Promoting Resilience in Stress Management for Adolescents With Type 1 Diabetes: A Randomized Clinical Trial.

Importance: Type 1 diabetes (T1D) requires demanding self-management health behaviors, and adolescents with T1D are at risk for poor psychosocial and medical outcomes. Developing resilience skills may help adolescents with T1D and elevated distress navigate common stressors and achieve positive outcomes. Objective: To test the efficacy of the Promoting Resilience in Stress Management (PRISM) intervention on levels of hemoglobin A1c (HbA1c), diabetes distress, self-management behaviors, resilience, and quality of life among adolescents. Design, Setting, and Participants: This phase 3, parallel, 1:1 randomized clinical trial that followed up 172 participants for 12 months was conducted from January 1, 2020, to November 30, 2022, at each of 2 children's hospitals, in Seattle, Washington, and Houston, Texas. Participants were ages 13 to 18 years with T1D for at least 12 months and elevated diabetes distress. Intervention: PRISM, a manualized, skills-based, individual intervention program that teaches stress management, goal setting, reframing, and meaning-making, facilitated by a coach and accompanied by a digital app, was delivered in three 30- to 60-minute sessions approximately 2 weeks apart. Main Outcomes and Measures: The 2 primary outcomes, diabetes distress and HbA1c levels, and 3 secondary outcomes, resilience, quality of life, and engagement in self-management behaviors, were assessed at baseline and 6 and 12 months after baseline. Linear mixed-effects regression models were used to evaluate associations between PRISM or usual care (UC) and these outcomes at both time points for the intention-to-treat population. Results: Among 172 adolescents (mean [SD] age, 15.7 [1.6] years), 96 were female (56%), and their baseline mean (SD) HbA1c level was 8.7% (2.0%). No differences were evident between PRISM and UC recipients in HbA1c levels (ß, -0.21 [95% CI, -0.65 to 0.22]; P = .33) or diabetes distress (ß, -2.71 [95% CI, -6.31 to 0.90]; P = .14) or any participant-reported outcome (eg, ß, 2.25 [95% CI, -0.30 to 4.80]; P = .08 for self-management behaviors) at 6 months. At 12 months, there was no statistically significant difference between arms in HbA1c levels (ß, -0.26 [95% CI, -0.72 to 0.19]; P = .25); however, PRISM recipients reported significantly greater amelioration of diabetes distress (ß, -4.59 [95% CI, -8.25 to -0.94]; P = .01) and improvement in self-management behaviors (ß, 3.4 [95% CI, 0.9 to 5.9]; P = .01) compared with UC recipients. Conclusions and Relevance: The findings in this randomized clinical trial of psychosocial and behavioral improvements associated with PRISM at 12 months illustrate the value of a strengths-based intervention. Integrating resilience skills-building with traditional diabetes care may be a promising approach for improving outcomes among adolescents with T1D and elevated diabetes distress. Trial Registration: ClinicalTrials.gov number: NCT03847194.

Clinical Features and Outcomes of Pediatric and Adult Patients Hospitalized for Coronavirus Disease 2019: A Comparison Across Age Strata.

Background: Coronavirus disease 2019 (COVID-19) continues to cause hospitalizations and severe disease in children and adults. Methods: This study compared the risk factors, symptoms, and outcomes of children and adults hospitalized for COVID-19 from March 2020 to May 2023 across age strata at 5 US sites participating in the Predicting Viral-Associated Inflammatory Disease Severity in Children with Laboratory Diagnostics and Artificial Intelligence consortium. Eligible patients had an upper respiratory swab that tested positive for severe acute respiratory syndrome coronavirus 2 by nucleic acid amplification. Adjusted odds ratios (aOR) of clinical outcomes were determined for children versus adults, for pediatric age strata compared to adolescents (12-17 years), and for adult age strata compared to young adults (22-49 years). Results: Of 9101 patients in the Predicting Viral-Associated Inflammatory Disease Severity in Children with Laboratory Diagnostics and Artificial Intelligence cohort, 1560 were hospitalized for COVID-19 as the primary reason. Compared to adults (22-105 years, n = 675), children (0-21 years, n = 885) were less commonly vaccinated (14.3% vs 34.5%), more commonly infected with the Omicron variant (49.5% vs 26.1%) and had fewer comorbidities (P < .001 for most comparisons), except for lung disease (P = .24). After adjusting for confounding variables, children had significantly lower odds of receiving supplemental oxygen (aOR, 0.57; 95% confidence interval, .35-.92) and death (aOR, 0.011; 95% confidence interval, <.01-.58) compa--red to adults. Among pediatric age strata, adolescents 12-17 years had the highest odds of receiving supplemental oxygen, high-flow oxygen, and ICU admission. Among adults, those 50-64 years had the highest odds of mechanical ventilation and ICU admission. Conclusions: Clinical outcomes of COVID-19 differed across pediatric and adult age strata. Adolescents experienced the most severe disease among children, whereas adults 50-64 years experienced the most severe disease among adults.

