Low Risk Profile Research Articles

Comparative analysis of stress echocardiography practice and complications in older compared to younger patients in the UK EVAREST Study: A large-scale, prospective, multicenter, observational study

Abstract Background/Introduction EVAREST is a large-scale prospective, multicenter, observational study evaluating the use and accuracy of stress echocardiography (SE) in patients recruited from 31 NHS hospitals. Purpose Sub-study analysis to assess whether SE practice and outcome varies with age of patients. Methods Patients were recruited sequentially on attendance at the SE clinic between March 2015 and March 2020. Differences in SE characteristics and outcomes were compared between two age groups separated by the median age of the study population into Younger and Older patients. Results We studied 7846 pts with a median age for all pts of 66 yrs. The mean age in the Younger Group was 55 (range 20-65) years and in the Older Group was 74 (range 66-94) years. An abnormal SE response occurred more commonly in the Older Group (19% vs 13%, p<0.001). Key demographic and risk factors that differed between groups were a higher proportion of females in the Older Group (2185 male, 1769 female) compared to the Younger group (2255 male, 1626 female), p=0.011, higher mean BMI in the Younger Group (29.61±5.8 vs 28.1±5.2 kg/m², p<0.001) and lower resting pulse pressure in the Older Group at 56.3±15.9 (95%CI 55.8-56.8) compared to 65.9±16.6 (95%CI 65.3-66.4), p<0.001. Exercise test was performed more commonly in the Younger Group compared to the Older Group (39% vs 23%, p<0.001). For those undergoing dobutamine stress, atropine was used more commonly in the Younger Group (36% vs 34%, p<0.001). However, dobutamine dosing was similar between groups, with the highest dose (40 µg/kg/min) achieved in 13% of the Younger Group and 14% of the Older Group, p=0.05. Ultrasound contrast was used less frequently in the Older Group (73% vs 70%, p=0.03) compared to the Younger group, (p<0.001). Complication rates were similar between groups with the Older Group having a lower peak SBP (150.7±29.3 (95%CI 149.7-151.7) vs 154.9±30.3 mm Hg (95%CI 153.8-155.9), p<0.001) and similar rates of an exaggerated BP response (defined as a peak SBP ≥220 mm Hg) evident in both groups (20% of the Younger Group compared to 21% of the Older Group, p=0.55). A low BP response (defined as peak systolic blood pressure <120 mm Hg) occurred in 8% of the Younger Group and 11% of the Older Group (p=0.001), while a severe hypotensive response (peak SBP<82 mm Hg) was very rare and occurred 0.31% of the Younger Group and 0.56% of the Older Group (p=0.09). Conclusions Stress echocardiography is being performed in patients with a wide age range from 20 to 94 years of age within the UK. Older patients undergoing stress echocardiography are more likely to be female and have a relatively lower cardiovascular risk profile. Delivery of stress echocardiography differs significantly with age, with lower contrast use and more frequent use of dobutamine. However, there is no evidence of higher rates of complications in older patients that might limit use of stress echocardiography in older populations.

Community characteristics and substance-free activity and service access predict membership in alcohol use disorder risk profiles.

Community characteristics (e.g., alcohol access, poverty) are associated with alcohol use disorder (AUD) at the population level, and person-level AUD severity indicators (e.g., drinking practices, problems) predict heterogeneity in individual AUD risk profiles and recovery outcomes. Guided by behavioral economic theory, this study investigated whether residing in relatively enriched communities with substance-free reward sources, greater health/behavioral health care access, lower alcohol access, and less poverty were associated with less risky individual AUD risk profiles. This secondary analysis combined an integrated data set of individual natural recovery attempts with zip code community characteristics obtained from public data sources. Four AUD latent risk profiles, previously derived from individual problem severity indicators that predicted 1-year recovery outcomes, were predicted by zip code-level substance-free reward sources, alcohol access, health/behavioral health care access, and poverty surrounding AUD recovery (N = 528). As hypothesized, multinomial regression analyses indicated that greater community access to substance-free reward sources (educational services, religious organizations, sports/fitness/recreation programs, fresh food) and lower community poverty were associated with lower AUD risk profiles compared with higher AUD risk profiles. This pattern was most pronounced in comparisons between a global lower risk profile and a higher risk profile characterized by high alcohol dependence and alcohol-related psychosocial problems. Alcohol access and health care access did not differentiate profile membership. Results suggest that community characteristics contribute to heterogeneity in individual drinking problem development, and community enrichment may offer a promising approach to AUD prevention and promotion of positive recovery outcomes. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Design, synthesis, and structural investigations of novel (S)-amide derivatives as promising ACE inhibitors

Novel derivatives of potential angiotensin converting enzyme (ACE-I) inhibitors (compounds 5a-e) were synthesized by reacting homophthalic anhydride with methyl esters of L-amino acids (L-isoleucine, L-phenylalanine, L-tyrosine, L-methionine, and L-serine). This reaction resulted in yields of 85% for compound 5a, 83% for compound 5b, 84% for compound 5c, 80% for compound 5d, and 85% for compound 5e. All the synthesized compounds were characterized by 1D and 2D NMR methods. In silico ADME properties of compounds 5a-e conform to Lipinski’s drug rules. The in silico toxicological determination of the synthesized compounds suggest that compound 5a exhibits significant potential for adverse effects, such as causing hormonal imbalances. In comparison, the remaining compounds 5b-c demonstrate a lower risk profile. In silico biological activities of compounds 5a-e in the active site of ACE-I were determined by docking, which were then compared to the FDA approved antihypertensive drugs enalalapril and lisinopril. Docking studies revealed that compound 5b (ΔGcomp = −8.851 kcal/mol) possesses the greatest binding affinity in the Zn2+ binding site of ACE-I compared to those of lisinoprilat (ΔGcomp = −8.066 kcal/mol) and enalapril (ΔGcomp = −7.187 kcal/mol), strongly suggesting a great potential to be a lead candidate for novel antihypertensive drug development.

