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Chromosome 15q11q13 is among the least stable regions in the genome due to its highly complex genomic architecture. Low copy repeat elements at 15q13.3 facilitate recurrent copy number variants (CNVs), with deletions established as pathogenic and "CHRNA7" implicated as a candidate gene. However, the pathogenicity of duplications of "CHRNA7" is unclear, as they are found in affected probands as well as in reportedly healthy parents and unaffected control individuals. We evaluated 18 children with microduplications involving "CHRNA7," identified by clinical chromosome microarray analysis (CMA). Comprehensive phenotyping revealed high prevalence of developmental delay/intellectual disability, autism spectrum disorder, and attention deficit/hyperactivity disorder. As "CHRNA7" duplications are the most common CNVs identified by clinical CMA, this study provides anticipatory guidance for those involved with care of affected individuals.

Dear Editor, A 75-year-old female patient with a 20-year history of presumed cutaneous and mucosal lichen planus (LP) and a 4-year history of bilateral conductive hearing loss presented with acute bilateral otalgia, otorrhoea and (a) violaceous flat-topped papules on the lower extremities. This is the first reported case of otic LP complicated by TM perforation.[1] At the 2-month follow-up, her aural symptoms improved and TM perforations completely resolved with compounded topical 1% tacrolimus in mineral oil. [Extracted from the article]

Introduction: This study aimed to characterize the severity of bleeding and its association with short-term neurologic outcomes in pediatric ECMO., Methods: Multicenter retrospective cohort study of pediatric ECMO patients at 10 centers utilizing the Pediatric ECMO Outcomes Registry (PEDECOR) database from December 2013-February 2019. Subjects excluded were post-cardiac surgery patients and those with neonatal pathologies. A novel ECMO bleeding scale was utilized to categorize daily bleeding events. Poor short-term neurologic outcome was defined as an unfavorable Pediatric Cerebral Performance Category (PCPC) or Pediatric Overall Performance Category (POPC) (score of >3) at hospital discharge., Results: This study included 283 pediatric ECMO patients with a median (interquartile range [IQR]) age of 1.3 years [0.1, 9.0], ECMO duration of 5 days [3.0, 9.5], and 44.1% mortality. Unfavorable PCPC and POPC were observed in 48.4% and 51.3% of patients at discharge, respectively. Multivariable logistic regression analysis included patient's age, cannulation type, duration of ECMO, need for cardiopulmonary resuscitation, acute kidney injury, new infection, and vasoactive-inotropic score. As the severity of bleeding increased, there was a corresponding increase in the likelihood of poor neurologic recovery, shown by increasing odds of unfavorable neurologic outcome (PCPC), with an adjusted odds ratio (aOR) of 0.77 (confidence interval [CI] 0.36-1.62), 1.87 (0.54-6.45), 2.97 (1.32-6.69), and 5.56 (0.59-52.25) for increasing bleeding severity (grade 1 to 4 events, respectively). Similarly, unfavorable POPC aOR (CI) was 1.02 (0.48-2.17), 2.05 (0.63-6.70), 5.29 (2.12-13.23), and 5.11 (0.66-39.64) for bleeding grade 1 to 4 events., Conclusion: Short-term neurologic outcomes in pediatric ECMO are proportional to the severity of bleeding events. Strategies to mitigate bleeding events could improve neurologic recovery in pediatric ECMO., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Jun Teruya: Evaheart member of DSMB and STAGO honoraria for presentation: Ahmed Said: supported by the Children’s Discovery Institute Faculty Development Award at Washington University in St. Louis: Marie Steiner: Teaching contract (managing coagulation) with Medtronic and study advisory board for Octapharma (AT in Adult CPB heparin resistance). All other authors report no conflicts of interest.

Objective: Neurodevelopmental delay is common in children who undergo surgery for Congenital Heart Disease (CHD) in infancy. Cardiac surgery associated acute kidney injury (CS-AKI) occurs frequently in the paediatric cardiac Intensive care unit (ICU). Cardiac surgery associated acute kidney injury (CS-AKI) is associated with worse neurodevelopmental scores and delay in cognitive, language, and motor domains in children with CHD. No known data exist regarding the association of CS-AKI and motor and language subscales. In this study, we explored the relationship between CS-AKI and receptive and expressive language, as well as gross and fine motor delay., Methods: This was a single centre retrospective observational cohort study. Children who underwent surgery for CHD and developed recurrent CS-AKI in the first year of life who had follow-up neurodevelopmental testing using the Bayley Scale of Infant Development Version III were included. Neurodevelopmental delay subscales assessed included: receptive and expressive language, fine and motor skills., Results: The study cohort included 203 children. Recurrent CS-AKI was significantly associated with lower scores in receptive and expressive language, as well as fine and gross motor on unadjusted analyses. On adjusted analyses, recurrent CS-AKI was significantly associated with severe receptive language delay., Conclusion: The independent association of recurrent CS-AKI with severe language delay in children who undergo surgery for CHD in infancy is novel. Our findings may contribute to the understanding of language impairment in this population. Further studies are required to better understand this relationship and any potentially modifiable factors.

Introduction: Despite rapid advances in liquid biopsy for circulating tumor DNA (ctDNA), its prognostic value for venous thromboembolism (VTE) in patients with cancer is underexplored, particularly in underserved and minoritized populations., Methods: We analyzed data from 1,038 cancer patients who underwent ctDNA measurement for oncologic care at a large safety-net hospital system in the US. We investigated the association between ctDNA and VTE after adjusting for cancer type, stage, treatment, and time from initial diagnosis using Fine-Gray models. We further assessed the discrimination of the genetic, clinical-only, and combined models using the area under the time-dependent receiver operating characteristic curve (AUC)., Results: The presence of pathogenic ctDNA was independently associated with VTE after adjusting for clinical variables. Independent of tumor type, the number of pathogenic ctDNA mutations was predictive of future VTE risk (adjusted subdistribution hazard ratio 2.75, 1.94, and 1.38 for ≥3, 2, and 1 pathogenic mutation, respectively, compared to none; p<0.0001). The association was primarily driven by mutations in KRAS, PTEN, CDKN2A, NF1, and EGFR genes. Compared to the clinical-only model (AUC 0.71, 95% CI 0.64-0.76), the combined clinical and ctDNA model had a numerically higher time-dependent AUC (AUC 0.74, 95% CI 0.67-0.80)., Conclusions: CtDNA testing may serve as an adjunctive tool to clinical risk assessment models in cancer patients to improve personalized VTE risk assessment and management., (Copyright © 2024 International Society on Thrombosis and Haemostasis. All rights reserved.)

