Age dictates brain functional connectivity and axonal integrity following repetitive mild traumatic brain injuries in mice.

Traumatic brain injuries (TBI) present a major public health challenge, demanding an in-depth understanding of age-specific symptoms and risk factors. Aging not only significantly influences brain function and plasticity but also elevates the risk of hospitalizations and death following TBIs. Repetitive mild TBIs (rmTBI) compound these issues, resulting in cumulative and long-term brain damage in the brain. In this study, we investigate the impact of age on brain network changes and white matter properties following rmTBI by employing a multi-modal approach that integrates resting-state functional magnetic resonance imaging (rsfMRI), graph theory analysis, diffusion tensor imaging (DTI), and neurite orientation dispersion and density imaging (NODDI). Our hypothesis is that the effects of rmTBI are worsened in aged animals, with this group showing more pronounced alterations in brain connectivity and white matter structure. Utilizing the closed-head impact model of engineered rotational acceleration (CHIMERA) model, we conducted rmTBIs or sham (control) procedures on young (2.5-3-months-old) and aged (22-months-old) male and female mice to model high-risk groups. Functional and structural imaging unveiled age-related reductions in communication efficiency between brain regions, while injuries induced opposhigh-risking effects on the small-world index across age groups, influencing network segregation. Functional connectivity analysis also identified alterations in 79 out of 148 brain regions by age, treatment (sham vs. rmTBI), or their interaction. Injuries exerted pronounced effects on sensory integration areas, including insular and motor cortices. Age-related disruptions in white matter integrity were observed, indicating alterations in various diffusion directions (mean diffusivity, radial diffusivity, axial diffusivity, and fractional anisotropy) and density neurite properties (dispersion index, intracellular and isotropic volume fraction). Neuroinflammation, assessed through Iba-1 and GFAP markers, correlated with higher dispersion in the optic tract, suggesting a neuroinflammatory response in injured aged animals compared to sham aged. These findings offer insight into the interplay between age, injuries, and brain connectivity, shedding light on the long-term consequences of rmTBI.

24-Hour ambulatory blood pressure monitoring 7 years after intensive care unit admission.

BACKGROUND: Children who develop acute kidney injury (AKI) in the pediatric intensive care unit (PICU) may be at higher risk of long-term chronic kidney disease and hypertension. The objectives of this study were to determine the prevalence of post-discharge hypertension and albuminuria using reference-standard measurements in children admitted to the PICU, and evaluate their association with AKI. METHODS: Single-center longitudinal cohort study of children admitted to the PICU from 2005 to 2010 with 7-8 years of follow-up (n = 207). Patients were excluded if they had pre-existing chronic kidney disease, were deceased, lived > 3.5-h drive away, were unwilling/unable to provide consent/assent, or had a clotting disorder. AKI was defined by the Kidney Disease: Improving Global Outcomes creatinine definition. Office blood pressure was evaluated using age, sex, and height-based percentiles. Hypertension was defined using 24-h ambulatory blood pressure monitoring (ABPM). Albuminuria was defined as first morning urine albumin:creatinine ratio ≥ 30 mg/g. Prevalence of blood pressure outcomes was calculated. The association between AKI and outcomes was evaluated using multivariable regression. RESULTS: Sixty of 207 (29%) children developed AKI during PICU admission. Overall, 6% had albuminuria and 21% had elevated office blood pressure or worse. One-hundred-and-seventy-seven (86%) patients had successful ABPM data. Of these, 10 (6%) had white coat, 18 (10%) had masked, and 5 (3%) had ambulatory hypertension. There was no statistically significant difference in outcomes across AKI stages. CONCLUSIONS: Blood pressure abnormalities are common in children 7 years after PICU admission. Future studies with longer follow-up are needed to further evaluate the association between AKI and hypertension. A higher-resolution version of the graphical abstract is available as Supplementary information.

Pregabalin for Recurrent Seizures in Critical Illness: A Promising Adjunctive Therapy, Especially for cyclic Seizures.