Successful Management of Early Postoperative Small Bowel Obstruction Using Steroid: a Case Report

Background: Early Postoperative Small Bowel Obstruction (EPSBO) is a primary factor contributing to death and morbidity after pelvic and abdominal surgery. Although it is frequently regarded as a surgical emergency, the most recent research indicates that non-operative management is always preferable unless there are complications.Case: A 53-year-old woman came with symptoms of small bowel obstruction and a history of hysterectomy three weeks earlier. The patient refused surgical intervention, so a conservative approach was taken. She was given methylprednisolone 500 mg/day in two doses daily for three consecutive days, in addition to nasogastric tube insertion and symptomatic therapy. After three days of follow-up, the patient showed symptoms improvement, and the abdominal X-Ray and CT Scan showed no abnormal findings.Discussion: The majority of Early Postoperative Small Bowel Obstruction (EPSBO) cases, according to the most recent research, may be managed without surgery. Additionally, due to their anti-inflammatory properties, some medications, like corticosteroids, have been found to be beneficial and effective for EPSBO. This is because they may help resolve the obstruction and lessen the edema and fibrin deposition associated with EPSBO following abdominal surgery.Conclusion: Conservative therapy with steroids appears promising due to its lower risk profile and greater patient comfort. However, the exact mechanism and its efficacy in treating EPSBO have yet to be fully concluded, so further research is still needed.Keywords: Corticosteroids, non-operative intervention, small bowel obstruction

Subtypes of mental health difficulties and levels of resilience in Spanish adolescents

Emotional and behavioral difficulties are common among adolescents, and the role of psychological resilience in mitigating their impact needs further investigation. This study aimed to examine profiles of mental health difficulties combined with resilience levels in 1,425 Spanish adolescents at-risk. The participants were 1425 adolescents (59.9% girls). Mental health profiles were determined using the Strengths and Difficulties Questionnaire and the Connor-Davidson Resilience Scale (CD-RISC-10) via Latent Profile Analysis and compared for sociodemographic variables and mental health associated variables. Five profiles emerged: Subclinical (16%), Externalizing Problems (19%), Internalizing Problems (22%), Low Risk (32.5%), and Well-Adjusted (10%). Females had higher risk. Well-Adjusted and Low-Risk profiles differed significantly in all variables. Well-Adjusted profile had the lowest distress and psychosocial difficulties, and the highest quality of life; while the Subclinical profile showed the opposite pattern. Identifying and validating risk groups for emotional and behavioral difficulties, considering resilience, enables interventions promoting emotional well-being and preventing mental health challenges.

ESG Factors, Returns and Volatility: A Tale From Brazilian Market Data

Objective: This study aims to investigate the relationship between Environmental, Social, and Governance (ESG) factors and financial market performance in Brazil. The objective is to understand the impact of ESG scores on firms’ returns and risk profiles, thereby informing investment strategies and policy decisions. Theoretical Framework: The research is grounded in theories of sustainable finance and risk management, with emphasis on how ESG integration can influence financial outcomes. Notable frameworks include Cochrane’s “factor zoo” and the role of investor attention and analyst coverage in mitigating crash risk. Method: Data for the study was obtained from the Refinitiv Eikon database, covering firm-level ESG characteristics and market data, such as returns and volatility. Ordinary least squares (OLS) regression was used to analyze cross-sectional data, exploring the relationship between ESG scores and financial performance metrics across various sectors. Results and Discussion: The results show no significant relationship between returns and ESG scores. However, a negative and statistically significant relationship was found between ESG scores and volatility, suggesting that firms with higher ESG ratings tend to exhibit lower risk. ESG Controversies Score (ECSC) displayed negative correlations with other ESG metrics, indicating that companies involved in controversies tend to have lower overall ESG scores. Research Implications: These findings suggest that while ESG scores may not directly influence returns, they play a role in risk management, highlighting the importance of ESG factors for investors seeking lower-risk profiles. Originality/Value: This research contributes to the understanding of ESG’s role in the Brazilian market, offering empirical evidence on how ESG integration can shape financial performance and risk, providing a nuanced view of ESG’s impact on investment decisions.