Chronic rejection (CR) is a progressive immunological injury that frequently leads to long-term liver allograft dysfunction and loss. Although CR remains an important indication for retransplantation, as transplant immunosuppression has evolved, its prevalence in adults undergoing liver transplantation (LT) has declined. However, the incidence and factors that lead to CR in pediatric LT are poorly defined. Therefore, we sought to systematically measure CR's incidence and assess both the risk factors for developing CR and outcomes in a large cohort of pediatric recipients of LT. In this single-center study, we retrospectively analyzed and compared relevant recipient characteristics, surgical details, immunosuppression, graft, and patient survival in the CR and control groups over a 17-year period. After a median time of 1.9 years after LT, 19/356 recipients of LT (5.3%) developed CR in our cohort. Posttransplant lymphoproliferative disorder ( p = 0.01), infections ( p = 0.02), autoimmune liver diseases (HR = 7.3, p = <0.01), Black race (HR = 11.5, p = 0.01), and 2 or more episodes of T cell mediated rejection (HR = 5.1, p = <0.01) were associated with CR development. The retransplantation rate among CR cases was 15.8% at a median follow-up time of 4.1 years. Overall, patient survival was lower in the CR group (78.9%) versus controls (91.1%). While CR incidence in our pediatric cohort was lower than previously reported rates of >12%, the CR group had a higher graft failure rate that required retransplantation and lower overall patient survival. Thus, identifying risk factors may warrant specialized immunosuppression protocols and closer posttransplantation monitoring to reduce the risk of morbidity and mortality from CR., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Objectives: Data on US caregiver perceptions on coronavirus disease 2019 (COVID-19) and COVID-19 vaccination are limited. We identified trends in and associations with COVID-19 vaccine hesitancy in caregivers of hospitalized children., Methods: Cross-sectional surveys on pediatric COVID-19 disease and vaccine attitudes, behaviors, and beliefs were administered across study years (December 8, 2020-April 5, 2021, November 30, 2021-March 15, 2022, and October 26, 2022-March 15, 2023). English and Spanish-speaking caregivers of hospitalized children ages 6 months to 11 years were included. General vaccine hesitancy was assessed using the Parent Attitudes about Childhood Vaccines survey., Results: Of 1268 caregivers from diverse backgrounds, one-third vaccinated or intended to vaccinate their child. Half endorsed fear of their child receiving the COVID-19 vaccine and were concerned the vaccine was new. Over time, more believed "the COVID-19 vaccine does not work" and fewer agreed "children who are otherwise healthy can die from COVID-19." Study season (2022-2023), older child age, higher income, child receipt of influenza vaccine, caregiver receipt of COVID-19 vaccine, and not being worried about vaccine novelty were positively associated with child vaccination. Intent to vaccinate was negatively associated with study season (2022-2023), Parent Attitudes about Childhood Vaccines score ≥50, lack of child influenza and caregiver COVID-19 vaccination, lack of fear of their child "getting COVID-19" and being "worried that the COVID-19 vaccine is new." The majority who intended to vaccinate were willing to immunize before discharge., Conclusions: Vaccine novelty and perceived lack of need were associated with refusal. Caregiver COVID-19 and child influenza vaccine acceptance were positively associated with COVID-19 vaccine acceptance. The inpatient setting offers the opportunity to improve vaccine uptake., (Copyright © 2024 by the American Academy of Pediatrics.)

Venous thromboembolism (VTE) poses a significant risk to cancer patients receiving systemic therapy. The generalizability of pan-cancer models to lymphomas is limited. Currently, there are no reliable risk prediction models for thrombosis in patients with lymphoma. Our objective was to create a risk assessment model (RAM) specifically for lymphomas. We performed a retrospective cohort study to develop Fine and Gray sub-distribution hazard model for VTE and pulmonary embolism (PE)/ lower extremity deep vein thrombosis (LE-DVT) respectively in adult lymphoma patients from the Veterans Affairs national healthcare system (VA). External validations were performed at the Harris Health System (HHS) and the MD Anderson Cancer Center (MDACC). Time-dependent c-statistic and calibration curves were used to assess discrimination and fit. There were 10,313 (VA), 854 (HHS), and 1858 (MDACC) patients in the derivation and validation cohorts with diverse baseline. At 6 months, the VTE incidence was 5.8% (VA), 8.2% (HHS), and 8.8% (MDACC), respectively. The corresponding estimates for PE/LE-DVT were 3.9% (VA), 4.5% (HHS), and 3.7% (MDACC), respectively. The variables in the final RAM included lymphoma histology, body mass index, therapy type, recent hospitalization, history of VTE, history of paralysis/immobilization, and time to treatment initiation. The RAM had c-statistics of 0.68 in the derivation and 0.69 and 0.72 in the two external validation cohorts. The two models achieved a clear differentiation in risk stratification in each cohort. Our findings suggest that easy-to-implement, clinical-based model could be used to predict personalized VTE risk for lymphoma patients., (© 2024 Wiley Periodicals LLC.)

Introduction Neck adiposity has been related to cardiovascular risk in healthy and nonhealthy individuals. Our objective was to evaluate the utility of anatomic neck measurements extracted from computed tomography (CT) examinations as a predictor of cardiovascular disease and its risk factors. Methods We investigated patients who had a CT neck examination with intravenous contrast performed at two hospitals between 2013 and 2020. Patients with a neck malignancy, prior neck surgery, age <18 years, incomplete demographic information, and inadequate image quality were excluded. We performed 18 separate measurements of neck anatomy which were correlated with cardiovascular risk factors and disease, as well as relevant lab values and medications. All multivariable linear regressions were controlled for gender and BMI. Associations with p<0.05 were considered statistically significant. The measurements were then used to predict hypertension using random forest, a non-linear prediction algorithm. Results Approximately 20,000 neck CT examinations with contrast were performed between 2013-2020. After applying the inclusion criteria, 458 patients remained in the study population. Eight measurements (all of which include a component of neck adiposity) showed a statistically significant association between anatomic measurements and cardiovascular risk factors. The risk factor most often associated with increases in CT measurements was type 2 diabetes. Accordingly, patients on insulin treatment had a significantly higher average for all eight measurements. Significant measurement increases were also found in those previously diagnosed with hyperlipidemia and in those being treated with hypertension medications. The area under the receiver operating characteristic (AUROC) value of the random forest prediction algorithm was 0.68, meaning our measurements were a good predictor of hypertensive disease status. Conclusion Adipose tissue measurements extracted from CT examinations of the neck are associated with cardiovascular risk factors including hypertension, diabetes, and hyperlipidemia. Machine learning models of anatomic neck measurements can potentially identify patients at risk for cardiovascular disease., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Baylor College of Medicine Institutional Review Board issued approval H-47632. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Lopez et al.)

Background: There is uncertainty in the management of cancer-associated isolated splanchnic vein thrombosis (SpVT)., Objectives: To describe the natural history of SpVT by cancer type and thrombus composition and to review anticoagulation (AC) practices and associated rates of usual-site venous thromboembolism (VTE), major and clinically relevant nonmajor bleeding (MB/CRNMB), recanalization/progression, and mortality., Methods: We performed a retrospective cohort study in patients with SpVT at 2 cancer care centers in Houston, Texas. We estimated the incidence of usual-site VTE and MB/CRNMB at 6 months using competing risk methods and examined venous patency in a subset of patients with repeat imaging. We assessed associations with mortality using Cox regression., Results: Among 15 342 patients with an incident cancer diagnosis from 2011 to 2020, we identified 298 with isolated SpVT. Patients with hepatocellular carcinoma (HCC) and SpVT (n = 146) had the highest disease prevalence (20%), lowest rate of AC treatment (2%), and similar rate of usual-site VTE (4.2%) vs those without SpVT (5.2%) at 6 months, though tumor thrombus vs bland was associated with worse overall survival. In patients with non-HCC bland SpVT (n = 114), AC (n = 37) was more common in those with non-upper gastrointestinal cancers and fewer comorbidities. AC was associated with more recanalization (44% vs 15%, P = .041) but no differences in usual-site VTE, MB/CRNMB, or mortality at 6 months., Conclusion: Cancer-associated isolated SpVT is a common but heterogeneous thrombotic disease that is treated differently from usual-site VTE. Tumor thrombus is a negative prognostic factor. Initiation of AC in bland thrombi requires judicious consideration of thrombotic and bleeding risk., Competing Interests: Declaration of competing interests The authors declare no competing financial interests., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Background: The transition of the Accreditation Council for Graduate Medical Education (ACGME) to milestone assessment creates opportunities for collaboration and shared assessments across graduate medical programs. Breaking bad news is an essential communication skill that is a common milestone across almost every medical specialty. The purpose of this study was to develop and pilot an integrated milestone assessment (IMA) tool for breaking bad news using ACGME milestone criteria and to compare the IMA tool with the existing SPIKES protocol., Methods: The IMA tool was created using sub-anchors in professionalism and interpersonal communication skills that are applicable to every specialty and to the ability to break bad news. Two cases of breaking bad news, designed to be "easy" and "intermediate" in difficulty, were used to assess basic skills in breaking bad news in first-year medical residents from six residency specialties. Eight standardized patients were trained to portray the cases in sessions held in November 2013 and May 2014. Standardized patients completed an assessment checklist to evaluate each resident's performance in breaking bad news based on their use of the SPIKES protocol and IMA tool. Residents answered post-encounter questions about their training and comfort in breaking bad news. The association between SPIKES and IMA scores was investigated by simple linear regression models and Spearman rank correlations., Results: There were 136 eligible medical residents: 108 (79.4%) participated in the first session and 97 (71.3%) participated in the second session, with 96 (70.6%) residents participating in both sessions. Overall, we were able to identify residents that performed at both extremes of the assessment criteria using the integrated milestone assessment (IMA) and the SPIKES protocol. Interestingly, residents rated themselves below "comfortable" on average., Conclusion: We developed an integrated milestone assessment (IMA) that was better than the SPIKES protocol at assessing the skill of breaking bad news. This collaborative assessment tool can be used as supplement tool in the era of milestone transformation. We aim assess our tool in other specialties and institutions, as well as assess other shared milestones across specialties., (© 2024. The Author(s).)

