Nomogram model for predicting medication adherence in patients with various mental disorders based on the Dryad database

Objective
Treatment compliance among psychiatric patients is related to disease outcomes. How to assess patient compliance remains a concern. Here, we established a predictive model for medication compliance in patients with psychotic disorders to provide a reference for early intervention in treatment non-compliance behaviour.

Design
Clinical information for 451 patients with psychotic disorders was downloaded from the Dryad database. The Least Absolute Shrinkage and Selection Operator regression and logistic regression were used to establish the model. Bootstrap resampling (1000 iterations) was used for internal validation and a nomogram was drawn to predict medication compliance. The consistency index, Brier score, receiver operating characteristic curve and decision curve were used for model evaluation.

Setting
35 Italian Community Psychiatric Services.

Participants
451 patients prescribed with any long-acting intramuscular (LAI) antipsychotic were consecutively recruited, and assessed after 6 months and 12 months, from December 2015 to May 2017.

Results
432 patients with psychotic disorders were included for model construction; among these, the compliance rate was 61.3%. The Drug Attitude Inventory-10 (DAI-10) and Brief Psychiatric Rating Scale (BPRS) scores, multiple hospitalisations in 1 year and a history of long-acting injectables were found to be independent risk factors for treatment noncompliance (all p

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Novembre 2024

Targeting squalene epoxidase restores anti-PD-1 efficacy in metabolic dysfunction-associated steatohepatitis-induced hepatocellular carcinoma

Objective
Squalene epoxidase (SQLE) promotes metabolic dysfunction-associated steatohepatitis-associated hepatocellular carcinoma (MASH-HCC), but its role in modulating the tumour immune microenvironment in MASH-HCC remains unclear.

Design
We established hepatocyte-specific Sqle transgenic (tg) and knockout mice, which were subjected to a choline-deficient high-fat diet plus diethylnitrosamine to induce MASH-HCC. SQLE function was also determined in orthotopic and humanised mice. Immune landscape alterations of MASH-HCC mediated by SQLE were profiled by single-cell RNA sequencing and flow cytometry.

Results
Hepatocyte-specific Sqle tg mice exhibited a marked increase in MASH-HCC burden compared with wild-type littermates, together with decreased tumour-infiltrating functional IFN-+ and Granzyme B+ CD8+ T cells while enriching Arg-1+ myeloid-derived suppressor cells (MDSCs). Conversely, hepatocyte-specific Sqle knockout suppressed tumour growth with increased cytotoxic CD8+ T cells and reduced Arg-1+ MDSCs, inferring that SQLE promotes immunosuppression in MASH-HCC. Mechanistically, SQLE-driven cholesterol accumulation in tumour microenvironment underlies its effect on CD8+ T cells and MDSCs. SQLE and its metabolite, cholesterol, impaired CD8+ T cell activity by inducing mitochondrial dysfunction. Cholesterol depletion in vitro abolished the effect of SQLE-overexpressing MASH-HCC cell supernatant on CD8+ T cell suppression and MDSC activation, whereas cholesterol supplementation had contrasting functions on CD8+ T cells and MDSCs treated with SQLE-knockout supernatant. Targeting SQLE with genetic ablation or pharmacological inhibitor, terbinafine, rescued the efficacy of anti-PD-1 treatment in MASH-HCC models.

Conclusion
SQLE induces an impaired antitumour response in MASH-HCC via attenuating CD8+ T cell function and augmenting immunosuppressive MDSCs. SQLE is a promising target in boosting anti-PD-1 immunotherapy for MASH-HCC.

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Novembre 2024

Abstract 4131228: Where Adults with Advanced Heart Failure Die: Insights from the CDC-WONDER Database

