Characteristics and Outcomes of Children and Young Adults With Sepsis Requiring Continuous Renal Replacement Therapy: A Comparative Analysis From the Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK).

OBJECTIVES: Pediatric sepsis-associated acute kidney injury (AKI) often requires continuous renal replacement therapy (CRRT), but limited data exist regarding patient characteristics and outcomes. We aimed to describe these features, including the impact of possible dialytrauma (i.e., vasoactive requirement, negative fluid balance) on outcomes, and contrast them to nonseptic patients in an international cohort of children and young adults receiving CRRT. DESIGN: A secondary analysis of Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK), an international, multicenter, retrospective study. SETTING: Neonatal, cardiac and PICUs at 34 centers in nine countries from January 1, 2015, to December 31, 2021. PATIENTS: Patients 0-25 years old requiring CRRT for AKI and/or fluid overload. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 1016 patients, 446 (44%) had sepsis at CRRT initiation and 650 (64%) experienced Major Adverse Kidney Events at 90 days (MAKE-90) (defined as a composite of death, renal replacement therapy [RRT] dependence, or > 25% decline in estimated glomerular filtration rate from baseline at 90 d from CRRT initiation). Septic patients were less likely to liberate from CRRT by 28 days (30% vs. 38%; p < 0.001) and had higher rates of MAKE-90 (70% vs. 61%; p = 0.002) and higher mortality (47% vs. 31%; p < 0.001) than nonseptic patients; however, septic survivors were less likely to be RRT dependent at 90 days (10% vs. 18%; p = 0.011). On multivariable regression, pre-CRRT vasoactive requirement, time to negative fluid balance, and median daily fluid balance over the first week of CRRT were not associated with MAKE-90; however, increasing duration of vasoactive requirement was independently associated with increased odds of MAKE-90 (adjusted OR [aOR], 1.16; 95% CI, 1.05-1.28) and mortality (aOR, 1.20; 95% CI, 1.1-1.32) for each additional day of support. CONCLUSIONS: Septic children requiring CRRT have different clinical characteristics and outcomes compared with those without sepsis, including higher rates of mortality and MAKE-90. Increasing duration of vasoactive support during the first week of CRRT, a surrogate of potential dialytrauma, appears to be associated with these outcomes.

Cardiac atrial pathology in Duchenne muscular dystrophy.

INTRODUCTION/AIMS: Duchenne muscular dystrophy (DMD) is characterized by fibrofatty replacement of muscle. This has been documented in the ventricular myocardium of DMD patients, but there is limited description of atrial involvement. The purpose of this study is to examine the arrhythmia and ectopy burden in patients with DMD and non-DMD dilated cardiomyopathy (DCM) and to characterize the cardiac histopathologic changes in DMD patients across the disease spectrum. METHODS: This was a retrospective analysis of age-matched patients with DMD and non-DMD DCM who received a Holter monitor and cardiac imaging within 100 days of each other between 2010 and 2020. Twenty-four-hour Holter monitors were classified based on the most recent left ventricular ejection fraction at the time of monitoring. Cardiac histopathologic specimens from whole-heart examinations at the time of autopsy from three DMD patients and one DCM patient were reviewed. RESULTS: A total of 367 patients with 1299 Holter monitor recordings were included over the study period, with 94% representing DMD patients and 6% non-DMD DCM. Patients with DMD had more atrial ectopy across the cardiac function spectrum (p < 0.05). There was no difference in ventricular ectopy. Four DMD patients developed symptomatic atrial arrhythmias. Autopsy specimens from DMD patients demonstrated fibrofatty infiltration of both atrial and ventricular myocardium. DISCUSSION: The atrial myocardium in patients with DMD is unique. Autopsy specimens reveal fibofatty replacement of the atrial myocardium, which may be a nidus for both ectopy and arrhythmias in DMD patients.

Socioeconomic Influences on Outcomes Following Congenital Heart Disease Surgery.

