpO2). Using renal NIRS, urine biomarkers, and perinatal factors, logistic regression was performed to develop a model that predicted AKI. RESULTS: AKI occurred in 20 of 38 neonates (53%). During the first 96 HOL, Rsat was higher, and RFTOE was lower in the AKI group vs. the no AKI group (P < 0.001). Rsat > 70% had a fair predictive performance for AKI at 48-84 HOL (AUC 0.71-0.79). RFTOE ≤ 25 had a good predictive performance for AKI at 42-66 HOL (AUC 0.8-0.83). The final statistical model with the best fit to predict AKI (AUC = 0.88) included RFTOE at 48 HOL (P = 0.012) and pH of the infants' first postnatal blood gas (P = 0.025). CONCLUSIONS: Lower RFTOE on renal NIRS and pH on infant first blood gas may be early predictors for AKI in neonates with HIE receiving therapeutic hypothermia. A higher resolution version of the Graphical abstract is available as Supplementary information.

Evaluation of lung ultrasound to detect volume overload in children undergoing dialysis.

BACKGROUND: Lung ultrasound is a well-established technique to assess extravascular lung water, a proxy for volume status, in the adult population. Despite its utility, the data are limited supporting the use of ultrasound to evaluate fluid volume status among pediatric patients. Our study uses a simplified ultrasound protocol to evaluate changes in extravascular lung water, represented by b-lines, among pediatric patients undergoing hemodialysis. METHODS: This prospective single-center study included children from birth to 18 years of age. The number of b-lines per ml/kg of fluid removed was compared prior to, at the midpoint, and following termination of dialysis. An 8-zone protocol was utilized, and b-lines were correlated to hemoconcentration measured by the CRIT-LINE® hematocrit. RESULTS: Six patients with a total of 26 hemodialysis sessions were included in this study. The b-line measurements post-dialysis were 2.27 (p < 0.001; 94%CI -3.31, -1.22) lower relative to pre-dialysis. The number of b-lines was reduced by 1.69 (p < 0.001; -2.58, -0.80) between pre-dialysis and at the midpoint of dialysis and by 0.58 (p = 0.001; -0.90, -0.24) between the midpoint of dialysis and post-dialysis. A 1 mL/kg fluid loss correlated to a decrease in the original b-lines by 0.079. An inverse relationship (r = -0.54; 95% CI: -0.72, -0.34; p < 0.001) was noted between the b-lines and the patients' hematocrit levels. CONCLUSIONS: A simplified 8-zone ultrasound protocol can assess fluid volume change in real time and correlates with hematocrit levels obtained throughout dialysis. This provides a valuable method for monitoring fluid status in volume overloaded patient populations. A higher resolution version of the Graphical abstract is available as Supplementary information.

Urine Biomarkers for the Assessment of Acute Kidney Injury in Neonates with Hypoxic Ischemic Encephalopathy Receiving Therapeutic Hypothermia.

OBJECTIVE: To evaluate the predictive performance of urine biomarkers for acute kidney injury (AKI) in neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia. STUDY DESIGN: We performed a multicenter prospective observational study of 64 neonates. Urine specimens were obtained at 12, 24, 48, and 72 hours of life and evaluated for neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), cystatin C, interleukin-18 (IL-18), tissue inhibitor of metalloproteinases 2 (TIMP2), and insulin-like growth factor-binding protein 7 (IGFBP7). Logistic regression models with receiver operating characteristics for area under the curve (AUC) were used to assess associations with neonatal modified KDIGO (Kidney Disease: Improving Global Outcomes) AKI criteria. RESULTS: AKI occurred in 16 of 64 infants (25%). Neonates with AKI had more days of vasopressor drug use compared with those without AKI (median [IQR], 2 [0-5] days vs 0 [0-2] days; P = .026). Mortality was greater in neonates with AKI (25% vs 2%; P = .012). Although NGAL, KIM-1, and IL-18 were significantly associated with AKI, the AUCs yielded only a fair prediction. KIM-1 had the best predictive performance across time points, with an AUC (SE) of 0.79 (0.11) at 48 hours of life. NGAL and IL-18 had AUCs (SE) of 0.78 (0.09) and 0.73 (0.10), respectively, at 48 hours of life. CONCLUSIONS: Urine NGAL, KIM-1, and IL-18 levels were elevated in neonates with HIE receiving therapeutic hypothermia who developed AKI. However, wide variability and unclear cutoff levels make their clinical utility unclear.

