School Absenteeism Among Racially and Ethnically Minoritized Transgender High School Students and Their Peers: A Cross-Sectional Study.

PURPOSE: To explore absenteeism among racially and ethnically minoritized transgender youth (trans REMY) compared to their White transgender (trans WY) and racially and ethnically minoritized cisgender (cis REMY) peers and identify associated psychosocial factors. METHODS: Biennial California Healthy Kids Survey 2017-2019 data was analyzed with a weighted sample of California's secondary school population. Students reported past 30-day absences due to mental health and harassment, depressive symptoms, suicidal ideation, cyberbullying, victimization, and school connectedness. Poisson and linear regression compared absenteeism and psychosocial factors among peer groups. For trans REMY, Poisson regression assessed associations between absenteeism and psychosocial factors. Analyses were adjusted for grade, sex, and socioeconomic status. RESULTS: The analytical sample (n = 25,085) included 206 trans REMY, 64 trans WY, and 24,815 cis REMY. Trans REMY had higher relative risk of absenteeism due to mental health concerns and harassment compared to cis REMY (adjusted relative risk 2.9, 95% confidence interval 2.1-4.0 and adjusted relative risk 8.1, 95% confidence interval 4.0-16.6, respectively) but similar risk when compared to trans WY. For trans REMY, depressive symptoms, suicidal ideation, and victimization were associated with higher relative risk of absenteeism due to mental health concerns. Cyberbullying was associated with a higher risk of absenteeism due to harassment. Higher school connectedness was associated with lower risk of absenteeism due to mental health concerns. DISCUSSION: Trans REMY reported higher rates of school absenteeism due to mental health concerns and harassment compared to some of their peers. Mental health symptoms, victimization, cyberbullying, and school connectedness were associated with absenteeism among trans REMY.

The burden of pediatric critical illness among pediatric oncology patients in low- and middle-income countries: A systematic review and meta-analysis.

BACKGROUND: Pediatric oncology patients have increased risk for critical illness; outcomes are well described in high-income countries (HICs); however, data is limited for low- and middle-income countries (LMICs). METHODS: We systematically searched PubMed, EMBASE, Web of Science, CINAHL and Global Health databases for articles in 6 languages describing mortality in children with cancer admitted to intensive care units (ICUs) in LMICs. Two investigators independently assessed eligibility, data quality, and extracted data. We pooled ICU mortality estimates using random effect models. RESULTS: Of 3641 studies identified, 22 studies were included, covering 4803 ICU admissions. Overall pooled mortality was 30.3 % [95 % Confidence-interval (CI) 21.7-40.6 %]. Mechanical ventilation [odds ratio (OR) 12.2, 95 %CI:6.2-24.0, p-value<0.001] and vasoactive infusions [OR 6.3 95 %CI:3.3-11.9, p-value<0.001] were associated with ICU mortality. CONCLUSIONS: ICU mortality among pediatric oncology patients in LMICs is similar to that in HICs, however, this review likely underestimates true mortality due to underrepresentation of studies from low-income countries.

Ethnic differences in the manifestation of early-onset type 2 diabetes.

INTRODUCTION: We undertook phenotypic characterization of early-onset and late-onset type 2 diabetes (T2D) in adult black African and white European populations with recently diagnosed T2D to explore ethnic differences in the manifestation of early-onset T2D. RESEARCH DESIGN AND METHODS: Using the Uganda Diabetes Phenotype study cohort of 500 adult Ugandans and the UK StartRight study cohort of 714 white Europeans with recently diagnosed islet autoantibody-negative T2D, we compared the phenotypic characteristics of participants with early-onset T2D (diagnosed at <40 years) and late-onset T2D (diagnosed at ≥40 years). RESULTS: One hundred and thirty-four adult Ugandans and 113 white Europeans had early-onset T2D. Compared with late-onset T2D, early-onset T2D in white Europeans was significantly associated with a female predominance (52.2% vs 39.1%, p=0.01), increased body mass index (mean (95% CI) 36.7 (35.2-38.1) kg/m2 vs 33.0 (32.4-33.6) kg/m2, p<0.001), waist circumference (112.4 (109.1-115.6) cm vs 108.8 (107.6-110.1) cm, p=0.06), and a higher frequency of obesity (82.3% vs 63.4%, p<0.001). No difference was seen with the post-meal C-peptide levels as a marker of beta-cell function (mean (95% CI) 2130.94 (1905.12-2356.76) pmol/L vs 2039.72 (1956.52-2122.92), p=0.62).In contrast, early-onset T2D in Ugandans was associated with less adiposity (mean (95% CI) waist circumference 93.1 (89.9-96.3) cm vs 97.4 (95.9-98.8) cm, p=0.006) and a greater degree of beta-cell dysfunction (120 min post-glucose load C-peptide mean (95% CI) level 896.08 (780.91-1011.24) pmol/L vs 1310.10 (1179.24-1440.95) pmol/L, p<0.001), without female predominance (53.0% vs 57.9%, p=0.32) and differences in the body mass index (mean (95% CI) 27.3 (26.2-28.4) kg/m2 vs 27.9 (27.3-28.5) kg/m2, p=0.29). CONCLUSIONS: These differences in the manifestation of early-onset T2D underscore the need for ethnic-specific and population-specific therapeutic and preventive approaches for the condition.