Postpartum Glucose Monitoring in Pregnant Women with Gestational Diabetes Mellitus: A Dual Center Experience.

OBJECTIVE: Gestational diabetes mellitus (GDM) is known to be a predisposing factor in the development of type 2 diabetes mellitus in affected mothers and their offspring. Current guidelines recommend a two-hour postpartum glucose tolerance test (OGTT) in patients with a history of GDM. However, compliance rates for ordering and completion has been reported as suboptimal. The COVID-19 pandemic has had significant impact on healthcare systems, requiring the adaptation of novel strategies to manage patients. So far, there is a paucity of data on how this impacts compliance rates for the oral glucose tolerance test. We aimed to compare the compliance rate and impact of the pandemic on OGTT ordering and completion between a women's hospital and a community health center. METHODS: A dual center retrospective cohort study was carried out to compare the compliance for ordering and completion of the two-hour postpartum OGTT in women diagnosed with GDM between a women's hospital and community health center two years pre-COVID-19 (2018-2019) and during the COVID-19 pandemic (2020-2021). RESULTS: 2569 pregnancies were included during these time periods. Prior to the pandemic, the test ordering compliance at the women hospital was 30.2% vs 79.3% for the community health center. During the pandemic, the test ordering compliance at the women's hospital dropped to 24.8%, while it remained steady at the community center (80.8%). Correspondingly, there was a drop in test completion compliance rate at both centers during the pandemic when compared to rate before the pandemic. CONCLUSION: Diagnosis of GDM increased during the pandemic, which may be attributed to factors like sedentary lifestyles, and restructuring of care models, among others. There was increased test ordering and test completion compliance at the community health center compared to the women's hospital, which can be attributed to routine follow-ups and other factors.

Effectiveness of Cord blood as a Strategy to rule out Conjugated Hyperbilirubinemia.

Early detection of biliary atresia is crucial for timely intervention and improved outcomes in infants with elevated conjugated bilirubin levels. This study aims to investigate the viability of cord blood gas analysis as a novel method for assessing conjugated bilirubin levels. Infants with high heel stick levels also showed elevated cord blood bilirubin levels, indicating that cord blood testing could replace the need for repeat heel stick tests, especially benefiting low birth weight infants. Ongoing research, including larger cohorts and alternative bilirubin measurement methods, will further validate this innovative screening approach. Infants with biliary atresia have high conjugated bilirubin levels at birth. As a result, infants can be screened with newborn conjugated bilirubin measurements, to allow for early detection, timely treatment, and the best chances of delaying or even avoiding the need for a liver transplant [1]. An important limitation of screening, however, is that infants must undergo a separate blood test. To overcome this limitation, we investigated whether conjugated bilirubin measurements from cord blood could be useful.

Utility of Cystatin C-based Equation for the Estimation of Glomerular Filtration Rate in a Pediatric Population.

