Sorted-cell sequencing on HCC specimens reveals EPS8L3 as a key player in CD24/CD13/EpCAM-triple positive, stemness-related HCC cells.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a heterogeneous cancer with varying levels of liver tumor initiating or cancer stem cells in the tumors. We aimed to investigate the expression of different liver cancer stem cell (LCSC) markers in human HCCs, and identify their regulatory mechanisms in stemness-related cells. METHODS: We used an unbiased, single-marker sorting approach by flow cytometry, fluorescence-activated cell sorting, and transcriptomic analyses on HCC patients' resected specimens. Knockdown approach was employed and relevant functional assays were conducted on the identified targets of interest. RESULTS: Flow cytometry on a total of 60 HCC resected specimens showed significant heterogeneity in the expression of LCSC markers, with CD24, CD13, and EpCAM mainly contributing to this heterogeneity. Concomitant expression of CD24, CD13 and EpCAM was detected in 32 HCC samples, and this was associated with advanced tumor stages. Transcriptomic sequencing on the HCC cells sorted for these individual markers identified EPS8L3 as a common gene associated with the three markers and was functionally validated in HCC cells. Knocking down EPS8L3 suppressed the expression of all three markers. To search for the upstream regulation of EPS8L3, we found SP1 bound to EPS8L3 promoter to drive EPS8L3 expression. Furthermore, using Akt inhibitor MK2206, we showed that Akt-signaling-driven SP1 drove the expression of the three LCSC markers CONCLUSIONS: Our findings suggest that Akt-signaling-driven SP1 promotes EPS8L3 expression, which is critical in maintaining the downstream expression of CD24, CD13 and EpCAM. The findings provide insight into potential LCSC-targeting therapeutic strategies.

Associations between periodontitis and serum anti-malondialdehyde-acetaldehyde antibody concentrations in rheumatoid arthritis: A case-control study.

BACKGROUND: Malondialdehyde-acetaldehyde (MAA) adducts lead to generation of anti-MAA autoantibodies and have been independently identified in inflamed periodontal and rheumatoid arthritis (RA) tissues. This study evaluates serum samples from RA cases and osteoarthritis (OA) controls to quantify associations between periodontal clinical measures, alveolar bone loss (ABL), and anti-Porphyromonas gingivalis, anti-Prevotella intermedia, and anti-Fusobacterium nucleatum antibody concentrations with anti-MAA antibody concentrations. METHODS: Participants (n = 284 RA cases, n = 330 OA controls) underwent periodontal clinical assessments and ABL measurements. Serum immunoglobulin (Ig) A, IgG, and IgM anti-MAA and serum IgG antibacterial antibody concentrations were quantified by enzyme-linked immunosorbent assay (ELISA). Analyses utilized simple linear regression and multivariable adjusted models. RESULTS: No significant associations of periodontal clinical measures with serum anti-MAA were found. Moderate (p = 0.038 and p = 0.036, respectively) and high ABL (p = 0.012 and p = 0.014, respectively) in RA cases (but not in OA) were positively associated with IgG and IgM anti-MAA. Anti-P. gingivalis and anti-P. intermedia antibody concentrations were positively associated with IgA (p = 0.001 for both), IgG (p = 0.007 and p = 0.034, respectively), and IgM anti-MAA antibody concentrations (p < 0.001 and p = 0.020, respectively), while anti-F. nucleatum was positively associated with IgG anti-MAA (p = 0.042), findings that were similar across groups. CONCLUSIONS: A positive association was demonstrated between ABL and serum IgG and IgM anti-MAA antibody concentrations that was unique to RA and not observed in OA. Serum anti-P. gingivalis, anti-P. intermedia, and anti-F. nucleatum antibody concentrations displayed significant associations with anti-MAA antibody in both groups. These findings suggest MAA may play a role in the interrelationship between the periodontium and RA.

The Glycemia Risk Index Predicts Performance of Diabetes Self-Management Habits in Youth With Type 1 Diabetes Mellitus.

