Fast Track Intervention Effects and Mechanisms of Action Through Established Adulthood.

Early preventive interventions can improve outcomes in childhood, but the most effective interventions can continue to deliver benefits through the life course. The Fast Track intervention, a randomized controlled trial for children at risk of conduct problems, has lowered psychopathology, substance use problems, and criminality and elevated happiness at age 25. However, research has not studied whether the intervention's effects continue further into established adulthood. In addition, little is known about the mechanisms through which the intervention may affect adult outcomes. We attempted to answer both questions by simultaneously estimating the intervention's direct effect on adult outcomes at age 31 and the intervention's indirect effects on those outcomes via interpersonal, intrapersonal, and academic competencies gained through the intervention. Participants included the Fast Track intervention (n = 445; 72.4% male) and high-risk control samples (n = 446; 66.4% male). Direct and total effects of random assignment to Fast Track on age 31 outcomes were not significant. However, our analyses showed that Fast Track's improvements to interpersonal and intrapersonal skills in childhood served as catalysts for better life outcomes at age 31. Higher interpersonal skills led to fewer externalizing, internalizing, and substance use problems, reduced criminality and sexual partners, in addition to increased general health and full-time employment. Improved intrapersonal skills led to greater strength. There were no significant indirect pathways via academic skills. Our findings inform understanding of how a childhood preventive intervention can improve adjustment and behaviors into established adulthood.

Depression risk and resilience in a diverse sample of older adults in the United States.

Living in poor and physically deteriorating neighborhoods is associated with heightened likelihood of experiencing depression. At the same time, not all people experience their neighborhoods in the same way. We predicted and tested the possibility that variability in this association can be explained by the social support that people derive both from their personal networks and other people residing in the same neighborhood, and that this moderation varies by race/ethnicity. Health and Retirement Study data (2018/2020 waves) were used to evaluate the role of individual-level and contextual risk and resilience factors in association with depression among US older non-Hispanic white adults (n = 4,986, mean age 67 years), non-Hispanic black adults (n = 1,342, mean age 65 years), and Hispanic adults (n = 937, mean age 64 years). Four notable findings emerged. First, perceived neighborhood disorder was related to increased depression risk for non-Hispanic white and black participants, but not Hispanic participants. Second, participants residing in census tracts with higher poverty rates were more likely to report depression. Third, non-Hispanic white participants residing in census tracts with greater Hispanic resident density had reduced depression risk. This same pattern was not observed among non-Hispanic black participants. Finally, perceived support from family was associated with reduced depression risk among all participants. These data suggest both individual- and contextual-level sources of risk and resiliency for depression. The implications for theories that seek to explain the relative resilience to neighborhood disorder observed among US Hispanic residents are discussed.

Preferred and Actual Places of Death Among Patients with Advanced Cancer: A Single-centre Cohort Study in Japan.

Objectives: Achieving a 'good death' is one of the important goals of palliative care. Providing goal-concordant care and an environment tailored to the patient's preferences can contribute to a 'good death'. However, the concordance rate between the preferred and actual places of death among advanced cancer patients in Japan is less explored. This study aimed to identify the concordance between patients' preferred and actual places of death and the associated factors among patients with advanced cancer in Japan. Materials and Methods: Patients with advanced cancer who underwent chemotherapy at Tohoku University Hospital between January 2015 and January 2016 were enrolled and followed up for 5 years. The enrolled patients were asked about their preference for their place of death. The response options were: "Own home," "General ward" and "Palliative care unit (PCU)." We compared the actual place of death with the patient's preference through a follow-up review of the medical records. Results: A total of 157 patients with advanced cancer were enrolled between January 2015 and January 2016. Of these patients, 22.9% (11/48) died at home according to their preference, 64.0% (16/25) in the general ward and 37.9% (11/29) in the PCU. Only thirty-seven (37.3%) patients died where they wanted, based on the comparison between patients' preferences and actual places of death. Conclusion: The concordance rate between the preferred and actual places of death is not high in Japan. Improving concordance between patients' preferences and actual places of death has the potential to improve end-of-life care.

Effect of Obstructive Sleep Disorder Treatment on Posttraumatic Stress Disorder Symptoms: A Literature Review.