Integration of ChatGPT Into a Course for Medical Students: Explorative Study on Teaching Scenarios, Students' Perception, and Applications.

Background: Text-generating artificial intelligence (AI) such as ChatGPT offers many opportunities and challenges in medical education. Acquiring practical skills necessary for using AI in a clinical context is crucial, especially for medical education. Objective: This explorative study aimed to investigate the feasibility of integrating ChatGPT into teaching units and to evaluate the course and the importance of AI-related competencies for medical students. Since a possible application of ChatGPT in the medical field could be the generation of information for patients, we further investigated how such information is perceived by students in terms of persuasiveness and quality. Methods: ChatGPT was integrated into 3 different teaching units of a blended learning course for medical students. Using a mixed methods approach, quantitative and qualitative data were collected. As baseline data, we assessed students' characteristics, including their openness to digital innovation. The students evaluated the integration of ChatGPT into the course and shared their thoughts regarding the future of text-generating AI in medical education. The course was evaluated based on the Kirkpatrick Model, with satisfaction, learning progress, and applicable knowledge considered as key assessment levels. In ChatGPT-integrating teaching units, students evaluated videos featuring information for patients regarding their persuasiveness on treatment expectations in a self-experience experiment and critically reviewed information for patients written using ChatGPT 3.5 based on different prompts. Results: A total of 52 medical students participated in the study. The comprehensive evaluation of the course revealed elevated levels of satisfaction, learning progress, and applicability specifically in relation to the ChatGPT-integrating teaching units. Furthermore, all evaluation levels demonstrated an association with each other. Higher openness to digital innovation was associated with higher satisfaction and, to a lesser extent, with higher applicability. AI-related competencies in other courses of the medical curriculum were perceived as highly important by medical students. Qualitative analysis highlighted potential use cases of ChatGPT in teaching and learning. In ChatGPT-integrating teaching units, students rated information for patients generated using a basic ChatGPT prompt as "moderate" in terms of comprehensibility, patient safety, and the correct application of communication rules taught during the course. The students' ratings were considerably improved using an extended prompt. The same text, however, showed the smallest increase in treatment expectations when compared with information provided by humans (patient, clinician, and expert) via videos. Conclusions: This study offers valuable insights into integrating the development of AI competencies into a blended learning course. Integration of ChatGPT enhanced learning experiences for medical students.

Community-Derived Recommendations for Improving Gender Affirmation of Black and Latine Transgender/Nonbinary Youth.