Comparison of 6 cycles of isatuximab with lenalidomide, bortezomib and dexamethasone (I-VRd) versus 3 cycles of I-VRd followed by one cycle of high-dose melphalan in newly diagnosed low-risk multiple myeloma. Protocol for a multicenter, prospective, randomized, phase II clinical trial (ELIAS-Trial)

Newly diagnosed multiple myeloma patients who are eligible for transplant usually receive several induction cycles of therapy, followed by one or two cycles of high-dose melphalan and autologous stem cell transfusion. In myeloma patients, high-dose melphalan improves overall survival and progression-free survival. However, melphalan exposure increases the risk of secondary malignancies and may lead to the transformation of residual myeloma cells into more aggressive clones, which may accelerate relapse. It remains to be determined whether low-risk patients also derive additional benefit from high-dose melphalan therapy compared with less toxic regimens. Here we publish the study protocol of a multicenter, interventional, controlled, randomized, prospective and open-label phase II trial to investigate whether patients with a low-risk profile (R-ISS stage I, characterized by a low tumor burden and the absence of negative cytogenetic findings or elevated LDH levels) and a standard-risk gene expression profile (using the SKY92 GEP assay) can be sufficiently treated with intensified consolidation regimens without prior high-dose melphalan chemotherapy. The primary objective is to assess whether three cycles of isatuximab, bortezomib, lenalidomide and dexamethasone (I-VRd) followed by stem cell apheresis and three additional cycles of I-VRd will result in a non-inferior rate of complete remission (CR) combined with MRD-negativity at week 40 after the start of induction therapy compared to three cycles of I-VRd followed by standard of care treatment (such as stem cell apheresis, high-dose melphalan, and autologous stem cell transplantation). We hypothesize that this approach could reduce toxicity, cost of treatment and the likelihood of the development of a more malignant plasma cell clone, while improving overall survival (OS) and progression-free survival (PFS) in newly diagnosed low risk myeloma patients.EU Trial Number2022-500453-16-00, https://clinicaltrials.gov/study/NCT05665140, identifier NCT05665140. Registration Date: 21.07.2022.

Alexithymia and estimated 10-year cardiovascular disease risk in healthy adults: a community-based cross-sectional study.

This cohort study aimed to explore whether and to what extent alexithymia would be associated with cardiovascular disease (CVD) risk over an estimated 10-year period, over and above established clinical cofactors (i.e., depressive symptoms, quality of life, sociodemographic, anthropometric, lifestyle, and biological data), in a low-risk population of blood donors. A sample of 1,021 adult Italian blood donors (age 46.9 ± 8.39; 61.2% men) was consecutively recruited. The 10-year-CVD risk score was estimated using the CUORE risk score (CRS). Sociodemographic, lifestyle, anthropometric, biological, and psychological (i.e., quality of life, depressive symptoms, and alexithymia) CVD risk data were assessed using validated self-report measures or clinical records. As expected, most participants (78.5%) had a low CVD risk (CRS < 3%) and an overall low-risk profile for all the parameters. Compared with subjects at low risk of CVD (n = 911, 78.5%), those with high risk (i.e., rated ≥3 on CUORE risk assessment; n = 250, 21.5%) reported higher levels of alexithymia (p < 0.001). Subjects with higher alexithymia (n = 236, 23.1%) reported higher levels of psychosocial impairment, depressive symptoms, and biological risk variables for CVD. Alexithymia was significantly associated with 10-year CVD risk (OR = 1.02, 95% CI = 1.01-1.04, p = 0.009), even after adjusting for key sociodemographic and clinical risk variables. Although limited by the cross-sectional design, this study is the first to show that alexithymia leads to a higher risk for 10-year CVD estimate in healthy subjects with low-risk profile, regardless of known biomarkers and traditional CVD risk factors.

Transcatheter vs Surgical Aortic Valve Replacement in Bicuspid Aortic Valves.

Recent approval of transcatheter aortic valve replacement (TAVR) in patients at lower risk profiles has resulted in a real-world expansion in patients with bicuspid aortic valves (BAV), otherwise excluded from trials comparing TAVR with surgical aortic valve replacement (SAVR). This study compared perioperative and longitudinal outcomes between BAV patients undergoing TAVR vs SAVR. Using the United States Centers for Medicare and Medicaid Services inpatient claims database, we evaluated all beneficiaries with BAV undergoing isolated SAVR or TAVR (2018-2022). Comorbidities and frailty were accounted for using validated metrics with doubly robust risk adjustment using inverse probability weighting, multilevel regression models, and competing-risk time to event analysis. Subgroup analysis evaluated patients <75 years with low surgical risk (<4%). The study included 11,289 BAV patients (8123 SAVR and 3166 TAVR). Accounting for age, comorbidities, and frailty, TAVR was associated with lower procedural mortality (odds ratio, 0.40; P < .001) but higher pacemaker (12.4% vs 2.3%; odds ratio, 5.4; P < .001), longitudinal stroke (2.4% vs 1.5%; hazard ratio [HR], 1.35; P < .001), and all-cause mortality (8.8% vs 5.7%; HR, 1.49; P < .001) compared with SAVR. The young low-risk subgroup (5393 SAVR and 1731 TAVR) highlighted similar findings, with TAVR associated with higher longitudinal stroke (2.1% vs 1.7%; HR, 1.22; P= .017) and composite stroke, valve reintervention, or death (8.1% vs 5.9%; HR, 1.37; P < .001) compared with SAVR. Among Medicare beneficiaries with BAV, TAVR was associated with lower index in-hospital mortality but also lower 5-year risk-adjusted freedom from longitudinal stroke compared with SAVR, even in the youngest low-risk patients.