BACKGROUND: The Glycemia Risk Index (GRI) was developed in adults with diabetes and is a validated metric of quality of glycemia. Little is known about the relationship between GRI and type 1 diabetes (T1D) self-management habits, a validated assessment of youths' engagement in habits associated with glycemic outcomes. METHOD: We retrospectively examined the relationship between GRI and T1D self-management habits in youth with T1D who received care from a Midwest pediatric diabetes clinic network. The GRI was calculated using seven days of continuous glucose monitor (CGM) data, and T1D self-management habits were assessed ±seven days from the GRI score. A mixed-effects Poisson regression model was used to evaluate the total number of habits youth engaged in with GRI, glycated hemoglobin A1c (HbA1c), age, race, ethnicity, and insurance type as fixed effects and participant ID as a random effect to account for multiple clinic visits per individual. RESULTS: The cohort included 1182 youth aged 2.5 to 18.0 years (mean = 13.8, SD = 3.5) comprising 50.8% male, 84.6% non-Hispanic White, and 64.8% commercial insurance users across a total of 6029 clinic visits. Glycemia Risk Index scores decreased as total number of habits performed increased, suggesting youth who performed more self-management habits achieved a higher quality of glycemia. CONCLUSIONS: In youth using CGMs, GRI may serve as an easily obtainable metric to help identify youth with above target glycemia, and engagement/disengagement in the T1D self-management habits may inform clinicians with suitable interventions for improving glycemic outcomes.

Dispensing of Glucagon-Like Peptide-1 Receptor Agonists to Adolescents and Young Adults, 2020-2023.

This study uses data from US retail pharmacies to assess national GLP-1RA dispensing to adolescents and young adults from 2020-2023.

A Primary Care-Based Weight Navigation Program.

Importance: Evidence-based weight management treatments (WMTs) are underused; strategies are needed to increase WMT use and patients' weight loss. Objective: To evaluate the association of a primary care-based weight navigation program (WNP) with WMT use and weight loss. Design, Setting, and Participants: This cohort study comprised a retrospective evaluation of a quality improvement program conducted from October 1, 2020, to September 30, 2021. Data analysis was performed from August 2, 2022, to March 7, 2024. Adults with obesity and 1 or more weight-related condition from intervention and control sites in a large academic health system in the Midwestern US were propensity matched on sociodemographic and clinical factors. Exposure: WNP, in which American Board of Obesity Medicine-certified primary care physicians offered weight-focused visits and guided patients' selection of preference-sensitive WMTs. Main Outcomes and Measures: Primary outcomes were feasibility measures, including rates of referral to and engagement in the WNP. Secondary outcomes were mean weight loss, percentage of patients achieving 5% or more and 10% or more weight loss, referral to WMTs, and number of antiobesity medication prescriptions at 12 months. Results: Of 264 patients, 181 (68.6%) were female and mean (SD) age was 49.5 (13.0) years; there were no significant differences in demographic characteristics between WNP patients (n = 132) and matched controls (n = 132). Of 1159 WNP-eligible patients, 219 (18.9%) were referred to the WNP and 132 (11.4%) completed a visit. In a difference-in-differences analysis, WNP patients lost 4.9 kg more than matched controls (95% CI, 2.11-7.76; P < .001), had 4.4% greater weight loss (95% CI, 2.2%-6.4%; P < .001), and were more likely to achieve 5% or more weight loss (odds ratio [OR], 2.90; 95% CI, 1.54-5.58); average marginal effects, 21.2%; 95% CI, 8.8%-33.6%) and 10% or more weight loss (OR, 7.19; 95% CI, 2.55-25.9; average marginal effects, 17.4%; 95% CI, 8.7%-26.2%). Patients in the WNP group were referred at higher rates to WMTs, including bariatric surgery (18.9% vs 9.1%; P = .02), a low-calorie meal replacement program (16.7% vs 3.8%; P < .001), and a Mediterranean-style diet and activity program (10.6% vs 1.5%; P = .002). There were no between-group differences in antiobesity medication prescribing. Conclusions and Relevance: The findings of this cohort study suggest that WNP is feasible and associated with greater WMT use and weight loss than matched controls. The WNP warrants evaluation in a large-scale trial.

