Failure to Thrive, Metabolic Acidosis, and Diarrhea in a 7-Week-Old Infant.

A 7-week-old infant presented to the emergency department with fussiness, decreased oral intake, loose stool, and respiratory distress for 2 days. The patient was born full-term with an uncomplicated birth history but had a history of slow weight gain. He was alert, but toxic-appearing at presentation, hypothermic with signs of dehydration, and with respiratory failure. He was found to have severe anion gap metabolic acidosis, hypokalemia, elevated lactate, and hyperammonemia. He responded well to initial resuscitation and was admitted to the ICU for intravenous electrolyte replacement, bowel rest, and respiratory support. A workup was pursued for failure to thrive with severe malnutrition, hyperammonemia, hyperlactatemia, anemia, vitamin D deficiency, and electrolyte abnormalities. After stabilization, he was restarted on enteral feeds and had a recurrence of loose stool and severe electrolyte abnormalities, which were refractory to enteral supplementations and required readmission to the ICU. His hospital course extended several weeks, included several subspecialty consultations, and ended with a surprising diagnosis of exclusion based on his clinical response to therapy.

Patterns of Multiple Organ Dysfunction and Renal Recovery in Critically Ill Children and Young Adults Receiving Continuous Renal Replacement Therapy.

OBJECTIVES: Acute kidney injury requiring dialysis (AKI-D) commonly occurs in the setting of multiple organ dysfunction syndrome (MODS). Continuous renal replacement therapy (CRRT) is the modality of choice for AKI-D. Mid-term outcomes of pediatric AKI-D supported with CRRT are unknown. We aimed to describe the pattern and impact of organ dysfunction on renal outcomes in critically ill children and young adults with AKI-D. DESIGN: Retrospective cohort. SETTING: Two large quarternary care pediatric hospitals. PATIENTS: Patients 26 y old or younger who received CRRT from 2014 to 2020, excluding patients with chronic kidney disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Organ dysfunction was assessed using the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score. MODS was defined as greater than or equal to two organ dysfunctions. The primary outcome was major adverse kidney events at 30 days (MAKE30) (decrease in estimated glomerular filtration rate greater than or equal to 25% from baseline, need for renal replacement therapy, and death). Three hundred seventy-three patients, 50% female, with a median age of 84 mo (interquartile range [IQR] 16-172) were analyzed. PELOD-2 increased from 6 (IQR 3-9) to 9 (IQR 7-12) between ICU admission and CRRT initiation. Ninety-seven percent of patients developed MODS at CRRT start and 266 patients (71%) had MAKE30. Acute kidney injury (adjusted odds ratio [aOR] 3.55 [IQR 2.13-5.90]), neurologic (aOR 2.07 [IQR 1.15-3.74]), hematologic/oncologic dysfunction (aOR 2.27 [IQR 1.32-3.91]) at CRRT start, and progressive MODS (aOR 1.11 [IQR 1.03-1.19]) were independently associated with MAKE30. CONCLUSIONS: Ninety percent of critically ill children and young adults with AKI-D develop MODS by the start of CRRT. Lack of renal recovery is associated with specific extrarenal organ dysfunction and progressive multiple organ dysfunction. Currently available extrarenal organ support strategies, such as therapeutic plasma exchange lung-protective ventilation, and other modifiable risk factors, should be incorporated into clinical trial design when investigating renal recovery.

Fetal bladder morphology as a predictor of outcome in fetal lower urinary tract obstruction.