BACKGROUND: Gender affirmation is a process by which gender-diverse individuals are supported in their gender identity. Parents are critical in how gender-diverse youth, including Black and Latine transgender/nonbinary youth (BLTY), access various forms of gender affirmation-for example, social and medical transition. Culturally relevant supports are needed to bolster how BLTY and their parents navigate gender affirmation. PURPOSE: This study aimed to explore recommendations for aiding BLTY and parents in navigating the youth's gender journey. METHODS: Semi-structured interviews were conducted with parents of BLTY, BLTY, and BLT young adults (BLTYAs) recruited from clinics, community organizations, and social media. Interviews focused on gender affirmation and recommendations to promote BLTY's gender affirmation. Primary and secondary analysts coded transcripts using a priori and emergent codes. For this analysis, excerpts pertaining to recommended supports were analyzed to identify themes. RESULTS: Ten parents of BLTY, 10 BLTY (14-18 years), and 23 BLTYAs (18-30 years) participated. Participants provided recommendations at different socio-ecological levels. On the societal level, participants recommended improvements in media representation of racial and ethnic minority gender-diverse individuals. For organizations, participants recommended more clinicians who shared minoritized identities, clinicians knowledgeable in gender-affirming care, affordability of gender-affirming services, and school-based education regarding gender diversity. On interpersonal/individual levels, they suggested culturally informed peer support among BLTY and parents, including support groups, peer mentors, and camps with individuals who share their minoritized identities. CONCLUSIONS: Participants provided salient insights to supporting gender affirmation of BLTY, which can inform intervention development for BLTY and their families.

Black and Latine transgender/nonbinary youth (BLTY) have multiple minoritized identities as they are both racial/ethnic minorities and are gender diverse. These youth face unique challenges in being supported in their gender identity, and their parents face barriers to supporting their gender journey. Unfortunately, approaches to assisting BLTY and their parents in navigating this journey are poorly understood. We interviewed 10 BLTY, 10 related parents of the BLTY, and 23 Black and Latine transgender/nonbinary young adults (BLTYAs) recruited from clinics, community organizations, and social media. In this study, we explored their recommendations for better supporting and affirming BLTY. These recommendations targeted different areas of BLTY's lives. On a broader societal level, participants advocated media representation of gender-diverse individuals of color. For medical and mental health organizations, participants recommended more clinicians knowledgeable in supporting gender-diverse youth and more clinicians who share similar backgrounds with BLTY. For interpersonal and individual relationships, they recommended peer support groups and mentors for BLTY and parents of BLTY. These comprehensive recommendations from BLTY, parents, and BLTYAs can be implemented to better support BLTY in their gender identity through culturally based interventions in different domains.

Parental Gender Affirmation Model: A culturally informed framework.

Benefits of parental gender-affirming behaviors on the mental health and well-being of the broader gender-expansive youth population have been extensively documented. However, the nature and impact of these behaviors have not been explored by centering Black and Latine transgender/non-binary youth (BLTY). This article offers a new framework called the "Parental Gender Affirmation Model." This framework conceptualizes parental gender-affirming behaviors toward BLTY through the lenses of intersectional stigma and cultural gender norms and uses the Theory of Planned Behavior and Modified Gender Affirmation Model as foundational frameworks. We analyzed qualitative data from 43 interviews with BLTY, parents of BLTY, and Black and Latine transgender/non-binary young adults from California in the United States to develop the framework. The "Parental Gender Affirmation Model" starts with behavioral antecedents and ends with impacts of these behaviors on BLTY's well-being. This framework will inform the development of critically needed, culturally-informed interventions to support parental gender affirmation of BLTY.

Eating Disorders in Sexual and Gender Minority Adolescents.

PURPOSE OF REVIEW: To consolidate recent literature addressing eating disorders and disordered eating behaviors among sexual and gender minority (SGM) adolescents, including but not limited to lesbian, gay, bisexual, transgender, and queer (LGBTQ) adolescents. RECENT FINDINGS: Sexual and gender minority adolescents are at heightened vulnerability to eating disorders and disordered eating behaviors compared to their cisgender and heterosexual peers, potentially due to minority stress, gender norms, objectification, and the influence of the media, peers, and parents. We report findings from recent literature on the epidemiology and prevalence, assessment, mental health comorbidity, quality of life and psychosocial functioning, risk and protective factors, and treatment and interventions for eating disorders in sexual and gender minority adolescents. Addressing eating disorders in sexual and gender minority adolescents requires an integrated approach consisting of screening, tailored treatment, and comprehensive support to address intersectional challenges. Gender-affirming and trauma-informed care approaches may be considered.

Sex differences in electrolyte abnormalities indicating refeeding syndrome risk among hospitalized adolescents and young adults with eating disorders.

