The LCHADD Mouse Model Recapitulates Early-Stage Chorioretinopathy in LCHADD Patients.

Purpose: Recent studies have shown that the retinal pigment epithelium (RPE) relies on fatty acid oxidation (FAO) for energy, however, its role in overall retinal health is unknown. The only FAO disorder that presents with chorioretinopathy is long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD). Studying the molecular mechanisms can lead to new treatments for patients and elucidate the role of FAO in the RPE. This paper characterizes the chorioretinopathy progression in a recently reported LCHADD mouse model. Methods: Visual assessments, such as optokinetic tracking and fundus imaging, were performed in wildtype (WT) and LCHADD mice at 3, 6, 10, and 12 months of age. Retinal morphology was analyzed in 12-month retinal cross-sections using hematoxylin and eosin (H&E), RPE65, CD68, and TUNEL staining, whereas RPE structure was assessed using transmission electron microscopy (TEM). Acylcarnitine profiles were measured in isolated RPE/sclera samples to determine if FAO was blocked. Bulk RNA-sequencing of 12 month old male WT mice and LCHADD RPE/sclera samples assessed gene expression changes. Results: LCHADD RPE/sclera samples had a 5- to 7-fold increase in long-chain hydroxyacylcarnitines compared to WT, suggesting an impaired LCHAD step in long-chain FAO. LCHADD mice have progressively decreased visual performance and increased RPE degeneration starting at 6 months. LCHADD RPE have an altered structure and a two-fold increase in macrophages in the subretinal space. Finally, LCHADD RPE/sclera have differentially expressed genes compared to WT, including downregulation of genes important for RPE function and angiogenesis. Conclusions: Overall, this LCHADD mouse model recapitulates early-stage chorioretinopathy seen in patients with LCHADD and is a useful model for studying LCHADD chorioretinopathy.

Regional Differences in the US in Outcomes with Preeclampsia.

This study explores preeclampsia outcomes across US regions and examines regional differences in specific preeclampsia-associated pregnancy complications and disease management. Patient-reported measures were obtained from The Preeclampsia Registry, an open-access database composed of women with at least one pregnancy diagnosed with a hypertensive disorder of pregnancy. Pregnancies and associated outcomes were stratified by US region (Northeast, Midwest, South and West). Among 2,667 pregnancies of which 92% were in White women, maximum systolic blood pressure at any time in pregnancy was highest among women in the South and Midwest (p=0.039). Furthermore, more women in the South received pre-pregnancy antihypertensives (p=0.026) and antenatal steroids (p=0.025) and delivered at an earlier gestational age (p=0.014) compared to women in other regions. Pregnancy complications such as elevated liver enzymes were higher in women in the South (p=0.019), and women in the South and West had additional end-organ damage such as renal complications (p<0.001) and hemolysis (p=0.008) as compared to women in other regions. Further investigation is needed to assess whether healthcare access or policy could be contributing to these regional discrepancies.

Transdiagnostic Sleep and Circadian Intervention in Youth: Long-term Follow-up of a Randomized Controlled Trial.