Differences in protein expression in Alzheimer’s disease patients based on risk factors for amyloid‐related imaging abnormalities

AbstractBackgroundThe exact mechanism underlying amyloid‐related imaging abnormalities (ARIA) is unknown. Several factors explain ARIA risk, including the presence of microbleeds, APOE4 carriership, and very low Aβ42 levels. The cerebrospinal fluid (CSF) proteome reflects ongoing mechanisms and, thereby, provides an accessible fluid to refine risk of ARIA development. In this explorative study, we aimed to determine how the CSF proteome relates to the ARIA risk profile and identify potential biomarkers for ARIA risk.MethodWe included AD dementia patients who were Aβ42/tTau ratio positive (n=156; median age: 67 IQR:60‐72, 38% F, median MMSE‐score: 19.8 IQR:17‐24). We dichotomized all risk factors: microbleeds were divided in 0 (M‐, n=123) or &gt;0 (M+, n=33), APOE4 status was divided in carriers (APOE4+, n=96) and non‐carriers (APOE4‐, n=60), CSF Aβ42 levels were separated based on the median (Low and High). We also defined a high and low risk profile: patients with M+APOE4+AL (n=13) and M‐APOE4‐AH (n=23). CSF proteomics were performed using antibody‐based proteomics (Olink), and we selected 288 proteins previously shown to be related to AD (del Campo et al., 2022). With linear regression analysis (with age and sex corrections), we compared protein levels per risk group.ResultWe identified 20 proteins that were differentially expressed in M+ versus M‐, 7 proteins in APOE4+ versus APOE4‐, 3 proteins in Aβ42L versus Aβ42H, and 49 proteins in M+APOE4+AL to M‐APOE4‐AH. The top proteins include EGFR, CRTAC1, AXL, CNTN1, and TIMP4. Overall, almost all proteins were downregulated in the ARIA risk group and most proteins were not overlapping between risk groups.ConclusionThese results show that there are differences based on the ARIA risk profile. The differentiating proteins could provide extra information on the ongoing biological processes that increase ARIA risk and in the future aid to refine ARIA risk. Potentially, these results could aid in the development of a new biomarker for ARIA risk. Future analysis focus on further understanding the proteins involved and validating the findings.

Colorectal Cancer Incidence and Mortality After Negative Colonoscopy Screening Results

The current recommendation for a 10-year rescreening interval after a negative colonoscopy screening (NCS) result has been questioned, with some studies showing a persistently lower risk of colorectal cancer (CRC) after NCS results. To examine long-term CRC incidence and mortality after NCS results (ie, no presence of CRC or polyps) and according to a risk score based on major demographic and lifestyle risk factors. In this cohort study, 3 prospective US population-based cohorts from the Nurses' Health Study, Nurses' Health Study II, and Health Professionals Follow-up Study were followed up from 1988 and 1991 to 2020. Data from the National Health and Nutrition Examination Survey (NHANES) from the January 1, 2017, to December 31, 2018, cycle were used to compare the risk profile distribution with that of the general US population. Data analysis was performed from October 2023 to August 2024. Time-varying status of NCS results and risk score. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% CIs for incidence and mortality of CRC. A total of 195 453 participants (median [IQR] age, 44 [37-56] years at baseline; 81% female) were followed up for a median (IQR) of 12 (6-20) years. Among 81 151 individuals with NCS results and 114 302 without endoscopy, 394 and 2229 CRC cases and 167 and 637 CRC deaths, respectively, were documented. Negative colonoscopy screening results were consistently associated with lower CRC incidence (HR, 0.51; 95% CI, 0.44-0.58) and mortality (HR, 0.56; 95% CI, 0.46-0.70) for 20 years. Among individuals with NCS results, those with an intermediate risk (scores, 6-7) and low risk (scores, 0-5) did not reach the 10-year cumulative incidence of CRC (0.78%) of the high-risk individuals (scores, 8-12) until 16 and 25 years after initial screening, respectively. These findings provide evidence for shared decision-making between patients and physicians to consider extending the rescreening intervals after an NCS result beyond the currently recommended 10 years, particularly for individuals with a low-risk profile. These results showed, as a proof of concepts, the importance of considering known CRC risk factors when making decisions for colonoscopy rescreening.

BIOM-60. UNDERSTANDING THE INTERSECTION OF RACE, SEX, AND GENOMIC PROFILES IN MENINGIOMA PATHOPHYSIOLOGY

Abstract BACKGROUND While meningioma incidence and outcomes vary by sex and race, the potential underlying molecular differences possibly contributing to these disparities are less understood. Herein, we explore the clinical and genomic characteristics of meningiomas across groups characterized by age and sex. METHODS We analyzed adult patients with primary meningiomas resected from 2012 to 2023. Patients underwent whole exome sequencing, and demographic data were categorized into four groups based on self-reported race and sex, which included White females, White Males, Black females, and Black males. The primary analyses involved comparisons of tumor characteristics, socioeconomic status (median zip code income, % with high school diploma, health insurance status, distance from hospital), genomics, and recurrence rates. RESULTS The study included 509 primary meningiomas. White females exhibited low-risk genomic profiles characterized by driver mutations in KLF4 (+/- TRAF7) (p=0.010) and POLR2A (p=0.045), with no associated CNVs (p=0.410). This benign molecular profile correlated with lower WHO grades (p=0.013) and a lower incidence of recurrence (p=0.0003). Black females had meningiomas enriched with Hedgehog pathway mutations (p=0.0035) and a predilection for the anterior skull base (p=0.034), leading to an increased risk of recurrence (p=0.026). White males showed an aggressive genomic profile, including chromosome 1p loss (p=0.025) and 10q loss (p=0.067), associated with a high risk of recurrence (p=0.0002). Black males had meningiomas with chromosome 14q loss (p=0.0002), the highest incidence of high-grade meningiomas (p=0.048), and a 4.5-fold increased risk of recurrence (OR 4.5 [1.6-11.8]; p=0.006). Black males also experienced the worst progression-free survival (HR 5.5 [2.5-12.4]; p&amp;lt;0.0001), independent of WHO grade, extent of resection, and socioeconomic status. CONCLUSIONS Each demographic has a distinct molecular profile that correlates with clinical behavior in a race and sex-specific manner. Black males are disproportionately affected by biologically aggressive meningiomas, leading to higher tumor grade and recurrence rates.

