Effect Of Treatment Research Articles

Use of MM-SES-CD Endoscopic Improvement Thresholds Enhances Effect Size Differentiation between Adalimumab vs. Placebo: A Post-hoc Analysis of the EXTEND Trial.

The Modified Multiplier of the SES-CD (MM-SES-CD) refines the assessment of endoscopic Crohn's Disease (CD) severity by differentially weighting parameters in the original SES-CD. A threshold of <22.5 for MM-SES-CD suggests endoscopic remission and correlates with a low risk of long-term disease progression. This study examines whether MM-SES-CD-defined endoscopic remission (ER) and response criteria are more sensitive to treatment effects compared to conventional SES-CD definitions. This post-hoc analysis of the EXTEND trial compared various SES-CD and MM-SES-CD definitions of ER and endoscopic response in CD patients treated with adalimumab or placebo. The study included participants with moderate-severe CD and a baseline MM-SES-CD score ≥22.5. The primary outcome of ER, defined as MM-SES-CD <22.5, was evaluated at weeks 12 and 52. AUC analyses compared thresholds for predicting week 52 ER. Of the 100 participants (77.5% of the EXTEND population), 51 received adalimumab and 49 placebo. At week 12, 62% achieved MM-SES-CD ≥20% reduction from baseline, compared to 39% with SES-CD ≥50% reduction. At week 52, 56.9% of adalimumab-treated participants achieved MM-SES-CD <22.5, compared to 10.2% in the placebo group. MM-SES-CD ≥20% reduction at week 12 better predicted week 52 ER than SES-CD ≥50% reduction (AUC: 0.73 vs. 0.62, p=0.002). MM-SES-CD definitions improved discrimination between treatment and placebo and offered superior predictive accuracy for week 52 ER. Its use may enhance trial efficiency and better predict long-term disease outcomes.

Myopia control strategies: A systematic review and meta-meta-analysis.

To summarise pooled estimates of the efficacies of various myopia control interventions, as drawn from published meta-analyses. PubMed, SCOPUS and Web of Science were searched from inception to February 2024 for systematic reviews and meta-analyses reporting treatment effects of various myopia control strategies. The qualities of the included meta-analyses were assessed using the 16-item A MeaSurement Tool to Assess systematic Reviews (AMSTAR) 2. An intervention was defined as having a clinically significant effect if it resulted in a change in spherical equivalent refraction (SER) of ≥0.50 D/year or axial length (AL) change of ≤-0.18 mm/year. A total of 38 studies were identified. The overall respective changes in SER and AL, mean difference (95% CI) were high-concentration (≥0.5%) atropine 0.67 D (0.58-0.77) and -0.24 mm (-0.36 to -0.11); moderate-concentration (>0.05% to <0.5%) atropine 0.48 D (0.34-0.62) and -0.23 mm (-0.27 to -0.19); low-concentration (0.01%, 0.025%, 0.05%) atropine 0.33 D (0.23-0.43) and -0.14 mm (-0.19 to -0.09); orthokeratology -0.47 mm (-0.66 to -0.28); peripheral plus soft contact lenses 0.30 D (0.18-0.42) and -0.35 mm (-0.62 to -0.08); peripheral plus spectacles 0.77 D (0.40-1.14) and -0.43 mm (-0.78 to -0.08); multifocal spectacles 0.21 D (0.11-0.31); repeated low-level red light therapy 0.55 D (0.46-0.65) and -0.25 mm (-0.29 to -0.20); outdoor time 0.17 D (0.16-0.18) and -0.04 mm (-0.06 to -0.01). High and moderate concentrations of atropine, orthokeratology, peripheral plus spectacles and repeated low-level red light demonstrated clinically significant effects on slowing AL elongation, while high and moderate concentrations of atropine, peripheral plus spectacles and repeated low-level red light demonstrated clinically significant effects on slowing SER progression.

An experimental study on the diagnostic advantage of dual-energy computed tomography over single-energy scan to evaluate the treatment effect following transcatheter arterial chemoembolization.