Circulation, Volume 150, Issue Suppl_1, Page A4131228-A4131228, November 12, 2024. Background:Adults with heart failure (HF) are becoming more and more prevalent. The location of death and related disparities in these patients are poorly understood.Aim:The purpose of the study was to look at the locations of adult deaths from HF and identify any age, race, or ethnicity-related variations over a 25-year period.Methods:The Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research Database provided death certificate data and the National Center for Health Statistics provided individual-level mortality data for the trend-level analysis of adults aged (20-64 and 65+ years) conducted from 1999-2023. Hospital, home, hospice and nursing home/long-term care were the categories for the places of death.Results:Between 1999 and 2023, a total of 7,644,759 adult deaths from HF were recorded (87.9% White, 53.4% female). HF-related deaths decreased from 1999 (3.60% and 143.6 AAMR) to 2010 (3.47% and 123.1 AAMR). From 2010 onwards, a gradual rise is seen, with the rate of HF deaths reaching 5.18% and 168.1 AAMR in 2023. Notably, deaths at home increased from 18.41% (50,648 of 275,132) in 1999 to 33.47% (132,470 of 395,826) in 2023 and deaths in hospice/nursing homes increased from 30.95% (85,144 of 275,132) in 1999 to 34.71% (116,634 of 336,014) in 2017 and then sudden fall was observed until 2023 to 29.54% (116,931 of 395,826). Older adults (65+) were more likely to die in inpatient facilities. Gender, ethnicity, and urbanization influenced the place of death, with males, whites, and those residing in large metropolitan areas more likely to die in medical facilities.Conclusion:Prioritize end-of-life planning for HF patients with poor prognosis, regardless of age, to improve quality of life and death.

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Novembre 2024

Abstract 4144512: Impact of Nutritional Status on Transcatheter Edge-to-Edge Repair Outcomes in Mitral Regurgitation: Insights from a National Database Analysis

Circulation, Volume 150, Issue Suppl_1, Page A4144512-A4144512, November 12, 2024. Introduction:Transcatheter edge-to-edge repair of the mitral valve with the MitraClip has offered a less invasive percutaneous alternative to surgical repair in select candidates with mitral regurgitation. Various factors impact the outcomes of MitraClip. We investigated the impact of nutritional status on the outcomes of MitraClip.Methods:Utilizing the nationwide inpatient sample data for years from January 1, 2016, and December 31, 2021, patients who underwent MitraClip were identified. They were categorized based on obesity and protein energy malnutrition (PEM). Statistical significance was assigned at p

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Novembre 2024

Abstract 4144542: In-Hospital Outcomes of Open Mitral Valve Repair or Replacement versus Percutaneous Mitral Valve Repair or Replacement in patients with Prior Mediastinal Radiation: Insight from The National Inpatient Database (2015-2020)

Circulation, Volume 150, Issue Suppl_1, Page A4144542-A4144542, November 12, 2024. Background:Radiation associated heart disease has a wide spectrum of manifestations including pericardial disease, coronary artery disease, and valvular heart disease. Mitral valve regurgitation is the second most common valvular dysfunction in patients with prior mediastinal radiation.Research Question:What are the outcomes of percutaneous or transcatheter mitral valve replacement/repair (T-MVR) versus surgical mitral valve replacement/repair (S-MVR) in patients with prior mediastinal radiation.Methods:The National Inpatient Sample (NIS) was analyzed from 2015-2020 to identify patients with mediastinal tumors and prior exposure to radiation therapy undergoing mitral valve repair/replacement. We subclassified the data into hospitalizations for S-MVR and T-MVR. Baseline characteristics were compared between the two groups and multivariate logistic regression was used to analyze hospitalization outcomes.Results:A total of 1725 patients with prior mediastinal radiation were hospitalized for MVR; 1110 (64.3%) patients underwent S-MVR and 615 (35.6%) patients underwent T-MVR. On a multivariable analysis, the odds of MACCE [aOR: 2.21; 95 % CI: (1.87-4.01); p

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Novembre 2024

Abstract 4143265: Unveiling Gender Disparities in Chagas Disease patients with cardiac involvement: Insights from the NIS Database

Circulation, Volume 150, Issue Suppl_1, Page A4143265-A4143265, November 12, 2024. Background:Chagas disease (CD) is caused by a protozoan named Trypanosoma cruzi, in its chronic stage it may present with organ involvement, including the heart. Previous studies suggest that being a male is associated with increased mortality in CD. Understanding gender disparities associated with this condition is imperative for better patient management.Hypothesis:Gender has an impact on the outcome of CD with cardiac involvement.Aim:To investigate if gender has an impact on the clinical outcomes of CD with cardiac involvement.Methods:We examined the National Inpatient Sample data from 2016-2020, and conducted a retrospective descriptive study. We included all patients 18 years and older, male and female, diagnosed with CD with cardiac involvement. We excluded patients who were younger than 18 years of age. Baseline socio-demographic characteristics, comorbidities, and outcomes of the two groups were described. Hypothesis testing for categorical variables was performed using Chi-Square. Continuous variables were tested with a Student t-test. Statistical significance was defined as a two-tailed p-value of