Objective: To determine the prevalence and timing of autism spectrum disorder diagnosis in a cohort of congenital heart disease (CHD) patients receiving neurodevelopmental follow-up and identify associated risk factors., Method: Retrospective single-centre observational study of 361 children undergoing surgery for CHD during the first 6 months of life. Data abstracted included age at autism spectrum disorder diagnosis, child and maternal demographics, and medical history., Results: Autism spectrum disorder was present in 9.1% of children with CHD, with a median age at diagnosis of 34 months and 87.9% male. Prematurity, history of post-operative extracorporeal membrane oxygenation, and seizures were higher among those with autism (p = 0.013, p = 0.023, p = 0.001, respectively). Infants with autism spectrum disorder were older at the time of surgery (54 days vs 13.5 days, p = 0.002), and infants with surgery at ≥ 30 days of age had an increased risk of autism spectrum disorder (OR 2.31; 95% CI =1.12, 4.77, p = 0.023). On multivariate logistic regression analysis, being male (OR 4.85, p = 0.005), surgery ≥ 30 days (OR 2.46, p = 0.025), extracorporeal membrane oxygenation (OR 4.91, p = 0.024), and seizures (OR 4.32, p = 0.003) remained associated with increased odds for autism spectrum disorder. Maternal age, race, ethnicity, and surgical complexity were not associated., Conclusions: Children with CHD in our cohort had more than three times the risk of autism spectrum disorder and were diagnosed at a much earlier age compared to the general population. Several factors (male, surgery at ≥ 30 days, post-operative extracorporeal membrane oxygenation, and seizures) were associated with increased odds of autism. These findings support the importance of offering neurodevelopmental follow-up after cardiac surgery in infancy.

Purpose: Performance status (PS), an essential indicator of patients' functional abilities, is often documented in clinical notes of patients with cancer. The use of natural language processing (NLP) in extracting PS from electronic medical records (EMRs) has shown promise in enhancing clinical decision-making, patient monitoring, and research studies. We designed and validated a multi-institute NLP pipeline to automatically extract performance status from free-text patient notes., Patients and Methods: We collected data from 19,481 patients in Harris Health System (HHS) and 333,862 patients from veteran affair's corporate data warehouse (VA-CDW) and randomly selected 400 patients from each data source to train and validate (50%) and test (50%) the proposed pipeline. We designed an NLP pipeline using an expert-derived rule-based approach in conjunction with extensive post-processing to solidify its proficiency. To demonstrate the pipeline's application, we tested the compliance of PS documentation suggested by the American Society of Clinical Oncology (ASCO) Quality Metric and investigated the potential disparity in PS reporting for stage IV non-small cell lung cancer (NSCLC). We used a logistic regression test, considering patients in terms of race/ethnicity, conversing language, marital status, and gender., Results: The test results on the HHS cohort showed 92% accuracy, and on VA data demonstrated 98.5% accuracy. For stage IV NSCLC patients, the proposed pipeline achieved an accuracy of 98.5%. Furthermore, our analysis revealed a documentation rate of over 85% for PS among NSCLC patients, surpassing the ASCO Quality Metrics. No disparities were observed in the documentation of PS., Conclusion: Our proposed NLP pipeline shows promising results in extracting PS from free-text notes from various health institutions. It may be used in longitudinal cancer data registries.