OBJECTIVE: We evaluate survival of fetuses with severe Lower Urinary Tract Obstruction (LUTO) based on bladder morphology. We hypothesize that fetuses with a "floppy" appearing bladder on initial prenatal ultrasound will have worse infant outcomes than fetuses with full/rounded bladders. METHOD: We retrospectively reviewed all cases of LUTO evaluated in our fetal center between January 2013 and December 2021. Ultrasonographic assessment, renal biochemistry, and bladder refilling contributed to a "favorable" or "unfavorable" evaluation. Bladder morphology on initial ultrasound was classified as "floppy" or "full/rounded." Vesicoamniotic shunting was offered for favorably evaluated fetuses. Baseline demographics, ultrasound parameters, prenatal evaluations of fetal renal function, and infant outcomes were collected. Fetuses diagnosed with severe LUTO were included in analysis using descriptive statistics. The primary outcome measured was survival at 6 months of life. RESULTS: 104 LUTO patients were evaluated; 24 were included in analysis. Infant survival rate at 6 months was 60% for rounded bladders and 0% for floppy bladders (p = 0.003). Bladder refill adequacy was lower in fetuses with floppy bladders compared with rounded bladders (p value < 0.00001). CONCLUSION: We propose that bladder morphology in fetuses with severe LUTO may be a prognostication factor for predicting infant outcomes and provides a valuable, noninvasive assessment tool.

Utility of kidney ultrasonography during initial evaluation of pediatric nephrotic syndrome.

BACKGROUND: Current guidelines note a gap in high-quality evidence regarding utility of kidney ultrasonography (KUS) during initial evaluation of nephrotic syndrome (NS) due to presumed minimal change disease (pMCD). However, KUS is frequently obtained at our institution. This retrospective chart review assessed incidence and impact of abnormal sonographic findings in these patients. METHODS: Patients 1-18 years, newly diagnosed at our institution with NS from pMCD between 2011 and 2021, were identified. Hypertension, urinalysis, kidney function, and steroid responsiveness data were collected. Imaging findings were abstracted from radiology reports. Clinical impact of KUS was defined by actions taken in response to KUS. RESULTS: A total of 173 patients identified with new NS; 98 met inclusion criteria. Of these, 54% had KUS during the initial encounter. Demographic and laboratory data did not differ between those with and without KUS. KUS were abnormal in 70% of studies: increased kidney echogenicity (39.6%) and nephromegaly (35.8%) were the most common abnormal findings. Other findings included decreased corticomedullary differentiation, lobular kidney contour, solitary simple kidney cyst, and mild unilateral hydronephrosis. Steroid resistance was not associated with either nephromegaly or abnormal echogenicity. CONCLUSIONS: Our data showed no clinically relevant ultrasound findings causing deviations from the standard of care for pMCD. There was no association between KUS findings and steroid resistance. These data suggest there is little to no benefit from routine KUS imaging in patients with pMCD upon initial presentation. A higher resolution version of the Graphical abstract is available as Supplementary information.

Review of acute kidney injury and progression to chronic kidney disease in pediatric patients undergoing hematopoietic cell transplant.

While acute kidney injury (AKI) after hematopoietic cell transplant (HCT) has been well-described in pediatric patients, literature regarding the long term renal consequences of HCT-related AKI, the development of chronic kidney disease (CKD), and CKD care in pediatric patients post-HCT is limited. CKD affects almost 50% of patients after HCT with multifactorial etiology including infection, nephrotoxic medications, transplant-associated thrombotic microangiopathy, graft-versus-host disease, and sinusoidal obstruction syndrome. As renal function declines in CKD, eventually progressing to end stage kidney disease (ESKD), mortality increases and is more than 80% among patients requiring dialysis. Using society guidelines and current literature, this review summarizes definitions and etiologies of and management strategies among patients with AKI and CKD post-HCT with an emphasis on albuminuria, hypertension, nutrition, metabolic acidosis, anemia, and mineral bone disease. The goal of this review is to aid early identification and intervention in patients with renal dysfunction prior to development of ESKD, and to discuss ESKD and renal transplant in these patients post-HCT.

Utility of serial conventional troponin testing for emergency department patients stratified by HEART score and symptom timing.