PURPOSE: To explore whether continuous positive airway pressure (CPAP) adherence among adult patients with obstructive sleep apnea (OSA) and posttraumatic stress disorder (PTSD) affects the PTSD Checklist (PCL), a validated tool that measures severity of PTSD symptoms. METHOD: Studies focusing on PTSD and OSA were searched in PubMed and CINAHL databases. Inclusion and exclusion criteria were applied, decreasing the article yield to nine. All articles chosen focused on the adult population and were conducted in North America. RESULTS: The literature review yielded eight observational cohort studies and one descriptive study. Seven studies were conducted with Veterans and all studies used the PCL tool. Three themes were identified: (a) Trauma and OSA, (b) OSA and PTSD Symptoms, and (c) CPAP Therapy and PTSD Symptoms. An area of further study is assessing how CPAP adherence might affect improvement in PTSD symptoms and how adherence can be improved. CONCLUSION: OSA is correlated with more severe PTSD symptoms, but CPAP use is associated with improvement in PTSD symptoms. The literature reviewed found PCL scores improved up to 10 points within 3 months of CPAP use. These findings highlight the importance of collaboration between mental health and sleep medicine professionals and opportunity for further study in this area. [Journal of Psychosocial Nursing and Mental Health Services, xx(xx), xx-xx.].

Severe Clinical Phenotypes of Heterozygous Females With X-Linked Chronic Granulomatous Disease.

CLINICAL IMPLICATIONS: Female X-linked chronic granulomatous disease (XL-CGD) carriers may develop severe clinical disease including infections with CGD-defining pathogens and inflammatory disorders. Similar to males with XL-CGD, female carriers warrant ongoing evaluation and prophylaxis where indicated.

Peace, equanimity and acceptance in the cancer experience: validation of the German version (PEACE-G) and associations with mental health, health-related quality of life and psychological constructs.

BACKGROUND: Systematic reviews and meta-analyses reveal the importance of an accepting attitude towards cancer for mental health and functional coping. The aim of this study was to examine the psychometric properties of the German translation of the Peace, Equanimity, and Acceptance in the Cancer Experience (PEACE) questionnaire (Mack et al., 2008) and to investigate its associations with mental health, health-related quality of life (HRQoL) and related constructs. METHODS: The German version of the PEACE (PEACE-G) was created and validated with cancer patients in a cross-sectional two center questionnaire study. Construct validity was tested with confirmational factor analyses (CFA); Cronbach's alpha was used to determine internal consistency of items. We further examined associations with depression (PHQ-8), anxiety (GAD-7), distress (NCCN distress thermometer), HRQoL (SF-12), psychological flexibility (AAQ-II), resilience (RS-11) and acceptance scales, to evaluate concurrent and divergent validity. RESULTS: N = 213 cancer patients with different tumor entities participated in this study. Results of the CFA replicated the two-factor solution of the original PEACE (peaceful acceptance and struggle with illness) with satisfactory psychometric properties. Peaceful acceptance showed negative associations with depression, anxiety, distress, psychological inflexibility, and positive associations with HRQoL, acceptance, resilience, and mindfulness. Results of sensitivity analyses indicate a third factor (injustice/anger). CONCLUSIONS: The results demonstrate the validity and reliability of PEACE-G in cancer patients and point to the essential role of acceptance- and mindfulness-based interventions in psycho-oncology. Further studies are needed to investigate the different facets of struggle with the cancer illness.

Patient, Parent, and Oncologist Perspectives and Recommendations on the Right Way to Talk About Prognosis in Advanced Childhood Cancer.