Objectives: Existing literature provides limited data about ICU characteristics and pediatric extracorporeal cardiopulmonary resuscitation (E-CPR) outcomes. We aimed to evaluate the associations between patient and ICU characteristics, and outcomes after E-CPR in the pediatric cardiac population., Design: Retrospective analysis of the Virtual Pediatric System database (VPS, LLC, Los Angeles, CA)., Setting: PICUs categorized as either cardiac-only versus mixed ICU cohort type., Patients: Consecutive cardiac patients less than 18 years old experiencing cardiac arrest in the ICU and resuscitated using E-CPR., Interventions: None., Measurements and Main Results: Event and time-stamp filtering identified E-CPR events. Patient, hospital, and event-related variables were aggregated for independent and multivariable mixed effects logistic regression to assess the association between ICU cohort type and survival. Among ICU admissions in the VPS database, 2010-2018, the prevalence of E-CPR was 0.07%. A total of 671 E-CPR events (650 patients) comprised the final cohort; congenital heart disease (84%) was the most common diagnosis versus acquired heart diseases. The majority of E-CPR events occurred in mixed ICUs (67%, n = 449) and in ICUs with greater than 20 licensed bed capacity (65%, n = 436). Survival to hospital discharge was 51% for the overall cohort. Independent logistic regression failed to reveal any association between survival to hospital discharge and ICU type (ICU type: cardiac ICU, odds ratio [OR], 1.01; 95% CI, 0.71-1.44; p = 0.95). However, multivariable logistic regression revealed an association between cardiac surgical patients and greater odds for survival (OR, 2.03; 95% CI, 1.40-2.95; p < 0.001). Also, there was an association between ICUs with capacity greater than 20 (vs not) and lower survival odds (OR, 0.65; 95% CI, 0.43-0.96)., Conclusions: The overall prevalence of E-CPR among critically ill children with cardiac disease observed in the VPS database is low. We failed to identify an association between ICU cohort type and survival. Further investigation into organizational factors is warranted., Competing Interests: Dr. Thiagarajan’s institution received funding from the U.S. Department of Defense: Peer Reviewed Medical Research Program Clinical Trial Award Number W81XWH2210301: Trial of Indication-based Transfusion of Red blood cells in Extracorporeal membrane oxygenation; he received funding from the Society of Critical Care Medicine and the Extracorporeal Life Support Organization. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Transplantation-associated thrombotic microangiography (TA-TMA) is a disorder that causes severe complications after allogeneic hematopoietic cell transplantation (allo-HCT). Diagnosing TA-TMA is challenging because of the lack of standardized criteria. In this study, we aimed to evaluate the new TA-TMA consensus definition from the American Society for Transplantation and Cellular Therapy (ASTCT) panel as part of an ongoing prospective pediatric cohort study, and also to compare the impact and outcomes of using the current definition of clinical TMA (cTMA) versus the new consensus definition. We included patients age 0 to 18 years who underwent their first allo-HCT between May 2021 and January 2023 at Texas Children's Hospital. We compared the incidence, biomarkers, and outcomes of TA-TMA applying the previous and recently proposed screening algorithms and definitions. Whereas use of the classic microangiopathic hemolytic anemia (MAHA)-based cTMA definition led to an incidence of 12.7% by day 100 post-transplantation, the ASTCT-HR definition doubled the incidence to 28.5% by day 100. In contrast to patients with a concordant diagnosis (+/+), who had significantly worse post-transplantation survival, those reclassified as TA-TMA only by the new definition (-/+) had a significantly different prognosis (100% survival at day 100) despite the lack of TMA-directed therapy. Furthermore, biomarkers of the terminal and alternative complement pathways (sC5b9 and Ba, respectively) were significantly elevated compared with non-TMA patients around day 15 in the concordant group (+/+) but not in the discordant group (-/+). The recently proposed ASTCT consensus TA-TMA diagnosis is more sensitive and allows earlier recognition of manifestation that requires closer clinical monitoring but risks overdiagnosis and overtreatment. We recommend additional prospective validation., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Metabolic biomarkers with pathophysiological relevance is lacking in pediatric diabetes. We aimed to identify novel metabolic biomarkers in pediatric type 1 (T1D) and type 2 diabetes (T2D). We hypothesized that (1) targeted plasma metabolomics, focused on plasma amino acid concentrations, could identify distinctively altered patterns in children with T1D or T2D, and (2) there are specific changes in concentrations of metabolites related to branch chain amino acids (BCAA) and arginine metabolism in children with T2D., Methods: In a pilot study, we enrolled children with T1D (n = 15) and T2D (n = 13), and healthy controls (n = 15). Fasting plasma amino acid concentrations were measured by ultra-performance liquid chromatography, and compared between the groups after adjustment for confounding factors., Results: The mean age (SD) of participants was 16.4 (0.9) years. There were no group differences in age, gender, race/ethnicity, or 24-h protein intake. Mean BMI percentile was higher in the T2D than the T1D group or controls (p < 0.001). The T2D group had lower arginine, citrulline, glutamine, glycine, phenylalanine, methionine, threonine, asparagine and symmetric dimethylarginine (SDMA) but higher aspartate than controls, after adjusting for BMI percentiles (all p < 0.05). Children with T2D also had lower glycine but higher ornithine, proline, leucine, isoleucine, valine, total BCAA, lysine and tyrosine than those with T1D after adjusting for confounding factors (all p < 0.05). Children with T1D had lower phenylalanine, methionine, threonine, glutamine, tyrosine, asymmetric dimethylarginine (ADMA) and SDMA than controls (all p < 0.05)., Conclusions: Children with T2D and T1D have distinct fasting plasma amino acid signatures that suggest varying pathogenic mechanisms and could serve as biomarkers for these conditions., Competing Interests: Declaration of competing interest The authors have no conflict of interest to disclose., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Introduction: Patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) require indwelling central venous catheters. The comparative incidence, risk, and outcome of isolated catheter-related deep venous thrombosis (CR-DVT) versus pulmonary embolism/lower-extremity DVT (PE/LE-DVT) remains unclear., Materials and Methods: We conducted a retrospective cohort study for patients undergoing allo-HSCT from 2006 to 2019. CR-DVT and PE/LE-DVT outcomes were screened using ICD codes and radiology reports and confirmed by medical record reviews. Cox regression models were used to assess the association between thrombotic outcomes and pertinent baseline and time-varying covariates. The impact of thrombotic events within 1-year post-transplant (time-varying) on overall mortality was also assessed., Results: Among 2879 patients, the cumulative incidence of isolated CR-DVT and PE/LE-DVT at 12 months was 4.2 % and 4.8 %, respectively. The strongest time-varying predictor for onset of CR-DVT and PE/LE-DVT was hospitalization inpatient status (HR 3.71 [95 % CI 2.16-6.37] and 3.99 [95 % CI 2.00-7.99], respectively). Other overlapping variables included lymphoma diagnosis and BMI > 35 kg/m 2 , whereas acute GVHD grades 2-4 were found to be significantly associated with risk of PE/LE-DVT but not CR-DVT. After adjusting for baseline variables and acute GVHD, the occurrences of CR-DVT and PE/LE-DVT were both independently associated with increased overall mortality (HR 1.58 [95 % CI 1.23-2.02] and HR 1.53 [95 % CI 1.19-1.97], respectively)., Conclusions: We observed a high incidence of both CR-DVT and PE/LE-DVT with overlapping and unique risk factors. CR-DVT was also associated with increased mortality similar to PE/LE-DVT. Standardized strategies targeting high-risk hospitalization periods may help mitigate the development of thrombotic outcomes post-transplant., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: Venous thromboembolism (VTE), especially pulmonary embolism (PE) and lower extremity deep vein thrombosis (LE-DVT), is a serious and potentially preventable complication for patients with cancer undergoing systemic therapy., Methods: Using retrospective data from patients diagnosed with incident cancer from 2011-2020, we derived a parsimonious risk assessment model (RAM) using least absolute shrinkage and selection operator regression from the Harris Health System (HHS, n = 9,769) and externally validated it using the Veterans Affairs (VA) health care system (n = 79,517). Bootstrapped c statistics and calibration curves were used to assess external model discrimination and fit. Dichotomized risk strata using integer scores were created and compared against the Khorana score (KS)., Results: Incident VTE and PE/LE-DVT at 6 months occurred in 590 (6.2%) and 437 (4.6%) patients in HHS and 4,027 (5.1%) and 3,331 (4.2%) patients in the VA health care system. Assessed at the time of systemic therapy initiation, the new RAM included components of the KS with the modified cancer subtype, cancer staging, systemic therapy class, history of VTE, history of paralysis/immobility, recent hospitalization, and Asian/Pacific Islander race. The c statistic was 0.71 in HHS and 0.68 in the VA health care system (compared with 0.65 and 0.60, respectively, for KS). Furthermore, the new RAM appropriately reclassified 28% of patients and increased the proportion of VTEs in the high-risk group from 37% to 68% in the validation data set., Conclusion: The novel RAM stratified patients with cancer into a high-risk group with 8%-10% cumulative incidence of VTE and 7% PE/LE-DVT at 6 months ( v 3% and 2%, respectively, in the low-risk group). The model had improved performance over the original KS and doubled the number of VTE events in the high-risk stratum. We encourage additional external validation from prospective studies.[Media: see text].

Introduction: Chloral hydrate (CH) has long been utilized as a pediatric procedural sedation agent. However, very little is published describing CH use in a pediatric intensive care unit (PICU) setting. The aim of this retrospective observational cohort study was to investigate and describe the use of CH in mechanically-ventilated, critically ill children at a large pediatric tertiary referral hospital. Methods: Data were extracted from the hospital electronic medical record and a locally maintained registry of all children admitted to the PICU between 2012 and 2017. Patients admitted to the cardiovascular ICU were not included in this review. The clinical and pharmacy data for 3806 consecutive PICU admissions of mechanically-ventilated, critically ill children were examined. Results: 283 admissions received CH during their first ICU stay. CH-exposed children were younger (16 months vs. 35 months, p < 0.001), the median total dose of CH (indexed to duration of ventilation) was 11 mg/kg/day, the median time to first CH dose was 3 days and more CH doses were administered at night (1112 vs. 958, p < 0.001). We constructed a propensity score to adjust for the differences in patients with and without CH exposure using logistic regression including variables of age, sex, diagnosis, and PRISM3 score. After adjustment, the median length of mechanical ventilation was 5 days longer in the CH-exposed group (95% Confidence Interval [CI] 4-6) compared to unexposed CH patients. Similarly, the median length of ICU duration was 9.4 days longer (95% CI 7.1-11.6) and median length of hospital admission duration was 13.2 days longer (95% CI 7.8-18.6) in CH-exposed patients compared to CH-non-exposed. After adjustment, CH-exposed patients had a 9% higher median exposure to HFOV (95% CI 3.9-14.6), but did not have higher median exposures to new tracheostomy (95% CI -0.4-2.2) or ECMO (95% CI -0.2-5.0). Discussion: As part of an extended sedation regimen in mechanically-ventilated and critically ill children, CH is associated with somewhat higher complexity of illness and longer ICU durations., Competing Interests: Author JC was employed by Tableau Software. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ettinger, Kiskaddon, McNeely, Craycraft, Rogers, Achuff, Guffey and Musick.)