OBJECTIVE: This preregistered study compared the effects of the Transdiagnostic Sleep and Circadian Intervention (TranS-C) with psychoeducation (PE) about sleep, health, yoga, meditation, and outdoor appreciation activities on sleep and circadian functioning, health risk, and sleep health behaviors at long-term follow-up (LTFU), an average of 8 years following treatment. We also examined if more sleep health behaviors at LTFU were associated with better sleep and circadian functioning at LTFU and if better sleep and circadian functioning were associated with lower health risk at LTFU. METHOD: At baseline, we randomly assigned adolescents with an eveningness chronotype to TranS-C (n = 89) or PE (n = 87). Of this sample, we assessed 106 young adults (mean age at follow-up = 22.5 years; n = 55 from TranS-C; n = 51 from PE) an average of 8 years following treatment. RESULTS: Despite TranS-C (vs PE) sustaining improvement in circadian functioning through 12-month follow-up, at LTFU, there were no significant differences between the conditions on any outcome, including sleep and circadian functioning, risks in 5 health domains indexed by self-report and ecological momentary assessment, sleep health behaviors, and physical measurements. Across both conditions, measures indicating poorer sleep and circadian functioning were associated with higher health risk across multiple domains, and more sleep health behaviors were associated with lower levels of eveningness at LTFU. CONCLUSION: These results provide an important window into the influence of development on long-term outcomes for youth and raise the possibility that interventions for youth could be enhanced with a focus on habit formation. CLINICAL TRIAL REGISTRATION INFORMATION: Maintaining Behavior Change: A 6-Year Follow-up of Adolescent 'Night-owls'; https://www. CLINICALTRIALS: gov/; NCT05098782. STUDY PREREGISTRATION INFORMATION: Long-term Follow-up of Young Adults Who Received TranS-C to Modify Eveningness Chronotype in Adolescence; https://osf.io/; d5a4g. DIVERSITY & INCLUSION STATEMENT: We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. We worked to ensure sex and gender balance in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper self-identifies as living with a disability. One or more of the authors of this paper received support from a program designed to increase minority representation in science.

Preformed Vesicle Approach to LNP Manufacturing Enhances Retinal mRNA Delivery.

Complete encapsulation of nucleic acids by lipid-based nanoparticles (LNPs) is often thought to be one of the main prerequisites for successful nucleic acid delivery, as the lipid environment protects mRNA from degradation by external nucleases and assists in initiating delivery processes. However, delivery of mRNA via a preformed vesicle approach (PFV-LNPs) defies this precondition. Unlike traditional LNPs, PFV-LNPs are formed via a solvent-free mixing process, leading to a superficial mRNA localization. While demonstrating low encapsulation efficiency in the RiboGreen assay, PFV-LNPs improved delivery of mRNA to the retina by up to 50% compared to the LNP analogs across several benchmark formulations, suggesting the utility of this approach regardless of the lipid composition. Successful mRNA and gene editors' delivery is observed in the retinal pigment epithelium and photoreceptors and validated in mice, non-human primates, and human retinal organoids. Deploying PFV-LNPs in gene editing experiments result in a similar extent of gene editing compared to analogous LNP (up to 3% on genomic level) in the Ai9 reporter mouse model; but, remarkably, retinal tolerability is significantly improved for PFV-LNP treatment. The study findings indicate that the LNP formulation process can greatly influence mRNA transfection and gene editing outcomes, improving LNP treatment safety without sacrificing efficacy.

Thoracic irrigation for prevention of secondary intervention after thoracostomy tube drainage for hemothorax: A Western Trauma Association multi-center study.

BACKGROUND: Retained hemothorax (rHTX) requiring intervention occurs in up to 20% of patients who undergo chest tube (TT) placement for a hemothorax (HTX). Thoracic irrigation at the time of TT placement decreases the need for secondary intervention in this patient group but those findings are limited because of the single center design. A multi-center study was conducted to evaluate the effectiveness of thoracic irrigation. METHODS: A multi-center, prospective, observational study was conducted between June 2018 and July 2023. Eleven sites contributed patients. Patients were included if they had a TT placed for a HTX and were excluded if: age < 18 years, TT for pneumothorax, thoracotomy or VATS performed within 6 hours of TT, TT >24 hours after injury, TT removed <24 hours, or death within 48 hours. Thoracic irrigation was performed at the discretion of the attending. Each hemithorax was considered separately if bilateral HTX. The primary outcome was secondary intervention for HTX-related complications (rHTX, effusion, or empyema). Secondary intervention was defined as: TT placement, instillation of thrombolytics, VATS, or thoracotomy. Irrigated and non-irrigated hemithoraces were compared using a propensity weighted analysis with age, sex, mechanism of injury, Abbreviated Injury Scale (AIS) chest and TT size as predictors. RESULTS: 493 patients with 462 treated hemothoraces were included, 123 (25%) had thoracic irrigation at TT placement. There were no significant demographic differences between the cohorts. Fifty-seven secondary interventions were performed, 10 (8%) and 47 (13%) in the irrigated and non-irrigated groups, respectively (p = 0.015). Propensity weighted analysis demonstrated a reduction in secondary interventions in the irrigated cohort (Odds Ratio 0.56 (0.34-0.85); p = 0.005). CONCLUSION: This Western Trauma Association multi-center study demonstrates a benefit of thoracic irrigation at the time of TT placement for a HTX. Thoracic irrigation reduces the odds of a secondary intervention for rHTX-related complications by 44%. LEVEL OF EVIDENCE: Therapeutic Study, Level II.