BACKGROUND: The HEART score for risk stratifying chest pain patients in the emergency department (ED) has been widely adopted in clinical practice, but is often employed with nonconformant serial troponin measurements. OBJECTIVE: The primary objective of this study was to examine the utility of obtaining a second conventional 3-h troponin I (TnI) level in ED patients presenting with potential acute coronary syndrome (ACS), stratified by HEART score and duration of symptoms. METHODS: This was a retrospective cohort study of consecutive adult ED patients with a complete HEART score. We assessed the utility of repeat TnI measurement by examining the positivity rate of ΔTnI = [Second TnI] - [Initial TnI] stratified by HEART score and time elapsed since onset or resolution of symptoms. Major adverse cardiac events (MACE) within 6 weeks of index visit were assessed. RESULTS: A total of 944 patients were included with 433 (45.9%) assigned a low risk HEART score 0-3. Of the 268 (61.9%) low risk HEART score patients receiving a second TnI, only 3 (1.1%, [0.2-3.2%]) resulted in a positive ΔTnI, one of which occurred in the setting of an elevated initial TnI. Overall, patients presenting within 3 h of symptoms were more likely to experience positive ΔTnI, index MACE and MACE at 6 weeks compared to patients presenting ≥3 h since symptoms onset/resolution and patients with unknown timing of symptoms (15.9% vs 11.0% vs 10.3%, p < 0.001; 10.0% vs 5.3% vs 4.6%, p = 0.021; 12.7% vs 6.6% vs 6.4%, p = 0.047). CONCLUSION: Our data suggest serial measurement of conventional troponin provides limited added benefit in low risk HEART score patients, regardless of duration and timing of symptoms. Conversely, serial troponin measurement may confer utility in moderate/high risk HEART score patients, particularly those presenting within 3 h of symptoms.

Kidney Injury in Children after Hematopoietic Stem Cell Transplant.

Hematopoietic cell transplant (HCT), used for treatment of many malignant and non-malignant pediatric diseases, is associated with serious complications, limiting this therapy's benefit. Acute kidney injury (AKI), seen often after HCT, can occur at different stages of the transplant process and contributes to morbidity and mortality after HCT. The etiology of AKI is often multifactorial, including kidney hypoperfusion, nephrotoxicity from immunosuppressive and antimicrobial agents, and other transplant-related complications such as transplant-associated thrombotic microangiopathy and sinusoidal obstructive syndrome. Early recognition of AKI is crucial to prevent further AKI and associated complications. Initial management includes identifying the etiology of AKI, preventing further kidney hypoperfusion, adjusting nephrotoxic medications, and preventing fluid overload. Some patients will require further support with kidney replacement therapy to manage fluid overload and AKI. Biomarkers of AKI, such as neutrophil gelatinase-associated lipocalin can aid in detecting AKI before a rise in serum creatinine, allowing earlier intervention. Long-term kidney dysfunction is also prominent in this population. Therefore, long-term follow-up and monitoring of renal function (glomerular filtration rate, microalbuminuria) is required along with management of hypertension, which can contribute to chronic kidney disease.

Genetic testing in children with nephrolithiasis and nephrocalcinosis.

BACKGROUND: Diagnosing genetic kidney disease has become more accessible with low-cost, rapid genetic testing. The study objectives were to determine genetic testing diagnostic yield and examine predictors of genetic diagnosis in children with nephrolithiasis/nephrocalcinosis (NL/NC). METHODS: This retrospective multicenter cross-sectional study was conducted on children ≤ 21 years old with NL/NC from pediatric nephrology/urology centers that underwent the Invitae Nephrolithiasis Panel 1/1/2019-9/30/2021. The diagnostic yield of the genetic panel was calculated. Bivariate and multiple logistic regression were performed to assess for predictors of positive genetic testing. RESULTS: One hundred and thirteen children (83 NL, 30 NC) from 7 centers were included. Genetic testing was positive in 32% overall (29% NL, 40% NC) with definite diagnoses (had pathogenic variants alone) made in 11.5%, probable diagnoses (carried a combination of pathogenic variants and variants of uncertain significance (VUS) in the same gene) made in 5.4%, and possible diagnoses (had VUS alone) made in 15.0%. Variants were found in 28 genes (most commonly HOGA1 in NL, SLC34A3 in NC) and 20 different conditions were identified. Compared to NL, those with NC were younger and had a higher proportion with developmental delay, hypercalcemia, low serum bicarbonate, hypophosphatemia, and chronic kidney disease. In multivariate analysis, low serum bicarbonate was associated with increased odds of genetic diagnosis (ß 2.2, OR 8.7, 95% CI 1.4-54.7, p = 0.02). CONCLUSIONS: Genetic testing was high-yield with definite, probable, or possible explanatory variants found in up to one-third of children with NL/NC and shows promise to improve clinical practice. A higher resolution version of the Graphical abstract is available as Supplementary information.