Background: Juvenile localized scleroderma (LS) and systemic sclerosis (SSc) are rare pediatric conditions often associated with severe morbidities. Delays in diagnosis are common, increasing the risk for permanent damage and worse outcomes. This study explored caregiver perspectives on barriers they encountered while navigating diagnosis and care for their child's scleroderma., Methods: In this cross-sectional study, caregivers of juvenile LS or SSc patients were recruited from a virtual family scleroderma educational conference and a juvenile scleroderma online interest group. The survey queried respondents about their child's condition and factors affecting diagnosis and treatment., Results: The response rate was 61% (73/120), with 38 parents of LS patients and 31 parents of SSc patients. Most patients were female (80%) and over half were non-Hispanic white (55%). Most families had at least one person with a college education or higher (87%), traveled ≤ 2 h to see their rheumatologist (83%), and had private insurance (75%). Almost half had an annual household income ≥ $100,000 (46%). Families identified the following factors as barriers to care: lack of knowledge about scleroderma in the medical community, finding reliable information about pediatric scleroderma, long wait times/distances for a rheumatology/specialist appointment, balance of school/work and child's healthcare needs, medication side effects, and identifying effective medications. The barrier most identified as a major problem was the lack of knowledge about juvenile scleroderma in the medical community. Public insurance, household income less than $100,000, and Hispanic ethnicity were associated with specific barriers to care. Lower socioeconomic status was associated with longer travel times to see the rheumatologist/specialist. Diagnosis and systemic treatment initiation occurred at greater than one year from initial presentation for approximately 28% and 36% of patients, respectively. Families of LS patients were commonly given erroneous information about the disease, including on the need and importance of treating active disease with systemic immunosuppressants in patients with deep tissue or rapidly progressive disease., Conclusion: Caregivers of children with LS or SSc reported numerous common barriers to the diagnosis, treatment, and ongoing care of juvenile scleroderma. The major problem highlighted was the lack of knowledge of scleroderma within the general medical community. Given that most of the caregiver respondents to the survey had relatively high socioeconomic status, additional studies are needed to reach a broader audience, including caregivers with limited English proficiency, geographical limitations, and financial constraints, to determine if the identified problems are generalizable. Identifying key care barriers will help direct efforts to address needs, reduce disparities in care, and improve patient outcomes., (© 2023. The Author(s).)

Data on outcomes and interventions for children with sickle cell disease (SCD) admitted to a pediatric intensive care units (PICU) are unknown. We provide the first comprehensive multi-center report on PICU interventions associated with death, the need for invasive respiratory support or stroke among critically ill children with SCD. We collected retrospective multi-center cohort data from January 1, 2012 to December 31, 2019 utilizing the Virtual Pediatric Systems, LLC database. We identified 3388 unique children with SCD, accounting for a total of 5264 PICU admissions from 138 PICUs. The overall mortality rate for the PICU admissions cohort was 1.8% (95/5264 PICU admissions, 95/3388 [2.8%] of all unique patients), the rate of needing of needing Invasive Respiratory Support (IRS, a composite category of exposure) was 21.3% (872/4093 PICU admissions with complete data) and the overall rate of stroke (ischemic or hemorrhagic) was 12.5% (657/5264 PICU admissions). In multivariable analysis adjusting for admission age category, sex, race/ethnicity, PRISM-3 score at admission, exposure to IRS, quartile of unit volume of patients with SCD, and patient origin, admitted children who needed invasive respiratory support (IRS) had higher adjusted odds ratios for mortality (adjusted odds ratio [aOR], 19.72; 95% confidence interval [CI] 8.98-43.29; p < 0.001), although admitted children > 2 years old had decreased aOR for needing IRS (aOR 0.25-0.62; 95% CI 0.16-0.94; p < 0.001-0.025). By contrast, admitted children > 2 years old had a strikingly increased aOR for stroke (aOR 7.57-16.32; 95% CI 2.25-52.15; p < 0.001). These groups may represent PICU-specific subsets of patients with SCD who are at higher risk for more serious illness and should deserve early consideration for referral to a pediatric institution providing comprehensive care for patients with SCD., (© 2023. The Author(s).)

Background: Caregivers play an important role in maintaining a functioning graft after pediatric liver transplantation. Therefore, the psychosocial factors of both patients and caregivers can have a critical impact on transplant outcomes. Appropriate assessment and recognition of these factors pre-transplantation may allow transplant teams to better define the needs of pediatric organ recipients and develop specific countermeasures, which may then contribute toward improving transplant outcomes., Methods: We studied 136 pediatric LT recipients followed at Texas Children's Hospital. Licensed social workers conducted comprehensive pre-transplant assessments on each patient, consisting of 22 psychosocial variables that were thought to impact adherence, which were reviewed during our study period. Non-adherence was determined using the MLVI for up to 4 years after transplantation. Biopsy-confirmed rejection episodes were assessed in the first 3 years after liver transplantation., Results: Factors significantly associated with non-adherence (defined as MLVI >2) included parental age and parental education level at assessment, type of insurance, and household income. The number of ACR episodes trended higher in patients with non-adherence, and these patients had a higher number of moderate to severe rejection episodes but this trend was not statistically significant., Conclusions: Psychosocial characteristics such as parental age, education level, insurance, and household income may contribute significantly to suboptimal adherence to medications after transplantation. Identification of these psychosocial factors and early intervention is essential to the success and equitable care of our pediatric LT recipients., (© 2022 Wiley Periodicals LLC.)

Background and Aims: Detailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis., Approach and Results: A targeted enzyme-linked immunosorbent assay-based panel of nine biomarkers (lysyl oxidase, tissue inhibitor matrix metalloproteinase (MMP) 1, connective tissue growth factor [CTGF], IL-8, endoglin, periostin, Mac-2-binding protein, MMP-3, and MMP-7) was examined in children with biliary atresia (BA; n = 187), alpha-1 antitrypsin deficiency (A1AT; n = 78), and Alagille syndrome (ALGS; n = 65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM were 9 years and 9.5 kPa. After adjusting for covariates, there were positive correlations among LSM and endoglin ( p = 0.04) and IL-8 ( p < 0.001) and MMP-7 ( p < 0.001) in participants with BA. The best prediction model for LSM in BA using clinical and lab measurements had an R2 = 0.437; adding IL-8 and MMP-7 improved R2 to 0.523 and 0.526 (both p < 0.0001). In participants with A1AT, CTGF and LSM were negatively correlated ( p = 0.004); adding CTGF to an LSM prediction model improved R2 from 0.524 to 0.577 ( p = 0.0033). Biomarkers did not correlate with LSM in ALGS. A significant number of biomarker/lab correlations were found in participants with BA but not those with A1AT or ALGS., Conclusions: Endoglin, IL-8, and MMP-7 significantly correlate with increased LSM in children with BA, whereas CTGF inversely correlates with LSM in participants with A1AT; these biomarkers appear to enhance prediction of LSM beyond clinical tests. Future disease-specific investigations of change in these biomarkers over time and as predictors of clinical outcomes will be important., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Background: Mohs surgeons routinely encounter squamous cell carcinoma at surgical margins and often base the decision to take another layer on the severity of atypia observed. Currently, no criteria exists for distinguishing borderline histological patterns that could be interpreted differently as actinic keratosis (AK), squamous cell carcinoma in situ (SCCIS), or AK with focal SCCIS., Objective: To assess interrater concordance amongst Mohs surgeons in distinguishing AK from SCCIS when evaluating Mohs frozen sections., Methods: Seventeen slides were selected and converted into digitally formatted cases. They were compiled into an electronic survey and distributed to the American College of Mohs Surgery., Results: Overall &kappa; was 0.26 corresponding to weak agreement between raters compared to the standard, with &kappa; of 0.34 for AK and 0.37 for SCCIS., Conclusion: There exists notable variability among Mohs surgeons who interpret the spectrum of in situ carcinoma differently. Ongoing learning and consensus building among Mohs surgeons and trainees can aid in quality patient care, even if there may not be agreement on every case. J Drugs Dermatol. 2023;22(2):199-194. doi:10.36849/JDD.7084.