BACKGROUND: Pregabalin (PGB) is an effective adjunctive treatment for focal epilepsy and acts by binding to the alpha2-delta subunit of voltage-gated calcium channels to reduce excitatory neurotransmitter release. Limited data exist on its use in the neurocritical care setting, including cyclic seizures-a pattern of recurrent seizures occurring at nearly regular intervals. Although the mechanism underpinning cyclic seizures remains elusive, spreading excitation linked to spreading depolarizations may play a role in seizure recurrence and periodicity. PGB has been shown to increase spreading depolarization threshold; hence, we hypothesized that the magnitude of antiseizure effect from PGB is more pronounced in patients with cyclic versus noncyclic seizures in a critically ill cohort with recurrent seizures. METHODS: We conducted a retrospective case series of adults admitted to two academic neurointensive care units between January 2017 and March 2019 who received PGB for treatment of seizures. Data collected included demographics, etiology of brain injury, antiseizure medications, and outcome. Continuous electroencephalogram recordings 48 hours before and after PGB administration were reviewed by electroencephalographers blinded to the administration of antiseizure medications to obtain granular data on electrographic seizure burden. Cyclic seizures were determined quantitatively (i.e., < 50% variation of interseizure intervals for at least 50% of consecutive seizures). Coprimary outcomes were decrease in hourly seizure burden in minutes and decrease in seizure frequency in the 48 hours after PGB initiation. We used nonparametric tests for comparison of seizure frequency and burden and segmented linear regression to assess PGB effect. RESULTS: We included 16 patients; the median age was 69 years, 11 (68.7%) were women, three (18.8%) had undergone a neurosurgical procedure, and five (31%) had underlying epilepsy. All seizures had focal onset; ten patients (62.5%) had cyclic seizures. The median hourly seizure burden over the 48 hours prior to PGB initiation was 1.87 min/hour (interquartile range 1.49-8.53), and the median seizure frequency was 1.96 seizures/hour (interquartile range 1.06-3.41). In the 48 hours following PGB (median daily dose 300 mg, range 75-300 mg), the median number of seizures per hour was reduced by 0.80 seizures/hour (95% confidence interval 0.19-1.40), whereas the median hourly seizure burden decreased by 1.71 min/hour (95% confidence interval 0.38-3.04). When we compared patients with cyclic versus noncyclic seizures, there was a relative decrease in hourly seizure frequency (- 86.7% versus - 2%, p = 0.04) and hourly seizure burden (- 89% versus - 7.8%, p = 0.03) at 48 hours. CONCLUSIONS: PGB was associated with a relative reduction in seizure burden in neurocritically ill patients with recurrent seizures, especially those with cyclic seizures, and may be considered in the therapeutic arsenal for refractory seizures. Whether this effect is mediated via modulation of spreading depolarization requires further study.

Inter-Rater Reliability of the Pizzi Health and Wellness Assessment (PHWA).

The objective of this study is to determine the inter-rater reliability of the Pizzi Health and Wellness Assessment (PHWA) by comparing the consistency in scores between clients and their caregivers in the following areas of participation: social, physical, family, occupational, mental/emotional, and spiritual. A retrospective inter-rater correlational design was used to analyze the agreement of scores from a convenience sample consisting of two groups: clients with disabilities (n = 19) and their healthy caregivers (n = 19). Inter-rater reliability was calculated using correlations for the PHWA as a whole, and for the current level of participation and wishing to improve participation subsections. Inter-rater reliability as calculated by an Intraclass Correlation Coefficient, and either the Pearson or Spearman rho correlation and found to be reliable between clients and caregivers (rICC = .636, p < .001; rho = .642, p < .001). More specifically, current level of participation demonstrated acceptable reliability (rICC = .513, p < .001; r = .521, p < .001) as did wishing to improve participation (rICC = .689, p < .001; r = .725, p < .001). This supports the PHWA as a clinically relevant health and wellness occupational therapy assessment.

24-hour ambulatory blood pressure monitoring 9 years after pediatric cardiac surgery: a pilot and feasibility study.