BACKGROUND: The accurate assessment of kidney function is vital for the early detection of kidney damage. The estimated glomerular filtration rate GFR (eGFR) from serum cystatin C (CysC) and creatinine-based equations are commonly used in clinical practice as an alternative to the invasive measured glomerular filtration rate (mGFR), which is the usually accepted overall best index of kidney function in health and disease. Recently the CKiD under 25 (CkiD U25) equations have been shown to perform well in children and young adults with chronic kidney disease (CKD). In this focused report, we evaluated the performance of the CkiD U25 equations alongside 3 non-race-corrected (NRC) eGFR equations commonly used in pediatrics in our cohort. METHODS: mGFR measured following the intravenous injection of tracer Tc-99mDTPA was retrospectively compared with eGFR from these equations in 57 patients (6 months to 22 years) from different races/ethnicities. Ordinary least squares regression analyses were used to assess correlation between the mGFRs and eGFRs. RESULTS: The average mGFR for this cohort was 84.1 mL/min/1.73 m2. The NRC creatinine equations overestimated eGFR across all groups, with the lowest bias for CKiD U25-creatinine (22.59 mL/min/1.73 m2). The best correlations to mGFR, P30, and lowest biases were the CKiD U25-CysC (0.6281, 80.7%, 3.72 mL/min/1.73 m2) and Schwartz CysC (0.6372, 77.2%, -4.68 mL/min/1.73 m2). CONCLUSIONS: Overall, both CKiD U25-CysC and Schwartz CysC provide a good estimation of mGFR with the CKiD U25-CysC having the overall best performance compared to mGFR in our study.

Dawn-to-dusk dry fasting decreases circulating inflammatory cytokines in subjects with increased body mass index.

Background: The circadian rhythm involves numerous metabolic processes, including sleep/awakening, body temperature regulation, hormone secretion, hepatic function, cellular plasticity, and cytokine release (inflammation), that appear to have a dynamic relationship with all the processes above. Studies have linked various cytokines to the chronic state of low-grade inflammation and oxidative stress in obesity. Dawn-to-dusk dry fasting (DDDF) could alleviate the adverse effects of obesity by decreasing inflammation. This study examined the effects of DDDF on circulating inflammatory cytokines in subjects with increased body mass index (BMI). Methods: The current observational prospective study included adult subjects with a BMI equal to or greater than 25 kg/m2 who practiced the annual religious 30-day DDDF. Individuals with significant underlying medical conditions were excluded to limit confounding factors. All subjects were evaluated within two weeks before 30-day DDDF, within the fourth week of 30-day DDDF, and within two weeks after 30-day DDDF. Multiple cytokines and clinical health indicators were measured at each evaluation. Results: Thirteen subjects (10 men and three women) with a mean age of 32.9 years (SD = 9.7 years) and a mean BMI of 32 kg/m2 (SD = 4.6 kg/m2) were included. An overall associated decrease in the levels of multiple cytokines with DDDF was observed. A significant decrease in the mean interleukin 1 beta level was observed within the fourth week of 30-day DDDF (P = 0.045), which persisted even after the fasting period (P = 0.024). There was also a significant decrease in the mean levels of interleukin 15 (IL-15) (P = 0.014), interleukin 1 receptor antagonist (P = 0.041), macrophage-derived chemokine (MDC) (P = 0.013), and monokine induced by interferon gamma/chemokine (C-X-C motif) ligand 9 (P = 0.027) within the fourth week of 30-day DDDF and in the mean levels of fibroblast growth factor 2 (P = 0.010), interleukin 12 p40 subunit (P = 0.038), interleukin 22 (P = 0.025) and tumor necrosis factor alpha (P = 0.046) within two weeks after 30-DDDF. In terms of anthropometric parameters, there was a decrease in mean body weight (P = 0.032), BMI (P = 0.028), and hip circumference (P = 0.007) within the fourth week of 30-day DDDF and a decrease in mean weight (P = 0.026), BMI (P = 0.033) and hip circumference (P = 0.016) within two weeks after 30-day DDDF compared with the levels measured within two weeks before 30-day DDDF. Although there was no significant correlation between changes in weight and changes in circulating inflammatory cytokines, there was a significant positive correlation between changes in waist circumference and changes in specific inflammatory cytokines (e.g., IL-15, MDC, platelet-derived growth factor, soluble CD40L, vascular endothelial growth factor A) within the fourth week of 30-day DDDF and/or two weeks after 30-day DDDF. A significant decrease in mean average resting heart rate within the fourth week of 30-day DDDF was also observed (P = 0.023), and changes between average resting heart rate and changes in interleukin-8 levels within the fourth week of 30-day DDDF compared with baseline levels were positively correlated (r = 0.57, P = 0.042). Conclusion: DDDF appears to be a unique and potent treatment to reduce low-grade chronic inflammation caused by obesity and visceral adiposity. Further studies with more extended follow-up periods are warranted to investigate the long-term anti-inflammatory benefits of DDDF in individuals with increased BMI.

Validation of a whole blood machine learning strategy for distinguishing between bacterial and viral infection in a pediatric hospital setting.