PURPOSE: Clear prognostic communication is associated with improvements in quality of life and suffering for children with advanced illness. Yet recent evidence demonstrates that pediatric oncologists often avoid, defer, or soften prognostic disclosure. We aimed to describe pediatric cancer shareholder perspectives on quality prognostic communication to inform design of an intervention to improve prognostic disclosure in advanced childhood cancer. METHODS: Semi-structured interviews were conducted with a purposeful sample of pediatric patients with cancer (n = 20), parents (n = 20), and oncologists (n = 20) representing six institutions across five states. Rapid analysis was performed using the National Cancer Institute core communication functions to organize domains of inquiry. RESULTS: Three main themes were endorsed by participants regarding the ideal timing of prognostic disclosure: early, ongoing, individualized. Although each group emphasized the need for an individualized approach, oncologists rarely elicited patient/parent preferences for prognostic communication and more commonly inferred what a patient/family wanted to hear. Participants described five key pillars for how to facilitate quality prognostic disclosure: conversation leadership, overall attendance, patient inclusion, location, and atmosphere. They also identified four themes around ideal prognostic content: range of information, use of numbers, population-level versus patient-specific information, and tone/delivery. Discordant recommendations between patients/parents and oncologists emerged for how much and what information to share. CONCLUSION: Pediatric cancer shareholders advocated for diverse, and sometimes conflicting, approaches for prognostic disclosure. Although nearly all participants endorsed the importance of individualized prognostic disclosure, specific strategies to encourage or facilitate person-centered prognostic conversation are lacking. Future research will focus on collaboration with pediatric patients, parents, and oncologists to codesign a clinical intervention to improve prognostic communication for children with advanced cancer and their families.

Characterization of lignin-degrading enzyme PmdC, which catalyzes a key step in the synthesis of polymer precursor 2-pyrone-4,6-dicarboxylic acid.

Pyrone-2,4-dicarboxylic acid (PDC) is a valuable polymer precursor that can be derived from the microbial degradation of lignin. The key enzyme in the microbial production of PDC is 4-carboxy-2-hydroxymuconate-6-semialdehyde (CHMS) dehydrogenase, which acts on the substrate CHMS. We present the crystal structure of CHMS dehydrogenase (PmdC from Comamonas testosteroni) bound to the cofactor NADP, shedding light on its three-dimensional architecture, and revealing residues responsible for binding NADP. Using a combination of structural homology, molecular docking, and quantum chemistry calculations, we have predicted the binding site of CHMS. Key histidine residues in a conserved sequence are identified as crucial for binding the hydroxyl group of CHMS and facilitating dehydrogenation with NADP. Mutating these histidine residues results in a loss of enzyme activity, leading to a proposed model for the enzyme's mechanism. These findings are expected to help guide efforts in protein and metabolic engineering to enhance PDC yields in biological routes to polymer feedstock synthesis.

Reduced Nicotine Cigarettes and E-Cigarettes in High-Risk Populations: 3 Randomized Clinical Trials.

Importance: Prohibiting the sale of commonly preferred e-cigarette flavors (eg, fruity and sweet) to discourage use among youths poses a risk of diminishing efforts to decrease smoking in adults. Objective: To compare reductions in smoking achieved in adults with psychiatric conditions or lower educational level using very low nicotine content (VLNC) cigarettes alone, combined with e-cigarettes limited to tobacco flavor (TF), or combined with e-cigarettes in participant-preferred flavors. Design, Setting, and Participants: Three randomized clinical trials were conducted for 16 weeks from October 2020 through November 2023 at the University of Vermont, Brown University, and Johns Hopkins University. Participants were adults who smoked daily and were not planning to quit in the next 30 days. These participants were from 3 at-risk populations: those with affective disorders, exemplifying mental illness; those with opioid use disorder, exemplifying substance use disorders; and females of reproductive age with a high-school education or less, exemplifying lower educational level. Participants were randomly assigned to 1 of 4 experimental conditions: (1) normal nicotine content (NNC) cigarettes only; (2) VLNC cigarettes only; (3) VLNC cigarettes plus e-cigarettes with classic TF (hereafter, VLNC + TF); and (4) VLNC cigarettes plus e-cigarettes with preferred flavors (hereafter, VLNC + PF). Interventions: The NNC cigarettes contained 15.8 mg nicotine/g tobacco, the VLNC cigarettes contained 0.4 mg nicotine/g tobacco, the VLNC + TF had pods containing 5% nicotine by weight and only classic TF, and the VLNC + PF had pods containing 5% nicotine in 8 flavors (including fruity and sweet) from which participants selected 3 flavors. Main Outcomes and Measures: The primary outcome was mean total cigarettes smoked per day (CPD) during week 16. Tobacco-related biomarkers were assessed, including total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a tobacco-specific carcinogen. Results: A total of 326 participants (mean [SD] age, 40.09 [10.79] years; 243 females [74.5%]) from 3 randomized clinical trials were included. The VLNC cigarettes decreased total CPD, with least square (LS) means (SEMs) of 22.54 (1.59) in the NNC, 14.32 (1.32) in the VLNC, 11.76 (1.18) in the VLNC + TF, and 7.63 (0.90) in the VLNC + PF conditions. Each VLNC condition differed significantly from NNC, with an adjusted mean difference (AMD) of -8.21 (95% CI, -12.27 to -4.16; P < .001) in the VLNC, -10.78 (95% CI, -14.67 to -6.90; P < .001) in the VLNC + TF, and -14.91 (95% CI, -18.49 to -11.33; P < .001) in the VLNC + PF conditions. Participants in the VLNC + PF condition also decreased smoking below the VLNC and the VLNC + TF conditions (AMDs, -6.70 [95% CI, -9.84 to -3.55; P < .001] and -4.13 [95% CI, -7.05 to -1.21; P = .02]); the VLNC and VLNC + TF conditions did not differ significantly. Consistent with decreases in CPD, NNAL levels in the VLNC + PF condition were lower than in all other conditions, with AMDs (in pmol/mg creatinine) of -0.94 (95% CI, -1.41 to -0.47; P < .001) compared with the NNC condition, -0.47 (95% CI, -0.87 to -0.08; P = .03) compared with the VLNC condition, and -0.46 (95% CI, -0.83 to -0.10; P = .04) compared with the VLNC + TF condition. Conclusions and Relevance: These results provide further evidence that a reduced-nicotine standard for cigarettes has the potential to decrease smoking and tobacco-toxicant exposure in high-risk populations and that these effects may be enhanced when adults can access e-cigarettes in commonly preferred flavors. Trial Registration: ClinicalTrials.gov Identifiers: NCT04092387, NCT04090879, NCT04092101.