Evaluation of Mpox Exposures and Outcomes in Workplaces, 6 Jurisdictions, June 1-August 31, 2022.

OBJECTIVES: The risk for mpox virus (MPXV) transmission in most workplaces has not been thoroughly assessed in the context of the 2022 global mpox outbreak. Our objectives were to describe mpox case patients who worked while infectious and the subsequent workplace contact tracing efforts, risk assessments, and outcomes. METHODS: The Centers for Disease Control and Prevention requested information from health departments in the United States in September 2022 to identify people with confirmed or probable mpox who worked outside the home while infectious, either before or after diagnosis, from June 1 through August 31, 2022. We collected and summarized data on demographic, clinical, and workplace characteristics of case patients and workplace contact investigations. We stratified data by industry and occupation categories. RESULTS: In total, 102 case patients were reported by 6 jurisdictions. The most common industries were accommodation and food services (19.8%) and professional business, management, and technical services (17.0%). Contact investigations identified 178 total contacts; 54 cases (52.9%) had no contacts identified. Of 178 contacts, 54 (30.3%) were recommended to receive postexposure prophylaxis (PEP) and 18 (10.1%) received PEP. None of the contacts developed a rash or were tested for orthopox or mpox, and none were reported to have confirmed or probable mpox. CONCLUSION: Data from 6 jurisdictions suggest that the risk of MPXV transmission from workers to others in workplace settings in many industries is low. These findings might support future updates to exposure risk classifications and work activity recommendations for patients. These findings also demonstrate the importance of collecting and analyzing occupation and industry data in case reports to better understand risks in workplaces.

Gendered racial microaggressions and stress in PAs who are Black women.

OBJECTIVE: This mixed-methods study explored whether physician associates/assistants (PAs) who are Black women (for brevity, called Black women PAs throughout this article) experience gendered racial microaggressions and whether these experiences correlated with psychologic distress. The phrase Black women encompasses those who identify with the sociocultural roles, behaviors, and expressions of being a Black woman. METHODS: We conducted an online survey of Black women PAs using the Gendered Racial Microaggressions Scale during a 2-month period in 2019. RESULTS: Black women PAs experienced gendered racial microaggressions in clinical settings. Gendered racial microaggressions were correlated with stress, being silenced and marginalized, and assumptions of beauty and sexual objectification. No correlations were found between stress and the angry Black woman and strong Black woman variables. CONCLUSIONS: This study revealed that Black women have interlocking forms of oppression related to their race and gender, which are associated with psychologic distress. Awareness of these occurrences can reduce the unknowing perpetuation of gendered racial microaggressions and create cultural awareness practices.

Compassion-Focused Therapy for the Treatment of ICD-11-Defined Complex Posttraumatic Stress Disorder.

The most effective treatments for ICD-11-defined complex posttraumatic stress disorder (CPTSD) remain unknown. Further research is needed to determine whether such treatments for CPTSD are the same as or different from-or require integration with-existing gold standard treatments for posttraumatic stress disorder (PTSD). Individuals with CPTSD experience the hallmark symptoms of PTSD (i.e., reexperiencing symptoms, avoidance symptoms, and the pervasive sense of perceived threat) and pervasive disturbances in self-organization, including affective dysregulation, negative self-concept, and difficulties with interpersonal relationships. Compassion-focused therapy (CFT) is a transdiagnostic approach that was originally developed to treat shame and self-criticism. CFT helps individuals learn how to regulate their emotions, shift their emotional response style from shaming and self-critical to wise and understanding, and engage in more compassionate and rewarding patterns of relating to self and others. This article describes CFT's possible application in the treatment of CPTSD and delineates areas for future research.