Extracorporeal membrane oxygenation in children receiving haematopoietic cell transplantation and immune effector cell therapy: an international and multidisciplinary consensus statement.

Use of extracorporeal membrane oxygenation (ECMO) in children receiving haematopoietic cell transplantation (HCT) and immune effector cell therapy is controversial and evidence-based guidelines have not been established. Remarkable advancements in HCT and immune effector cell therapies have changed expectations around reversibility of organ dysfunction and survival for affected patients. Herein, members of the Extracorporeal Life Support Organization (ELSO), Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network (HCT and cancer immunotherapy subgroup), the Pediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation (EBMT), the supportive care committee of the Pediatric Transplantation and Cellular Therapy Consortium (PTCTC), and the Pediatric Intensive Care Oncology Kids in Europe Research (POKER) group of the European Society of Pediatric and Neonatal Intensive Care (ESPNIC) provide consensus recommendations on the use of ECMO in children receiving HCT and immune effector cell therapy. These are the first international, multidisciplinary consensus-based recommendations on the use of ECMO in this patient population. This Review provides a clinical decision support tool for paediatric haematologists, oncologists, and critical care physicians during the difficult decision-making process of ECMO candidacy and management. These recommendations can represent a base for future research studies focused on ECMO selection criteria and bedside management.

Two to Tango: Kidney-Lung Interaction in Acute Kidney Injury and Acute Respiratory Distress Syndrome.

Acute Kidney Injury (AKI) is an independent risk factor for mortality in hospitalized patients. AKI syndrome leads to fluid overload, electrolyte and acid-base disturbances, immunoparalysis, and propagates multiple organ dysfunction through organ "crosstalk". Preclinical models suggest AKI causes acute lung injury (ALI), and conversely, mechanical ventilation and ALI cause AKI. In the clinical setting, respiratory complications are a key driver of increased mortality in patients with AKI, highlighting the bidirectional relationship. This article highlights the challenging and complex interactions between the lung and kidney in critically ill patients with AKI and acute respiratory distress syndrome (ARDS) and global implications of AKI. We discuss disease-specific molecular mediators and inflammatory pathways involved in organ crosstalk in the AKI-ARDS construct, and highlight the reciprocal hemodynamic effects of elevated pulmonary vascular resistance and central venous pressure (CVP) leading to renal hypoperfusion and pulmonary edema associated with fluid overload and increased right ventricular afterload. Finally, we discuss the notion of different ARDS "phenotypes" and the response to fluid overload, suggesting differential organ crosstalk in specific pathological states. While the directionality of effect remains challenging to distinguish at the bedside due to lag in diagnosis with conventional renal function markers and lack of tangible damage markers, this review provides a paradigm for understanding kidney-lung interactions in the critically ill patient.

Early Cumulative Fluid Balance and Outcomes in Pediatric Allogeneic Hematopoietic Cell Transplant Recipients With Acute Respiratory Failure: A Multicenter Study.