BACKGROUND: Children undergoing cardiac surgery are at risk of high blood pressure (BP), a risk factor for cardiovascular and kidney disease. Twenty-four-hour ambulatory BP monitoring (ABPM) is a reference standard hypertension (HTN) test. Little data exist on ABPM abnormalities in children several years post cardiac surgery. This study aimed to (a) determine ABPM feasibility; (b) describe and compare ABPM measures and abnormalities (percent load, masked HTN [MH]; non-dipping, mean systolic/diastolic BP > 95th percentile; pre-HTN (ABPM); white-coat HTN [WCH]) to casual BP; and (c) compare BP in patients with and without acute kidney injury (AKI). METHODS: Prospective, follow-up pilot study of children (0-18 years) who underwent cardiac surgery from 2007 to 2009 at Montreal Children's Hospital. We recorded if participants had post-operative AKI and assessed the following outcomes at 9-year follow-up: casual BP classified by three single-visit measures (normal; elevated BP [eBPSingleVisit]; HTNSingleVisit); ABPM. Bivariable analyses were used to compare characteristics between groups. RESULTS: Twenty-three patients (median [interquartile range], 8.6 [8.0, 9.0] years post cardiac surgery) were included; 16 (70%) male. Six participants (26%) had eBPSingleVisit or higher. On ABPM, 11 (48%) had ≥ 1 abnormality: 9 (39%) had non-dipping; 3 (13%) had pre-HTN; 3 (13%) had WCH; none had HTN or MH. There were no differences in ABPM according to AKI status. CONCLUSION: Our pilot study determined that ABPM was feasible in children years after cardiac surgery and frequently identified ABPM abnormalities. Future research in larger populations is needed to define specific risk factors for HTN in children after cardiac surgery.

Serum Creatinine Monitoring After Acute Kidney Injury in the PICU.

OBJECTIVES: It is unknown whether children with acute kidney injury during PICU admission have kidney function monitored after discharge. Objectives: 1) describe postdischarge serum creatinine monitoring after PICU acute kidney injury and 2) determine factors associated with postdischarge serum creatinine monitoring. DESIGN: Secondary analysis of longitudinal cohort study data. SETTING: Two PICUs in Montreal and Edmonton, Canada. PATIENTS: Children (0-18 yr old) surviving PICU admission greater than or equal to 2 days from 2005 to 2011. Exclusions: postcardiac surgery and prior kidney disease. Exposure: acute kidney injury by Kidney Disease: Improving Global Outcomes serum creatinine definition. INTERVENTIONS: None. MEASUREMENTS: Primary outcome: postdischarge serum creatinine measured by 90 days, 1 year, and 5-7 years. SECONDARY OUTCOMES: Healthcare events and nephrology follow-up. ANALYSIS: Proportions with outcomes; logistic regression to evaluate factors associated with the primary outcome. Kaplan-Meier analysis of time to serum creatinine measurement and healthcare events. MAIN RESULTS: Of n = 277, 69 (25%) had acute kidney injury; 29/69 (42%), 34/69 (49%), and 51/69 (74%) had serum creatinine measured by 90 days, 1 year, and 5-7 year postdischarge, respectively. Acute kidney injury survivors were more likely to have serum creatinine measured versus nonacute kidney injury survivors at all time points (p ≤ 0.01). Factors associated with 90-day serum creatinine measurement were inpatient nephrology consultation (unadjusted odds ratio [95% CI], 14.9 [1.7-127.0]), stage 2-3 acute kidney injury (adjusted odds ratio, 3.4 [1.1-10.2]), and oncologic admission diagnosis (adjusted odds ratio, 10.0 [1.1-93.5]). A higher proportion of acute kidney injury versus nonacute kidney injury survivors were readmitted by 90 days (25 [36%] vs 44 [21%]; p = 0.01) and 1 year (33 [38%] vs 70 [34%]; p = 0.04). Of 24 acute kidney injury survivors diagnosed with chronic kidney disease or hypertension at 5-7 year follow-up, 16 (67%) had serum creatinine measurement and three (13%) had nephrology follow-up postdischarge. CONCLUSIONS: Half of PICU acute kidney injury survivors have serum creatinine measured within 1-year postdischarge and follow-up is suboptimal for children developing long-term kidney sequelae. Knowledge translation strategies should emphasize the importance of serum creatinine monitoring after childhood acute kidney injury.

Pterygopalatine Fossa Blockade as Novel, Narcotic-Sparing Treatment for Headache in Patients with Spontaneous Subarachnoid Hemorrhage.