Race and Sex Disparities Among Emergency Medicine Chief Residents.

Importance: Physicians who belong to minoritized racial and ethnic groups remain underrepresented and underpromoted. Serving as a chief resident is an important position of leadership and prestige, and indicates a benchmark for future professional success. However, it is unknown if disparities in race and/or sex exist in the chief resident selection process. Objective: To describe race, ethnicity, and sex of emergency medicine (EM) chief residents and determine the association of racial identity and the intersectionality of race and sex for selecting chief residents in US emergency medicine departments. Design, Setting, and Participants: This cohort study analyzed data collected from the Association of American Medical Colleges and the Electronic Residency Application Service in the graduating classes of 2017 and 2018. Data were analyzed between December 2021 and January 2023. Main Outcomes and Measures: Relative risk (RR) of selection for chief residency for Black, Asian, and Hispanic EM residents in comparison with White counterparts. Results: Among 3408 studied residents, 738 (21.7%) served as chief resident (2253 male [66.1%]; 451 Asian [13.2%], 144 Black [4.2%], 158 Hispanic [4.6%], 239 more than 1 race [7.0%], 46 other [1.3%], and 2370 White [69.5%]). Of chiefs, 81 (11.0%) identified as Asian, 17 (2.3%) as Black, and 26 (3.5%) Hispanic. Asian residents were 78% (95% CI, 63%-96%) as likely to be promoted to chief resident compared with White peers, and Black residents were 51% (95% CI, 32%-80%) as likely as White residents. In our fully adjusted model, racial differences remained significant for Black residents, who were half as likely as white residents to be selected for chief residency (adjusted risk ratio [aRR], 0.55; 95% CI, 0.36-0.82). Overall, White women were most likely to be selected for chief residency and 20% more likely to be selected than White men counterparts (aRR, 1.20; 95% CI, 1.03-1.39). In comparison, women underrepresented in medicine (a category that included residents identified as Black, Hispanic, American Indian or Alaskan Native, and Native Hawaiian or Other Pacific Islander) were least likely to be selected for chief promotion, and 50% as likely to be selected for chief resident compared with White men (aRR, 0.50; 95% CI, 0.06-0.66). Conclusions and Relevance: In this 2024 nationally representative study of EM residents, chief promotion was lower among residents identifying as Asian or Black, and in particular, women underrepresented in medicine. This study's findings suggest further review of chief resident selection process by residency programs and accreditation bodies is needed to ensure workforce equity for promotion and opportunities for leadership.

Racial/ethnic differences in the acute effects of reduced nicotine content cigarettes among adolescents who smoke.