OBJECTIVES: To evaluate the associations between early cumulative fluid balance (CFB) and outcomes among critically ill pediatric allogeneic hematopoietic cell transplant (HCT) recipients with acute respiratory failure, and determine if these associations vary by treatment with renal replacement therapy (RRT). METHODS: We performed a secondary analysis of a multicenter retrospective cohort of patients (1mo - 21yrs) post-allogeneic HCT with acute respiratory failure treated with invasive mechanical ventilation (IMV) from 2009 to 2014. Fluid intake and output were measured daily for the first week of IMV (day 0 = day of intubation). The exposure, day 3 CFB (CFB from day 0 through day 3 of IMV), was calculated using the equation [Fluid in - Fluid out] (liters)/[PICU admission weight](kg)*100. We measured the association between day 3 CFB and PICU mortality with logistic regression, and the rate of extubation at 28 and 60 days with competing risk regression (PICU mortality = competing risk). RESULTS: 198 patients were included in the study. Mean % CFB for the cohort was positive on day 0 of IMV, and increased further on days 1-7 of IMV. For each 1% increase in day 3 CFB, the odds of PICU mortality were 3% higher (adjusted odds ratio (aOR) 1.03, 95% CI 1.00-1.07), and the rate of extubation was 3% lower at 28 days (adjusted subdistribution hazard ratio (aSHR) 0.97, 95% CI 0.95-0.98) and 3% lower at 60 days (aSHR 0.97, 95% CI 0.95-0.98). When day 3 CFB was dichotomized, 161 (81%) had positive and 37 (19%) had negative day 3 CFB. Positive day 3 CFB was associated with higher PICU mortality (aOR 3.42, 95% CI 1.48-7.87) and a lower rate of extubation at 28 days (aSHR 0.30, 95% CI 0.18-0.48) and 60 days (aSHR 0.30, 95% 0.19-0.48). On stratified analysis, the association between positive day 3 CFB and PICU mortality was significantly stronger in those not treated with RRT (no RRT: aOR 9.11, 95% CI 2.29-36.22; RRT: aOR 1.40, 95% CI 0.42-4.74). CONCLUSIONS: Among critically ill pediatric allogeneic HCT recipients with acute respiratory failure, positive and increasing early CFB were independently associated with adverse outcomes.

Novel scoring system for determining fetal candidacy for prenatal intervention for severe congenital lower urinary tract obstruction.

OBJECTIVES: To evaluate a novel scoring system that combines several prenatal parameters for selecting ideal candidates for fetal intervention, and for predicting postnatal survival in patients with severe fetal lower urinary tract obstruction (LUTO). METHODS: We retrospectively reviewed all cases of severe LUTO evaluated for fetal intervention in a single large fetal center between January 2013 and December 2017. A scoring system for determining fetal candidacy for intervention was retrospectively developed based on postnatal outcomes. The proposed scoring system included fetal urinary biochemistry, renal ultrasound parameters, initial bladder volume, and degree of bladder refill. Relevant demographic characteristics, ultrasound reports and laboratory results were reviewed. Receiver operating characteristic (ROC) curves were used to select the cut-off values for initial bladder volume and degree of bladder refill and to evaluate the performance of the scoring system in predicting postnatal death. RESULTS: Of the 79 LUTO patients evaluated, 31 were eligible for the study. The overall 6-month postnatal survival was 64.5 % (20/31). A scoring system (0-8) was suggested with 2 points for unfavorable biochemistry, 4 points for ultrasound evidence of dysplastic kidneys, 1 point for inadequate initial bladder volume and 1 point for inadequate bladder refill. Scores>3 (N = 7) were associated with 0 % 6-month survival. The ROC curve for predicting postnatal mortality showed area under curve (AUC) of 0.82 (95 % CI 0.65-0.99). Subgroup analysis within subjects who underwent fetal intervention (N = 22) also confirmed the significance of the distribution of the scoring system between groups who survived and those who did not after adjustment for GA at delivery (p = 0.01). CONCLUSION: We propose a novel scoring system for antenatal evaluation of patients with severe LUTO which may be useful in selecting those candidates most appropriate for intervention and in counseling parents about predicted postnatal outcome.

Diagnosis, grading and management of toxicities from immunotherapies in children, adolescents and young adults with cancer.