Chronic Subdural Hematomas-A Retrospective Analysis of the Internal Architecture and Evaluation of Risk Factors for Recurrences After Surgical Therapy.

Background: Chronic subdural hematoma (CSDH) is increasingly common due to the aging population and widespread use of anticoagulant and antiplatelet medications. The objective of this study is to examine the internal composition of CSDH and explore potential risk factors associated with its recurrence. Methods: This retrospective study analyzed data from 189 patients who underwent surgery in our department between 2014 and 2018. Recorded data included demographics, clinical information, details of surgical interventions, computer tomography (CT) scans, neurological assessments, and follow-up data. The outcome was evaluated clinically and through CT follow-up conducted 4-12 weeks post-surgery. CT scans measured various parameters, including hematoma thickness, hyperdense regions, chronic components, and membrane presence. Results: Patients after the evacuation of CSDH were significantly more common males (66.1%, p > 0.001) had a significantly higher BMI (p < 0.001, 61.6%), arterial hypertension (p < 0.001, 68.3%), and the intake of anticoagulant therapy (p < 0.001, 58%). The recurrence rate was 18.6% after 4 weeks and 2.1% after 8-12 weeks. After uni- and multivariable analysis, the initial hemispheric type (p = 0.019, HR: 3.191; p = 0.012, HR: 3.810) and the increasing preoperative midline shift in CT (p = 0.028, HR: 1.114; p = 0.041, HR: 1.107) were found as independent predictors for recurrence. Overall, outcomes were favorable with a modified Rankin scale (mRS) of 0-2 at discharge (72%), after 4 (89.7%) and 12 (87%) weeks. Conclusion: According to our data, increasing midline shift before surgery and initial hemispheric type of hematoma were independent predictors of recurrence. Most patients achieved an excellent outcome with a low-risk profile.

Abstract 011: Early multi‐center experience with the NEVA VS in the treatment of subarachnoid hemorrhage‐related cerebral vasospasm

Introduction Cerebral vasospasm represents a formidable challenge in the aftermath of subarachnoid hemorrhage (SAH), significantly contributing to morbidity and mortality. This life‐threatening and potentially reversible complication is conventionally addressed through percutaneous transluminal balloon angioplasty (PTA) or intra‐arterial (IA) infusion of vasodilators, particularly when standard medical therapies prove ineffective. However, these endovascular interventions often fall short in efficacy or are marred by elevated complication rates, including vessel rupture and thromboembolic events. The persistent issue of frequent recurrence underscores a pressing unmet need in vasospasm management. In this context, the NeVa VS (Vesalio)—a patented, retrievable nitinol stent—emerges as a novel solution engineered explicitly for cerebral vasospasm post‐aneurysmal rupture. Notably, it is the sole device approved for this application in the United States. This study delineates our initial clinical experiences utilizing the NeVa VS device. Methods Our study encompassed 23 patients across seven US centers, all treated with the NeVa VS device. Of 24 cases analyzed to date, all were confronting refractory symptomatic cerebral vasospasm after aSAH. The deployment of NeVa VS involved a 0.021” or 0.027” ID micro‐catheter, positioning the stent across the affected vasospasm segment. Following a recommended 5‐10 minute interval, allowing the self‐expanding nitinol structure to dilate the constricted vessel segment mechanically, the device was resheathed into the microcatheter and removed. We aimed to evaluate intraoperative efficacy, user experience, safety parameters, and preliminary outcomes in this patient cohort. Parameters such as vessel caliber pre‐ and post‐intervention, procedural metrics, and outcomes—including symptom relief, patient status changes, and adverse events—were meticulously analyzed. Outcomes Comprehensive outcomes were ascertained for 23 patients. The median age was 42 years (±13, SD); 74% were female, and 70% were of Hispanic/Latino ethnicity. The device was deployed, on average 12 days (±8) after the index hemorrhage, in total 24 times (1.0 per case) in the MCA (57%) or basilar artery (43%) for an average of 6.4 minutes (±2.7). MAC/sedation was utilized in 17% of cases. With one exception, all treatments were deemed successful (96%) with significant improvement in the degree of spasm from 78% pre‐ and 22% post‐intervention, and no safety events occurred, in particular, no ischemic strokes or intraprocedural ruptures. Four patients (17%) required additional treatment, on average 11.0 days after the first treatment. Conclusion In this preliminary multi‐center study, the NeVa VS device demonstrates a 96% success rate in performing a safe and efficacious single‐stage intervention to address severe stenosis secondary to vasospasm post‐aSAH. The device's ability to control vessel expansion and preserve distal flow offers a significant advantage over traditional balloon angioplasty. It also exhibits a lower risk profile concerning vessel rupture and the option to utilize MAC/sedation instead of solely general anesthesia in selected cases (17%), marking a significant advancement in neurointerventional therapy for symptomatic vasospasm.