Similar symptoms between viral and bacterial diseases often make diagnosis difficult. This study assessed the clinical performance of the newly cleared whole-blood Bacterial versus Viral Score assay in our pediatric cohort to the previously validated serum assay and emergency department physician diagnosis. This assay shows excellent agreement (R = 0.997) with the serum assay and has great diagnostic accuracy when compared to physician diagnosis.

CADHERIN-11 regulation of myeloid phagocytes and autoimmune inflammation in murine lupus.

BACKGROUND AND OBJECTIVE: Understanding the regulation of efferocytosis by myeloid phagocytes is important in identifying novel targets in systemic lupus erythematosus (SLE). Cadherin-11 (CDH11), a cell adhesion molecule, is implicated in inflammatory arthritis and fibrosis and recently been shown to regulate macrophage phagocytosis. The extent and mechanism of this regulation is unknown. Our objective was to examine the extent to which CDH11 regulates myeloid phagocytes and contributes to autoimmunity and tissue inflammation. METHODS: We analyzed efferocytosis in macrophages and dendritic cells (DCs) from WT and Cdh11-/- mice and investigated the mechanisms in vitro. We investigated the role of CDH11 in disease development in vivo using the pristane induced lupus model. To translate the clinical relevance of CDH11 in human disease, we measured serum CDH11 levels in two independent pediatric SLE (pSLE) cohorts and healthy controls. RESULTS: Using bone marrow derived macrophages (BMDMs) and DCs (BMDCs), we found impaired efferocytosis in phagocytes from Cdh11-/- mice, mediated by downregulated efferocytosis receptor expression and RhoGTPase activation. Specifically, loss of CDH11 downregulated Mertk expression and Rac1 activation in BMDMs, and integrin αVß3 expression and Cdc42 activation in BMDCs, highlighting distinct pathways. In vivo, Cdh11-/- mice displayed defective efferocytosis and increased accumulation of apoptotic debris in pristane-induced lupus. Further, Cdh11-/- mice had enhanced systemic inflammation and autoimmune inflammation with increased anti-dsDNA autoantibodies, splenomegaly, type I interferons, and inflammatory cytokines. Paradoxically, at the tissue level, Cdh11-/- mice were protected against glomerulonephritis, indicating a dual role in murine lupus. Finally, SLE patients had increased serum CDH11 compared to controls. CONCLUSION: This study highlights a novel role of CDH11 in regulating myeloid cells and efferocytosis and its potential as a contributor to development in autoimmunity murine lupus. Despite the increase in autoimmunity, Cdh11-/- mice developed decreased tissue inflammation and damage.

Path Towards Biopsy-Free Diagnosis of Celiac Disease in Pediatric Patients.

BACKGROUND: Laboratory testing for celiac disease in pediatric patients integrates serology, genetic susceptibility and duodenal biopsy examination. The 2023 American College of Gastroenterology guidelines recommend a biopsy-free approach in pediatric patients utilizing tissue transglutaminase antibody titers >10 times upper limit of normal and subsequent endomysial antibody seropositivity as sufficient for diagnosis. The objective of this study is to assess the diagnostic accuracy of biopsy-free approach at our pediatric hospital. METHODS: We conducted a retrospective study involving pediatric patients who underwent biopsy for diagnostic confirmation of celiac disease between May 2019 and May 2023. For these patients, the tissue transglutaminase and endomysial antibody test results were retrieved and performance of biopsy-free approach was assessed using the duodenal histology as the gold standard for celiac disease diagnosis. RESULTS: Tissue transglutaminase antibody titers >10 times upper limit of normal alone demonstrated a positive predictive value of 99% for identifying celiac disease in children. Although endomysial antibody testing is underutilized at our center, its inclusion further improved the predictability to 100 %. CONCLUSION: Positive predictive value of tissue transglutaminase antibody titers >10 times upper limit of normal is sufficiently high for celiac disease diagnosis in children and may allow for deferral of duodenal biopsy at diagnosis.

Cystic fibrosis-related diabetes screening at a large pediatric center.