Cancer immunotherapies are associated with remarkable therapeutic response rates but also with unique and severe toxicities, which potentially result in rapid deterioration in health. The number of clinical applications for novel immune effector-cell therapies, including chimeric antigen receptor (CAR)-expressing cells, and other immunotherapies, such as immune-checkpoint inhibitors, is increasing. In this Consensus Statement, members of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Hematopoietic Cell Transplantation-Cancer Immunotherapy (HCT-CI) Subgroup, Paediatric Diseases Working Party (PDWP) of the European Society of Blood and Marrow Transplantation (EBMT), Supportive Care Committee of the Pediatric Transplantation and Cellular Therapy Consortium (PTCTC) and MD Anderson Cancer Center CAR T Cell Therapy-Associated Toxicity (CARTOX) Program collaborated to provide updated comprehensive recommendations for the care of children, adolescents and young adults receiving cancer immunotherapies. With these recommendations, we address emerging toxicity mitigation strategies, we advocate for the characterization of baseline organ function according to age and discipline-specific criteria, we recommend early critical care assessment when indicated, with consideration of reversibility of underlying pathology (instead of organ failure scores) to guide critical care interventions, and we call for researchers, regulatory agencies and sponsors to support and facilitate early inclusion of young patients with cancer in well-designed clinical trials.

Characteristics and Clinical Outcomes of Prolonged Continuous Renal Replacement Therapy in Critically Ill Pediatric Patients.

OBJECTIVES: Paralleling improved outcomes in critically ill patients, survival for pediatric acute kidney injury has improved. Continuous renal replacement therapy is the preferred modality to optimize fluid and electrolyte management as well as nutritional support for children developing acute kidney injury in the PICU. However, some patients remain too fragile for transition to intermittent renal replacement therapies and require continuous renal replacement therapy for a prolonged period. Characteristics of this cohort and factors impacting outcomes are not well known. We aimed to describe the characteristics of pediatric patients requiring prolonged continuous renal replacement therapy and evaluate the factors impacting hospital survival. DESIGN: Retrospective chart review. SETTING: Tertiary PICU. PATIENTS: Children requiring prolonged continuous renal replacement therapy. Prolonged continuous renal replacement therapy was defined as continuous renal replacement therapy dependence greater than or equal to 28 days. Primary outcome was hospital mortality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: From 2013 to 2016, 344 patients received continuous renal replacement therapy, 36 (10%) received continuous renal replacement therapy for greater than or equal to 28 days. Seventeen patients (47%) were female. Overall mortality was 44% (16/36); 69% (11/16) of nonsurvivors died of sepsis. Pediatric Logistic Organ Dysfunction score was significantly higher in nonsurvivors. Mortality rate was significantly higher in patients who were neutropenic at continuous renal replacement therapy start. Neutropenia (defined as absolute neutrophil count < 1,500/mm) at continuous renal replacement therapy start was the only independent predictor of mortality. One in four survivors did not recover renal function and remained dialysis dependent. CONCLUSIONS: Prolonged continuous renal replacement therapy patients are at high risk of nonrecovery of renal function and require close monitoring. The majority of nonsurvivors in the study group died from sepsis. Neutropenia at continuous renal replacement therapy initiation was associated with increased risk of mortality. Progression of underlying disease process could explain the higher death rate in patients with neutropenia; however, inadequate treatment of infectious complications could be another explanation to explore further in future studies.

Neurodevelopmental Outcome in Infants with Lower Urinary Tract Obstruction Based on Different Degrees of Severity.