Associations between social determinants of health (SDOH) and adverse outcomes for children with congenital heart disease (CHD) are starting to be recognized; however, such links remain understudied. We examined the relationship between community-level material deprivation on mortality, readmission, and length of stay (LOS) for children undergoing surgery for CHD. We performed a retrospective cohort study of patients who underwent cardiac surgery at our institution from 2015 to 2018. A community-level deprivation index (DI), a marker of community material deprivation, was generated to contextualize the lived experience of children with CHD. Generalized mixed-effects models were used to assess links between the DI and outcomes of mortality, readmission, and LOS following cardiac surgery. The DI and components were scaled to provide mean differences for a one standard deviation (SD) increase in deprivation. We identified 1,187 unique patients with surgical admissions. The median LOS was 11 days, with an overall mortality rate of 4.6% and readmission rate of 7.6%. The DI ranged from 0.08 to 0.85 with a mean of 0.37 (SD 0.12). The DI was associated with increased LOS for patients with more complex heart disease (STAT 3, 4, and 5), which persisted after adjusting for factors that could prolong LOS (all p < 0.05). The DI approached but did not meet a significant association with mortality (p = 0.0528); it was not associated with readmission (p = 0.36). Community-level deprivation is associated with increased LOS for patients undergoing cardiac surgery. Future work to identify the specific health-related social needs contributing to LOS and identify targets for intervention is needed.

Relationship between predisposing and facilitating factors: Does it influence the risk of developing peri-operative pressure injuries?

This study examined the relationship between the personal predisposing factors of patients and the severity of pressure injuries (PIs) developed during surgery. This retrospective cohort study collected 439 cases of peri-operative PIs. Using binary logistic regression to identify the variables associated with PI severity, the effects of interactions between associated variables were then tested. The results of this study revealed that among the personal predisposing factors, only higher patient age (P = .001) and higher body mass index (P < .001) posed a greater risk of stage 2 PIs or higher. Among the surgery-related facilitating factors, only patients who were placed in the prone position during surgery and patients who lost ≥1000 mL of blood during surgery were at greater risk of stage 2 PIs or higher, compared, respectively, to those placed in the supine position and those who lost ≤100 mL of blood. Furthermore, the amount of blood lost during surgery moderated the influence of age on PI severity. For elderly patients who are expected to lose a large blood volume during surgery or lose an immeasurable amount of blood due to the use of cardiopulmonary bypass, taking more precautionary measures to prevent PIs is recommended.

Incidence and characteristics of arterial thromboemboli in patients with COVID-19.

BACKGROUND: Studies have reported COVID-19 as an independent risk factor for arterial thromboemboli. METHODS: From a cross-sectional sample, we determined the incidence and location of arterial thromboemboli (myocardial infarction, ischemic stroke, peripheral artery), stratified by COVID-19 status, in the RECOVER database, which included data on patients at 45 United States medical centers in 22 states. Epidemiological factors, clinical characteristics and outcomes were collected through a combination of individual chart review and automatic electronic query and recorded in REDCap®. We investigated the association of baseline comorbidities on the development of arterial thromboemboli and analyzed results based on the presence or absence of concomitant COVID-19 infection, testing this association with Chi-squared. We also described use of anticoagulants and statins. RESULTS: Data were collected on 26,974 patients, of which 13,803 (51.17%) tested positive for COVID-19. Incidence of arterial thromboemboli during hospitalization was 0.13% in patients who tested positive for COVID-19 and 0.19% in patients who tested negative. Arterial thromboemboli tended to be more common in extremities than in core organs (heart, kidney, lung, liver) in patients with COVID-19, odds ratio 2.04 (95% CI 0.707 - 5.85). Patients with COVID-19 were less likely to develop an arterial thrombus when on baseline statin medication (p=0.014). Presence of metabolic syndrome predicted presence of core arterial thrombus (p=0.001) and extremity arterial thrombus (p=0.010) in those with COVID-19. Arterial thromboemboli were less common in patients with COVID-19 than in those who tested negative for COVID-19. CONCLUSIONS: Presence of a composite metabolic syndrome profile may be associated with arterial clot formation in patients with COVID-19 infection.