We assessed the diagnostic advantage of dual-energy computed tomography (DECT) over single-energy computed tomography (SECT) to evaluate lipiodol accumulation in target lesions following transcatheter arterial chemoembolization (TACE). TACE was performed in 10 rabbits in whom the VX2 tumor was implanted in their left liver lobes. The miriplatin-lipiodol mixture was injected into the common hepatic artery. All rabbits were sacrificed 2 days after TACE, and the liver was harvested. CT was performed using both single-energy and dual-energy scan modes. The specimen was stained with Oil Red O to evaluate lipiodol accumulation; this was considered the reference standard. Mutual information (MI) was used to evaluate the significance of radiological-pathological correlation. Estimated iodine content values on iodine material density images were compared with actual values obtained using mass spectroscopy. Mean MI values were 0.69, 0.32, 0.83, 0.72, 0.65, and 0.58 for single-energy scan; iodine density images; and virtual monoenergetic images for energy levels of 40, 60, 80, and 100 keV, respectively. The MI value of the monochromatic image (40 keV) was the highest among all sequences. However, this was not significant compared with the single-energy scan (p = 0.81). A significant correlation was observed between the estimated and actual values of iodine content (Pearson's product moment coefficient = 0.70, p = 0.023). More accurate and quantitative lipiodol evaluation in targeted tumors after TACE can be achieved by applying DECT rather than SECT.

Abstract 4120534: Long-Term Outcomes After Medication, Coronary Stenting or Surgery for Men and Women With Three-Vessel Coronary Disease

Background: Sex is a vital prognostic factor in patients with coronary heart disease, however, the data on sex-treatment interaction among real-world patients with three-vessel coronary disease (TVD) are limited. Objectives: This study aimed to investigate the long-term outcomes after medication therapy (MT), percutaneous coronary intervention (PCI), and coronary artery bypass grafting surgery (CABG) according to sex in patients with TVD. Methods: Consecutive 8943 patients with TVD [2421 (27.1%) MT, 3825 (42.8%) PCI, and 2697 (30.2%) CABG] were enrolled from April 2004 to February 2011 at Fu Wai Hospital. The primary endpoint was cardiac death and major adverse cardiovascular and cerebrovascular events (MACCE), a composite of all-cause death, myocardial infarction (MI), stroke or repeat revascularization. The secondary endpoints were the components of MACCE. Results: Among 8943 TVD patients, 7122 (79.6%) were men and 1821 (20.4%) were women. While the number of women undergoing PCI was comparable to men, women opted for more MT and fewer CABG (Figure 1). During a median 6.6-year follow-up, CABG showed a lower risk of MACCE compared to PCI, with a similar treatment effect for women and men (female HR: 0.76; 95% CI: 0.60 to 0.97; male HR: 0.61, 95% CI: 0.55 to 0.69; p for interaction=0.222) (Figure 2 and Figure 3). CABG also showed lower risks of all-cause death, MI, and repeat revascularization, and a higher risk of stroke, which had no significant interaction with sex. PCI, compared to MT, was associated with lower risks of MACCE, all-cause death, and stroke and a higher risk of MI and repeat revascularization, without significant gender disparities. CABG versus MT was associated with lower risks of MACCE, all-cause death, MI and repeat revascularization and a higher risk of stroke, with a similar treatment effect for female and male patients (Figure 3). Conclusion: There was no significant sex differences in the risks of long-term outcomes of PCI vs. CABG, PCI vs. MT, and CABG vs. MT in real-world TVD patients.

Abstract 4119941: Identification of individuals who benefit from omega-3 fatty acid supplementation to prevent coronary heart disease: A machine-learning analysis of the VITAL