Autofluorescence is a biomarker of neural stem cell activation state.

Neural stem cells (NSCs) must exit quiescence to produce neurons; however, our understanding of this process remains constrained by the technical limitations of current technologies. Fluorescence lifetime imaging (FLIM) of autofluorescent metabolic cofactors has been used in other cell types to study shifts in cell states driven by metabolic remodeling that change the optical properties of these endogenous fluorophores. Using this non-destructive, live-cell, and label-free strategy, we found that quiescent NSCs (qNSCs) and activated NSCs (aNSCs) have unique autofluorescence profiles. Specifically, qNSCs display an enrichment of autofluorescence localizing to a subset of lysosomes, which can be used as a graded marker of NSC quiescence to predict cell behavior at single-cell resolution. Coupling autofluorescence imaging with single-cell RNA sequencing, we provide resources revealing transcriptional features linked to deep quiescence and rapid NSC activation. Together, we describe an approach for tracking mouse NSC activation state and expand our understanding of adult neurogenesis.

Association of Lipoprotein(a) with peri-coronary inflammation in persons with and without HIV infection.

BACKGROUND: Persons with human immunodeficiency virus (HIV) (PWH) have an increased risk of developing cardiovascular disease (CVD) compared to persons without HIV (PWoH). Lipoprotein(a) [Lp(a)] is a known atherosclerotic risk factor in PWoH, but there are no studies investigating Lp(a) and peri-coronary inflammation. OBJECTIVE: To investigate whether Lp(a) is associated with peri-coronary inflammation as assessed by the fat attenuation index (FAI) and activated monocytes and T lymphocytes in PWH and PWoH. METHODS: We measured plasma levels of Lp(a) at study entry in 58 PWH and 21 PWoH without CVD and who had FAI measurements. Associations of Lp(a) with FAI values of the right coronary artery (RCA) and left anterior descending artery were evaluated using multivariable regression models adjusted for potential confounders. Correlations between Lp(a) levels and systemic inflammatory markers and immune cell subsets were examined. RESULTS: Lp(a) was associated with greater peri-coronary inflammation among PWH compared to PWoH (ß=1.73, P=0.019) in the RCA, in adjusted models. Significant correlations were observed with certain inflammatory markers (tumor necrosis factor receptor [TNFR]-I, b=0.295, P<0.001; TNFR-II, b=0.270, P=0.002; high-sensitivity C-reactive protein, b=0.195, P=0.028). Significant correlations were found between Lp(a) levels and several markers of monocyte activation: CD16 -CD163+ (b= -0.199, P=0.024), and CD16 -DR+ MFI (b= -0.179, P=0.042) and T cell subset CD38+CD4+ TEMRA (b= 0.177, P= 0.044). CONCLUSIONS: Lp(a) was associated with greater peri-coronary inflammation in the RCA in PWH compared to PWoH, as well as with select systemic inflammatory markers and specific subsets of immune cells in peripheral circulation.

Daily micropractice can augment single-session interventions: A randomized controlled trial of self-compassionate touch and examining their associations with habit formation in US college students.

In this pre-registered study, we evaluated the effects of a single-session, self-guided intervention, leveraging daily micropractice (≤20 seconds/day practice) of self-compassionate touch to enhance self-compassion. We randomly assigned undergraduates (N = 135) to one of two conditions: a single-session intervention in which they were taught self-compassionate touch or a finger-tapping active control. Then, we instructed them to practice for 20 seconds/day for one month. At baseline (T1) and one-month follow-up (T2), participants completed assessments of self-compassion, growth mindset, positive affect, stress, psychopathology, habit formation, and more. In confirmatory, intention-to-treat analyses (N = 135), we found no significant effects on these outcomes. However, in confirmatory, per-protocol analyses (comparing the subsets from each condition who practiced>28 times, N = 45), self-compassionate touch, relative to active control, predicted T1-to-T2 increases in self-compassion (ß = 0.71, p = .025), and reductions in stress (ß = -0.62, p = .047) and psychopathology (ß = -0.61, p = .046). In exploratory intention-to-treat analyses (N = 135), we found the same pattern of effects as in the per-protocol analyses among those who practiced self-compassionate touch more frequently relative to active control. We discuss factors associated with habit formation of daily practice. Daily micropractices have the potential for augmenting single-session interventions and for offering help when more time-intensive approaches may be less accessible. CLINICAL TRIAL REGISTRATION NUMBER: NCT05199779.