BACKGROUND: Severe headache is a hallmark clinical feature of spontaneous subarachnoid hemorrhage (SAH), affecting nearly 90% of patients during index hospitalization, regardless of the SAH severity or presence of a culprit aneurysm. Up to 1 in 4 survivors of SAH experience chronic headaches, which may be severe and last for years. Data guiding the optimal management of post-SAH headache are lacking. Opioids, often in escalating doses, remain the guideline-recommended mainstay of acute therapy, but pain relief remains suboptimal. METHODS: This study is a case series of adult patients who received bilateral pterygopalatine fossa (PPF) blockade for the management of refractory headaches after spontaneous SAH (aneurysmal and non-aneurysmal) at a single tertiary care center. We examined pain scores and analgesic requirements before and after block placement. RESULTS: Seven patients (median age 54 years, 3 men, four aneurysmal and three non-aneurysmal) received a PPF-block between post-bleed day 6-11 during index hospitalization in the neurointensive care unit. The worst pain recorded in the 24-h period before the block was significantly higher than in the period 4 h after the block (9.1 vs. 3.1; p = 0.0156), and in the period 8 h after the block (9.1 vs. 2.8; p = 0.0313). The only complication was minor oozing from the needle insertion sites, which subsided completely with gauze pressure within 1 min. CONCLUSIONS: PPF blockade might constitute a promising opioid-sparing therapeutic strategy for the management of post-SAH headache that merits further prospective controlled randomized studies.

Kidney and blood pressure abnormalities 6 years after acute kidney injury in critically ill children: a prospective cohort study.

BACKGROUND: Acute kidney injury (AKI) in pediatric intensive care unit (PICU) children may be associated with long-term chronic kidney disease or hypertension. OBJECTIVES: To estimate (1) prevalence of kidney abnormalities (low estimated glomerular filtration rate (eGFR) or albuminuria) and blood pressure (BP) consistent with pre-hypertension or hypertension, 6 years after PICU admission; (2) if AKI is associated with these outcomes. METHODS: Longitudinal study of children admitted to two Canadian PICUs (January 2005-December 2011). Exposures (retrospective): AKI or stage 2/3 AKI (KDIGO creatinine-based definition) during PICU. Primary outcome (single visit 6 years after admission): presence of (a) low eGFR (<90 ml/min/1.73 m2) or albuminuria (albumin to creatinine ratio >30 mg/g) (termed "CKD signs") or (b) BP consistent with ≥pre-hypertension (≥90th percentile) or hypertension (≥95th percentile). RESULTS: Of 277 children, 25% had AKI. AKI and stage 2/3 AKI were associated with 2.2- and 6.6-fold higher adjusted odds, respectively, for the 6-year outcomes. Applying new hypertension guidelines attenuated associations; stage 2/3 AKI was associated with 4.5-fold higher adjusted odds for 6-year CKD signs or ≥elevated BP. CONCLUSIONS: Kidney and BP abnormalities are common 6 years after PICU admission and associated with AKI. Other risk factors must be elucidated to develop follow-up recommendations and reduce cardiovascular risk.

Follow-up after neonatal heart disease repair: watch out for chronic kidney disease and hypertension!

BACKGROUND: With advances in care, neonates undergoing cardiac repairs are surviving more frequently. Our objectives were to 1) estimate the prevalence of chronic kidney disease (CKD) and hypertension 6 years after neonatal congenital heart surgery and 2) determine if cardiac surgery-associated acute kidney injury (CS-AKI) is associated with these outcomes. METHODS: Two-center prospective, longitudinal single-visit cohort study including children with congenital heart disease surgery as neonates between January 2005 and December 2012. CKD (estimated glomerular filtration rate < 90 mL/min/1.73m2 or albumin/creatinine ≥3 mg/mmol) and hypertension (systolic or diastolic blood pressure ≥ 95th percentile for age, sex, and height) prevalence 6 years after surgery was estimated. The association of CS-AKI (Kidney Disease: Improving Global Outcomes definition) with CKD and hypertension was determined using multiple regression. RESULTS: Fifty-eight children with median follow-up of 6 years were evaluated. CS-AKI occurred in 58%. CKD and hypertension prevalence were 17% and 30%, respectively; an additional 15% were classified as having elevated blood pressure. CS-AKI was not associated with CKD or hypertension. Classification as cyanotic postoperatively was the only independent predictor of CKD. Postoperative days in hospital predicted hypertension at follow-up. CONCLUSIONS: The prevalence of CKD and hypertension is high in children having neonatal congenital heart surgery. This is important; early identification of CKD and hypertension can improve outcomes. These children should be systematically followed for the evolution of these negative outcomes. CS-AKI defined by current standards may not be a useful clinical tool to decide who needs follow-up and who does not.