Backgrounds: Randomized controlled trials (RCTs) have demonstrated benefits of marine omega-3 polyunsaturated fatty acids (omega-3 FA) supplementation for the prevention of coronary heart disease (CHD). However, it has not been clear which individuals would benefit the most from the supplementation. We sought to predict the individual treatment effect of omega-3 FA supplementation on CHD prevention and to develop an omega-3 effect score to stratify individuals according to their expected benefit from the supplementation. Methods: Among the 25,871 randomized participants without history of CVD in the VITamin D and OmegA-3 TriaL (VITAL), we applied machine-learning (ML) approaches to predict individual treatment effect of omega-3 FA supplementation on 5-year CHD risk (a composite of myocardial infarction, coronary revascularization, and CHD death) using 11 covariates pre-specified in the VITAL trial protocol. A 10-fold cross-validation was used and held-out test dataset was used for the evaluation. An omega-3 effect score was developed such that each covariate contributed linearly, and utility of the score was further evaluated by transportability analysis using the National Health and Nutrition Examination Survey (NHANES) data as the target population. Results: Omega-3 FA intervention led to absolute 0.48% [SE: 0.20] reduction in CHD in the total population. ML algorithms effectively stratified participants by their expected benefit according to individual factors; decreased CHD risk was observed in those with quintile 1 and 2 of the expected benefit (absolute CHD risk reduction %: 1.30 % [0.55] and 1.32 % [0.51] in quintile 1 and 2, respectively). Race, diabetes, and fish intake most contributed to the omega-3 effect score. CHD incidence rates per 1000 person-year were 5.5 [0.44] if treated and 8.5 [0.55] if not treated (35.3% reduction) in individuals with the score ≥11 (upper 40th percentile), and 3.9% [0.31] if treated and 3.4% [0.55] if not treated (14.7% increase) in those with the score &lt;11, respectively. The transportability of the utility of the score to baseline NHANES data was confirmed. Conclusion: In VITAL, ML approaches identified individuals who experienced greater CHD reduction from the omega-3 FA intervention, and an omega-3 effect score stratified the expected benefit. Although it warrants testing in a new RCT, the omega-3 effect score holds promise for guiding the indication of omega-3 FA supplementation in US primary prevention population.

Abstract 4116975: Safety signals with SGLT2 inhibitor use in diabetic males with erythrocytosis, but not in females: Findings from the CANVAS Program and CREDENCE trial

Backgrounds: Mediation analyses have shown that an increase in hematocrit (Hct) levels significantly contributes to the cardiorenal benefits of SGLT2 inhibitors (SGLT2i). However, given the link between erythrocytosis and poor prognosis, concerns remain about whether SGLT2i-induced erythropoiesis in patients with erythrocytosis may increase thromboembolic events (TE) including myocardial infarction (MI). Methods: We conducted a pooled analysis utilizing individual participant data from the CANVAS Program and the CREDENCE trial, both aimed to evaluate the efficacy and safety of canagliflozin versus placebo in diabetic patients. The primary outcome was a composite of MI, stroke, or any other TE. Sex-specific Cox analyses were performed to assess effect modifications by baseline Hct levels, treated as categorical (anemia, normal, and erythrocytosis) or continuous variable. Results: Of the participants for whom baseline Hct values were available (98.5% [14,321/14,543]), 35% were female. Canagliflozin significantly increased the percentage of erythrocytosis from baseline to 1 year in males (5.6% to 16.9%) and females (1.9% to 5.2%), unlike placebo. Overall, canagliflozin did not alter the risk of the primary outcome for either male (HR 0.97; 95% CI, 0.86–1.10) or female (HR 0.95; 95% CI, 0.78–1.15). In males, baseline Hct levels modified treatment effect on the primary outcome, whether treated as categorical or continuous variables (Pinteraction &lt;0.05), with benefits in anemic patients and harm in those with erythrocytosis (Figure). Meanwhile, no effect modifications were noted in females. In analyses for each component of the primary outcome, canagliflozin consistently reduced the risk of MI, stroke, and any TE in anemic male patients (HR 0.53, 0.49, and 0.71, respectively). However, mixed results were observed in those with erythrocytosis (HR 1.77, 0.62, and 1.11, respectively), suggesting detrimental effects on the primary outcome in these patients were primarily driven by MI. No heterogeneity by Hct was found for heart failure hospitalization or kidney outcome in both sexes. Conclusion: Canagliflozin may pose a safety concern regarding the risk of TE in diabetic male patients with erythrocytosis.

Analysis of behavioral flow resolves latent phenotypes.