BACKGROUND: Refeeding syndrome is the gravest possible medical complication in malnourished patients undergoing refeeding in the hospital. We previously reported that males with malnutrition secondary to eating disorders required more calories and had longer hospital stays than females; however, sex differences in electrolyte abnormalities indicating refeeding syndrome risk remain unknown. The objective of this study was to assess differences in electrolyte abnormalities indicating refeeding syndrome risk among male and female adolescents and young adults with eating disorders hospitalized for medical instability. METHODS: We retrospectively reviewed the electronic medical records of 558 patients aged 9-25 years admitted to the University of California, San Francisco Eating Disorders Program for medical instability between May 2012 and August 2020. Serum was drawn per standard of care between 5 and 7 am each morning and electrolyte abnormalities indicating refeeding syndrome risk were defined as: hypophosphatemia (< 3.0 mg/dL), hypokalemia (< 3.5 mEq/L), and hypomagnesemia (< 1.8 mg/dL). Logistic regression was used to assess factors associated with electrolyte abnormalities indicating refeeding syndrome risk. RESULTS: Participants included 86 (15.4%) males and 472 (84.6%) females, mean (SD) age 15.5 (2.8) years. Rates of refeeding hypophosphatemia (3.5%), hypokalemia (8.1%), and hypomagnesemia (11.6%) in males hospitalized with eating disorders were low, with no statistically significant differences from females. Older age was associated with higher odds of refeeding hypophosphatemia and hypomagnesemia. Lower percent median body mass index and greater weight suppression at admission were associated with higher odds of refeeding hypophosphatemia. CONCLUSIONS: Rates of electrolyte abnormalities indicating refeeding syndrome risk were low in males hospitalized for eating disorders and rates did not significantly differ from females. Together with our finding that males have higher caloric requirements and longer hospital length of stay, the finding that electrolyte abnormalities indicating refeeding syndrome risk were not greater in males than females supports future research to evaluate the safety and efficacy of higher calorie and/or faster advancing refeeding protocols for males.

Psilocybin therapy and anorexia nervosa: a narrative review of safety considerations for researchers and clinicians.

BACKGROUND: Clinical trials using psilocybin therapy to treat anorexia nervosa (AN) are currently underway. The safety and tolerability of psilocybin is of utmost importance in individuals with AN who may present unique medical vulnerabilities. The purpose of this review is to describe how the common physiologic adverse effects of psilocybin may impact medical complications experienced by individuals with AN in clinical trials of psilocybin therapy. MAIN BODY: The physiologic underpinnings of common adverse effects following psilocybin administration are described, including tachycardia, hypertension, electrocardiogram changes, nausea, headache, and lightheadedness. These anticipated physiologic changes are described in relation to the common medical correlates seen in individuals with AN. Risk mitigation strategies for each adverse effect are proposed. CONCLUSION: Early evidence suggests that psilocybin therapy is well-tolerated in individuals with AN. Understanding the unique medical complications of AN, and how they may be impacted by common physiologic adverse effects of psilocybin administration, leads to tailored risk mitigation strategies to enhance safety and tolerability of this novel intervention.

Mortality Predictors for Adult Patients with Mild-to-Moderate Traumatic Brain Injury: A Literature Review.

Traumatic brain injuries (TBIs) represent a significant public health concern, with mild-to-moderate cases comprising a substantial portion of incidents. Understanding the predictors of mortality among adult patients with mild-to-moderate TBIs is crucial for optimizing clinical management and improving outcomes. This literature review examines the existing research to identify and analyze the mortality predictors in this patient population. Through a comprehensive review of peer-reviewed articles and clinical studies, key prognostic factors, such as age, Glasgow Coma Scale (GCS) score, the presence of intracranial hemorrhage, pupillary reactivity, and coexisting medical conditions, are explored. Additionally, this review investigates the role of advanced imaging modalities, biomarkers, and scoring systems in predicting mortality following a mild-to-moderate TBI. By synthesizing the findings from diverse studies, this review aims to provide clinicians and researchers with valuable insights into the factors influencing mortality outcomes in adult patients with a mild-to-moderate TBI, thus facilitating more informed decision making and targeted interventions in clinical practice.

A research definition and framework for acute paediatric critical illness across resource-variable settings: a modified Delphi consensus.