Paucity of renal follow-up by school age after neonatal cardiac surgery.

INTRODUCTION: There are little data about renal follow-up of neonates after cardiovascular surgery and no guidelines for long-term renal follow-up. Our objectives were to assess renal function follow-up practice after neonatal cardiac surgery, evaluate factors that predict follow-up serum creatinine measurements including acute kidney injury following surgery, and evaluate the estimated glomerular filtration rate during follow-up using routinely collected laboratory values. METHODS: Two-centre retrospective cohort study of children 5-7 years of age with a history of neonatal cardiac surgery. Univariable and multivariable analyses were performed to determine factors associated with post-discharge creatinine measurements. Glomerular filtration rate was estimated for each creatinine using a height-independent equation. RESULTS: Seventeen of 55 children (30%) did not have any creatinine measured following discharge after surgery until the end of study follow-up, which occurred at a median time of 6 years after discharge. Of the 38 children who had the kidney function checked, 15 (40%) had all of their creatinine drawn only in the context of a hospitalisation or emergency department visit. Acute kidney injury following surgery did not predict the presence of follow-up creatinine measurements. CONCLUSIONS: A large proportion of neonates undergoing congenital heart repair did not have a follow-up creatinine measured in the first years following surgery. In those that did have a creatinine measured, there did not appear to be any identified pattern of follow-up. A follow-up system for children who are discharged from cardiac surgery is needed to identify children with or at risk of chronic kidney disease.

Long-term renal follow-up of children treated with cisplatin, carboplatin, or ifosfamide: a pilot study.

BACKGROUND: Childhood cancer survivors treated with cisplatin, ifosfamide, or carboplatin are at risk for late kidney and blood pressure (BP) abnormalities. Few studies have comprehensively evaluated kidney outcomes and 24-h ambulatory BP monitoring (ABPM) in this population. We aimed to describe chemotherapy-associated acute kidney injury (AKI) and late kidney outcomes using standardized definitions. METHODS: This was a single-center longitudinal pilot study of 23 children who participated in a previous study during cisplatin, carboplatin, or ifosfamide treatment. Medical charts were reviewed retrospectively. Available patients were approached for a study visit for blood and urine collection, BP measurement, and ABPM. AKI is defined by serum creatinine (SCr) rise (Kidney Disease: Improving Global Outcomes definition [SCr-AKI]). Electrolyte-AKI is defined by hypokalemia, hypophosphatemia, or hypomagnesemia. Chronic kidney disease (CKD) is defined by estimated glomerular filtration rate < 90 mL/min/1.73 m2, albuminuria, or proteinuria. Electrolyte-CKD is defined by low serum electrolyte concentration or electrolyte supplementation. RESULTS: Median age at chemotherapy start was 8.3 years; 9/23 (39%) were boys. Fourteen out of 23 (61%) patients had SCr-AKI during therapy; all developed electrolyte-AKI. Median 5.7 years post-chemotherapy, 7/22 (32%) had CKD, 11/23 (48%) had electrolyte-CKD, and 2/20 (10%) had hypertension. Fifteen out of 23 patients (65%) had either CKD, electrolyte-CKD, or hypertension. In ten patients available for a study visit (median 4.9 years post-chemotherapy), 1/10 (10%) had hypertension by ABPM; none had masked or white coat hypertension. All ten had at least one kidney abnormality (CKD, electrolyte-CKD, office pre-hypertension, or abnormal ABPM). CONCLUSIONS: Using standardized outcome definitions, children treated with cisplatin, carboplatin, or ifosfamide have a high prevalence of late kidney abnormalities. Research must elucidate best practice for post-cancer treatment follow-up and kidney complication treatment.

Urine biomarkers of acute kidney injury in noncritically ill, hospitalized children treated with chemotherapy.