OBJECTIVE: Reducing the nicotine content in cigarettes decreases their addictiveness and abuse liability, including among adolescents. Whether these effects differ by race/ethnicity is unknown. This study is a secondary analysis of previously published data collected between 2014-2017. We examined racial/ethnic differences in the effects of smoking cigarettes with varying nicotine content levels on subjective effects and tobacco withdrawal among adolescents who smoke daily. METHODS: Across two counterbalanced sessions, 50 adolescents recruited from Rhode Island (ages 15-19; 30 % Underrepresented Minorities [URM], 20 % Asians and Pacific Islanders [API]; 50 % Non-Hispanic Whites) self-administered a very low nicotine content (VLNC; 0.4 mg nicotine/g of tobacco) or normal nicotine content control (NNC; 15.8 mg/g) research cigarette following overnight abstinence. Subjective effects were reported post-administration and tobacco withdrawal outcomes were calculated from pre- to post-administration scores. Multilevel linear models tested main and interactive effects between cigarette nicotine content and race/ethnicity on all study outcomes. RESULTS: Participants reported lower positive subjective effects and reductions in smoking urges after smoking a VLNC cigarette relative to smoking an NNC cigarette (ps < 0.01). A main effect of race/ethnicity emerged, such that API (vs. URM and White) adolescents reported lower positive subjective effects, greater craving reduction, and higher cigarette aversion after smoking, regardless of nicotine content (ps < 0.05). Significant interactions were found between race/ethnicity and nicotine content for cigarette aversion, such that API adolescents rated VLNC (vs. NNC) cigarettes as less aversive than White and URM adolescents did (p = 0.03). CONCLUSIONS: Findings provide evidence that VLNC cigarettes may reduce abuse liability and tobacco withdrawal symptoms for adolescents across racial/ethnic groups and particularly for API youth.

IGF-1 and insulin receptors in LepRb neurons jointly regulate body growth, bone mass, reproduction, and metabolism.

Leptin receptor (LepRb)-expressing neurons are known to link body growth and reproduction, but whether these functions are mediated via insulin-like growth factor 1 receptor (IGF1R) signaling is unknown. IGF-1 and insulin can bind to each other's receptors, permitting IGF-1 signaling in the absence of IGF1R. Therefore, we created mice lacking IGF1R exclusively in LepRb neurons (IGF1RLepRb mice) and simultaneously lacking IGF1R and insulin receptor (IR) in LepRb neurons (IGF1R/IRLepRb mice) and then characterized their body growth, bone morphology, reproductive and metabolic functions. We found that IGF1R and IR in LepRb neurons were required for normal timing of pubertal onset, while IGF1R in LepRb neurons played a predominant role in regulating adult fertility and exerted protective effects against reproductive aging. Accompanying these reproductive deficits, IGF1RLepRb mice and IGF1R/IRLepRb mice had transient growth retardation. Notably, IGF1R in LepRb neurons was indispensable for normal trabecular and cortical bone mass accrual in both sexes. These findings suggest that IGF1R in LepRb neurons is involved in the interaction among body growth, bone development, and reproduction. Though only mild changes in body weight were detected, simultaneous deletion of IGF1R and IR in LepRb neurons caused dramatically increased fat mass composition, decreased lean mass composition, lower energy expenditure, and locomotor activity in both sexes. Male IGF1R/IRLepRb mice exhibited impaired insulin sensitivity. These findings suggest that IGF1R and IR in LepRb neurons jointly regulated body composition, energy balance, and glucose homeostasis. Taken together, our studies identified the sex-dependent complex roles of IGF1R and IR in LepRb neurons in regulating body growth, reproduction, and metabolism.

Functions of patient- and family-centered pediatric cancer communication in Pakistan.