Outcomes of atypical lobular hyperplasia managed by active surveillance or immediate surgery.

BACKGROUND: Atypical lobular hyperplasia (ALH) is typically diagnosed via needle core biopsy (NCB) and is commonly removed surgically in light of upgrade to malignancy rates of 1%-5%. As studies on radiographic outcomes of ALH managed by active surveillance (AS) are limited, we investigated the upgrade rates of surgically excised ALH as well as radiographic progression during AS. METHODS: In this retrospective study, 125 patients with 127 ALH lesions diagnosed via NCB at Weill Cornell Medicine from 2015 to 2021 were included. The upgrade rate to cancer was determined for patients who had surgical management ≤6 months after biopsy. Among patients with ALH managed by AS, we investigated radiographic progression on 6-month interval imaging. RESULTS: Of 127 ALH lesions, 75% (n = 95) were immediately excised and 25% (n = 32) were observed under AS. The upgrade rate of immediately excised ALH was 2.1% (n = 2; invasive ductal carcinoma [IDC], T1N0 and IDC, and T1Nx). In the AS cohort, no ALH lesions progressed radiographically during the follow-up period of 22.5 months (median), with all remaining stable (50%, n = 16), resolving (47%, n = 15), or decreasing in size (3%, n = 1). CONCLUSIONS: In this study, NCB-diagnosed ALH had a low upgrade to malignancy rate (2.1%), and no ALH lesions managed by AS progressed radiographically during the follow-up period of 22.5 months. These results support AS as the favorable option for patients with pure ALH on biopsy, with surgical excision for lesions that progress on surveillance.

Screening for diabetes distress and depression in routine clinical care for youth with type 1 diabetes.

OBJECTIVE: The purpose of this study is to examine diabetes distress as a potential mediator of the relationship between depression symptoms and diabetes outcomes, including hemoglobin A1c (hemoglobin A1c [HbA1c]) and diabetes management behaviors in a clinical sample of adolescents and young adults. METHODS: In a pediatric diabetes clinic, 716 youth (ages 12-21 years) completed measures of diabetes distress (Problem Areas in Diabetes-Teen [PAID-T]), a single-item of diabetes distress, and depression (Patient Health Questionnaire [PHQ-9]) as part of standard care. Electronic health records were extracted for the "Six Habits" and glycemic management (HbA1c). RESULTS: Overall, 3.6% (n = 26) of adolescents had clinically elevated diabetes distress and depression symptoms, 5.0% had diabetes distress alone, 8.7% had depression symptoms alone, and 82.7% had neither clinical elevation of diabetes distress nor depression symptoms. Results of mediation analysis demonstrated diabetes distress (both full and single-item measures) fully mediated the relationship between depression symptoms and HbA1c (p < .001). Also, mediation analysis results showcase incomplete mediation of the effect of the Six Habits score on HbA1c appears by PAID-T Diabetes Distress. CONCLUSIONS: In a clinical sample of youth with type 1 diabetes, both depressive symptoms and diabetes distress are associated with HbA1c. Furthermore, diabetes distress fully mediates the relationship between depressive symptoms and HbA1c. As part of standard clinical care, the single-item screener for diabetes distress captured similar results as the full-scaled PAID-T. With limited clinical resources, providers may consider focusing assessment and interventions on the psychological factor of diabetes distress within the diabetes clinic to maximize the impact on glycemic control and consider the use of single-item screening to identify distress.

Utilizing the Glucose and Insulin Response Shape of an Oral Glucose Tolerance Test to Predict Dysglycemia in Children with Overweight and Obesity, Ages 8-18 Years.