Utilization Pattern for Eculizumab Among Children With Hemolytic Uremic Syndrome.

Background: Hemolytic uremic syndrome (HUS) is a complex disease with multi-organ involvement. Eculizumab therapy is recommended for treatment of complement mediated hemolytic uremic syndrome (cHUS). However, there are few studies evaluating eculizumab therapy among children with HUS. The primary objectives of the study were to describe and identify factors associated with eculizumab therapy in children with HUS. Design/Methods: This large, retrospective, multi-center, cohort study used the Pediatric Health Information System (PHIS) database to identify the index HUS-related hospitalization among patients ≤18 years of age from September 23, 2011 (Food and Drug Administration approval date of eculizumab) through December 31, 2018. Multivariate analysis was used to identify independent factors associated with eculizumab therapy during or after the index hospitalization. Results: Among 1,885 children included in the study, eculizumab therapy was noted in 167 children with a median age of 3.99 years (SD ± 4.7 years). Eculizumab therapy was administered early (within the first 7 days of hospitalization) among 65% of children who received the drug. Mortality during the index hospitalization among children with eculizumab therapy was 4.2 vs. 3.0% without eculizumab therapy (p = 0.309). Clinical factors independently associated with eculizumab therapy were encephalopathy [odds ratio (OR) = 3.09; p ≤ 0.001], seizure disorder (OR = 2.37; p = 0.006), and cardiac involvement (OR = 6.36, p < 0.001). Conclusion(s): Only 8.9% of children received eculizumab therapy. Children who presented with neurological and cardiac involvement with severe disease were more likely to receive eculizumab therapy, and children who received therapy received it early during their index hospitalization. Further prospective studies are suggested to confirm these findings.

Cardiac Manifestation among Children with Hemolytic Uremic Syndrome.

OBJECTIVE: The primary objectives of the study were to describe the association between cardiac manifestations and in-hospital mortality among children with hemolytic uremic syndrome. STUDY DESIGN: Using the Pediatric Health Information System database, this retrospective, multicenter, cohort study identified the first hemolytic uremic syndrome-related inpatient visit among children ≤18 years (years 2004-2018). The frequency of selected cardiac manifestations and mortality rates were calculated. Multivariate analysis identified the association of specific cardiac manifestations and the risk of in-hospital mortality. RESULTS: Among 3915 patients in the analysis, 238 (6.1%) had cardiac manifestations. A majority of patients (82.8%; n = 197) had 1 cardiac condition and 17.2% (n = 41) had ≥2 cardiac conditions. The most common cardiac conditions was pericardial disease (n = 102), followed by congestive heart failure (n = 46) and cardiomyopathy/myocarditis (n = 34). The percent mortality for patients with 0, 1, or ≥2 cardiac conditions was 2.1%, 17.3%, and 19.5%, respectively. Patients with any cardiac condition had an increased odds of mortality (OR, 9.74; P = .0001). In additional models, the presence of ≥2 cardiac conditions (OR, 9.90; P < .001), cardiac arrest (OR, 38.25; P < .001), or extracorporeal membrane oxygenation deployment (OR, 11.61; P < .001) were associated with increased risk of in-hospital mortality. CONCLUSIONS: This study identified differences in in-hospital mortality based on the type of cardiac manifestations, with increased risk observed for patients with multiple cardiac involvement, cardiac arrest, and extracorporeal membrane oxygenation deployments.