Using susceptibility measures to prospectively predict ever use of electronic cigarettes among adolescents.

Preventing adolescents from using e-cigarettes is crucial given that e-cigarette use can lead to conventional cigarette smoking. In order to inform prevention efforts, the present study examined the role of susceptibility measures as well as psychosocial, behavioral, and environmental factors in prospectively predicting ever use of electronic cigarettes among adolescents. We analyzed Wave 1 and Wave 2 of the Population Assessment of Tobacco and Health (PATH), nationally representative longitudinal panel datasets. Nicotine naïve adolescents, ages 12-17 at baseline (N = 7933) were included in the study sample. Multivariable logistic regression was conducted to examine the determinants of adolescents' ever use of e-cigarettes. Overall, 12.3% (n = 983) of adolescents who were naïve to nicotine products at Wave 1 became ever users of e-cigarettes at Wave 2. Susceptibility to e-cigarette use at Wave 1 was a significant predictor of ever use at Wave 2 (adjusted odds ratio = 2.27; 95% CI = 1.92, 2.68). Adolescents who were not susceptible to e-cigarette use at Wave 1 but became ever users at Wave 2 were more likely to show a higher level of alcohol use, marijuana use, other substance use, have modified family, be exposed to secondhand tobacco smoke, and have a higher level of psychological problems. The specificity of susceptibility measure was 73.2% (5080/6936) and sensitivity was 57.3% (563/983). The findings of the present study appear to support the predictive validity of the susceptibility to e-cigarette use measure as a significant predictor of future e-cigarette use.

A Randomized Controlled Trial Comparing Loss versus Gain Incentives to Improve Adherence to an Obesity Treatment Intervention in Adolescents.

BACKGROUND/OBJECTIVES: Adherence to pediatric obesity treatment can be challenging. Monetary incentives improve adherence to lifestyle interventions, with incentives framed as loss often more effective than those framed as gain. The objectives of this study were to determine if monetary incentives in the form of gift cards would improve adherence to an obesity treatment intervention and whether framing the incentive as either loss or gain affected adherence. METHODS: Sixty adolescents with obesity (body mass index of ≥95th percentile for age and sex) were recruited from our pediatric obesity treatment program. They were randomized into one of three groups and given a monthly adherence score (AS) of up to 100 points. These points were based on completing a medical visit, reporting on diet intake, and measuring daily steps on a wearable tracker. The Gain Group (GG), N = 20, started each month with USD 0 in a virtual account and increased their monetary reward up to USD 100 depending on AS. The Loss Group (LG), N = 21, began each month with USD 100 in their virtual account, which decreased based on adherence. The Control Group (CG), N = 19, received USD 10 monthly. RESULTS: Adherence was highest in the GG, with 66.0 points, compared to the LG, with 54.9 points, and CG, with 40.6 points, with p < 0.01. The GG had greater adherence to their step goal (14.6) and dietary reporting (18.7) compared to the LG (10.0 and 13.9) and the CG (3.9 and 8.1), p < 0.005. CONCLUSIONS: Gain-framed incentives are superior to loss-framed ones in improving adherence to pediatric obesity treatments.

Outcomes of rheumatic fever in Uganda: a prospective cohort study.