BACKGROUND: Cisplatin (Cis), carboplatin (Carb), and ifosfamide (Ifos) are common nephrotoxic chemotherapies. Biomarkers of tubular injury may allow for early acute kidney injury (AKI) diagnosis. PROCEDURE: We performed a two-center (Canada, United States) pilot study to prospectively measure serum creatinine (SCr), urine neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-18 (IL-18) in children receiving Cis/Carb (27 episodes), Ifos (30 episodes), and in 15 hospitalized, nonchemotherapy patients. We defined AKI using the Kidney Disease Improving Global Outcomes (KDIGO) definition. We compared postchemotherapy infusion NGAL and IL-18 concentrations (immediate postdose to 3 days later) to pre-infusion concentrations. We calculated area under the receiver operating characteristic curve (AUC) for postinfusion biomarkers to discriminate for AKI. RESULTS: Prechemotherapy infusion NGAL and IL-18 concentrations were not higher than nonchemotherapy control concentrations. Increasing chemotherapy dose was associated with increasing postinfusion (0-4 hr after infusion) NGAL (P < 0.05). Post-Ifos, immediate postdose, and daily postdose NGAL and IL-18 were significantly higher than pre-infusion biomarker concentrations (P < 0.05), during AKI episodes. NGAL and IL-18 did not rise significantly after Cis-Carb infusion, relative to predose concentrations (P > 0.05). NGAL and IL-18 measured immediately after Ifos infusion discriminated for AKI with AUCs is 0.80 (standard error = 0.13) and 0.73 (standard error = 0.16), respectively. NGAL and IL-18 were not diagnostic of Cis-Carb-associated AKI. When AUCs were adjusted for age, all biomarker AUCs (Cis-Carb and Ifos) improved. CONCLUSION: Urine NGAL and IL-18 show promise as early AKI diagnostic tests in children treated with ifosfamide and may have a potential role in drug toxicity monitoring.

Previous aminoglycoside use and acute kidney injury risk in non-critically ill children.

OBJECTIVES: Aminoglycosides (AG) are a group of bactericidal antibiotics with nephrotoxic effects that are commonly used in the treatment of hospitialized children. We have examined previous AG treatment as a risk factor for acute kidney injury (AKI) during current AG treatment. STUDY DESIGN: We performed a retrospective cohort study of children ranging in age from 1 month to 18 years who were treated with AG between October 2008 and April 2012 at Montreal's Children's Hospital. Children for whom no serum creatinine data (SCr) were available and those with baseline renal disease were excluded from the analysis. Main exposures were prior AG use (number and hours of prior treatments) and time since last AG treatment. The main outcome was AKI, defined on the basis of the Kidney Disease: Improving Global Outcomes guidelines. Logistic regression was used to examine exposure-outcome associations. RESULTS: AG treatments episodes with Stage 1, 2, and 3 AKI, respectively, were associated with a median of 98 [interquartile range (IQR) 339], 231 (IQR 688), and 111 (IQR 505) h of prior AG treatment, respectively, versus non-AKI (median 0, IQR 54 h) (p < 0.0001). AKI episodes were associated with a mean (± standard deviation) of 1.5 ± 1.8 AG treatments in the previous 6 months, versus 0.9 ± 1.6 AG treatments for non-AKI. The number of AG-treatment days during the preceding 6 months [adjusted odds ratio (adjOR) 1.04, 95 % confidence interval (CI) 1.03-1.06; p < 0.001], younger age (adjOR 0.96, 95 % CI 0.93-0.99; p = 0.009), admission to hematology-oncology department (adjOR 3.88, 95 % CI 2.17-6.96; p < 0.001), and tobramycin use (adjOR 1.77, 95 % CI 1.04-3.02; p = 0.04) were independently associated with AKI. Episodes with Stage 1 and 2 AKI were associated with fewer days since last treatment compared to non-AKI treatment (p < 0.02 and p < 0.005, respectively; Mann-Whitney test). CONCLUSIONS: Based on these results, prior AG treatment is a risk factor for AKI and should be considered when dosing and monitoring hospitalized children being treated with AG.

Evaluation of height-dependent and height-independent methods of estimating baseline serum creatinine in critically ill children.