Background: Communication is an essential aspect of high-quality patient- and family-centered care. A model for pediatric cancer communication developed in the United States defined eight communication functions. The purpose of this study was to explore the relevance of these functions in Pakistan as part of an effort to understand the role of culture in communication. Materials and methods: Semi-structured interviews were conducted with 20 clinicians and 18 caregivers of children with cancer at two major cancer centers. Interviews were conducted in Urdu or English and transcribed and translated as necessary. Two independent coders used a priori codes related to the communication model as well as novel codes derived inductively. Thematic analysis focused on operationalization of the functional communication model. Results: Clinicians and caregivers in Pakistan discussed the importance of all eight communication functions previously identified including: information exchange, decision-making, managing uncertainty, enabling family self-management, responding to emotions, supporting hope, providing validation, and building relationships. The operationalization of these functions was influenced by Pakistani cultural context. For example, information-exchange included the importance of addressing preconceptions and community myths, while managing uncertainty included strong references to religion and faith-based coping. Essential to all eight functions was trust between the family and the medical team. Discussion: These findings support the use of this functional communication model in diverse pediatric oncology settings and emphasize the importance of trust. Culturally sensitive operationalization of these functions could inform the adaptation of tools to measure communication and interventions aimed at supporting the needs of parents of children with cancer.

Encorafenib plus binimetinib for BRAF V600E-mutant metastatic NSCLC: clinical implications of the phase 2 PHAROS study.

Drs. Ramalingam and Carlisle discuss the incidence and pathophysiology of BRAF V600E-mutant metastatic non-small cell lung cancer and current treatment options. The podcast provides an overview of the data from the recent Pfizer-sponsored phase 2 PHAROS (NCT03915951) study, which were the basis for the recent US Food and Drug Administration approval of encorafenib plus binimetinib for BRAF V600E-mutant metastatic non-small cell lung cancer.

Dietary Adherence to Recommendations among a Cohort of Adults and Teens with Celiac Disease Maintaining a Gluten-Free Diet Compared to a Nationally Representative Sample: A Cross-Sectional Study.

Celiac disease (CeD) is a common autoimmune condition, with a prevalence of ~1%. Currently, a gluten-free diet (GFD) is the only treatment option. Due to fortification rules excluding gluten-free products in the United States of America (U.S.A.), understanding the nutritional adequacy of a GFD is important for promoting optimal health among those with CeD. Cross-sectional examination of multiple 24 h dietary recalls from a study sample of 50 adults and 30 teens with CeD was used to determine nutritional adequacy and excesses according to U.S.A. recommendations. The results were compared with those of 15,777 adults and 2296 teens from a nationally representative sample not reporting CeD, the National Health and Nutrition Examination Survey (NHANES) 2009-2014. Compared with NHANES, our study population was more at risk of low folate and carbohydrate (adults) consumption, and of excessive niacin and vitamin A (teens), as well as saturated and total fat consumption (adults). Overall, though, compared with NHANES, our study participants had similar nutrient concerns but fewer nutritional imbalances, with some notable exceptions. In addition to maintaining a GFD, individuals with CeD should be counseled to maintain a balanced diet and to pay attention to nutrient-dense foods. Special attention should be given to teens in providing dietary counseling to potentially mitigate the risk of future morbidity.

From Parental Behavior to Sexual Function: Recent Advances in Oxytocin Research.

Purpose of Review: Oxytocin plays many diverse roles in physiological and behavioral processes, including social activity, parental nurturing, stress responses, and sexual function. In this narrative review, we provide an update on the most noteworthy recent findings in this fascinating field. Recent Findings: The development of techniques such as serial two-photon tomography and fiber photometry have provided a window into oxytocin neuroanatomy and real-time neuronal activity during social interactions. fMRI and complementary mapping techniques offer new insights into oxytocin's influence on brain activity and connectivity. Indeed, oxytocin has recently been found to influence the acquisition of maternal care behaviors and to mediate the influence of social touch on brain development and social interaction. Additionally, oxytocin plays a crucial role in male sexual function, affecting erectile activity and ejaculation, while its role in females remains controversial. Recent studies also highlight oxytocin's interaction with other neuropeptides, such as melanin-concentrating hormone, serotonin, and arginine vasopressin, influencing social and affective behaviors. Finally, an update is provided on the status of clinical trials involving oxytocin as a therapeutic intervention. Summary: The exploration of oxytocin's complexities and its interplay with other neuropeptides holds promise for targeted treatment in various health and disease contexts. Overall, these findings contribute to the discovery of new and specific pathways to allow therapeutic targeting of oxytocin to treat disorders.

Emapalumab Use in Patients With Rheumatologic Disease-Associated Hemophagocytic Lymphohistiocytosis in the United States: the REAL-HLH Study.