Common dysglycemia measurements including fasting plasma glucose (FPG), oral glucose tolerance test (OGTT)-derived 2 h plasma glucose, and hemoglobin A1c (HbA1c) have limitations for children. Dynamic OGTT glucose and insulin responses may better reflect underlying physiology. This analysis assessed glucose and insulin curve shapes utilizing classifications-biphasic, monophasic, or monotonically increasing-and functional principal components (FPCs) to predict future dysglycemia. The prospective cohort included 671 participants with no previous diabetes diagnosis (BMI percentile ≥ 85th, 8-18 years old); 193 returned for follow-up (median 14.5 months). Blood was collected every 30 min during the 2 h OGTT. Functional data analysis was performed on curves summarizing glucose and insulin responses. FPCs described variation in curve height (FPC1), time of peak (FPC2), and oscillation (FPC3). At baseline, both glucose and insulin FPC1 were significantly correlated with BMI percentile (Spearman correlation r = 0.22 and 0.48), triglycerides (r = 0.30 and 0.39), and HbA1c (r = 0.25 and 0.17). In longitudinal logistic regression analyses, glucose and insulin FPCs predicted future dysglycemia (AUC = 0.80) better than shape classifications (AUC = 0.69), HbA1c (AUC = 0.72), or FPG (AUC = 0.50). Further research should evaluate the utility of FPCs to predict metabolic diseases.

Overview of Rheumatoid Arthritis-Associated Interstitial Lung Disease and Its Treatment.

Interstitial lung disease (ILD) is a common pulmonary complication of rheumatoid arthritis (RA), causing significant morbidity and mortality. Optimal treatment for RA-ILD is not yet well defined. Reliable prognostic indicators are largely byproducts of prior ILD progression, including low or decreasing forced vital capacity and extensive or worsening fibrosis on imaging. In the absence of validated tools to predict treatment response, decisions about whether to initiate or augment treatment are instead based on clinical judgment. In general, treatment should be initiated in patients who are symptomatic, progressing, or at high risk of poor outcomes. Retrospective data suggest that mycophenolate mofetil, azathioprine, and rituximab are likely effective therapies for RA-ILD. Abatacept is also emerging as a potential first-line treatment option for patients with RA-ILD. Further, recent data demonstrate that immunosuppression may be beneficial even in patients with a usual interstitial pneumonia (UIP) pattern on imaging, suggesting that immunosuppression should be considered irrespective of imaging pattern. Recent randomized controlled trials have shown that antifibrotic medications, such as nintedanib and likely pirfenidone, slow forced vital capacity decline in RA-ILD. Consideration can be given to antifibrotic initiation in patients progressing despite immunosuppression, particularly in patients with a UIP pattern. Future research directions include developing tools to predict which patients will remain stable from patients who will progress, discriminating patients who will respond to treatment from nonresponders, and developing algorithms for starting immunosuppression, antifibrotics, or both as first-line therapies.

Association Between Psychosocial Acuity and Glycemic Control in a Pediatric Type 1 Diabetes Clinic.

PURPOSE: The purpose of this study was to describe the frequency of psychosocial risk and its associations with glycemic levels in youth with type 1 diabetes (T1D) seen by social work staff during regular clinical care. METHODS: A retrospective longitudinal analysis of observational clinical data was conducted. Individuals (1-26 years) with known T1D who were seen at a pediatric diabetes clinic in a US academic medical center between 2014 and 2021 were included. Variables included psychosocial acuity, A1C, and demographic characteristics. Chi-square tests, Wilcoxon rank sum tests, and mixed linear regressions were used to examine associations between demographic variables, psychosocial acuity, and A1C. RESULTS: Of 966 patients, 513 (53.1%) were male, 76 (7.9%) were non-Hispanic Black, and 804 (83.2%) were non-Hispanic White. There was a mean of 6.9 annual social work encounters per patient, with 3 psychosocial domains measured at each visit. Results showed that as psychosocial acuity level increased, glycemic control decreased. There were significant differences in A1C according to race/ethnicity, insurance, age, and psychosocial acuity. CONCLUSIONS: In a real-world clinical population, psychosocial acuity was associated with glycemic control. Presenting for psychosocial issues in their diabetes clinic was associated with reduced glycemic control among youth with T1D. There is an opportunity to connect pediatric patients with appropriate mental health services and psychosocial supports.