Targeting Mitochondria during Cold Storage to Maintain Proteasome Function and Improve Renal Outcome after Transplantation.

Kidney transplantation is the preferred treatment for end-stage kidney disease (ESKD). Compared to maintenance dialysis, kidney transplantation results in improved patient survival and quality of life. Kidneys from living donors perform best; however, many patients with ESKD depend on kidneys from deceased donors. After procurement, donor kidneys are placed in a cold-storage solution until a suitable recipient is located. Sadly, prolonged cold storage times are associated with inferior transplant outcomes; therefore, in most situations when considering donor kidneys, long cold-storage times are avoided. The identification of novel mechanisms of cold-storage-related renal damage will lead to the development of new therapeutic strategies for preserving donor kidneys; to date, these mechanisms remain poorly understood. In this review, we discuss the importance of mitochondrial and proteasome function, protein homeostasis, and renal recovery during stress from cold storage plus transplantation. Additionally, we discuss novel targets for therapeutic intervention to improve renal outcomes.

Risk factors for early onset peritonitis: the SCOPE collaborative.

BACKGROUND: Peritoneal dialysis (PD) is the preferred chronic dialysis modality amongst pediatric patients. Peritonitis is a devastating complication of PD. Adult data demonstrates early onset peritonitis (EP) is associated with higher rates of subsequent peritonitis and technique failure. Limited data exists regarding EP in the pediatric population, here defined as peritonitis occurring within 60 days of catheter insertion. METHODS: PD catheter insertion practices and EP episodes were examined from the Standardizing Care to Improve Outcomes in Pediatric End Stage Renal Disease (SCOPE) collaborative database. RESULTS: There were 98 episodes of EP amongst 1106 PD catheters inserted. Multivariable analysis demonstrated a significant association between early use of the PD catheter and EP (P = 0.001). Age less than 1 year at the time of catheter insertion (P < 0.001), first catheter placed (P < 0.001) for the patient, use of a plastic adapter (P = 0.003), placement of sutures at the exit site (ES) (P = 0.032), and dressing change prior to 7 days post-operatively (P < 0.001) were all significantly associated with early PD catheter use. Concurrent placement of a hemodialysis catheter was associated with a decreased risk for early PD catheter use (P = 0.010). CONCLUSIONS: In this large cohort of pediatric PD recipients, 8.4% of PD catheters were associated with the development of EP. The finding of an association between early use of the PD catheter and EP represents a potentially modifiable risk factor to reduce infection rates within this patient population.

Acute kidney injury is associated with increased in-hospital mortality in mechanically ventilated children with trauma.

BACKGROUND: Acute kidney injury (AKI) is associated with significant morbidity and mortality in patients with critical illness; however, its impact on children with trauma is not fully unexplored. We hypothesized that AKI is associated with increased in-hospital mortality. METHODS: A retrospective review of consecutive mechanically ventilated patients aged 0 years to 20 years from 2004 to 2007 with trauma hospitalized at our institution was performed. Univariate and multivariate analyses were performed to identify whether AKI was a risk factor for hospital mortality. RESULTS: Eighty-eight patients met inclusion/exclusion criteria. The study cohort included 58 (66%) males with mean (SD) age of 11.6 (5.5) years (median, 13.25; range, 0.083-19.42 years) and mean (SD) Pediatric Expanded Logical Organ Dysfunction score of 24 (11) (median, 22; range 2-51). Mean pediatric intensive care unit length of stay (median, 11; range, 4-43) and duration of mechanical ventilation (median, 9; range, 3-34), was 13.5 (8.2) days and 11.2 (7.2) days, respectively. The mean (SD) Injury Severity Score for the cohort was 28 (14). Pediatric RIFLE identified those at risk (R), those with injury (I), or those with failure (F) in 30 (51%), 10 (17%), and 12 (21%) patients, respectively. There was a 10% (3 of 30 patients) mortality rate in those at risk, 30% (3 of 10 patients) in those with injury, and 33% (4 of 12 patients) in those with failure. AKI (injury and failure groups) was significantly associated with increased in-hospital mortality. CONCLUSION: Development of AKI (injury or failure) is a significant risk factor associated with in-hospital mortality. Our study highlights the need to consider both urine output as well as creatinine-based components of the pRIFLE criteria to define AKI. LEVEL OF EVIDENCE: Prognostic and epidemiological study, level II.