The accurate detection and quantification of rodent behavior forms a cornerstone of basic biomedical research. Current data-driven approaches, which segment free exploratory behavior into clusters, suffer from low statistical power due to multiple testing, exhibit poor transferability across experiments and fail to exploit the rich behavioral profiles of individual animals. Here we introduce a pipeline to capture each animal's behavioral flow, yielding a single metric based on all observed transitions between clusters. By stabilizing these clusters through machine learning, we ensure data transferability, while dimensionality reduction techniques facilitate detailed analysis of individual animals. We provide a large dataset of 771 behavior recordings of freely moving mice-including stress exposures, pharmacological and brain circuit interventions-to identify hidden treatment effects, reveal subtle variations on the level of individual animals and detect brain processes underlying specific interventions. Our pipeline, compatible with popular clustering methods, substantially enhances statistical power and enables predictions of an animal's future behavior.

The effect of comorbidity on 28-day perioperative mortality rate among non-cardiac surgical patients in Northwest Ethiopia: a prospective cohort study using propensity score matching.

Non-communicable diseases account for nearly three-fourths of global deaths impacting public health and development. Coexisting diseases can complicate the management of surgical diseases, increasing the risk of perioperative mortality. Despite this, few studies have examined the burden of comorbidities among surgical patients and their effect on perioperative outcomes in low-income countries. In this study, we assessed the impact of comorbidity burden on 28-day perioperative mortality using a prospective data set. This was a facility-based prospective cohort study. Adult patients aged ≥ 18 who underwent non-cardiac surgery were included. Patients were followed for 28 days following surgery. Perioperative data were collected using an electronic data collection system from June 01, 2019, to June 30, 2021, at Tibebe Ghion Specialized Hospital, Northwest, Ethiopia. A propensity score-matched analysis was employed to assess the effect of comorbidity on the 28-day perioperative mortality rate. Of the 3030 patients included in this study, 715 (23.59%) had at least one comorbidity. Based on the prevalence rate, the top four comorbid conditions observed were hypertension (0.050), cancer (0.036), diabetes mellitus (0.021), and human immunodeficiency virus (0.021). The 28-day perioperative mortality rate was shown to be significantly higher among patients with comorbidity, where 45 (6.29%) of the 715 patients with comorbidity died compared to 49 (2.12%) of the 2315 patients with no comorbidity (p-value < 0.0001). After propensity score matching potential confounders, patients who have comorbidity had a 2.52% (average treatment effect on treated (ATT) = 0.0252) higher risk of perioperative death at 28 days after surgery compared with patients who did not have comorbidity. This study found a moderate prevalence of comorbid illnesses among non-cardiac surgical patients, with comorbidity increasing the risk of 28-day perioperative mortality. Preoperative screening and optimization are highly recommended for patients with comorbid illness to decrease perioperative mortality rate.

Abstract 4118122: Effect of Beta Blockers on Exercise Capacity, Diastolic Function, and Quality of Life in Patients with Heart Failure with Preserved Ejection Fraction

Introduction: In recent landmark HFpEF trials, 75-80% of patients are taking beta blockers (BB) without clear evidence of clinical or symptomatic benefit. Patients with HFpEF commonly have comorbidities that have been classically managed with BB (AF, CAD, HTN), though the utility of this medication class for these conditions is being reconsidered. It remains unclear what impact BB use, in patients with HFpEF, has on exercise capacity, diastolic function, and quality of life. Hypothesis: We hypothesized that BB use is associated with worse exercise capacity, diastolic function, and quality of life in HFpEF patients. Methods: This retrospective cohort study was completed using deidentified patient data from the INDIE-HFpEF and RELAX clinical trials (two trials of HFpEF patients). Patients were divided into two groups based on BB use at trial enrollment. The primary outcomes were exercise capacity, diastolic function, and quality of life at baseline evaluation. A multivariate logistic regression model was used to assess for statistically significant differences after controlling for potentially confounding variables including age, sex, BMI, AF, prior MI, COPD, DM, HTN, serum creatinine, and NYHA functional class. Results: A total of 320 patients were included in this analysis, with 230 on BB (72%). Baseline demographics are shown in Table 1. Patients studied were older (68 years old), white (90%), obese (average BMI 34 kg/m 2 ) individuals with an average LVEF of 61%. Outcomes and multivariate linear regression results are shown in Table 2. After controlling for potential confounding variables, there were no differences in baseline exercise capacity [peak VO2 (mL/kg/min): 12.1 vs 13.2, P=0.233], diastolic function [average E/e’: 14 vs 12, P=0.125; LAVI (mL/m 2 ): 42 vs 37, P = 0.665; peak TR velocity (m/s): 2.8 vs 2.7, P = 0.165; PASP (mmHg): 41 vs 36, P = 0.357], quality of life [KCCQ: 54 vs 58, P = 0.206; MLHFQ 43 vs 46, P = 0.762], or NT-proBNP (633 vs 342; pg/mL, P = 0.208) in HFpEF patients on BB compared to those not on BB. Conclusion: There was no association with BB use and worse exercise capacity, diastolic function, or quality of life in HFpEF patients. This may be due to heterogenous treatment effects, with differing impact of BB based upon the underlying pathophysiology of unique HFpEF phenotypes. To definitively determine the impact of BB use in patients with HFpEF, both on clinical outcomes and symptoms, randomized controlled trials are necessary.