The true global burden of paediatric critical illness remains unknown. Studies on children with life-threatening conditions are hindered by the absence of a common definition for acute paediatric critical illness (DEFCRIT) that outlines components and attributes of critical illness and does not depend on local capacity to provide critical care. We present an evidence-informed consensus definition and framework for acute paediatric critical illness. DEFCRIT was developed following a scoping review of 29 studies and key concepts identified by an interdisciplinary, international core expert panel (n=24). A modified Delphi process was then done with a panel of multidisciplinary health-care global experts (n=109) until consensus was reached on eight essential attributes and 28 statements as the basis of DEFCRIT. Consensus was reached in two Delphi rounds with an expert retention rate of 89%. The final consensus definition for acute paediatric critical illness is: an infant, child, or adolescent with an illness, injury, or post-operative state that increases the risk for or results in acute physiological instability (abnormal physiological parameters or vital organ dysfunction or failure) or a clinical support requirement (such as frequent or continuous monitoring or time-sensitive interventions) to prevent further deterioration or death. The proposed definition and framework provide the conceptual clarity needed for a unified approach for global research across resource-variable settings. Future work will centre on validating DEFCRIT and determining high priority measures and guidelines for data collection and analysis that will promote its use in research.

Clinical characteristics of hospitalized male adolescents and young adults with atypical anorexia nervosa.

OBJECTIVE: To describe the clinical characteristics of male adolescents and young adults hospitalized for medical complications of atypical anorexia nervosa (atypical AN) and to compare their clinical characteristics with females with atypical AN and males with anorexia nervosa (AN). METHOD: A retrospective review of electronic medical records for patients with atypical AN and AN aged 9-25 admitted to the UCSF Eating Disorders Program from May 2012 to August 2020 was conducted. RESULTS: Among 21 males with atypical AN (mean age 15.1 ± 2.7, mean %mBMI 102.0 ± 11.8), medical complications evidenced by admission laboratory values included anemia (52.9%), vitamin D insufficiency/deficiency (52.6%), and zinc deficiency (31.6%). Compared with females with atypical AN (n = 69), males with atypical AN had longer length of stay (11.4 vs 8.4 days, p = .004), higher prescribed kcal at discharge (4114 vs 3045 kcal, p < .001), lower heart rate nadir (40.0 vs 45.8, p = .038), higher aspartate transaminase (AST, 37.9 vs 26.2 U/L, p = .032), higher alanine transaminase (ALT, 30.6 vs 18.3 U/L, p = .005), and higher rates of anemia (52.9% vs 19.4%, p = .005), with no differences in vitamin D, zinc, and vital signs. Compared with males with AN (n = 40), males with atypical AN had no significant differences in vital signs or laboratory assessments during the hospitalization. DISCUSSION: Atypical AN in males leads to significant medical comorbidity, and males with atypical AN require longer hospital stays compared to females with atypical AN. Rates of abnormal vital signs and abnormal serum laboratory values during hospital admissions do not differ in males with atypical AN compared to AN. PUBLIC SIGNIFICANCE: Adolescent and young adult males with atypical anorexia nervosa experience significant medical complications. Males with atypical anorexia nervosa had longer hospitalizations and higher prescribed nutrition at discharge than females. Medical complications of atypical anorexia nervosa in male adolescents and young adults were generally equal to those of male adolescents and young adults with anorexia nervosa. Clinicians should be aware of unique medical complications of males with atypical anorexia nervosa.

The Role of Multiparametric MRI and MRI-targeted Biopsy in the Diagnosis of Radiorecurrent Prostate Cancer: An Analysis from the FORECAST Trial.