BACKGROUND: Rheumatic heart disease is the largest contributor to cardiac-related mortality in children worldwide. Outcomes in endemic settings after its antecedent illness, acute rheumatic fever, are not well understood. We aimed to describe 3-5 year mortality, acute rheumatic fever recurrence, changes in carditis, and correlates of mortality after acute rheumatic fever. METHODS: We conducted a prospective cohort study of Ugandan patients aged 4-23 years who were diagnosed with definite acute rheumatic fever using the modified 2015 Jones criteria from July 1, 2017, to March 31, 2020, enrolled at three rheumatic heart disease registry sites in Uganda (in Mbarara, Mulago, or Lira), and followed up for at least 1 year after diagnosis. Patients with congenital heart disease were excluded. Patients underwent annual review, most recently in August, 2022. We calculated rates of mortality and acute rheumatic fever recurrence, tabulated changes in carditis, performed Kaplan-Meier survival analyses, and used Cox regression models to identify correlates of mortality. FINDINGS: Data were collected between Sept 1 and Sept 30, 2022. Of 182 patients diagnosed with definite acute rheumatic fever, 156 patients were included in the analysis. Of these 156 patients (77 [49%] male and 79 (51%) female; data on ethnicity not collected), 25 (16%) died, 21 (13%) had a cardiac-related death, and 17 (11%) had recurrent acute rheumatic fever over a median of 4·3 (IQR 3·0-4·8) years. 16 (24%) of the 25 deaths occurred within 1 year. Among 131 (84%) of 156 survivors, one had carditis progression by echo. Moderate-to-severe carditis (hazard ratio 12·7 [95% CI 3·9-40·9]) and prolonged PR interval (hazard ratio 4·4 [95% CI 1·7-11·2]) at acute rheumatic fever diagnosis were associated with increased cardiac-related mortality. INTERPRETATION: These are the first contemporary data from sub-Saharan Africa on medium-term acute rheumatic fever outcomes. Mortality rates exceeded those reported elsewhere. Most decedents already had chronic carditis at initial acute rheumatic fever diagnosis, suggesting previous undiagnosed episodes that had already compounded into rheumatic heart disease. Our data highlight the large burden of undetected acute rheumatic fever in these settings and the need for improved awareness of and diagnostics for acute rheumatic fever to allow earlier detection. FUNDING: Strauss Award at Cincinnati Children's Hospital, American Heart Association, and Wellcome Trust.

The Association Between Vasopressin and Adverse Kidney Outcomes in Children and Young Adults Requiring Vasopressors on Continuous Renal Replacement Therapy.

OBJECTIVES: Continuous renal replacement therapy (CRRT) and shock are both associated with high morbidity and mortality in the ICU. Adult data suggest renoprotective effects of vasopressin vs. catecholamines (norepinephrine and epinephrine). We aimed to determine whether vasopressin use during CRRT was associated with improved kidney outcomes in children and young adults. DESIGN: Secondary analysis of Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK), a multicenter, retrospective cohort study. SETTING: Neonatal, cardiac, PICUs at 34 centers internationally from January 1, 2015, to December 31, 2021. PATIENTS/SUBJECTS: Patients younger than 25 years receiving CRRT for acute kidney injury and/or fluid overload and requiring vasopressors. Patients receiving vasopressin were compared with patients receiving only norepinephrine/epinephrine. The impact of timing of vasopressin relative to CRRT start was assessed by categorizing patients as: early (on or before day 0), intermediate (days 1-2), and late (days 3-7). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 1016 patients, 665 (65%) required vasopressors in the first week of CRRT. Of 665, 248 (37%) received vasopressin, 473 (71%) experienced Major Adverse Kidney Events at 90 days (MAKE-90) (death, renal replacement therapy dependence, and/or > 125% increase in serum creatinine from baseline 90 days from CRRT initiation), and 195 (29%) liberated from CRRT on the first attempt within 28 days. Receipt of vasopressin was associated with higher odds of MAKE-90 (adjusted odds ratio [aOR], 1.80; 95% CI, 1.20-2.71; p = 0.005) but not liberation success. In the vasopressin group, intermediate/late initiation was associated with higher odds of MAKE-90 (aOR, 2.67; 95% CI, 1.17-6.11; p = 0.02) compared with early initiation. CONCLUSIONS: Nearly two-thirds of children and young adults receiving CRRT required vasopressors, including over one-third who received vasopressin. Receipt of vasopressin was associated with more MAKE-90, although earlier initiation in those who received it appears beneficial. Prospective studies are needed to understand the appropriate timing, dose, and subpopulation for use of vasopressin.