Unraveling the paradox: the impact of one or more traditional risk factors on short-term mortality following acute coronary syndromes.

Abstract Background It has been recently suggested that individuals without exposure to any standardized modifiable risk factors may have an increased risk of all-cause mortality from acute coronary syndromes (ACS) compared with their counterparts with one or more risk factors, including diabetes. Purpose To estimate the individual contribution of the four traditional risk factors to the risk of adverse outcomes from first ACS. Methods We analyzed data from 70,953 Caucasian patients presenting with first ACS, but without prior coronary heart disease in the International Survey of Acute Coronary Syndromes (ISACS) Archives registry network from October 2005 to January 2021. The primary outcome was all-cause mortality within 30 days after hospital admission. We calculated sex-specific risk ratios (RRs) stratifying traditional risk factors, current smoking, diabetes, hypercholesterolemia and hypertension into mutually exclusive categories using a balancing strategy by inverse probability weighting. Results Compared with patients presenting without risk factors, those with diabetes had significantly higher 30-day mortality in both women (RR, 1.29; 95% CI, 1.06-1.57) and men (RR, 1.40; 95% CI, 1.16-1.69). By contrast, patients who were current smokers or presented with a history of hypercholesterolemia or hypertension had significantly lower 30-day mortality than patients with no risk factors with RRs ranging from 0.53; 95% CI 0.42–0.67 in women who were smokers to 0.46; 95% CI 0.37–0.59 in men with hypercholesterolemia. The impact of diabetes on mortality was obscured in patients who concomitantly presented with diabetes and one more traditional risk factor. The RRs in combination with current smoking were 1.39; 95% CI 0.92 -2.09 in women and 0.89; 95% CI 0.68 -1.17 in men; with hypercholesterolemia: 0.91; 95% CI 0.66 -1.25 in women and 0.75; 95% CI 0.53–1.06 in men; with hypertension: 1.14; 95% CI 0.99–1.32 in women and 1.12; 95% CI 0.96–1.31 in men. Conclusions Diabetes confers a significant independent excess mortality risk at 30 days following ACS. Dilution bias in this setting refers to the weakening of the observed effect of diabetes because of the inclusion of "one more" risk factor with lower risk profile. Potential misinterpretation of the relationship between diabetes and death from ACS may negatively affect healthcare organization

The importance of comorbidities in idiopathic and associated with connective tissue disease pulmonary arterial hypertension: from the Spanish Registry of Pulmonary Hypertension (REHAP Registry)

Abstract Introduction Comorbidities play a major role in the prognosis of patients with pulmonary arterial hypertension (PAH). These comorbidities are present in more than 80% of patients diagnosed in the last years with idiopathic PAH (iPAH) and their presence is associated with increased morbidity and mortality although its influence on PAH associated with connective tissue disease (PAH-SSc) is unknown. We studied the impact of comorbidities on iPAH and PAH-SSc in the Spanish population. Methods We collected patients diagnosed with iPAH, heritable, associated with drug or toxine exposure and PAH-SSc between 2014 and 2023 from the Spanish Registry of Pulmonary Hypertension. Patients are classified into: no comorbidities, 1-2 comorbidities and ≥3 comorbidities. We analyzed the impact of comorbidities in baseline characteristics, exercise capacity and hemodynamic profile, as well as in the risk profile and initial treatment. Survival analyses estimated by Kaplan-Meier analysis using the log-rank test and Cox proportional hazard analyses were performed to determine the effects of baseline characteristics on survival. Results 757 patients were selected for this study. The characteristics of the patients are shown in Table 1. As the number of comorbidities increases (0/1-2/≥3) we found higher age (49/59/67 years; p&amp;lt;0.001), higher percentage of male sex (12.9/29.9/43.4%; p&amp;lt;0.001) and higher FC III at diagnosis (42.7/46.9/59.6%; p=0.013). We observed a shorter distance in 6MWD, higher NT-proBNP levels, lower DLCO and a less unfavorable hemodynamic profile (PAPm, PAWP, CI and PVR). The most frequent comorbidities were a history of smoking (46.4%), followed by arterial hypertension (41.5%), obesity (24.6%) and chronic kidney disease (19.2%). Diabetes mellitus, although less frequent, reached more than 55% in patients with ≥3 comorbidities (p&amp;lt;0.001). The presence of ≥ 3 comorbidities was more frequent in iPAH than PAH-SSc (p&amp;lt;0,001). Intermediate risk profile was the most common (58.4%) and this reached 68.7% in those with ≥3 comorbidities due to a lower number of patients in a low-risk profile (p&amp;lt;0.001). A statistically significant lower survival (p&amp;lt;0.001) was observed in patients with ≥ 3 comorbidities; however, we found no differences between 0 and 1-2 comorbidities at 7-year follow-up (Figure 1). Variables associated with mortality were male sex (HR 1.88, 95% CI 1,26 – 2.8), age (HR 1.04, 95% CI 1.02 – 1.06) and the presence of ≥3 comorbidities (HR 1.49, 95% CI 0.98 – 2.27), not the presence of connective tissue diseases, which were not associated with increased mortality in our study. Conclusions The presence of comorbidities in iPAH and PAH-SSc is very frequent in the Spanish population. They are associated with a worse clinical profile, risk profile, lower use of oral double theraphy and prostacyclins. The presence of ≥3 comorbidities is associated with worse survival, not the presence of 1-2 comorbidities or connective tissue disease.