BACKGROUND: The role of multiparametric magnetic resonance imaging (MRI) for detecting recurrent prostate cancer after radiotherapy is unclear. OBJECTIVE: To evaluate MRI and MRI-targeted biopsies for detecting intraprostatic cancer recurrence and planning for salvage focal ablation. DESIGN, SETTING, AND PARTICIPANTS: FOcal RECurrent Assessment and Salvage Treatment (FORECAST; NCT01883128) was a prospective cohort diagnostic study that recruited 181 patients with suspected radiorecurrence at six UK centres (2014 to 2018); 144 were included here. INTERVENTION: All patients underwent MRI with 5 mm transperineal template mapping biopsies; 84 had additional MRI-targeted biopsies. MRI scans with Likert scores of 3 to 5 were deemed suspicious. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: First, the diagnostic accuracy of MRI was calculated. Second, the pathological characteristics of MRI-detected and MRI-undetected tumours were compared using the Wilcoxon rank sum test and chi-square test for trend. Third, four biopsy strategies involving an MRI-targeted biopsy alone and with systematic biopsies of one to two other quadrants were studied. Fisher's exact test was used to compare MRI-targeted biopsy alone with the best other strategy for the number of patients with missed cancer and the number of patients with cancer harbouring additional tumours in unsampled quadrants. Analyses focused primarily on detecting cancer of any grade or length. Last, eligibility for focal therapy was evaluated for men with localised (≤T3bN0M0) radiorecurrent disease. RESULTS AND LIMITATIONS: Of 144 patients, 111 (77%) had cancer detected on biopsy. MRI sensitivity and specificity at the patient level were 0.95 (95% confidence interval [CI] 0.92 to 0.99) and 0.21 (95% CI 0.07 to 0.35), respectively. At the prostate quadrant level, 258/576 (45%) quadrants had cancer detected on biopsy. Sensitivity and specificity were 0.66 (95% CI 0.59 to 0.73) and 0.54 (95% CI 0.46 to 0.62), respectively. At the quadrant level, compared with MRI-undetected tumours, MRI-detected tumours had longer maximum cancer core length (median difference 3 mm [7 vs 4 mm]; 95% CI 1 to 4 mm, p < 0.001) and a higher grade group (p = 0.002). Of the 84 men who also underwent an MRI-targeted biopsy, 73 (87%) had recurrent cancer diagnosed. Performing an MRI-targeted biopsy alone missed cancer in 5/73 patients (7%; 95% CI 3 to 15%); with additional systematic sampling of the other ipsilateral and contralateral posterior quadrants (strategy 4), 2/73 patients (3%; 95% CI 0 to 10%) would have had cancer missed (difference 4%; 95% CI -3 to 11%, p = 0.4). If an MRI-targeted biopsy alone was performed, 43/73 (59%; 95% CI 47 to 69%) patients with cancer would have harboured undetected additional tumours in unsampled quadrants. This reduced but only to 7/73 patients (10%; 95% CI 4 to 19%) with strategy 4 (difference 49%; 95% CI 36 to 62%, p < 0.0001). Of 73 patients, 43 (59%; 95% CI 47 to 69%) had localised radiorecurrent cancer suitable for a form of focal ablation. CONCLUSIONS: For patients with recurrent prostate cancer after radiotherapy, MRI and MRI-targeted biopsy, with or without perilesional sampling, will diagnose cancer in the majority where present. MRI-undetected cancers, defined as Likert scores of 1 to 2, were found to be smaller and of lower grade. However, if salvage focal ablation is planned, an MRI-targeted biopsy alone is insufficient for prostate mapping; approximately three of five patients with recurrent cancer found on an MRI-targeted biopsy alone harboured further tumours in unsampled quadrants. Systematic sampling of the whole gland should be considered in addition to an MRI-targeted biopsy to capture both MRI-detected and MRI-undetected disease. PATIENT SUMMARY: After radiotherapy, magnetic resonance imaging (MRI) is accurate for detecting recurrent prostate cancer, with missed cancer being smaller and of lower grade. Targeting a biopsy to suspicious areas on MRI results in a diagnosis of cancer in most patients. However, for every five men who have recurrent cancer, this targeted approach would miss cancers elsewhere in the prostate in three of these men. If further focal treatment of the prostate is planned, random biopsies covering the whole prostate in addition to targeted biopsies should be considered so that tumours are not missed.

Sex differences in cholesterol and triglyceride levels among hospitalized adolescents and young adults with eating disorders.