Systolic Blood Pressure, Cardiovascular Health, and Neurocognitive in Adolescents.

BACKGROUND: We studied whether increased systolic blood pressure (SBP), as determined by auscultatory SBP, ambulatory SBP, and the number of cardiovascular health risk indicators, are associated with neurocognition in adolescents. METHODS: This cross-sectional study included 365 adolescents (mean age, 15.5 years) from 6 academic medical centers in the United States. The sample was 59.5% male, 52.6% White, with 23.9% of the caregivers having less than or equal to a high school degree. Primary exposures included the following: auscultatory SBP, ambulatory SBP, and the number of cardiovascular risk factors. Neurocognitive outcomes comprised nonverbal IQ, attention, and parent ratings of executive functions. RESULTS: After examining the models for the effects of targeted covariates (eg, maternal education), higher auscultatory SBP was associated with lower nonverbal IQ (ß=-1.39; P<0.001) and verbal attention (ß=-2.39; P<0.05); higher ambulatory 24 hours. SBP (ß=-21.39; P<0.05) and wake SBP (ß=-21.62; P<0.05) were related to verbal attention; and all 3 ambulatory blood pressure measures were related to sustained attention accounting for small to medium amounts of variance (adjusted R2=0.08-0.09). Higher ambulatory blood pressure sleep SBP also was significantly associated with parent ratings of behavior regulation (ß=12.61; P<0.05). These associations remained stable after a sensitivity analysis removed cases with hypertension. Number of cardiovascular risk factors performed similarly, with more risk factors being associated with lower nonverbal IQ (ß=-1.35; P<0.01), verbal attention (ß=-1.23; P<0.01), and all parent ratings of executive functions. CONCLUSIONS: Elevated SBP, even below the hypertension range, and general cardiovascular health are associated with neurocognitive outcomes in adolescents. How these findings might guide clinical care is worthy of additional study.

Cortisol Awakening Response and Stress in Female Nurses on Monthly Shift Rotations: A Longitudinal Study.

The majority of shift nurses are female, there is still an expectation that they fulfil the traditional role of women in the family in Asia, often conflicting with shift work, increases stress, and affects cortisol secretion patterns. This study was to understand the changes in the cortisol awakening response (CAR) and work stress in nursing personnel working in different shifts. We recruited 41 female shift nurses. We administered the Taiwan Nurse Stress Checklist (NSC), and the nurses themselves collected saliva samples upon waking and 30 minutes after waking for three consecutive days at home. The saliva samples enabled us to analyze the increase in cortisol levels following waking (CARi) of nurses working different shifts (day, evening, and night). We then analyzed the data obtained using a hierarchical linear model (HLM). The results indicated that in terms of stress from the inability to complete personal tasks, the regression coefficients of night-shift nurses vs. day-shift nurses (B = 4.39, p < .001) and night-shift nurses vs. evening-shift nurses (B = 3.95, p < .001) were positive, which means that night-shift nurses were under significantly greater stress than day-shift and evening-shift nurses. With regard to CARi, the regression coefficients of night-shift nurses vs. day-shift nurses (B = -3.41, p < .001) and night-shift nurses vs. evening-shift nurses (B = -2.92, p < .01) were negative, which means that night-shift nurses have significantly lower CARi values than day-shift and evening-shift nurses. With regard to cortisol levels 30 minutes after waking, the regression coefficients of night-shift nurses vs. day-shift nurses (B = -3.88, p < .01) and night-shift nurses vs. evening-shift nurses (B = -3.31, p < .01) were negative, which means that night-shift nurses have significantly lower cortisol levels 30 minutes after waking than day-shift and evening-shift nurses. These results indicate that female night-shift nurses display the lowest CARi and cortisol levels 30 minutes after waking and are more negatively affected by being unable to complete personal tasks.