Sleep duration and mental health in young adults.

BACKGROUND: The association between sleep duration and mental illness has been established in middle-aged and older populations, yet remains less explored in younger adults. Additionally, a common limitation to existing studies is the lack of statistical power to explore less common disorders. The purpose of this study was to examine sleep duration as a predictor for a range of mental disorders and well-being in a longitudinal sample of young adults. METHODS: Data were derived from two waves (w1, w2) of the SHoT survey, which invited all full-time university and college students in Norway. The response rates were 34.4 % (n = 62,498) in 2021 (w1) and 35.1 % (n = 59,554) 2022 (w2). This study utilized a nested longitudinal sample from both w1 and w2, encompassing 21,289 students. Demographics, sleep duration (w1), and mental health (w2) were measured by self-report questionnaires. Sex-stratified linear regression models and log-link binomial regression analyses were employed to determine the proportion and calculate the risk ratios, respectively, for mental illness across different sleep duration categories. RESULTS: The mean age of the sample was 24.8 years ± 4.5 years (w1). Students with shorter sleep durations, and to some degree longer sleep durations (illustrating a ᒐ-shaped association), exhibited a higher risk for all assessed mental disorders and well-being outcomes one year later, compared to students sleeping 8-9 h. The ᒐ-shaped trend was consistent for both female and male students. CONCLUSION: Sleep duration appears to be a transdiagnostic marker for mental health in young adults.

The Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) for serious mental illness in community mental health part 3: study protocol to evaluate sustainment in a hybrid type 2 effectiveness-implementation cluster-randomized trial.

BACKGROUND: Although research on the implementation of evidence-based psychological treatments (EBPTs) has advanced rapidly, research on the sustainment of implemented EBPTs remains limited. This is concerning, given that EBPT activities and benefits regularly decline post-implementation. To advance research on sustainment, the present protocol focuses on the third and final phase-the Sustainment Phase-of a hybrid type 2 cluster-randomized controlled trial investigating the implementation and sustainment of the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) for patients with serious mental illness and sleep and circadian problems in community mental health centers (CMHCs). Prior to the first two phases of the trial-the Implementation Phase and Train-the-Trainer Phase-TranS-C was adapted to fit the CMHC context. Then, 10 CMHCs were cluster-randomized to implement Standard or Adapted TranS-C via facilitation and train-the-trainer. The primary goal of the Sustainment Phase is to investigate whether adapting TranS-C to fit the CMHC context predicts improved sustainment outcomes. METHODS: Data collection for the Sustainment Phase will commence at least three months after implementation efforts in partnering CMHCs have ended and may continue for up to one year. CMHC providers will be recruited to complete surveys (N = 154) and a semi-structured interview (N = 40) on sustainment outcomes and mechanisms. Aim 1 is to report the sustainment outcomes of TranS-C. Aim 2 is to evaluate whether manipulating EBPT fit to context (i.e., Standard versus Adapted TranS-C) predicts sustainment outcomes. Aim 3 is to test whether provider perceptions of fit mediate the relation between treatment condition (i.e., Standard versus Adapted TranS-C) and sustainment outcomes. Mixed methods will be used to analyze the data. DISCUSSION: The present study seeks to advance our understanding of sustainment predictors, mechanisms, and outcomes by investigating (a) whether the implementation strategy of adapting an EBPT (i.e., TranS-C) to the CMHC context predicts improved sustainment outcomes and (b) whether this relation is mediated by improved provider perceptions of treatment fit. Together, the findings may help inform more precise implementation efforts that contribute to lasting change. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05956678 . Registered on July 21, 2023.