NIMG-56. MAGNETIC RESONANCE SPECTROSCOPY IN THE POST-TREATMENT METABOLIC CHARACTERIZATION OF BRAIN TUMORS OF GLIAL ORIGIN OF CENTRAL NERVOUS SYSTEM

Abstract BACKGROUND and Purpose Central Nervous System tumors have a very low incidence worldwide, however they constitute an important source of mortality and morbidity. Treatment for these types of tumors in adults may include surgery, radiosurgery, radiation therapy, chemotherapy, and targeted treatment. These treatments in brain tumors of glial origen in adults can produce changes in the pathophysiology of the tumor. The purpose of this study was to characterize the different metabolic patterns as effect of treatment and identify tumor recurrences. Materials and METHODS A prospective study was conducted with patients with low- and high-grade tumors treated, subjecting them to the single-voxel MRS and multivoxel MRSI protocol at 1.5 T. RESULTS Of the 44 patients included, 21 were histopathologically diagnosed as low-grade tumors and 23 as high-grade tumors. Of the low-grade tumors, 11 were caracterized as low-grade (mean Cho/NAA and NAA/Cr ratios 1.49 ((p=0.036) and 0.92 (p=0.038) respectively), 8 cases presented gliosis (mean Cho/NAA and NAA/Cr ratios 1.57 (p=0.028) and 1.36 (p=0.026) respectively), and 4 cases presented radiation necrosis (mean Cho/Cr ratios 2.14 (p=0.03)), (mean Cho/Cr and NAA/Cr ratios 1.25 (p=0.01) and 1.25 (p=0.00)) respectively). Furthermore, tumor recurrence that presented high Cho/NAA ratio were observed in 11 cases. Of the high-grade tumors, 13 were caracterized as high-grade (mean Cho/NAA and Cho/Cr ratios 2.24 (p=0.026) and 4.48 (p=0.026) respectively), 13 cases presented gliosis (mean Cho/NAA and NAA/Cr ratios 1.82 (p=0.028) and 0.64 (p=0.026)) respectively) and radiation necrosis was detected in 10 cases (mean Cho/Cr ratio 1.47 (p=0.03), (mean Cho/Cr and NAA/Cr ratios 2.25 (p=0.01) and 0.97 (p=0.00) respectively). Moreover, tumor recurrence that presented high Cho/NAA ratio were observed in 9 cases. CONCLUSION MRS and MRSI contribute to identifying the recurrences, to characterizing the different metabolic patterns as an effect of the treatment and differentiate between low and high grade tumors.

The impact of curative cancer treatment on sexual health – clinical results from the EORTC QLQ-SH22 validation study