Objective: Prematurity, low birth weight, genetic syndromes, extracardiac conditions, and secondary cardiac lesions are considered high-risk conditions associated with mortality after stage 1 palliation. We report the impact of these conditions on outcomes from a prospective multicenter improvement collaborative., Methods: The National Pediatric Cardiology Quality Improvement Collaborative Phase II registry was queried. Comorbid conditions were categorized and quantified to determine the cumulative burden of high-risk diagnoses on survival to the first birthday. Logistic regression was applied to evaluate factors associated with mortality., Results: Of the 1421 participants, 40% (575) had at least 1 high-risk condition. The aggregate high-risk group had lower survival to the first birthday compared with standard risk (76.2% vs 88.1%, P < .001). Presence of a single high-risk diagnosis was not associated with reduced survival to the first birthday (odds ratio, 0.71; confidence interval, 0.49-1.02, P = .066). Incremental increases in high-risk diagnoses were associated with reduced survival to first birthday (odds ratio, 0.23; confidence interval, 0.15-0.36, P < .001) for 2 and 0.17 (confidence interval, 0.10-0.30, P < .001) for 3 to 5 high-risk diagnoses. Additional analysis that included prestage 1 palliation characteristics and stage 1 palliation perioperative variables identified multiple high-risk diagnoses, poststage 1 palliation extracorporeal membrane oxygenation support (odds ratio, 0.14; confidence interval, 0.10-0.22, P < .001), and cardiac reoperation (odds ratio, 0.66; confidence interval, 0.45-0.98, P = .037) to be associated with reduced survival odds to the first birthday., Conclusions: The presence of 1 high-risk diagnostic category was not associated with decreased survival at 1 year. Cumulative diagnoses across multiple high-risk diagnostic categories were associated with decreased odds of survival. Further patient accrual is needed to evaluate the impact of specific comorbid conditions within the broader high-risk categories., (Copyright © 2022 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Children presenting with acute myocarditis may experience rapid clinical deterioration requiring extracorporeal membrane oxygenation (ECMO); however, our understanding of best practices and timing of ECMO initiation are lacking. We explored the relationships between pre-cannulation factors and survival in this high-acuity patient population., Design: Retrospective review of a large international registry. Primary outcome was survival to hospital discharge, stratified by incident cardiac arrest (CA) prior to ECMO and time to cannulation after intubation., Setting and Subjects: The Extracorporeal Life Support Organization registry was queried for patients less than or equal to 18 years old receiving ECMO support for myocarditis between 2007 and 2018. Exclusion criteria included being nonindex runs, non-venoarterial ECMO or missing data points for main variables studied., Interventions: None., Measurements and Main Results: Population characteristics and survival were compared using t test, Wilcoxon rank-sum test, or Fisher exact test. Multivariable logistic regression was used for significant factors in the unadjusted logistic regression. Among 506 index ECMO runs in pediatric patients with myocarditis, survival for the cohort was 72%, with no difference between early and late eras (2007-2012 vs 2013-2018; p = 0.69). Survivors demonstrated higher pre-ECMO pH levels as well as shorter intubation-to-cannulation (ITC) times (3 hr [interquartile range (IQR)], 1-14 hr vs 6 hr [IQR, 2-20 hr]; p = 0.021). CA occurred within 24 hours prior to ECMO cannulation, including extracorporeal cardiopulmonary resuscitation, in 54% of ECMO runs ( n = 273). Accounting for the interaction between pre-ECMO CA occurrence and ITC time, longer ITC time remained associated with lower survival for patients who did not experience a CA prior to ECMO, with adjusted odds ratio of 0.09 (IQR, 0.02-0.40; p = 0.002) for ITC time greater than or equal to 18 hours., Conclusions: The results of this multicenter analysis of ECMO utilization and outcomes for pediatric myocarditis suggest that patients approaching ECMO cannulation who have not experienced CA may have better survival outcomes if cannulated onto ECMO early after intubation., Competing Interests: Dr. Thiagarajan received funding from the Extracorporeal Life Support Organization and Society of Critical Care Medicine. Dr. Alexander’s institution received funding from Novartis. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: Infants who undergo surgery for congenital heart disease are at risk of neurodevelopmental delay. Cardiac surgery-associated acute kidney injury (CS-AKI) is common but its association with neurodevelopment has not been explored., Methods: This was a single-center retrospective observational study of infants who underwent cardiac surgery in the first year of life who had neurodevelopmental testing using the Bayley Scale for Infant Development, third edition. Single and recurrent episodes of stages 2 and 3 CS-AKI were determined., Results: Of 203 children with median age at first surgery of 12 days, 31% had one or more episodes of severe CS-AKI; of those, 16% had recurrent CS-AKI. Median age at neurodevelopmental assessment was 20 months. The incidence of delay was similar for patients with and patients without CS-AKI but all children with recurrent CS-AKI had a delay in one or more domains and had significantly lower scores in all three domains, namely, cognitive, language, and motor., Conclusions: This study has assessed the association of CS-AKI with neurodevelopmental delay after surgery for congenital heart disease in infancy. Infants who have recurrent CS-AKI in the first year of life are more likely to be delayed and have lower neurodevelopmental scores., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Among persons with type 1 diabetes (T1D), adolescents often experience the greatest challenge achieving optimal treatment engagement and glycemic targets. Risk-taking behaviors often increase during adolescence and may interfere with engagement in T1D care. We developed the Diabetes-Specific Risk-Taking Inventory (DSRI) to assess risky T1D self-management behaviors in adolescents with T1D. In the current study, we aimed to examine the DSRI's psychometric properties., Research Design and Methods: We surveyed a national sample of 224 adolescents from the T1D Exchange registry (M age = 16.9 ± 1.1, 49% female, M A1c = 8.5% ± 1.3, 76.8% on insulin pumps) in a cross-sectional design. Participants completed the DSRI and measures of engagement, general risk-taking, and executive functioning and reported on incidence of severe hypoglycemia and diabetic ketoacidosis over the past year., Results: The DSRI demonstrated reliability (internal consistency: α = 0.89; test-retest reliability: r = 0.86, p < 0.01). Concurrent validity was demonstrated through significant associations between the DSRI and T1D engagement (r = -0.75), general risk-taking (r = 0.57), executive dysfunction (r = 0.34), and report of severe hypoglycemia over the past year (r = 0.22). The DSRI accounted for unique variance in adolescents' most recent glycated hemoglobin, above and beyond other variables, indicating its incremental validity., Conclusions: Overall, initial psychometrics suggest the DSRI is a reliable and valid measure of risks that adolescents may take with their T1D care. This innovative self-report measure has potential to be an actionable clinical tool to screen for high-risk behaviors not routinely assessed in T1D clinical care., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Undermining in difficult-to-reach positions often requires a shift in body position or stretching over the surgical field to obtain adequate reach. We propose a technique of reversing the grip on undermining scissors that improves efficiency without sacrificing technique.