A group-based transdiagnostic sleep and circadian treatment for major depressive disorder: A randomized controlled trial.

OBJECTIVE: Sleep and circadian disturbance is highly comorbid with a range of psychological disorders, especially major depressive disorder (MDD). In view of the complexity of sleep and circadian problems in MDD, this study aimed to evaluate the efficacy of a group-based transdiagnostic intervention for sleep and circadian dysfunction (TranS-C) for improving depressive symptoms and sleep and circadian functions. METHOD: One hundred fifty-two adults diagnosed with comorbid MDD and sleep and circadian dysfunctions were randomized into TranS-C group treatment (TranS-C; n = 77) or care as usual (CAU; n = 75) control group. The TranS-C group received six weekly 2-hr group sessions of TranS-C, whereas the CAU group continued to receive usual care. Assessments were at baseline, immediate (Week 7), and 12-week (Week 19) posttreatment. Primary and secondary outcomes included depression, anxiety, sleep disturbances, fatigue, quality of life, and functional impairment. RESULTS: The TranS-C group showed significant improvement in depressive symptoms (p < .001, d = 0.84), insomnia severity (p < .001, d = 0.77), sleep disturbances (p < .001, d = 1.15), sleep-related impairment (p < .001, d = 1.22), fatigue (p < .001, d = 1.06), anxiety symptoms (p = .004, d = 0.67), quality of life (p < .001, d = 0.71), and sleep diary-derived parameters (ps < .05, d = 0.12-0.77) relative to the CAU group at immediate posttreatment. These treatment gains remained significant at 12-week follow-up. Significant improvement in functional impairment was also noted at 12-week follow-up. CONCLUSIONS: TranS-C was efficacious and acceptable in alleviating depressive symptoms and sleep and circadian disruptions in adults with MDD. The group format appears to be a low-cost, widely disseminable option to deliver TranS-C. Further research on TranS-C to examine its benefits on other psychiatric disorders is warranted. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

CD137+ tumor infiltrating lymphocytes predicts ovarian cancer survival.

OBJECTIVE: Ovarian cancer (OC) is the leading cause of death from gynecologic malignancy in the United States, and biomarkers of patient outcomes are limited. Data using immunohistochemical (IHC) analysis are mixed regarding whether and which tumor infiltrating lymphocytes (TILs) impact survival, and IHC does not adequately quantify rare cell populations, including CD137+ (4-1BB) tumor-reactive TILs. Our study investigates if a higher percentage of CD3+ CD137+ TILs is associated with improved overall survival (OS) in OC. METHODS: Flow cytometry was performed on viably banked OC digests. Chart review and statistical analysis were performed. Forty-seven patients were included, 40 of whom were diagnosed with high-grade serous ovarian carcinoma (HGSOC), papillary serous carcinoma, or undifferentiated histology. RESULTS: A high percentage of CD3+ CD137+ TILs correlated with improved OS (n = 40, r = 0.48, P = 0.0016). Subjects were divided into CD3+ CD137+ TIL high and low groups by the median. Subjects with high CD3+CD137+ TIL frequencies (>9.6%) had longer OS (Wilcoxon rank-sum test; P = 0.0032) and improved OS (logrank test; P = 0.007). Differences in CD3+ or CD3+ CD8+ TILs did not impact survival. CD3+ CD137+ TILs were predictive of OS regardless of germline mutation or debulking status. Analysis of subgroups including late stage HGSOC and late stage HGSOC with primary optimal cytoreduction indicated CD3+ CD137+ TILs correlated with improved OS after adjusting for age and PARP inhibitor use (P = 0.034 and P = 0.016, respectively). CONCLUSIONS: Prevalence of CD3+ CD137+ TILs in digested OC specimens is associated with improved OS, while general TIL markers are not. CD137 has the potential to be a novel biomarker for survival in OC.

Insulin resistance is associated with subclinical myocardial dysfunction and reduced functional capacity in heart failure with preserved ejection fraction.