BACKGROUND: Baseline serum creatinine (bSCr) is required for diagnosing acute kidney injury (AKI). In children, bSCr is commonly defined as the lowest measurement within 3 months of admission. Measured values are often missing and estimating bSCr using height-based glomerular filtration rate (GFR) equations is problematic when height is unavailable. METHODS: This is a retrospective cohort study including 538 children admitted to the intensive care unit (ICU) between 2003 and 2005 at two centers in Canada, with measured bSCr, height, and ICU-SCr values. We evaluated the bias, accuracy, and precision of back-calculating bSCr from height-dependent and height-independent GFR equations. Agreement of AKI defined using measured and estimated bSCr was calculated. Multivariate analyses were performed to assess the impact of bSCr estimation methods on the association between AKI and ICU mortality, length of stay, and duration of mechanical ventilation. RESULTS: Both methods underestimated bSCr by 1-3%, showed good accuracy (∼30% of patients with estimated bSCr within 10% of measured bSCr), but poor precision (wide 95% limits of agreement). The agreement between AKI defined by estimated versus measured bSCr was >80% (κ >0.5). The height-independent method performed best in children >13 years old; however, overall, both methods performed similarly across age subgroups. AKI was associated with longer stay, prolonged mechanical ventilation, and ICU mortality using measured and estimated bSCr. CONCLUSIONS: Height-dependent and height-independent bSCr estimation methods were comparable. This may have significant implications for performing pediatric AKI research using large databases, and in clinical care to define AKI when height is unknown.

Serum cystatin C for acute kidney injury evaluation in children treated with aminoglycosides.

BACKGROUND: Serum cystatin C (CysC) is a more accurate glomerular filtration rate marker than serum creatinine (SCr) and may rise more quickly with acute kidney injury (AKI). METHODS: We performed a prospective cohort study of 81 non-critically ill children during 110 aminoglycoside (AG) treatments. We calculated area under the curve (AUC) for CysC to diagnose SCr-defined AKI and predict persistent AKI. SCr-AKI definition was based on the Kidney Disease: Improving Global Outcomes (≥stage 1: ≥50 % or 26.5 µmol/l SCr rise from baseline; stage 2: SCr doubling); CysC-AKI was based on a modified version using CysC rise. RESULTS: SCr-AKI and CysC-AKI developed in 45 and 48 % treatments, respectively. CysC rise predicted stage 1 (AUC = 0.75, 95 % CI 0.60-0.90) and 2 (AUC = 0.85, 95 % CI 0.75-0.95) SCr-AKI 2 days before SCr-AKI attainment. The best combined sensitivity/specificity for percent CysC rise to predict stage 1 SCr-AKI was with a 44 % CysC rise (sensitivity = 65 %, specificity = 83 %). CysC rise on day of SCr-AKI development was associated with SCr-AKI ≥48 h (AUC = 0.73, 95 % CI 0.56-0.90) and ≥50 % persistent SCr rise at treatment end (AUC = 0.76, 95 % CI 0.61-0.90). CONCLUSIONS: CysC is as an early AKI biomarker and predictive of persistent AKI on aminoglycoside treatment.

Renal Function Follow-Up and Renal Recovery After Acute Kidney Injury in Critically Ill Children.

OBJECTIVES: To evaluate factors associated with renal recovery from acute kidney injury in critically ill children and the extent to which serum creatinine is measured before discharge. DESIGN: Retrospective cohort study. SETTING: Two PICUs at tertiary centers in Montreal, QC, Canada. PATIENTS: Children (< 18 yr old) admitted to the PICU between 2003 and 2005. Patients with end-stage renal disease, no healthcare number, died during admission, or admitted postcardiac surgery were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Acute kidney injury was defined using internationally accepted criteria (Kidney Disease: Improving Global Outcomes). Two renal recovery outcomes commonly used in the literature were evaluated: hospital discharge serum creatinine less than 1.5 and less than 1.15 times baseline. Proportions of patients with 1) serum creatinine measurements between PICU and hospital discharge and 2) renal recovery were calculated. Univariate and multivariate analyses were performed to determine factors associated with serum creatinine monitoring and nonrecovery after acute kidney injury. Of 2,033 patients included, 829 (40.8%) had serum creatinine measurements between PICU and hospital discharge. The odds of having a discharge serum creatinine measurement increased with acute kidney injury severity (stages 1, 2, 3 adjusted odds ratio [95% CI]: 1.49 [1.03-2.15], 2.52 [1.40-4.54], 7.87 [3.16-19.60], respectively). Acute kidney injury recovery was 92.5% when defined as serum creatinine less than 1.5 times baseline versus 75.9% when defined as less than 1.15 times baseline (p < 0.001). Stage 3 acute kidney injury was associated with having a discharge serum creatinine greater than or equal to 1.5 times baseline (adjusted odds ratio = 3.51 [1.33-9.19]). CONCLUSIONS: Less than half the PICU population had serum creatinine measured before hospital discharge. More severe acute kidney injury was associated with higher likelihood of serum creatinine monitoring and lower probability of acute kidney injury recovery. Future research should address knowledge translation on post-PICU acute kidney injury follow-up before hospital discharge.