OBJECTIVE: Rheumatologic disease-associated hemophagocytic lymphohistiocytosis (HLH), a rare, life-threatening, systemic hyperinflammatory syndrome, occurs as a complication of underlying rheumatologic disease. Real-world evidence is lacking on emapalumab, a fully human monoclonal antibody that neutralizes the proinflammatory cytokine interferon-gamma, approved for treating patients with primary HLH. METHODS: REAL-HLH, a retrospective medical chart review study conducted across 33 US hospitals, assessed real-world treatment patterns and outcomes in patients with HLH treated with ≥1 dose of emapalumab between November 20, 2018, and October 31, 2021. Data are presented for the subset of patients with rheumatologic disease-associated HLH. RESULTS: Fifteen of 105 patients (14.3%) had rheumatologic disease-associated HLH. Of these, 9 (60.0%) had systemic juvenile idiopathic arthritis, and 1 (6.7%) had adult-onset Still's disease. Median (range) age at HLH diagnosis was 5 (0.9-39) years. Most (9/15; 60.0%) patients initiated emapalumab in an intensive care unit. Emapalumab was most frequently initiated for treating refractory or recurrent (10/15; 66.7%) disease. Most patients received HLH-related therapies prior to (10/15; 66.7%) and concurrently (15/15; 100.0%) with emapalumab. Emapalumab-containing regimens stabilized or achieved physician-determined normalization of most laboratory parameters including fibrinogen (11/13; 84.6%), chemokine ligand 9 (7/8; 87.5%), and absolute neutrophil count (6/10; 60%), and reduced glucocorticoid dose by 80%. Overall survival and 12-month survival probability from emapalumab initiation were 86.7%. CONCLUSION: Emapalumab-containing regimens stabilized or normalized most key laboratory parameters, reduced glucocorticoid dose, and were associated with low disease-related mortality, thereby demonstrating potential benefits in patients with rheumatologic disease-associated HLH.

Percent Body Fat and Weight Status of Youth Participating in Pediatric Weight Management Programs in the Pediatric Obesity Weight Evaluation Registry.

Factors associated with change in percent body fat (%BF) of children in pediatric weight management (PWM) care may differ from those associated with change in weight status. Objective: To describe %BF and weight status at initial visits to 14 PWM sites, identify differences by sex, and evaluate factors associated with change over 6 months. Methods: Initial visits of 2496 males and 2821 females aged 5-18 years were evaluated. %BF was measured using bioelectrical impedance analysis. Results: Sex-specific logistic regressions [806 males (32.3%), 837 females (29.7%)] identified associations with primary outcomes: lower %BF and metabolically impactful ≥5-point drop in percent of the 95th BMI percentile (%BMIp95) over 6 months. At the initial visit, males had lower %BF and higher %BMIp95 than females. Over 6 months, males had significantly (p < 0.001) greater median drop in %BF (-1.4% vs. -0.4%) and %BMIp95 (-3.0% vs. -1.9%) and a higher frequency of decreased %BF (68.9% vs. 57.8%), but similar percentage with ≥5-point %BMIp95 drop (36.5% vs. 32.4%; p = 0.080). For males, factors significantly associated with decreased %BF (older age, ≥6 visits, lack of developmental or depression/anxiety concerns) were not related to having a ≥5-point %BMIp95 drop. For females, lack of depression/anxiety concern was significantly associated with decreased %BF but was not associated with ≥5-point %BMIp95 drop. Conclusions: There are differences by sex in initial visit %BF and %BMIp95 and in characteristics associated with changes in these measures. PWM interventions should consider evaluating body composition and sex-stratifying outcomes.

Astrocyte involvement in metabolic regulation and disease.

Astrocytes, the predominant glial cell type in the mammalian brain, influence a wide variety of brain parameters including neuronal energy metabolism. Exciting recent studies have shown that obesity and diabetes can impact on astrocyte function. We review evidence that dysregulation of astrocytic lipid metabolism and glucose sensing contributes to dysregulation of whole-body energy balance, thermoregulation, and insulin sensitivity. In addition, we consider the overlooked topic of the sex-specific roles of astrocytes and their response to hormonal fluctuations that provide insights into sex differences in metabolic regulation. Finally, we provide an update on potential ways to manipulate astrocyte function, including genetic targeting, optogenetic and chemogenetic techniques, transplantation, and tailored exosome-based therapies, which may lead to improved treatments for metabolic disease.