BACKGROUND: Obesity and insulin resistance are prevalent in heart failure with preserved ejection fraction (HFpEF) and are associated with adverse cardiovascular outcomes. Measuring insulin resistance is difficult outside of research settings, and its correlation to parameters of myocardial dysfunction and functional status is unknown. METHODS: A total of 92 HFpEF patients with New York Heart Association class II to IV symptoms underwent clinical assessment, 2D echocardiography, and 6-min walk (6 MW) test. Insulin resistance was defined by estimated glucose disposal rate (eGDR) using the formula: eGDR = 19.02 - [0.22 × body mass index (BMI), kg/m2] - (3.26 × hypertension, presence) - (0.61 × glycated hemoglobin, %). Lower eGDR indicates increased insulin resistance (unfavorable). Myocardial structure and function were assessed by left ventricular (LV) mass, average E/e' ratio, right ventricular systolic pressure, left atrial volume, LV ejection fraction, LV longitudinal strain (LVLS), and tricuspid annular plane systolic excursion. Associations between eGDR and adverse myocardial function were evaluated in unadjusted and multivariable-adjusted analyses using analysis of variance testing and multivariable linear regression. RESULTS: Mean age (SD) was 65 (11) years, 64 % were women, and 95 % had hypertension. Mean (SD) BMI was 39 (9.6) kg/m2, glycated hemoglobin 6.7 (1.6) %, and eGDR 3.3 (2.6) mg × kg-1 min-1. Increased insulin resistance was associated with worse LVLS in a graded fashion [mean (SD) -13.8 % (4.9 %), -14.4 % (5.8 %), -17.5 % (4.4 %) for first, second, and third eGDR tertiles, respectively, p = 0.047]. This association persisted after multivariable adjustment, p = 0.040. There was also a significant association between worse insulin resistance and decreased 6 MW distance on univariate analysis, but not on multivariable adjusted analysis. CONCLUSION: Our findings may inform treatment strategies focused on the use of tools to estimate insulin resistance and selection of insulin sensitizing drugs which may improve cardiac function and exercise capacity.

Early Versus Late Feeding After Percutaneous Endoscopic Gastrostomy Placement in Trauma and Burn.

INTRODUCTION: Timing to resume feeds after percutaneous endoscopic gastrostomy (PEG) placement continues to vary among US trauma surgeons. The purpose of this study was to assess differences in meeting nutritional therapy goals and adverse outcomes with early versus late enteral feeding after PEG placement. METHODS: This retrospective review included 364 trauma and burn patients who underwent PEG placement. Data included patient characteristics, time to initiate feeds, rate feeds were resumed, % feed volume goals on postoperative days 0-7, and complications. Statistical analysis was performed comparing two groups (feeds ≤ 6 h versus > 6 h) and three subgroups (< 4 h, 4-6 h, ≥ 6 h) based on data quartiles. Chi-square/Fisher's exact test, independent-samples t-test, and one-way analysis of variance were used to analyze the data. RESULTS: Mean time to initiate feeds after PEG was 5.48 ± 4.79 h. Burn patients received early feeds in a larger proportion. A larger proportion of trauma patients received late feeds. The mean % of goal feed volume met on postoperative day 0 was higher in the early feeding group versus the late (P < 0.001). There were no differences in adverse events, even after subgroup analysis of those who received feeds < 4 h after PEG placement. CONCLUSIONS: Patients with early initiation of feeds after PEG placement achieve a higher percentage of goals on day 0 without an increased rate of adverse events. Unfortunately, patients routinely fall short of their target tube feeding goals.

Efficacy of the Transdiagnostic Intervention for Sleep and Circadian Dysfunction for Depression Symptoms and Sleep-Wake Disruption in Older and Younger Adults: Secondary Age-Stratified Analysis of a Randomized Controlled Trial.