Cutaneous Hydrophilic Polymer Embolism: An Important and Overlooked Clinical Entity.

ABSTRACT: Hydrophilic polymer embolism from vascular medical devices is an underrecognized clinical entity that can cause deleterious end-organ ischemia and culminate in mortality. This is concerning as we are in the era where minimally invasive procedures are commonplace. Diagnosis is often made retrospectively after obtaining histopathological tissue samples showing endoluminal, cerebriform, amorphous, anucleate, basophilic, nonrefractile, nonpolarizable foreign body material. We detail 2 more cases of cutaneous hydrophilic polymer embolism to underscore its salient clinicopathological features and increase awareness of this important iatrogenic entity.

Neutrophil extracellular traps linked to idiopathic pulmonary fibrosis severity and survival.

Background: Idiopathic pulmonary fibrosis (IPF) leads to progressive loss of lung function and mortality. Understanding mechanisms and markers of lung injury in IPF is paramount to improving outcomes for these patients. Despite the lack of systemic involvement in IPF, many analyses focus on identifying circulating prognostic markers. Using a proteomic discovery method followed by ELISA validation in multiple IPF lung compartments and cohorts we explored novel markers of IPF survival. Methods: In our discovery analysis, agnostic label-free quantitative proteomics differentiated lung tissue protein expression based on survival trajectory (n=10). Following selection of the candidate pathway (neutrophil extracellular trap (NET) formation), we subsequently validated the presence of NETs in the IPF lung microenvironment using fully quantitative assays of known NET remnants in separate IPF cohorts (n=156 and n=52) with bronchoalveolar lavage fluid. We then assessed the correlation of these markers with baseline pulmonary function and survival. Results: Discovery lung tissue proteomics identified NET formation as significantly associated with poor IPF survival. Using fully quantitative confirmatory tests for reproducibility we confirmed the presence of NET markers in IPF BALF and found significant correlations with worse pulmonary function in both cohorts (p<0.03 and p = 0.04 respectively). In the survival cohort, higher levels of NET markers predicted worse survival after adjusting for gender, age, and baseline physiologic severity (hazard ratio range: 1.79-2.19). Conclusions: NET markers were associated with disease severity and worse survival in IPF. These findings suggest NET formation contributes to lung injury and decreased survival in IPF and may represent a potential therapeutic target.

The Alopecia Areata Severity and Morbidity Index (ASAMI) Study: Results From a Global Expert Consensus Exercise on Determinants of Alopecia Areata Severity.

Importance: Current measures of alopecia areata (AA) severity, such as the Severity of Alopecia Tool score, do not adequately capture overall disease impact. Objective: To explore factors associated with AA severity beyond scalp hair loss, and to support the development of the Alopecia Areata Severity and Morbidity Index (ASAMI). Evidence Review: A total of 74 hair and scalp disorder specialists from multiple continents were invited to participate in an eDelphi project consisting of 3 survey rounds. The first 2 sessions took place via a text-based web application following the Delphi study design. The final round took place virtually among participants via video conferencing software on April 30, 2022. Findings: Of all invited experts, 64 completed the first survey round (global representation: Africa [4.7%], Asia [9.4%], Australia [14.1%], Europe [43.8%], North America [23.4%], and South America [4.7%]; health care setting: public [20.3%], private [28.1%], and both [51.6%]). A total of 58 specialists completed the second round, and 42 participated in the final video conference meeting. Overall, consensus was achieved in 96 of 107 questions. Several factors, independent of the Severity of Alopecia Tool score, were identified as potentially worsening AA severity outcomes. These factors included a disease duration of 12 months or more, 3 or more relapses, inadequate response to topical or systemic treatments, rapid disease progression, difficulty in cosmetically concealing hair loss, facial hair involvement (eyebrows, eyelashes, and/or beard), nail involvement, impaired quality of life, and a history of anxiety, depression, or suicidal ideation due to or exacerbated by AA. Consensus was reached that the Alopecia Areata Investigator Global Assessment scale adequately classified the severity of scalp hair loss. Conclusions and Relevance: This eDelphi survey study, with consensus among global experts, identified various determinants of AA severity, encompassing not only scalp hair loss but also other outcomes. These findings are expected to facilitate the development of a multicomponent severity tool that endeavors to competently measure disease impact. The findings are also anticipated to aid in identifying candidates for current and emerging systemic treatments. Future research must incorporate the perspectives of patients and the public to assign weight to the domains recognized in this project as associated with AA severity.