Protein quantitative trait loci identifies genetic biomarkers of proteins associated with measures of myocardial fibrosis in new-onset, treatment naive rheumatoid arthritis

Abstract Introduction The excess risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) compared to the general population is attributed to chronic inflammation. Identifying the underlying mechanisms and shared inflammatory pathways more precisely would enable tailored treatment. Purpose To identify genetic variants associated with the cardio-metabolic-inflammatory proteomic signature in patients with early, treatment-naïve RA and low CVD risk. Methods The Coronary Artery Disease Evaluation in RA (CADERA) study was a bolt-on to a RCT of patients with early, treatment-naïve RA and low CVD risk profile (maximum of 1 traditional CVD risk factor and no diabetes mellitus). Normalised expression of 334 proteins from 75 CADERA patients who underwent cardiovascular magnetic resonance imaging (CMR) was measured using the Olink Proximity Extension Immunoassay across Inflammation, Cardiovascular II, III and Cardiometabolic panels. Genome-wide single nucleotide polymorphism (SNP) data were generated using the Illumina Global Screening Array and was imputed and checked for data quality using standard approaches. Proteins associated with CMR parameters were identified using Bayesian mixed effects linear regression. Protein quantitative trait locus (pQTL) analysis was then performed using linear regression models adjusted for age, gender, and systolic blood pressure. Cis-pQTLs were defined as SNPs within 1Mb of the protein-encoding gene, and significance threshold was set at 1e-5. Due to sample size, trans-pQTLs were not considered in this analysis. Linkage disequilibrium (LD) clumping was performed using PLINK software to identify index SNPs defined as the most significant variant in LD (r2 &amp;lt;0.5) within a region of +/- 250Kb. Results Following quality control 318 proteins and 5,971,781 SNPs were available for analysis in 75 CADERA patients. The median age was 51 years [inter-quartile range (IQR) 40 - 61] with 52/75 (69%) females, 40/75 (53%) current/ex-smokers, and median body mass index (BMI) 26.4kg/m2 (IQR 23.3 - 28). Participants had a median RA symptom duration of 21.9 weeks (IQR 14.4 - 32.7). Only 8/75 (10%) reported a history of hypertension, hypercholesteroaemia or family history of CVD. 54 out of 318 proteins were associated with CMR measures of myocardial fibrosis and/or vascular stiffness. 460 cis-pQTLs were identified for 20 out of the 318 proteins. LD clumping revealed 40 cis-pQTLs independently associated with these 20 proteins. Of these, NOTCH3 (rs34763630) was positively associated with extracellular volume, and SELPLG (rs7980427) was negatively associated with late gadolinium enhancement as detected on CMR (table 1). No other proteins with genetic support were associated with CMR measures. Conclusion This study for the first time, implicates genetic markers associated with two proteins as putative candidate biomarkers of CMR-identified myocardial fibrosis in new-onset RA that now warrant validation in an independent cohort.

Idiopathic pulmonary arterial hypertension, associated with connective tissue disease and comorbidities: prognostic differences? Results the Spanish Registry of pulmonary hypertension (REHAP Registry)

Abstract Introduction Idiopathic pulmonary arterial hypertension (iPAH) and associated with connective tissue disease (PAH-SSc) are the most frequent groups of pulmonary arterial hypertension (PAH) but their long-term survival is usually unequal. Comorbidities, increasing in frequency in these patients, show prognostic influences but it is not known whether these differ in both groups of patients. Methods We collected patients diagnosed with iPAH, heritable, associated with drug or toxine exposure and PAH-SSc between 2014 and 2023 from the Spanish Registry of Pulmonary Hypertension. Patients are classifies into iPAH and PAH-SSc. We analyzed baseline characteristics and the distribution of the different comorbidities in the two groups. Survival analyses estimated by Kaplan-Meier analysis using the log-rank test were done according to PAH etiology and comorbidities and Cox proportional hazard analyses were performed to determine the effects of baseline characteristics on survival. Results Seven hundred and fifty-seven patients were selected for this study. The characteristics of the patients are shown in Table 1. Patients with PAH-SSc compared to iPAH were older (62 vs 56 years), more female (81.8% vs 62.4%), had a more favorable hemodynamic profile, TAPSE/sPAP ratio and lower NT-proBNP levels. No differences were found in functional class or 6MWT. We found a higher proportion of patients in a low and intermediate risk profile, according to ESC, in patients with PAH-SSC as opposed to PAHi (46.8/50.9% vs. 29.3/64.5%; p&amp;lt;0.001). Regarding comorbidities, history of smoking (27.1 vs 54%; p&amp;lt;0-001), obesity (17.1 vs 20.7%; p&amp;lt;0.001) and diabetes (9.4 vs 22.1%; p&amp;lt;0.001) are less frequent in PAH-SSc than in iPAH. There are no differences in the rest of the comorbidities studied in the two groups of patients. In a survival analysis, we found no differences between patients with iPAH and PAH-SSc at 7-year follow-up. Patients with ≥ 3 comorbidities had statistically significantly higher mortality (p&amp;lt;0.001) compared to those with 0 or 1-2 comorbidities in both etiologies. There were no differences between 0 and 1-2 comorbidities. (Figure 1). Variables associated with mortality were male sex (HR 1.9, 95% CI 1,28 – 2.8), age (HR 1.04, 95% CI 1.02 – 1.06), the intermediate risk profile (HR 2.64, 95% CI 1.62 – 4.32) and high risk profile (HR 9.97, 95% CI 4.36 – 18.47), but not etiology. The presence of connective tissue diseases, were not associated with increased mortality. Conclusions Patients with PAH-SSc show lower comorbidities, better hemodynamic profile, RV-PA coupling and risk profile than those with iPAH. Comorbidity has a great relevance in survival but without differences according to etiology. The presence of male sex, age, the intermediate and high risk profile is associated with worse survival, but not the connective tissue diseases.