Context: Patients with severe respiratory failure from COVID-19 refractory to conventional therapies may be treated with extracorporeal membrane oxygenation (ECMO). ECMO requirement is associated with high mortality and prolonged hospital course. ECMO is a high-resource intervention with significant burdens placed on caregivers and families with limited data on the integration of palliative care consultation (PCC)., Objectives: To explore the role of standard vs. automatic PCC in the management of COVID patients on ECMO., Methods: Retrospective chart review of all COVID patients on ECMO admitted from March 2020 to May 2021 at a large volume academic medical center with subsequent analysis., Results: Forty-eight patients were included in the analysis. Twenty-six (54.2%) received PCC of which 42% of consults were automatically initiated. PCC at any point in admission was associated with longer duration on ECMO (24.5 vs. 37 days; P &lt; 0.05). Automatic PCC resulted in more family meetings than standard PCC (0 vs. 3; P &lt; 0.05) and appears to trend with reduced time on ECMO, shorter length of stay, and higher DNAR rates at death, though results were not significant. Decedents not receiving PCC had higher rates of no de-escalation of interventions at time of death (31% vs. 11%), indicating full intensive care measures continued through death., Conclusions: Among patients with COVID-19 receiving ECMO, PCC may be associated with a shift to DNAR status particularly with automatic PCC. There may be a further impact on length of stay, duration of time on ECMO and care plan at end of life., (Copyright © 2022 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

The epidemiology of cancer-associated thrombosis (CAT) among uninsured and vulnerable populations in the US is not well-characterized. We performed a retrospective cohort study for patients with newly diagnosed cancer from 2011 to 2020 at Harris Health System, which cares for uninsured residents in the Houston metropolitan area. Patient demographics, NCI comorbidity index, area of deprivation index (ADI), cancer histology, staging, and systemic therapy data were extracted. CAT included overall venous thromboembolism (VTE) or pulmonary embolism +/- lower extremity deep vein thrombosis (PE/LE-DVT) within 1 year of diagnosis. We used multivariable Fine-Gray models to assess the associations with CAT accounting for death as a competing risk. Among 15 342 patients, 74% were uninsured and 84% lived in socioeconomically disadvantaged neighborhoods. There were 16% Non-Hispanic White (NHW), 28% Non-Hispanic Black (NHB), 50% Hispanic (27% Mexican), and 6% Asian/Pacific Islanders (API). The 1-year CAT incidence rate was 14.6%. Overall VTE was lower for Hispanics versus NHW (SHR 0.87 [0.76-0.99]) and API versus NHW (SHR 0.58 [0.44-0.77]). PE/LE-DVT was higher for NHB versus NHW (SHR 1.18 [1.01-1.39]). CAT was also associated with chemotherapy-based regimens (+/- immunotherapy), age, obesity, cancer type/staging, VTE history, and recent hospitalization. NCI comorbidity and ADI scores were associated with mortality but not CAT. In a large cohort of underserved patients with cancer, we identified an elevated incidence of CAT with known and novel risk predictors. Hispanics had lower adjusted rates of CAT and mortality. Our findings highlight the need to investigate and incorporate vulnerable populations in clinical trials., (© 2022 Wiley Periodicals LLC.)

Background: Increasing numbers of adults with congenital heart disease (ACHD) undergo cardiac surgical procedures in children's hospitals, yet surgical outcomes data are limited. We sought to better understand the impact of preoperative risk factors on postoperative complications and cardiac intensive care unit (CICU) length of stay (LOS)., Methods: Surgical CICU admissions for patients aged 18 years and older in the Pediatric Cardiac Critical Care Consortium registry from August 2014 to January 2019 in 34 hospitals were included. Primary outcomes included prolonged LOS (defined as LOS ≥90th percentile) and major complications (cardiac arrest, extracorporeal membrane oxygenation, arrhythmia requiring intervention, stroke, renal replacement therapy, infection, and reoperation/reintervention)., Results: We analyzed 1764 surgical CICU admissions. Prolonged LOS was 7 days or longer. Eighteen patients (1.0%) died, of whom 9 (0.5%) died before the LOS cutoff and were excluded from analysis. Of 1755 CICU admissions, 8.8% (n = 156) had prolonged LOS, and 23.3% (n = 413) had 1 or more major complications. Several variables, including The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery 4/5 operation, 3 or more previous sternotomies, and preoperative renal dysfunction/dialysis were independent risk factors for both prolonged LOS and major complications (P < .05). Preoperative ventilation was associated with increased odds of prolonged LOS and preoperative arrhythmia with major complications., Conclusions: This analysis of postoperative ACHD care in pediatric CICUs found high complexity operations, 3 or more previous sternotomies, preoperative arrhythmias, renal dysfunction, and respiratory failure are associated with prolonged LOS and/or major complications. Future quality improvement initiatives focused on preoperative optimization and implementation of adult-specific perioperative protocols may mitigate morbidity in these patients undergoing cardiac surgical procedures at children's hospitals., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: Maturity-onset diabetes of the young (MODY) is often misdiagnosed as type 1/type 2 diabetes. We aimed to define patient characteristics to guide the decision to test for MODY in youth with diabetes., Research Design and Methods: Of 4750 patients enrolled in the Diabetes Registry at Texas Children's Hospital between July 2016 and July 2019, we selected ("Study Cohort", n = 350) those with: (1) diabetes diagnosis <25 years, (2) family history of diabetes in three consecutive generations, and (3) absent islet autoantibodies except for GAD65. We retrospectively studied their clinical and biochemical characteristics and available MODY testing results. Cluster analysis was then performed to identify the cluster with highest rate of MODY diagnosis., Results: Patients in the Study Cohort were 3.5 times more likely to have been diagnosed with MODY than in the overall Diabetes Registry (4.6% vs. 1.3%, p < 0.001). The cluster (n = 16) with the highest rate of clinician-diagnosed MODY (25%, n = 4/16) had the lowest age (10.9 ± 2.5 year), BMI-z score (0.5 ± 0.9), C-peptide level (1.5 ± 1.2 ng/ml) and acanthosis nigricans frequency (12.5%) at diabetes diagnosis (all p < 0.05). In this cluster, three out of five patients who underwent MODY genetic testing had a pathogenic variant., Conclusions: Using a stepwise approach, we identified that younger age, lower BMI, lower C-peptide, and absence of acanthosis nigricans increase likelihood of MODY in racially/ethnically diverse children with diabetes who have a multigenerational family history of diabetes and negative islet autoantibodies, and can be used by clinicians to select patients for MODY testing., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Research on venous thromboembolism (VTE) that relies only on the International Classification of Diseases (ICD) can misclassify outcomes. Our study aims to discover and validate an improved VTE computable phenotype for people with cancer., Methods: We used a cancer registry electronic health record (EHR)-linked longitudinal database. We derived three algorithms that were ICD/medication based, natural language processing (NLP) based, or all combined. We then randomly sampled 400 patients from patients with VTE codes (n = 1111) and 400 from those without VTE codes (n = 7396). Weighted sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated on the entire sample using inverse probability weighting, followed by bootstrapped receiver operating curve analysis to calculate the concordance statistic (c statistic)., Results: Among 800 patients sampled, 280 had a confirmed acute VTE during the first year after cancer diagnosis. The ICD/medication algorithm had a weighted PPV of 95% and a weighted sensitivity of 81%, with a c statistic of 0.90 (95% confidence interval [CI], 0.89-0.91). Adding Current Procedural Terminology codes for inferior vena cava filter removal or early death did not improve the performance. The NLP algorithm had a weighted PPV of 80% and a weighted sensitivity of 90%, with a c statistic of 0.93 (95% CI, 0.92-0.94). The combined algorithm had a weighted PPV of 98% at the higher cutoff and a weighted sensitivity of 96% at the lower cutoff, with a c statistic of 0.98 (95% CI, 0.97-0.98)., Conclusions: Our ICD/medication-based algorithm can accurately identify VTE phenotype among patients with cancer with a high PPV of 95%. The combined algorithm should be considered in EHR databases that have access to such capabilities., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Objectives: To determine if indices of alveolar gas exchange preextubation predict postextubation respiratory support needs as well as the need for escalation of therapies following infant cardiac surgery., Design: Retrospective chart review., Setting: Pediatric cardiac ICU in a quaternary-care teaching hospital., Patients: Infants less than 1 year old who underwent biventricular repair from January 2015 to December 2017., Interventions: None., Measurements and Main Results: Preextubation alveolar-arterial gradient, oxygenation index, oxygen saturation index, Pao 2 /Fio 2 ratio, and dead space ventilation (analyzed with both end-tidal carbon dioxide gradient and dead space fraction) were evaluated for each patient. All but dead space ventilation were associated with a higher level of noninvasive respiratory support immediately postextubation. Furthermore, impaired preextubation gas exchange was independently associated with escalation of respiratory support within the first 48-hour postextubation., Conclusions: Validated measures of alveolar gas exchange can be used as a tool to assess postextubation respiratory support needs including the risk of escalation of respiratory support in the first 48-hour postextubation. Prospective study with implementation of extubation guidelines, both for readiness and determination of early postextubation support, is needed to validate these findings., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: Social determinants of health (SDH) are known to impact hospital and intensive care unit (ICU) outcomes. Little is known about the association between SDH and pediatric rapid response (RR) events and understanding this impact will help guide future interventions aimed to eliminate health disparities in the inpatient setting., Objectives: The primary objective of this study is to describe the association between SDH and RR utilization (number of RR events, time to RR event, shift of event and caller). The secondary objective is to determine if SDH can predict hospital length of stay (LOS), ICU transfer, critical deterioration (CD), and mortality., Methods: A retrospective cohort study was conducted. We reviewed all RR events from 2016 to 2019 at a large, academic, pediatric hospital system including a level 1 trauma center and two satellite community campuses. All hospitalized patients up to age 25 who had a RR event during their index hospitalization were included. Exposure variables included age, gender, race/ethnicity, language, income, insurance status, chronic disease status, and repeat RR event. The primary outcome variables were hospital LOS, ICU transfer, CD, and mortality. The odds of mortality, CD events and ICU transfer were assessed using unadjusted and multivariable logistic regression. Associations with hospital LOS were assessed with unadjusted and multivariable quantile regression., Results: Four thousand five hundred and sixty-eight RR events occurred from 3,690 unique admissions and 3301 unique patients, and the cohort was reduced to the index admission. The cohort was largely representative of the population served by the hospital system and varied according to race and ethnicity. There was no variation by race/ethnicity in the number of RR events or the shift in which RR events occurred. Attending physicians initiated RR calls more for event for non-Hispanic patients of mixed or other race (31.6% of events), and fellows and residents were more likely to be the callers for Hispanic patients (29.7% of events, p = 0.002). Families who are non-English speaking are also less likely to activate the RR system (12% of total RR events, p = 0.048). LOS was longest for patients speaking languages other than Spanish or English and CD was more common in patients with government insurance. In adjusted logistic regression, Hispanic patients had 2.5 times the odds of mortality (95% CI: 1.43-4.53, p = 0.002) compared with non-Hispanic white patients., Conclusion: Disparities exist in access to and within the inpatient management of pediatric patients. Our results suggest that interventions to address disparities should focus on Hispanic patients and non-English speaking patients to improve inpatient health equity. More research is needed to understand and address the mortality outcomes in Hispanic children compared to other groups., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lawson, Acorda, Guffey, Bracken, Bavare, Checchia and Afonso.)