Associations between food insecurity and diabetes risk factors in US adolescents in the National Health and Nutrition Examination Survey (NHANES) 2007-2016.

OBJECTIVE: To evaluate the associations between household food insecurity and diabetes risk factors among lower-income US adolescents. DESIGN: Cross-sectional analysis. Household food security status was measured using the 18-item Food Security Survey Module. Simple and multivariable linear and logistic regressions were used to assess the association between food security status and fasting plasma glucose (FPG), oral glucose tolerance test (OGTT), HbA1C and homoeostatic model assessment - insulin resistance (HOMA-IR). The analyses were adjusted for household and adolescent demographic and health characteristics. SETTING: USA. PARTICIPANTS: 3412 US adolescents aged 12-19 years with household incomes ≤300 % of the federal poverty line from the National Health and Nutrition Examination Survey cycles 2007-2016. RESULTS: The weighted prevalence of marginal food security was 15·4 % and of food insecurity was 32·9 %. After multivariate adjustment, adolescents with food insecurity had a 0·04 % higher HbA1C (95 % CI 0·00, 0·09, P-value = 0·04) than adolescents with food security. There was also a significant overall trend between severity of food insecurity and higher HbA1C (Ptrend = 0·045). There were no significant mean differences in adolescents' FPG, OGTT or HOMA-IR by household food security. CONCLUSIONS: Food insecurity was associated with slightly higher HbA1c in a 10-year sample of lower-income US adolescents aged 12-19 years; however, other associations with diabetes risk factors were not significant. Overall, this suggests slight evidence for an association between food insecurity and diabetes risk in US adolescents. Further investigation is warranted to examine this association over time.

A Prospective Study Assessing the Efficacy and Toxicity of Stereotactic Body Radiation Therapy for Oligometastatic Bone Metastases.

Purpose: Stereotactic body radiation therapy (SBRT) is a promising treatment for oligometastatic disease in bone because of its delivery of high dose to target tissue and minimal dose to surrounding tissue. The purpose of this study is to assess the efficacy and toxicity of this treatment in patients with previously unirradiated oligometastatic bony disease. Methods and Materials: In this prospective phase II trial, patients with oligometastatic bone disease, defined as ≤3 active sites of disease, were treated with SBRT at Brigham and Women's Hospital/Dana Farber Cancer Center and Beth Israel Deaconess Medical Center between December 2016 and May 2019. SBRT dose and fractionation regimen were not protocol mandated. Local progression-free survival, progression-free survival, prostatic specific antigen progression, and overall survival were reported. Treatment-related toxicity was also reported. Results: A total of 98 patients and 126 lesions arising from various tumor histologies were included in this study. The median age of patients enrolled was 72.8 years (80.6% male, 19.4% female). Median follow-up was 26.7 months. The most common histology was prostate cancer (68.4%, 67/98). The most common dose prescriptions were 27/30 Gy in 3 fractions (27.0%, 34/126), 30 Gy in 5 fractions (16.7%, 21/126), or 30/35 Gy in 5 fractions (16.7%, 21/126). Multiple doses per treatment regimen reflect dose painting employing the lower dose to the clinical target volume and higher dose to the gross tumor volume. Four patients (4.1%, 4/98) experienced local progression at 1 site for each patient (3.2%, 4/126). Among the entire cohort, 2-year local progression-free survival (including death without local progression) was 84.8%, 2-year progression-free survival (including deaths as well as local, distant, and prostatic specific antigen progression) was 47.5%, and 2-year overall survival was 87.3%. Twenty-six patients (26.5%, 26/98) developed treatment-related toxicities. Conclusions: Our study supports existing literature in showing that SBRT is effective and tolerable in patients with oligometastatic bone disease. Larger phase III trials are necessary and reasonable to determine long-term efficacy and toxicities.