OBJECTIVE: Cystic Fibrosis Foundation guidelines recommend annual diabetes screening by oral glucose tolerance test (OGTT) in pediatric patients with cystic fibrosis (CF) starting at the age of 10 years. Adherence to these guidelines proves to be challenging, and the nationwide screening rates are still considered suboptimal. The aim of this study was to assess and improve the screening rates at our large pediatric center. METHODS: A 4-year retrospective audit of OGTT completion among pediatric patients with CF of age ≥10 years who are not yet diagnosed with diabetes was conducted. A collaborative working group was formed to identify the barriers to screening and formulate a quality improvement plan, which was monitored and evaluated for a 9-month period. RESULTS: Diabetes screening rates determined by OGTT completion at our center showed a gradual decline during the COVID-19 pandemic from 2019 to 2022. Following the implementation of the quality improvement plan during the summer of 2023, there was a marked increase in OGTT ordering compliance by providers as well as test completion by patients. Notably, the fractional OGTT completion rate rose from 45% during the preintervention phase (January-April 2023) to 70% during the postintervention phase (May-September 2023). CONCLUSION: Diabetes screening in pediatric patients with CF can be effectively improved by refining practices related to patient experience, care coordination, and laboratory testing strategies.

Reticulocyte hemoglobin equivalent as a marker to assess iron deficiency: A large pediatric tertiary care hospital study.

INTRODUCTION: Detection of iron deficiency (ID) remains challenging. We aimed to evaluate the performance of reticulocyte hemoglobin equivalent (Ret-He) as a potential diagnostic marker to assess ID and iron deficiency anemia (IDA) in a large pediatric cohort. METHODS: A total of 3158 patients (aged 15 days to 19 years with a median age of 8.5 years; 60.2% female) were retrospectively studied. Statistical analysis was performed (a) to evaluate relationship of Ret-He with other relevant complete blood count and iron panel parameters; (b) to compare the levels of Ret-He in ID and IDA groups to a control group; and (c) to assess sensitivity and specificity of Ret-He in ID, IDA, and anemia without ID groups. RESULTS: Ret-He values were significantly positively correlated to ferritin and transferrin saturation (TSAT). The median Ret-He was significantly lower in ID. A Ret-He cutoff of ≤30.0 pg distinguished cases of ID from the control group with a sensitivity of 90.2%, specificity of 59.5%, and area under curve (AUC) of 0.88. Ret-He showed better diagnostic performance in the IDA group and acceptable performance for ID without anemia. The sensitivity, specificity, and AUC were 90.1%, 80.9%, and 0.93 for IDA at cutoff value of ≤27.4 pg, and 80.8%, 51.1%, and 0.70 for ID without anemia at cutoff value of ≤30.8 pg, respectively. CONCLUSION: Our large pediatric tertiary care hospital study demonstrates that Ret-He is a reliable marker to help confirm IDA in pediatric population. However, further studies are needed for its use to capture the early stages of ID.

Best Practices for Effective Management of Point of Care Testing.

With the recent COVID-19 pandemic, point-of-care testing has gained tremendous attention, particularly in acute care settings. The point-of-care testing landscape is rapidly expanding and being contemplated for any crucial test with a central laboratory turnaround time >25% of the clinical decision time. A typical point-of-care testing program within a large hospital system encompasses a multitude of operators utilizing a wide range of devices across multiple testing sites. Thus, managing a large point-of-care testing network remains a daunting task with challenges related to staffing, standardization, quality management, training and competency assessment, and data management. This review will focus on understanding the general organization as well as the roles and responsibilities of various point-of-care testing stakeholders in addressing these challenges. More importantly, it will discuss the strategies and best practices for effective point-of-care testing management based on consensus recommendations from professional societies as well as our experience at Texas Childrens Hospital.

Stratification of Pediatric COVID-19 Cases Using Inflammatory Biomarker Profiling and Machine Learning.