OBJECTIVE: To determine postnatal neurodevelopmental (ND) outcomes for children with congenital lower urinary tract obstruction (LUTO) based on disease severity. METHODS: Twenty male infants with LUTO were classified prenatally as Stage 1 (normal amniotic fluid and renal function; n = 5), Stage 2 (signs of obstruction with preserved renal function; n = 13), and Stage 3 (signs of severe renal damage; n = 2). ND status was assessed using the Developmental Profile-3 test in 5 developmental domains (physical, adaptive behavior, social-emotional, cognitive, and communication). Each domain was considered to be delayed if standard scores were 2 or more SD below the mean. ND outcomes were compared between cases with an expected normal renal function (LUTO Stage 1) and those with impaired renal function (LUTO Stages 2 and 3). Results from cases with Stage 2 were also compared to those from Stage 3. ORs were calculated to predict risk for adverse ND outcome for each domain considering prenatal and postnatal factors. RESULTS: Gestational age (GA) at the diagnosis of LUTO was similar between both groups (Stage 1: 24.85 ± 7.87 vs. Stages 2 and 3: 21.4 ± 4.31 weeks; p = 0.24). Twelve of 15 cases with Stage 2 or 3 underwent vesicoamniotic shunt placement compared to none of Stage 1 fetuses (p < 0.01). No differences in GA at delivery were detected between the groups (37.9 ± 1.6 vs. 35.1 ± 3.6 weeks; p = 0.1). One of the infants in the Stage 2 and 3 groups received a kidney transplant during follow-up. One case (20%) from Stage 1 group required dialysis during the first 6 months of life, and 1 case from Stage 2 to 3 group required it during the first 6 months (p = 1.0), whereas 3 additional cases needed dialysis from 6 to 24 months (p = 0.6). Mean age at Developmental Profile 3 (DP-3) testing was 20.3 ± 12.3 months (Stage 1: 11.2 ± 8.6 vs. Stages 2 and 3: 23.4 ± 13.4 months; p = 0.07). Fifteen of the 20 patients (75%) had no ND delays. Of the 5 patients with ND delays, 4 received dialysis. No differences in ND outcomes between infants with LUTO Stage 1 and those with Stages 2 and 3 were detected except for a trend toward better physical development in Stage 1 (102.6 ± 11.6 vs. 80.7 ± 34.9; p = 0.05). Infants diagnosed with LUTO Stage 3 showed significantly lower adaptive scores than those diagnosed with Stage 2 (Stage 2: 101.9 ± 22.3 vs. Stage 3: 41.5 ± 30.4; p = 0.04) and a nonsignificant trend for lower results in physical (85.8 ± 33.0 vs. 47.5 ± 38.9; p = 0.1) and socio-emotional (94.7 ±17.9 vs. 73.5 ± 13.4; p = 0.1) domains. Infants who received dialysis showed 15-fold increased risk (95% CI 0.89-251) for delayed socio-emotional development (p = 0.06). Diagnosis of fetal renal failure increased the risk for delays in the adaptive domain 30-fold (95% CI 1.29-93.1; p = 0.03). Infants with abnormal renal function had 19 times (95% CI 1.95-292) increased risk for delays in the physical domain (p = 0.03). CONCLUSIONS: While most patients with LUTO do not exhibiting ND delays, our results support the importance of ND monitoring, especially in severe forms of LUTO, as increased severity of this condition may be associated with poorer ND outcomes.

OpenSFDI: an open-source guide for constructing a spatial frequency domain imaging system.

Significance: Spatial frequency domain imaging (SFDI) is a diffuse optical measurement technique that can quantify tissue optical absorption (µa) and reduced scattering (µs') on a pixel-by-pixel basis. Measurements of µa at different wavelengths enable the extraction of molar concentrations of tissue chromophores over a wide field, providing a noncontact and label-free means to assess tissue viability, oxygenation, microarchitecture, and molecular content. We present here openSFDI: an open-source guide for building a low-cost, small-footprint, three-wavelength SFDI system capable of quantifying µa and µs' as well as oxyhemoglobin and deoxyhemoglobin concentrations in biological tissue. The companion website provides a complete parts list along with detailed instructions for assembling the openSFDI system.

Aim: We describe the design of openSFDI and report on the accuracy and precision of optical property extractions for three different systems fabricated according to the instructions on the openSFDI website.

Approach: Accuracy was assessed by measuring nine tissue-simulating optical phantoms with a physiologically relevant range of µa and µs' with the openSFDI systems and a commercial SFDI device. Precision was assessed by repeatedly measuring the same phantom over 1 h.

Results: The openSFDI systems had an error of 0 ± 6 % in µa and -2 ± 3 % in µs', compared to a commercial SFDI system. Bland-Altman analysis revealed the limits of agreement between the two systems to be ± 0.004 mm - 1 for µa and -0.06 to 0.1 mm - 1 for µs'. The openSFDI system had low drift with an average standard deviation of 0.0007 mm - 1 and 0.05 mm - 1 in µa and µs', respectively.