Weight Loss Treatment and Longitudinal Weight Change Among Primary Care Patients With Obesity.

Importance: Among individuals with obesity, 5% or greater weight loss can improve health. Weight management treatments (WMT) include nutrition counseling, very low-calorie meal replacement (MR), antiobesity medications (AOM), and bariatric surgery; however, little is known about how these WMT are associated with weight change among individual patients and populations. Objective: To characterize weight status and WMT use among primary care patients and assess associations between WMT and weight trajectories. Design, Setting, and Participants: Retrospective, population-based cohort study of primary care patients from 1 academic health system in Michigan between October 2015 and March 2020 using cross-sectional analysis to compare obesity prevalence and WMT utilization. For patients with obesity and WMT exposure or matched controls, a multistate Markov model assessing associations between WMT and longitudinal weight status trajectories was used. Data were analyzed from October 2021 to October 2023. Exposures: Cross-sectional exposure was year: 2017 or 2019. Trajectory analysis exposures were WMT: nutrition counseling, MR, AOM, and bariatric surgery. Main Outcomes and Measures: Cross-sectional analysis compared mean body mass index (BMI), obesity prevalence, and, among patients with obesity, prospective WMT use. The trajectory analysis examined longitudinal weight status using thresholds of ±5% and 10% of baseline weight with primary outcomes being the 1-year probabilities of 5% or greater weight loss for each WMT. Results: Adult patients (146 959 participants) consisted of 83 636 female participants (56.9%); 8940 (6.1%) were Asian, 14 560 (9.9%) were Black, and 116 664 (79.4%) were White. Patients had a mean (SD) age of 49.6 (17.7) years and mean (SD) BMI of 29.2 (7.2). Among 138 682 patients, prevalence of obesity increased from 39.2% in 2017 to 40.7% in 2019; WMT use among patients with obesity increased from 5.3% to 7.1% (difference: 1.7%; 95% CI, 1.3%-2.2%). In a multistate model (10 180 patients; 33 549 patient-years), the 1-year probability of 5% or greater weight loss without WMT exposure was 15.6% (95% CI, 14.3%-16.5%) at reference covariates. In contrast, the probability of 5% or greater weight loss was more likely with year-long exposures to any WMT (nutrition counseling: 23.1%; 95% CI, 21.3%-25.1%; MR: 54.6%; 95% CI, 46.5%-61.2%; AOM: 27.8%; 95% CI, 25.0%-30.5%; bariatric surgery: 93.0%; 95% CI, 89.7%-95.0%). Conclusions and Relevance: In this cohort study of primary-care patients with obesity, all WMT increased the patient-level probability of achieving 5% or greater weight loss, but current rates of utilization are low and insufficient to reduce weight at the population level.

Demographic and Clinical Factors Associated With SARS-CoV-2 Spike 1 Antibody Response Among Vaccinated US Adults: the C4R Study.

This study investigates correlates of anti-S1 antibody response following COVID-19 vaccination in a U.S. population-based meta-cohort of adults participating in longstanding NIH-funded cohort studies. Anti-S1 antibodies were measured from dried blood spots collected between February 2021-August 2022 using Luminex-based microsphere immunoassays. Of 6245 participants, mean age was 73 years (range, 21-100), 58% were female, and 76% were non-Hispanic White. Nearly 52% of participants received the BNT162b2 vaccine and 48% received the mRNA-1273 vaccine. Lower anti-S1 antibody levels are associated with age of 65 years or older, male sex, higher body mass index, smoking, diabetes, COPD and receipt of BNT16b2 vaccine (vs mRNA-1273). Participants with a prior infection, particularly those with a history of hospitalized illness, have higher anti-S1 antibody levels. These results suggest that adults with certain socio-demographic and clinical characteristics may have less robust antibody responses to COVID-19 vaccination and could be prioritized for more frequent re-vaccination.