Cystatin C and neutrophil gelatinase-associated lipocalin as markers of renal function in pediatric heart transplant recipients.

We hypothesized that use of Schwartz formula underestimates the prevalence of CKD in PHT recipients. This study determined the prevalence and risk factors for CKD in PHT using novel methods-serum cystatin C, CKiD formula, Revised Schwartz formula, s- and u-NGAL. Serum BUN, creatinine, cystatin C and s- and u-NGAL were measured after prospective enrollment. Schwartz formula GFR was compared with novel methods. CKD was defined as CKiD GFR < 90 mL/min/1.73 m(2) . The s- and u-NGAL were compared between those with and without CKD. Potential risk factors for CKD were analyzed. Seventy-nine patients (46 male children or boys), mean age 9.9 ± 5.8 yr formed the study cohort. The prevalence of mild and moderate CKD was 2- to 3-fold higher using novel methods compared to Schwartz formula. u-NGAL and u-NGAL/Cr were significantly higher in patients with CKD. u- and s-NGAL had negative correlation with estimates of GFR. Women were at a higher risk for CKD (odds ratio 8.7) as was longer duration since transplant (p = 0.009). In conclusion, use of novel methods of GFR estimation unmasked 2- to 3-fold increased prevalence of CKD in PHT. Women and those with longer duration since transplant are at higher risk for CKD.

Bone mineral status in pediatric heart transplant recipients: a retrospective observational study of an "at risk" cohort.

There is a paucity of literature assessing the burden of bone loss in PHT recipients. We sought to describe the bone mineral status in PHT recipients by doing a retrospective medical record review of those who underwent evaluation of BMD when clinically indicated. Data collected included patient demographics, BMD evaluations, serum calcium, phosphorus, alkaline phosphatase, cumulative steroid dose, osseous complications and their management. Of 149 PHT recipients, 26 underwent BMD evaluation. This evaluation was done at a median of 3.4 yrs after PHT. There total serum calcium, phosphorus and alkaline phosphatase were similar at transplant and BMD study. The median BMD Z-scores were: whole body -0.09 (1.5 to -5.13) and lumbar spine -1.1 (1.5 to -5.16). Bone loss (Z-score <-1) was present in 14 (53.8%). Three patients had spinal fractures and/or avascular necrosis of various bones. Treatment included calcitrol and bisphosphonates; and vertebroplasty for spinal fracture. Bone loss was present in a significant proportion of PHT recipients and may be associated with fractures and avascular necrosis. More than half of our "at risk" cohort had bone loss. Careful surveillance of these patients should be performed to prevent morbidity.

The development of a competency-based assessment rubric to measure resident milestones.

BACKGROUND: The outcomes-based assessment rubric is a novel systematic instrument for documenting improvement in clinical learning. APPROACH: This article describes the development of a rubric aimed at introducing specific performance indicators to measure the Accreditation Council for Graduate Medical Education competencies. RESULTS: The potential benefits and implications for medical education include specifying performance indicators and outcomes, ensuring that assessment is coherent and consistent for all residents, measuring resident outcomes based on real-life criteria, providing opportunities for residents to demonstrate proficiency in a specific competency and outcome level, and improving the quality of assessment.

Incorporating the ACGME educational competencies into morbidity and mortality review conferences.

BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME) mandates that residents be trained in six core educational competencies. Practice-based learning and improvement (PBLI), one of the six competencies, is defined as the investigation and evaluation of one's own patient care. Morbidity and Mortality Conference, a frequently used venue to review the clinical outcome of hospitalized patients, provides the opportunity to teach and assess PBLI. DESCRIPTION: We report an approach to Morbidity and Mortality Conference that includes a systematic analysis of the ACGME core competencies and their application to a clinical case, a regular review of the factors that defines high-quality patient care, and a focused discussion of the PBLI competency. EVALUATION: Preliminary data indicate that our residents preferred this revised method for conducting Morbidity and Mortality Conference. CONCLUSION: Our adaptation to Morbidity and Mortality Conference provides a systematic review of the core competencies and their relevance to clinical decision making, with the ultimate goal of improving patient care.

Laparoscopic Tenckhoff catheter placement in children using a securing suture in the pelvis: comparison to the open approach.

BACKGROUND/PURPOSE: Secure placement of peritoneal dialysis (PD) catheters in the pelvis has been described by various techniques. We describe minimally invasive placement using an Endo Close device, securing the catheter in the pelvis, and compare this method with standard open technique in children. METHODS: A retrospective institutional review was conducted for children requiring PD access from 2001 to 2007. Patients were grouped into laparoscopic with secure placement (SP) and open placement (OP) groups. Groups were cohort-matched based on age, paying particular attention to the number of catheter migrations. RESULTS: Twenty-seven patients underwent 36 procedures in SP, whereas 23 patients in OP had 32 catheter-related procedures. Exit site infections were decreased in SP (0.57 vs 1.33 episodes per patient-year). There was no difference in the number of catheter migrations (3 vs 5); however, time to migration was statistically longer in the SP group (9 vs. 2.4 months, P < .05). CONCLUSIONS: Laparoscopic placement of PD catheters using a securing suture in the pelvis is a more durable technique when compared to open placement. Extending the catheter migration time is important in children when PD is used as a bridge to renal transplantation.

Factors related to long-term renal transplant function in children.

Short-term renal allograft survival in children has improved. It is therefore important to determine the factors leading to long-term graft function. To this end, we evaluated patients in the NAPTRCS registry who were <12 years old when they received their renal transplant between 1987 and 1993. Children with 10 years of post-transplant follow-up were compared to those in whom the transplant failed within 10 years. Children with a failed transplant within 10 years of the surgery tended to be older, female, and non-Caucasian; they also manifested obstructive uropathy less often and had focal segmental glomerulosclerosis more often, and they received more deceased donor kidneys. Children with a failed renal transplant had fewer HLA donor and recipient matches, received pre-transplant dialysis compared to a preemptive transplant, required dialysis in the first week post-transplant, and required more antihypertensives the first month post-transplant. Allograft function was examined at 10 years. Patients with continued allograft function and a serum creatinine

Defining family-centered rounds.

BACKGROUND: Physicians are required to provide safe, effective, and high-quality care that is patient-centered. Continuing to meet the educational needs of residents and medical students in the setting of patient-centered care will require developing new models for hospital "work rounds." Family-centered rounds is a model of communicating and learning between the patient, family, medical professionals, and students on an academic, inpatient ward setting. Unfortunately, in the medical literature, there is no consensus on the definition of family-centered rounds. SUMMARY: Despite the increased utilization of hospitalists and the recognition that bedside teaching has many benefits, bedside rounds are underutilized. In this article, we present a description of family-centered rounds that is supported by a review of the literature on bedside teaching, family-centered care, and interdisciplinary care. The key difference between family-centered rounds and traditional bedside teaching is the active participation of the patient and family in the discussion. Interdisciplinary care implies that professionals from a variety of disciplines work collaboratively to develop a unified care plan. Family-centered rounding provides an interface between families and medical professionals that allows education of medical students and residents as well as the development of a unified care plan. CONCLUSIONS: Family-centered rounds hold potential to create a patient-centered environment, enhance medical education, and improve patient outcomes. The model is a planned, purposeful interaction that requires the permission of patients and families as well as the cooperation of physicians, nurses, and ancillary staff.