OBJECTIVE: To determine sex differences in cholesterol and triglyceride levels among adolescents and young adults hospitalized for medical complications of eating disorders. METHODS: A retrospective electronic medical record review of patients aged 9-25 years admitted to the University of California, San Francisco Eating Disorders Program for medical stabilization, between 2012 and 2020, was conducted. Non-fasting total cholesterol and triglycerides were collected; however, LDL and HDL levels were not available. RESULTS: Among 83 males and 441 females, mean ± SD age was 15.5 ± 2.8 years, 64.1% had anorexia nervosa, and admission percent median body mass index was 87.3 ± 13.9. The proportion of males and females with high total cholesterol (13.3% vs. 18.1%, Cramer's V = 0.05, p = .28) and high triglyceride levels (9.6% vs. 8.1%, Cramer's V = 0.02, p = .63) did not differ. Mean total cholesterol levels were higher in females compared to males (F 169.6 ± 41.1 mg/dL vs. M 154.5 ± 45.1 mg/dL, Cohen's d = 0.36, p = .003), although a majority were within the normal range. In adjusted linear regression models, male (compared to female) sex (B = -14.40, 95% CI -24.54, -4.27) and higher percent median body mass index (B = -0.33, 95% CI -0.60, -0.06) were associated with lower total cholesterol levels in adjusted models (R2 = 0.04). DISCUSSION: Building on prior work showing equally severe complications of eating disorders in males compared to females, we did not find sex differences in those presenting with high total cholesterol or triglycerides. Future research is needed to understand the pathophysiology and role of dyslipidemia in acute malnutrition, and the impact of nutritional rehabilitation and weight restoration. PUBLIC SIGNIFICANCE: We found that the proportion of male and female adolescents and young adults hospitalized for medical complications of an eating disorder with high total cholesterol did not significantly differ. Although average total cholesterol levels were higher in female compared to male patients with eating disorders, a majority of these levels remained within the normal range. Patients with more severe malnutrition had a higher risk of elevated total cholesterol levels. Clinicians should consider monitoring cholesterol levels in young people hospitalized for restrictive eating disorders.

Mortality Risk Factors in Pediatric Onco-Critical Care Patients and Machine Learning Derived Early Onco-Critical Care Phenotypes in a Retrospective Cohort.

OBJECTIVES: To use supervised and unsupervised statistical methodology to determine risk factors associated with mortality in critically ill pediatric oncology patients to identify patient phenotypes of interest for future prospective study. DESIGN: This retrospective cohort study included nonsurgical pediatric critical care admissions from January 2017 to December 2018. We determined the prevalence of multiple organ failure (MOF), ICU mortality, and associated factors. Consensus k-means clustering analysis was performed using 35 bedside admission variables for early, onco-critical care phenotype development. SETTING: Single critical care unit in a subspeciality pediatric hospital. INTERVENTION: None. PATIENTS: There were 364 critical care admissions in 324 patients with underlying malignancy, hematopoietic cell transplant, or immunodeficiency reviewed. MEASUREMENTS: Prevalence of multiple organ failure, ICU mortality, determination of early onco-critical care phenotypes. MAIN RESULTS: ICU mortality was 5.2% and was increased in those with MOF (18.4% MOF, 1.7% single organ failure [SOF], 0.6% no organ failure; p ≤ 0.0001). Prevalence of MOF was 23.9%. Significantly increased ICU mortality risk was associated with day 1 MOF (hazards ratio [HR] 2.27; 95% CI, 1.10-6.82; p = 0.03), MOF during ICU admission (HR 4.16; 95% CI, 1.09-15.86; p = 0.037), and with invasive mechanical ventilation requirement (IMV; HR 5.12; 95% CI, 1.31-19.94; p = 0.018). Four phenotypes were derived (PedOnc1-4). PedOnc1 and 2 represented patient groups with low mortality and SOF. PedOnc3 was enriched in patients with sepsis and MOF with mortality associated with liver and renal dysfunction. PedOnc4 had the highest frequency of ICU mortality and MOF characterized by acute respiratory failure requiring invasive mechanical ventilation at admission with neurologic dysfunction and/or severe sepsis. Notably, most of the mortality in PedOnc4 was early (i.e., within 72 hr of ICU admission). CONCLUSIONS: Mortality was lower than previously reported in critically ill pediatric oncology patients and was associated with MOF and IMV. These findings were further validated and expanded by the four derived nonsynonymous computable phenotypes. Of particular interest for future prospective validation and correlative biological study was the PedOnc4 phenotype, which was composed of patients with hypoxic respiratory failure requiring IMV with sepsis and/or neurologic dysfunction at ICU admission.

Lipid droplets modulate proteostasis, SQST-1/SQSTM1 dynamics, and lifespan in C. elegans.