While pediatric COVID-19 is rarely severe, a small fraction of children infected with SARS-CoV-2 go on to develop multisystem inflammatory syndrome (MIS-C), with substantial morbidity. An objective method with high specificity and high sensitivity to identify current or imminent MIS-C in children infected with SARS-CoV-2 is highly desirable. The aim was to learn about an interpretable novel cytokine/chemokine assay panel providing such an objective classification. This retrospective study was conducted on four groups of pediatric patients seen at multiple sites of Texas Children's Hospital, Houston, TX who consented to provide blood samples to our COVID-19 Biorepository. Standard laboratory markers of inflammation and a novel cytokine/chemokine array were measured in blood samples of all patients. Group 1 consisted of 72 COVID-19, 70 MIS-C and 63 uninfected control patients seen between May 2020 and January 2021 and predominantly infected with pre-alpha variants. Group 2 consisted of 29 COVID-19 and 43 MIS-C patients seen between January and May 2021 infected predominantly with the alpha variant. Group 3 consisted of 30 COVID-19 and 32 MIS-C patients seen between August and October 2021 infected with alpha and/or delta variants. Group 4 consisted of 20 COVID-19 and 46 MIS-C patients seen between October 2021 andJanuary 2022 infected with delta and/or omicron variants. Group 1 was used to train an L1-regularized logistic regression model which was tested using five-fold cross validation, and then separately validated against the remaining naïve groups. The area under receiver operating curve (AUROC) and F1-score were used to quantify the performance of the cytokine/chemokine assay-based classifier. Standard laboratory markers predict MIS-C with a five-fold cross-validated AUROC of 0.86 ± 0.05 and an F1 score of 0.78 ± 0.07, while the cytokine/chemokine panel predicted MIS-C with a five-fold cross-validated AUROC of 0.95 ± 0.02 and an F1 score of 0.91 ± 0.04, with only sixteen of the forty-five cytokines/chemokines sufficient to achieve this performance. Tested on Group 2 the cytokine/chemokine panel yielded AUROC = 0.98 and F1 = 0.93, on Group 3 it yielded AUROC = 0.89 and F1 = 0.89, and on Group 4 AUROC = 0.99 and F1 = 0.97. Adding standard laboratory markers to the cytokine/chemokine panel did not improve performance. A top-10 subset of these 16 cytokines achieves equivalent performance on the validation data sets. Our findings demonstrate that a sixteen-cytokine/chemokine panel as well as the top ten subset provides a highly sensitive, and specific method to identify MIS-C in patients infected with SARS-CoV-2 of all the major variants identified to date.

Comparison of random urine protein/creatinine ratio with 24-hour urine protein in suspected pre-eclampsia.

Introduction: Proteinuria is one of the classical criteria for the diagnosis of pre-eclampsia. The gold standard remains the measurement of 24-h urine protein which is time consuming and prone to preanalytical errors. Random urine protein creatinine ratio (UPCR) is endorsed by clinical practice guidelines as a faster alternative. The aim of this study was to evaluate the correlation between the 24-h urine protein excretion and UPCR in the identification of proteinuria in suspected preeclamptic patients. Method: A total of 51 women with suspected pre-eclampsia from the maternal fetal clinic of our institution were retrospectively studied. The correlation between the UPCR in random urine samples and protein excretion in the 24-h urine collection was determined by Deming Regression analysis and Pearson correlation on EP evaluator and SPSS respectively. Result: There was a significant positive correlation between the numerical values obtained by 24-h urine protein and the UPCR (R = 0.88, P < 0.001). Concordance analysis showed 81.1% positive agreement for proteinuria between methods (>300 mg/24hr and >0.3) and 71.4% negative agreement. The clinical sensitivity and specificity of the UPCR was 74% and 69% respectively. Conclusion: Overall, UPCR was well correlated with 24-h urine protein and could be an effective and compliant screening tool to indicate proteinuria in preeclamptic patients.

Unique Hemoglobinopathy Pattern Following Treatment with Voxelotor.

OBJECTIVE: Voxelotor, a FDA-approved drug for the treatment of patients with sickle cell disease (SCD), inhibits hemoglobin S (HbS) polymerization and increases total hemoglobin via hemolysis reduction. This drug has shown unique patterns in hemoglobin fractionation, affecting its interpretation. We aimed to evaluate whether these voxelotor-induced changes can be linked to improvement of hemolysis markers in pediatric patients on voxelotor. METHODS: A total of 15 patients (age 12 to 20 years; 40% females) on voxelotor were evaluated to compare changes in the hemoglobin fractionation by capillary electrophoresis, total hemoglobin, reticulocyte percentage (retic%), lactate dehydrogenase (LDH), and bilirubin measurements before and after the recorded date of voxelotor prescription. RESULTS: Hemoglobin fractionation showed changes in the profile of 60% (9/15) of the patients studied. Out of the 9 patients for which voxelotor showed changes in the hemoglobin fractionation, 44% (4/9) had an increase of >1 g/dL in their total hemoglobin after voxelotor treatment was started. Assessment of other hemolysis markers available showed decreased LDH (4/4), retic % (6/8), and bilirubin (3/4). CONCLUSIONS: Unique pattern of hemoglobin fractionation analysis following therapy with voxelotor has potential as a tool for the assessment of response and/or compliance to voxelotor for the treatment of SCD.