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Novembre 2024

Abstract 4144555: Atrial Fibrillation Catheter Ablation among Patients with Mediastinal Radiation; Insight from The National Inpatient Database (2015-2020)

Circulation, Volume 150, Issue Suppl_1, Page A4144555-A4144555, November 12, 2024. Introduction/Background:Radiation therapy (RT) is one of the most common treatment modalities for mediastinal cancers. RT has multiple adverse cardiovascular effects and it has been identified as an independent risk factor for atrial fibrillation (AF). The efficacy of catheter ablation in AF is well established, however there is limited data on procedural safety and outcomes in patients with mediastinal cancers and history of radiationMethods:The National Inpatient Sample (NIS) was analyzed from 2015-2020 to identify admissions for AF catheter ablation among patients with previous history of mediastinal radiation exposure using the 10-PCS (International Classification of Diseases, procedure coding system) codes. Baseline characteristics were compared between the two groups and multivariate logistic regression was used to analyze hospitalization outcomes.Results:We identified 257,240 admissions for AF catheter ablation of which 1720 patients (0.67%) had a history of mediastinal radiation exposure. In the adjusted analysis, the odds of in-hospital mortality (aOR 0.639, 95% CI 0.34-1.20, p 0.1637), major complications (aOR 0.876, 95% CI 0.73-1.05, p 0.1443), any gastrointestinal or hematological complication (aOR 0.853, 95% CI 0.63-1.15, p 0.3017), renal complications (aOR 1.017, 95% CI 0.88-1.18, p 0.0509) were similar in both cohorts. The odds of any cardiovascular complication (aOR 0.825, 95% CI 0.70-0.97, p 0.0208) was lower and odds of any pulmonary complication (aOR 1.433, 95% CI 1.27-1.62, p

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Novembre 2024

Abstract 4136984: Low Occurence of Fetal Extranodal Findings and AV Interval Prolongation in Prospectively Followed High Titer Anti-Ro Pregnancies

Circulation, Volume 150, Issue Suppl_1, Page A4136984-A4136984, November 12, 2024. .Background:Third-degree atrioventricular block (AVB) is the most common manifestation of Anti-Ro antibody associated fetal cardiac disease. Extranodal findings of isolated cardiac echogenicity, valvulitis with insufficiency and AV interval prolongation have been reported but not described in large prospective series.Aims:To report the occurrence and outcomes of extranodal findings in subjects followed prospectively since 2020 in STOP BLOQ (Surveillance and Treatment to Prevent Fetal AV block Likely to Occur Quickly) and the Registry for Neonatal Lupus (RNL).Methods:We reviewed fetal echo reports from pregnant STOP BLOQ and RNL Anti-Ro antibody subjects. Pregnancies with high ( >1000 EU for anti-Ro52 or 60) antibody titers measured in a core research lab underwent surveillance with home fetal heart rate monitoring (FHRM) 3x/day and weekly or bi-weekly fetal echos from 17- 26 gestational weeks. Low titer subjects underwent echo or no surveillance based on local site protocol. We evaluated cardiac function, effusions, cardiac echogenicity and its location, any tricuspid (TV) or mitral (MV) insufficiency trivial or >trivial) and AV conduction times (170 ms)Results:Echo reports were available in 622 prospectively followed pregnancies (376 high (40/376 with a previously affected child) and 246 low-titer pregnancies. All had subjectively normal ventricular function and none had effusions. Seven fetuses, 2 low and 5 high titer at 19 (range 16.7-21.7) weeks demonstrated cardiac echogenicity (n=6), AV or semilunar valve insufficiency (n=2) or AV interval 150-170 ms (n=2) (Table). Subjects 1 and 2, both high titer and treated with prophylactic Plaquenil (400 mg/d before 10 gestational weeks), had prior fetal AVB. Subject #1 had normal AV conduction but MV and TV echogenicity and moderate insufficiency of both valves which resolved in days after IVIG and dexamethasone (dex) treatment, but 3° AVB developed at 19 weeks after dex wean. Subjects 2-7 received no treatment and extranodal findings did not progress to cardiac dysfunction or AVB. During the same time period, 10 high titer subjects developed 2° or 3° AVB.Conclusion:Anti-Ro associated extranodal findings are rare, occurring in 1% of pregnancies overall and in 5% of pregnancies with a previously affected child. Unlike AVB, extranodal findings can occur in low titer pregnancies. The role of treatment for isolated extranodal findings in the absence of cardiac dysfunction is unclear.