In several long-lived Caenorhabditis elegans strains, such as insulin/IGF-1 receptor daf-2 mutants, enhanced proteostatic mechanisms are accompanied by elevated intestinal lipid stores, but their role in longevity is unclear. Here, while determining the regulatory network of the selective autophagy receptor SQST-1/SQSTM1, we uncovered an important role for lipid droplets in proteostasis and longevity. Using genome-wide RNAi screening, we identified several SQST-1 modulators, including lipid droplets-associated and aggregation-prone proteins. Expansion of intestinal lipid droplets by silencing the conserved cytosolic triacylglycerol lipase gene atgl-1/ATGL enhanced autophagy, and extended lifespan. Notably, a substantial amount of ubiquitinated proteins were found on lipid droplets. Reducing lipid droplet levels exacerbated the proteostatic collapse when autophagy or proteasome function was compromised, and significantly reduced the lifespan of long-lived daf-2 animals. Altogether, our study uncovered a key role for lipid droplets in C. elegans as a proteostatic mediator that modulates ubiquitinated protein accumulation, facilitates autophagy, and promotes longevity.

CritCom: assessment of quality of interdisciplinary communication around deterioration in pediatric oncologic patients.

Background: High-quality clinical care requires excellent interdisciplinary communication, especially during emergencies, and no tools exist to evaluate communication in critical care. We describe the development of a pragmatic tool focusing on interdisciplinary communication during patient deterioration (CritCom). Methods: The preliminary CritCom tool was developed after a literature review and consultation with a multidisciplinary panel of global experts in communication, pediatric oncology, and critical care to review the domains and establish content validity iteratively. Face and linguistic validity were established through cognitive interviews, translation, and linguistic synthesis. We conducted a pilot study among an international group of clinicians to establish reliability and usability. Results: After reviewing 105 potential survey items, we identified 52 items across seven domains. These were refined through cognitive interviews with 36 clinicians from 15 countries. CritCom was piloted with 433 clinicians (58% nurses, 36% physicians, and 6% other) from 42 hospitals in 22 countries. Psychometric testing guided the refinement of the items for the final tool. CritCom comprised six domains with five items each (30 total). The final tool has excellent reliability (Cronbach's alpha 0.81-0.86), usability (93% agree or strongly agree that the tool is easy to use), and similar performance between English and Spanish tools. Confirmatory factor analysis was used to establish the final 6-domain structure. Conclusions: CritCom is a reliable and pragmatic bilingual tool to assess the quality of interdisciplinary communication around patient deterioration for children in diverse resource levels globally. Critcom results can be used to design and evaluate interventions to improve team communication.

Genes Involved by Dexamethasone in Prevention of Long-Term Memory Impairment Caused by Lipopolysaccharide-Induced Neuroinflammation.

Inflammatory activation within the brain is linked to a decrease in cognitive abilities; however, the molecular mechanisms implicated in the development of inflammatory-related cognitive dysfunction and its prevention are poorly understood. This study compared the responses of hippocampal transcriptomes 3 months after the striatal infusion of lipopolysaccharide (LPS; 30 µg), resulting in memory loss, or with dexamethasone (DEX; 5 mg/kg intraperitoneal) pretreatment, which abolished the long-term LPS-induced memory impairment. After LPS treatment, a significant elevation in the expression of immunity/inflammatory-linked genes, including chemokines (Cxcl13), cytokines (Il1b and Tnfsf13b), and major histocompatibility complex (MHC) class II members (Cd74, RT1-Ba, RT1-Bb, RT1-Da, and RT1-Db1) was observed. DEX pretreatment did not change the expression of these genes, but significantly affected the expression of genes encoding ion channels, primarily calcium and potassium channels, regulators of glutamate (Slc1a2, Grm5, Grin2a), and GABA (Gabrr2, Gabrb2) neurotransmission, which enriched in such GO biological processes as "Regulation of transmembrane transport", "Cognition", "Learning", "Neurogenesis", and "Nervous system development". Taken together, these data suggest that (1) pretreatment with DEX did not markedly affect LPS-induced prolonged inflammatory response; (2) DEX pretreatment can affect processes associated with glutamatergic signaling and nervous system development, possibly involved in the recovery of memory impairment induced by LPS.