Study Objectives: (1) To determine the sensitivity and specificity of the home sleep apnea test (HSAT) performed in typically developing children who were diagnosed with moderate to severe obstructive sleep apnea during overnight attended laboratory polysomnography (LPSG). (2) To determine the utility of a screening questionnaire to identify children at increased risk for obstructive sleep apnea., Methods: Participants completed 2 consecutive study nights, the first night with the HSAT followed by LPSG on the second night. The SHOOTS questionnaire, composed of 6 questions (snoring, hyperactivity, obesity, observed apnea, tonsillar hypertrophy, and sleepiness) concerning sleep-disordered breathing, was administered by the clinician before the first study night., Results: Thirty-eight participants completed both studies. The mean age was 13.8 ± 3.0 years. Twenty (53%) were male. Most participants were obese. The mean LPSG total sleep time was 7.34 ± 1.19 hours; the mean HSAT total recording time was 8.86 ± 1.73 hours ( P < .001). The median obstructive apnea-hypopnea index for LPSG and HSAT was 6.6 and 0.8 events/h, respectively. For an obstructive apnea-hypopnea index ≥ 3.1 events/h by HSAT, the sensitivity was 71.43% (95% confidence interval, 41.9-91.6) and the specificity was 95.83% (95% confidence interval, 78.9-99.9) for identifying those with an LPSG obstructive apnea-hypopnea index of ≥ 10 events/h. For a SHOOTS score with ≥ 4 "yes" responses, the sensitivity and specificity were 85.7% (95% confidence interval, 57.2-98.2) and 54.2% (95% confidence interval, 32.8-74.4), respectively, for identifying those with an LPSG obstructive apnea-hypopnea index ≥ 10 events/h., Conclusions: Using HSAT, we clinically applied cutoff values to identify moderate to severe obstructive sleep apnea in typically developing children. The SHOOTS questionnaire may aid in identifying children at risk for obstructive sleep apnea and who are candidates for HSAT., Citation: Revana A, Vecchio J, Guffey D, Minard CG, Glaze DG. Clinical application of home sleep apnea testing in children: a prospective pilot study. J Clin Sleep Med. 2022;18(2):533-540., (© 2022 American Academy of Sleep Medicine.)

Background: The maximum tolerated dose of peanut protein following peanut oral immunotherapy (POIT) is unknown because most research studies have not examined very high thresholds., Objective: To define the maximum dose tolerated by patients on POIT and severity of allergic reactions after a 1-month period of treatment discontinuation., Methods: In a phase 2 3-year POIT open-label study, we enrolled participants age 5 to 13 years with a 1-year build-up period followed by a 2-year daily maintenance dose of 3900 mg with assessment of the maximum tolerated dose using double-blind placebo-controlled food challenges (DBPCFCs) of 26,225 mg cumulative dose of peanut protein. The DBPCFC was performed at baseline, after 12-month build-up, at 2 year of maintenance, and after a 1-month period of treatment discontinuation. Biomarkers were assessed every 6 weeks for the first 6 months of therapy. A general linear mixed model was used for analysis., Results: The mean maximum cumulative tolerated dose after 12 months increased by 12,063 mg (P < .001) (n = 12), slightly decreased during maintenance (n = 11), and significantly decreased by 7593 mg after avoidance for 1 month (P = .03) (n = 6). Biomarker analysis revealed decreases in cytokine expression within the first 6 weeks of initiation of POIT and decreased peanut-IgG 4 and increased cytokine expression after 1 month of discontinuation. The DBPCFC reaction severity, examined through a symptom score with 1 point for each defined symptom, decreased after 12 months, but did not significantly change after 1 month of POIT discontinuation., Conclusions: The evaluation of POIT and sustained unresponsiveness by maximum tolerated dose by DBPCFCs in this small phase 2 trial showed that desensitization is diminished, with 100% loss of tolerated dose after 1 month of avoidance following 3 years of treatment., (Copyright © 2021. Published by Elsevier Inc.)