Pediatric vitamin D: Pseudo-hypervitaminosis.

BACKGROUND: Vitamin D toxicity is rare in pediatric population. Falsely elevated levels of 25-hydroxyvitamin D have been reported as a major challenge with immunoassay methods for quantifying vitamin D metabolites. CASE PRESENTATION AND METHOD: Here, we present two pediatric cases of falsely elevated 25-hydroxyvitamin D that resulted in unnecessary further testing. We also report significant same-day variation in the measurement of 25-hydroxyvitamin D using the Abbott i2000SR immunoassay. Samples were spun twice and their values were confirmed with the gold standard liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for confirmation. CONCLUSION: The addition of a centrifugation step prior to sample testing resolved the variation observed in the measurement of 25-hydroxyvitamin D levels. The patient samples were confirmed with instruments from a different vendor and LC-MS/MS. Re-centrifugation of samples resolved the variation in the 25-hydroxyvitamin D values.

SARS-CoV-2 Antibody Titers and Severity of Multisystem Inflammatory Syndrome in Children.

OBJECTIVE: Multisystem inflammatory syndrome in children (MIS-C) is a rare yet serious pathological consequence of SARS-CoV-2 infection which is reported 4-12 weeks after the onset of COVID-19 in children and adolescents. The most common hyper-inflammatory conditions mimicking the clinical presentation of MIS-C include Kawasaki disease and toxic shock syndrome. The surveillance criteria of MIS-C were recently revised by US Center for Disease Control and Prevention to improve diagnostic precision. Although previous studies have shown that SARS-CoV-2 antibody titers correlate with COVID-19 severity, their relation to MIS-C severity remains poorly understood and the aim of the study was to investigate this. METHODS: As all the MIS-C patients get a SARS-CoV-2 antibody test performed on the first day of hospitalization, here we attempted to stratify risk for adverse outcomes due to MIS-C based on the SARS-CoV-2 antibody titers. RESULTS: Our studies demonstrated that SARS-CoV-2 antibody titers, specifically Total (IgG/IgM/partial IgA), Nucleocapsid IgG, and Spike IgM, do not correlate with MIS-C severity assessed based on the ICU admission, inotropic support, and mechanical respiratory support requirements. CONCLUSION: Therefore, it might not be appropriate to predict the clinical course of patients presenting with MISC based on quantitative serology testing.

Increased Adipocyte Hypertrophy in Patients with Nascent Metabolic Syndrome.

Background and Aims: Metabolic Syndrome (MetS), a global problem, predisposes to an increased risk for type 2 diabetes and premature cardiovascular disease. While MetS is associated with central obesity, there is scanty data on adipocyte hypertrophy, increased fat cell size (FCS), in MetS. The aim of this study was to investigate FCS status in adipose tissue (AT) biopsy of patients with nascent MetS without the confounding of diabetes, cardiovascular disease, smoking, or lipid therapy. Methods and Results: Fasting blood and subcutaneous gluteal AT biopsies were obtained in MetS (n = 20) and controls (n = 19). Cardio-metabolic features, FFA levels, hsCRP, and HOMA-IR were significantly increased in patients with MetS. Waist-circumference (WC) adjusted-FCS was significantly increased in patients with MetS and increased with increasing severity of MetS. Furthermore, there were significant correlations between FCS with glucose, HDL-C, and the ratio of TG: HDL-C. There were significant correlations between FCS and FFA, as well as endotoxin and monocyte TLR4 abundance. Additionally, FCS correlated with readouts of NLRP3 Inflammasome activity. Most importantly, FCS correlated with markers of fibrosis and angiogenesis. Conclusions: In conclusion, in patients with nascent MetS, we demonstrate WC-adjusted increase in FCS from gluteal adipose tissue which correlated with cellular inflammation, fibrosis, and angiogenesis. While these preliminary observations were in gluteal fat, future studies are warranted to confirm these findings in visceral and other fat depots.