Multimodal Integrative Genomics and Pathology Analyses in Neoadjuvant Nivolumab Treatment for Intermediate and Locally Advanced Hepatocellular Carcinoma.

Introduction: Immunotherapy has resulted in pathologic responses in hepatocellular carcinoma (HCC), but the benefits and molecular mechanisms of neoadjuvant immune checkpoint blockade are largely unknown. Methods: In this study, we evaluated the efficacy and safety of preoperative nivolumab (anti-PD-1) in patients with intermediate and locally advanced HCC and determined the molecular markers for predicting treatment response. Results: Between July 2020 and November 2021, 20 treatment-naive HCC patients with intermediate and locally advanced tumors received preoperative nivolumab at 3 mg/kg for 3 cycles prior to surgical resection. Nineteen patients underwent surgical resection on trial. Seven (36.8%) of the 19 patients had major pathologic tumor necrosis (≥60%) in the post-nivolumab resection specimens, with 3 having almost complete (>90%) tumor necrosis. The tumor necrosis was hemorrhagic and often accompanied by increased or dense immune cell infiltrate at the border of the tumors. None of the patients developed major adverse reactions contradicting hepatectomy. RNA-sequencing analysis on both pre-nivolumab tumor biopsies and post-nivolumab resected specimens showed that, in cases with major pathologic necrosis, the proportion of CD8 T cells in the HCC tissues predominantly increased after treatment. Moreover, to investigate noninvasive biomarker for nivolumab response, we evaluated the copy number variation (CNV) using target-panel sequencing on plasma cell-free DNA of the patients and derived a CNV-based anti-PD-1 score. The score correlated with the extent of tumor necrosis and was validated in a Korean patient cohort with anti-PD-1 treatment. Conclusion: Neoadjuvant nivolumab demonstrated promising clinical activity in intermediate and locally advanced HCC patients. We also identified useful noninvasive biomarker predicting responsiveness.

Parenting attitudes and behaviors among parents involved with the child welfare system and affected by substance use disorders.

BACKGROUND: Co-occurring parental substance use and child maltreatment is a serious concern in the U.S child welfare system. OBJECTIVE: The aim of the study was to examine parenting attitudes and practices among parents who participated in Ohio START (Sobriety, Treatment, And Reducing Trauma), a statewide initiative that provides support to families affected by co-occurring parental substance use and child maltreatment. PARTICIPANTS AND SETTING: Study 1 involved quantitative data collected from 73 enrolled parents through pre-test and post-test telephone surveys. Study 2 (parent interviews) involved qualitative data collected through in-depth interviews with 34 enrolled parents. METHODS: The paired-sample t-test and the McNemar test were conducted in Study 1 and thematic analysis was conducted in Study 2. RESULTS: Quantitative analysis indicated significant improvements in parental expectations of children (t = -3.42, p = .001, Cohen's d = -0.40), parent-child family roles (t = -5.74, p < .001, Cohen's d = -0.67), and children's power and independence (t = -3.42, p = .001, Cohen's d = -0.40). Qualitative analysis revealed six themes related to changes in parenting after participation in Ohio START: (1) Being present for children, (2) Engaging in activities with children, (3) Enjoyment in providing care to children, (4) Maintaining employment for financial stability, (5) Better emotion regulation and stress management, and (6) a sense of pride. CONCLUSIONS: Our findings demonstrate positive changes in parenting attitudes and practices among parents who participated in Ohio START and provide further support for the potential merits of this model and its continued expansion throughout Ohio.