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Novembre 2024

Abstract 4139135: Trends in Stroke Related Mortality in Atrial Fibrillation Patients Aged 25 and Older in the United States: Insights from the CDC WONDER Database

Circulation, Volume 150, Issue Suppl_1, Page A4139135-A4139135, November 12, 2024. Background:Stroke associated with atrial fibrillation (AF) is a significant cause of mortality. This CDC analysis delves into mortality trends due to stroke in AF patients aged ≥ 25 years, from 1999 to 2020. By analyzing extensive datasets we scrutinized how factors such as gender, race, region of residence, and level of urbanization intersect with mortality rates.Methods:Death data from 1999 to 2020 was analyzed using the Centers for Disease Control and Prevention database, employing ICD codes I48 for AF and I64 for stroke. Age-adjusted mortality rate (AAMR) per 100,000 people with 95% confidence intervals was calculated for the total population, stratified by gender, race, urban/rural status, and census region. The Joinpoint regression software was used to calculate annual percentage change (APC) trend for each stratification.Results:In the U.S. between 1999 and 2020, total of 331,106 deaths occurred among adults due to AF associated with stroke. Deaths occurred predominantly in medical facilities (43.2%). The overall AAMR for AF associated stroke decreased from 26.8 per 100,000 in 1999 to 18.4 in 2020, with an AAPC of -2.05 (p value < 0.000001). Additionally, AAMR declined significantly from 1999 to 2018 (APC: -2.65, p value = 0.012398), followed by an increase from 2018 to 2020 (APC: 3.90, p value = 0.220356). Women had slightly higher AAMRs compared to men (men: 6.6; women: 7.1). The AAMR for women reduced substantially from 1999 to 2020 than for men. AAMRs varied among racial/ethnic groups, with White patients having the highest AAMR (7.4), followed by Blacks (5.4), American Indian or Alaska Natives (4.6), Asian or Pacific Islanders (4.5), and Hispanic population (4.1). AAMRs decreased for all races except for Black population. Geographically, AAMRs ranged from 4.3 in Nevada to 11.9 in Vermont, with the Western region showing the highest mortality (AAMR: 7.9). Nonmetropolitan areas had slightly higher AAMRs than metropolitan areas, with both experiencing a decrease over the study period.Conclusion:This analysis depicts significant disparities in mortality rates attributed to stroke associated with AF and underscores the need for larger population-based studies to further understand the primary factors influencing the observed geographical, racial, and gender differences. Targeted interventions and equitable healthcare access are crucial to mitigate these disparities and improve outcomes for this population.

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Novembre 2024

Abstract 4143130: Regression of Inflammation in Chronic Chagas Disease Using Specific Anti-Parasitic Therapy Is Associated With an Activated Immune Profile Before Therapy and Increased Levels of IL-17 After Therapy

Circulation, Volume 150, Issue Suppl_1, Page A4143130-A4143130, November 12, 2024. Background:Chagas disease (CD), caused by Trypanosoma cruzi, leads to chronic Chagas cardiomyopathy, one of the deadliest and most debilitating cardiopathies. Benznidazole (BZN) is the medication of choice in Brazil, effective during the acute phase, but its efficacy during the chronic phase is unclear.Aims:To determine if BZN treatment reduces cardiac inflammation and fibrosis via magnetic resonance imaging (MRI) and its association with the circulating immune profile of CD patients.Methods:We collected cardiac images and plasma from a cohort of CD patients before and 6 months after BZN treatment. We performed: 1- MRI of left and right ventricle function and volumes, T1 (MAPA T1), T2 mapping (MAPA T2), and extracellular volume (ECV); 2- analysis of soluble factors including cytokines, chemokines, and growth factors using the Bio-48 Plex Human Cytokine Screening Panel kit. Changes in the variables MAPAT1, MAPAT2, and ECV were used to classify the improvement of CD patients undergoing BZN therapy. Patients with the greatest reductions in these variables post-therapy, compared to pre-therapy, were considered to have greater clinical improvement. Thus, patients were divided into two groups: greater clinical improvement (GCI; n=15) and smaller clinical improvement (SCI; n=15) (figure 1). Data were analyzed using GraphPad Prism 8 software with statistical significance set at p

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Novembre 2024