Biomarkers for Early Acute Kidney Injury Diagnosis and Severity Prediction: A Pilot Multicenter Canadian Study of Children Admitted to the ICU.

OBJECTIVE: Acute kidney injury occurs early in PICU admission and increases risks for poor outcomes. We evaluated the feasibility of a multicenter acute kidney injury biomarker urine collection protocol and measured diagnostic characteristics of urine neutrophil gelatinase-associated lipocalin, interleukin-18, and liver fatty acid binding protein to predict acute kidney injury and prolonged acute kidney injury. DESIGN: Prospective observational pilot cohort study. SETTING: Four Canadian tertiary healthcare PICUs. PATIENTS: Eighty-one children 1 month to 18 years old. Exclusion criteria were as follows: cardiac surgery, baseline severe kidney disease, and inadequate urine or serum for PICU days 1-3. INTERVENTIONS: PICUs performed standardized urine collection protocol to obtain early PICU admission urine samples, with deferred consent. MEASUREMENTS AND MAIN RESULTS: Study barriers and facilitators were recorded. Acute kidney injury was defined based on Kidney Disease: Improving Global Outcomes serum creatinine criteria (acute kidney injuryserum creatinine) and by serum creatinine and urine output criteria (acute kidney injuryserum creatinine+urine output) Prolonged acute kidney injury was defined as acute kidney injury duration of 48 hours or more. PICU days 1-3 neutrophil gelatinase-associated lipocalin, interleukin-18, and liver fatty acid binding protein were evaluated for acute kidney injury prediction (area under the curve). Biomarkers on the first day of acute kidney injury attainment (day 1 acute kidney injury) were evaluated for predicting prolonged acute kidney injury. Eighty-two to 95% of subjects had urine collected from PICU days 1-3. Acute kidney injuryserum creatinine developed in 16 subjects (20%); acute kidney injuryserum creatinine+urine output developed in 38 (47%). On PICU day 1, interleukin-18 predicted acute kidney injuryserum creatinine with area under the curve=0.82, but neutrophil gelatinase-associated lipocalin and liver fatty acid binding protein predicted acute kidney injuryserum creatinine with area under the curve of less than or equal to 0.69; on PICU day 2, area under the curve was higher (not shown). Interleukin-18 and liver fatty acid binding protein on day 1 acute kidney injury predicted prolonged acute kidney injuryserum creatinine (area under the curve=0.74 and 0.83, respectively). When acute kidney injuryserum creatinine+urine output was used to define acute kidney injury, biomarker area under the curves were globally lower. CONCLUSIONS: Protocol urine collection to procure early admission samples is feasible. Individual biomarker acute kidney injury prediction performance is highly variable and modest. Larger studies should evaluate utility and cost effectiveness of using early acute kidney injury biomarkers.

Update on Neurocritical Care of Stroke.

PURPOSE OF REVIEW: This review will highlight the recent advancements in acute ischemic stroke diagnosis and treatment, with special attention to new features and recommendations of stroke care in the neurocritical care unit. RECENT FINDINGS: New studies suggest that pre-hospital treatment of stroke with mobile stroke units and telestroke technology may lead to earlier stroke therapy with intravenous tissue plasminogen activator (tPA), and recent studies show tPA can be given in previously contraindicated situations. More rapid automated CT perfusion and angiography may demonstrate a vascular penumbra for neuroendovascular intervention. Further, the greatest advance in acute stroke treatment since 2014 is the demonstration that neuroendovascular catheter-based thrombectomy with stent retrievers recanalizing intracranial large vessel occlusion (LVO) improves both recanalization and long-term outcomes in several trials. Hemorrhagic transformation and severe large infarct cerebral edema remain serious post-stroke challenges, with new guidelines describing who and when patients should get medical or surgical intervention. The adage "time is brain" directs the most evidence-based approach for rapid stroke diagnosis for tPA eligible and LVO recanalization using an orchestrated team approach. The neurocritical care unit is the appropriate location to optimize stroke outcomes for the most severely affected stroke patients.