OBJECTIVE: Perform a secondary analysis examining the efficacy of the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) for depression symptom responses, and explore changes in potential target mechanisms. DESIGN: Secondary analysis of a randomized controlled trial with convenience age subsamples (younger (20-49 year; n = 52) versus and older (50-71 years; n = 35)). SETTING: Community mental health clinics. PARTICIPANTS: Eighty-seven adults with serious mental illness. INTERVENTION: TranS-C versus treatment as usual (TAU). MEASUREMENTS: Outcomes were depression symptoms (Quick Inventory of Depression Symptoms), insomnia symptoms (Insomnia Severity Index), and objective sleep-wake rhythm measures (interdaily stability and relative amplitude). RESULTS: Depression response rates (≥50% symptom reductions) were higher in the TranS-C (35.0%) than the TAU (8.8%) group 6-months postintervention (χ2 = 10.3, p = 0.001). There was a medium effect of TranS-C versus TAU on depression symptoms 6-months postintervention (Cohen's d = -0.40, 95% confidence interval (CI): -0.81, 0.01). In both age groups, there were large treatment effects on insomnia symptoms post-treatment (Cohen's d >0.90). In the older subsample, there were additionally medium treatment effects on post-treatment interdaily stability (Cohen's d = 0.60, 95% CI: -0.11, 1.61). Post-treatment reductions in insomnia symptoms correlated with depression symptom reduction 6-months later in the younger subsample (Spearman rho = 0.59, n = 20, p = 0.008). In older adults, postintervention increases in interdaily stability correlated with depression symptom reductions 6-months later (Spearman rho = -0.52, n = 15, p = 0.049). CONCLUSION: Confirmatory trials are needed, given the low age-specific sample sizes here, to determine if TranS -C's produces durable depression responses by increasing sleep-wake rhythm stability in older adults and improving insomnia symptoms in younger adults. BRIEF ARTICLE SUMMARY: The authors evaluated preliminary efficacy of a behavioral intervention that targets sleep/sleep-wake rhythms, the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C), for depression symptoms in people with serious mental illness. TranS-C was associated with higher depression response rates than treatment as usual 6-months postintervention. The degree of depression symptom response 6-months later was related to the degree of treatment phase improvements in interdaily stability (in older adults) and reduction in insomnia severity (in younger adults). A pragmatic nonpharmacologic intervention, the Transdiagnostic Intervention for Sleep and Circadian Dysfunction, has preliminary efficacy for improving sleep-wake factors and depression symptoms.

MultiCenter Study of Intra-Abdominal Abscess Formation After Major Operative Hepatic Trauma.

INTRODUCTION: One of the significant complications of operative liver trauma is intra-abdominal abscesses (IAA). The objective of this study was to determine risk factors associated with postoperative IAA in surgical patients with major operative liver trauma. METHODS: A retrospective multi-institutional study was performed at 13 Level 1 and Level 2 trauma centers from 2012 to 2021. Adult patients with major liver trauma (grade 3 and higher) requiring operative management were enrolled. Univariate and multivariate analyses were performed. RESULTS: Three hundred seventy-two patients were included with 21.2% (n = 79/372) developing an IAA. No difference was found for age, gender, injury severity score, liver injury grade, and liver resections in patients between the groups (P > 0.05). Penetrating mechanism of injury (odds ratio (OR) 3.42, 95% confidence interval (CI) 1.54-7.57, P = 0.02), intraoperative massive transfusion protocol (OR 2.43, 95% CI 1.23-4.79, P = 0.01), biloma/bile leak (OR 2.14, 95% CI 1.01-4.53, P = 0.04), hospital length of stay (OR 1.04, 95% CI 1.02-1.06, P < 0.001), and additional intra-abdominal injuries (OR 2.27, 95% CI 1.09-4.72, P = 0.03) were independent risk factors for IAA. Intra-abdominal drains, damage control laparotomy, total units of packed red blood cells, number of days with an open abdomen, total abdominal surgeries, and blood loss during surgery were not found to be associated with a higher risk of IAA. CONCLUSIONS: Patients with penetrating trauma, massive transfusion protocol activation, longer hospital length of stay, and injuries to other intra-abdominal organs were at higher risk for the development of an IAA following operative liver trauma. Results from this study could help to refine existing guidelines for managing complex operative traumatic liver injuries.