CXCR3-Flavonoid Interaction: A Novel Therapeutic Approach in Cancer Immunotherapy

Objective: To investigate the interactions between select flavonoids (Luteolin, Quercetin, Apigenin, Kaempferol, and Amorphine) and the CXCR3 receptor, evaluating their potential as novel therapeutic agents in cancer immunotherapy. Methods: Molecular docking simulations were employed to analyze flavonoid-CXCR3 receptor interactions. Comprehensive in silico ADMET analyses were conducted to assess pharmacokinetic properties and toxicity profiles of the compounds. Results: Flavonoids exhibited high-affinity binding to the CXCR3 receptor, with binding affinities ranging from -8.7 to -13.0 kcal/mol. Amorphine demonstrated the highest binding affinity (-13.0 kcal/mol), indicating superior inhibition potential. Luteolin showed optimal ADME characteristics, including favorable oral bioavailability (62%) and blood-brain barrier permeability (log BB -1.911). Molecular docking analyses identified critical amino acid residues (TYR205, TYR308, TRP109, PHE131, and ASN132) in flavonoid-CXCR3 interactions. In silico toxicity predictions suggested low risk profiles for all examined flavonoids. Conclusion: This study provides evidence for the potential of flavonoids as CXCR3 receptor antagonists in cancer immunotherapy. The elucidated molecular interactions and favorable ADMET profiles warrant further investigation of these compounds. Future research should focus on optimization of flavonoid-based CXCR3 inhibitors, preclinical and clinical evaluations, and assessment of their immunomodulatory effects within the tumor microenvironment. These findings contribute to the development of novel, flavonoid-derived therapeutic strategies in cancer treatment.

Real-world evidence on pulmonary arterial hypertension: interim analysis from the Italian observational study INSPECTIO

Abstract Background Pulmonary arterial hypertension (PAH) is a rare, progressive disease leading to right-sided heart failure. The interest in risk assessment based on non-invasive parameters is growing, and insights from clinical practice are needed in this regard. INSPECTIO is an Italian observational study aimed at filling this knowledge gap. The results of an interim analysis at month 12 are presented below. Purpose The primary objective was to assess the change from baseline to month 12 in the number of the non-invasive low-risk parameters among World Health Organization functional class, 6-minutes walking distance, Brain Natriuretic Peptide (BNP) or N-terminal proBNP. Secondary objectives are the evaluation of echocardiographic and haemodynamic parameters, and the proportion of patients in which the therapy was optimized according to the guidelines. Methods Prospective, multicentre study on PAH patients at low/intermediate mortality risk treated with macitentan and/or selexipag as part of the oral combination therapy. Results Among 177 patients who were enrolled in 29 centres, 148 patients [median age 63.0 years (Q1/Q3: 53.5/73.0), 76.4% females] completed the 12-month follow up and were considered for this analysis. The median time from PAH diagnosis was 22.6 months (4.9/60.1). Sixty-four (43.2%) patients had idiopathic PAH; 4 (2.7%) heritable; 80 (54.1%) associated with other diseases [58 (72.5%) connective tissue disease, 11 (13.8%) congenital heart disease corrected for at least one year, 5 (6.3%) portal hypertension, 5 (6.3%) human immunodeficiency virus infection, 1 (1.3%) drug and toxins]. At baseline, 45.9% patients and 28.4% were in double and triple oral combination therapy, respectively. Primary objective: at month 12, the number of noninvasive low-risk parameters increased in 43 (29.1%) patients and remained stable in 80 (54.1%) patients [mean change 0.16 (p=0.017)]. The values at baseline, at month 12 and the change from baseline for each noninvasive parameter are shown in Table 1. Mean right atrial (RA) area (end-systole) and tricuspid annular plane systolic excursion (TAPSE) remained unchanged while a reduction of systolic pulmonary artery pressure (sPAP) was observed. Regarding the haemodynamic parameters, the mean pulmonary arterial pressure decreased [median change -4.5, (p=0.0346)], while cardiac index, pulmonary vascular resistance, and RA pressure remained stable (Table 2). The number of patients on triple therapy increased from 42 to 51 (+21.4%). Conclusions This study confirms that a noninvasive low-risk profile can be achieved with current combination PAH therapy. The modest or absent changes in echocardiographic and hemodynamic parameters suggest that treatment of PAH in real world is yet to be improved; on the other hand, the optimization of therapy in a significant portion of patients can possibly account for the improvement or stabilization observed.Noninvasive parametersEcho and hemodynamic parameters