Conclusion: The openSFDI provides a customizable hardware platform for research groups seeking to utilize SFDI for quantitative diffuse optical imaging.

Nephronophthisis due to a novel DCDC2 variant in a patient from African-Caribbean descent: A case report.

Nephronophthisis-19 (NPHP19) due to truncating mutations in the DCDC2 gene has only been described previously in two patients. We describe a new case in a patient from the island country of Saint Vincent and the Grenadines, in the West Indies. This condition is a renal-hepatic ciliopathy with phenotypic characteristics that include hepatosplenomegaly, hepatic fibrosis with bile cholestasis, increased kidney echogenicity, and end-stage renal disease.Here, we report a 13-year-old African-Caribbean female with areas of absence of heterozygosity suggesting parental consanguinity or identity by decent due to the founder effect, harboring a novel homozygous pathogenic variant (c.383C>G, p.S128*) in exon 3 of DCDC2. Her phenotype is consistent with the other two known cases of NPHP19, however, this patient also presents psychiatric symptoms. These psychiatric findings were not present in the first two documented cases, and we discuss possible etiologies of these symptoms. Our study presents the first patient from the West Indies with NPHP19, and also highlights the need to investigate the frequency of pathogenic variants within at-risk populations.

Diagnosis, grading, and treatment recommendations for children, adolescents, and young adults with sinusoidal obstructive syndrome: an international expert position statement.

Sinusoidal obstructive syndrome, also known as hepatic veno-occlusive disease, is a potentially life-threatening complication that occurs in children undergoing haemopoietic stem-cell transplantation (HSCT). Differences in the incidence of genetic predisposition and clinical presentation of sinusoidal obstructive syndrome between children and adults have rendered the historical Baltimore and Seattle diagnostic criteria insufficient for children. In 2017, the European Society for Blood and Marrow Transplantation (EBMT) proposed the first paediatric diagnostic and severity grading guidelines for sinusoidal obstructive syndrome, intended for implementation across European centres. However, universally accepted paediatric criteria are needed to ensure prompt diagnosis, definitive treatment, and improved outcomes for children, adolescents, and young adults with sinusoidal obstructive syndrome, and to facilitate international clinical research collaboration. We convened an international panel of multidisciplinary experts including physicians with expertise in HSCT, paediatric intensive care, nephrology, hepatology, radiology, pathology, and transfusion medicine; HSCT advanced-practice providers and medical trainees; pharmacists; and translational and basic science researchers from the Pediatric Acute Lung Injury and Sepsis Investigators Network, the EBMT, the Pediatric Blood and Marrow Transplant Consortia, and several other institutions with extensive experience in sinusoidal obstructive syndrome. Panellists convened at The University of Texas, MD Anderson Cancer Center (Houston, TX, USA) in February, 2019, to evaluate the available evidence. In this expert position statement paper, we provide consensus recommendations for the international implementation of guidelines for the diagnosis, severity grading, and treatment of sinusoidal obstructive syndrome among children, adolescents, and young adults. We endorse universal adoption of paediatric diagnostic guidelines for sinusoidal obstruction syndrome as proposed by the EBMT, and provide implementation guidance for standardisation across centres; we have further proposed adjunctive use of age-appropriate organ-specific toxicity criteria for severity grading and provided prophylaxis and treatment considerations among children and adolescent and young adult patients. Key recommendations include: (1) liver biopsy, portal venous wedge pressure, and reversal of portal venous flow on Doppler ultrasonography should not be used for the routine diagnosis of sinusoidal obstructive syndrome in children, adolescents, and young adults; (2) platelet refractoriness can be defined as a corrected count increment of less than 5000-7500 following at least two sequential ABO-compatible fresh platelet transfusions; (3) hepatomegaly is best defined as an absolute increase of at least 1 cm in liver length at the midclavicular line; and if a baseline measurement is not available, hepatomegaly can be defined as greater than 2 SDs above normal for age; and (4) the presence and volume of ascites can be categorised as mild (minimal fluid by liver, spleen, or pelvis), moderate (<1 cm fluid), or severe (fluid in all three regions with >1 cm fluid in at least two regions).