BackgroundThe European Organization of Research and Treatment of Cancer (EORTC) has recently developed and validated a patient-reported outcome measure (PROM) for sexual health (SH) in cancer patients. Here, we present results from a secondary analysis of the EORTC QLQ-SH22 validation study. The objective was to investigate the impact of cancer treatment on SH over the disease trajectory into survivorship in patients who underwent curative treatment.MethodsParticipants completed the EORTC QLQ-SH22 and the EORTC QLQ-C30 assessing SH and Quality of Life. We analyzed differences in SH of patients on active cancer treatment compared to patients off-treatment (cross sectional group comparison) as well as changes in SH during the course of treatment (from pre-treatment to follow-up).ResultsOur sample consisted of n = 394 (66.2% females) curatively treated cancer patients with 34% of patients being on-treatment and 66% of patients being in their follow-up after primary treatment (off-treatment group). Compared to patients off- treatment, patients on active cancer treatment experienced less sexual satisfaction (p = .021, Cohen’s d = .36) and libido (p < .001, d = .60) and had higher levels of fatigue (p < .001, d = .50). Importance of sexual activity, masculinity and femininity did not differ between groups. Treatment effects on sexual activity decreased with treatment completion (p < .001, d = .50). Patients undergoing intensified treatment (chemotherapy, radiation, or endocrine treatment) reported more treatment effects (subscale EORTC QLQ-SH22) compared to patients undergoing surgery only.ConclusionOur results highlight the negative impact of oncological treatment on SH and how increasing treatment intensity further impair SH. Sexual satisfaction and libido improve after treatment completion while other aspects (e.g. masculinity/femininity) do not change during survivorship. We suggest monitoring of SH from the start of cancer treatment on and beyond into survivorship using PROMs as part of routine cancer care. Routine monitoring allows systematic identification of patient’s SH problems and may improve awareness as well as target intervention for those in need of care.

Effect of treatment on quality of life of rural asthmatic children

Introduction: Medications relieve symptoms of asthma but affected children are significantly bothered by physical, educational and emotional impairments. Urban studies from India evaluated on how this disease affects quality of life. Aim of our study was to evaluate quality of life of rural asthmatic children both before as well as after the treatment. Methods: Asthmatic children 7 to 17 years visiting to rural tertiary care teaching hospital were included. Tool used for the study was Pediatric Asthma Quality of Life Questionnaire - Standard (PAQLQS) which were measured at the time of inclusion and four weeks after treatment. It assessed the QOL (Quality of Life) under symptoms, activity limitation and emotional function domains. Mean difference in pre and post treatment PAQLQ score was assessed. Results: Total 46 children were included from rural setup. Majority were male 60% and had a normal BMI (54%) which was followed by undernutrition (28%). Majority children in both age group 7-11year and 12-17 year, presented with moderate asthma (80%) and (62%) (according to GINA 2022) respectively followed by mild. The rural cohort post treatment showed significant improvement in individual (p&lt;0.005) as well as in overall PAQLQ post treatment (p&lt;0.002). Conclusion: The study has highlighted that good asthma control even after short duration of treatment helped in improvement quality of life of affected children. To maintain quality of life it is expected that the patient remains adhered to proper treatment.

Soil and plant cations as affected by application of wood ash, biochar, and papermill biosolids

AbstractRecycling woody biomass for application to croplands is one option to divert materials from landfills and simultaneously improve degraded soil properties. Considering the diversity of materials that vary widely in characteristics, an understanding of the comparative effects of a single or combined application of these byproducts is missing with regards to soil C accumulation and availability of base and metallic cations. A field study was conducted in Québec City, QC, Canada, to assess the effects relative to untreated control of wood ash (10 and 20 Mg dry wt. ha−1), pine biochar (10 Mg dry wt. ha−1), papermill biosolids (12 Mg PB dry wt. ha−1), and a combination of wood ash and PB on soil C, pH, and cations in a circumneutral loamy soil. The site was cropped to a corn (Zea mays L.)–soybean [Glycine max (L.) Merr.] rotation. All materials were applied before corn planting and the effects of treatment were followed over two growing seasons. Applying wood ash resulted in the statistically largest increases (p &lt; 0.01) in soil pH, percentage base saturation, and Mehlich‐3 K, Ca, Mg, Zn, and Cd. Wood ash also increased K concentration in straw and total K accumulation for both plants, but its effect on plant metallic cations was limited. With a single application, PB only increased Mehlich‐3 Ca with no further effect when combined with wood ash, while pine biochar was limited to sequester soil C. Therefore, this study indicated that wood ash could benefit a corn–soybean rotation by enhancing soil quality and crop yield.

Eight-Year Outcomes of Cardiosphere-Derived Cells in Single Ventricle Congenital Heart Disease.

Cardiosphere-derived cell (CDC) infusion was associated with better clinical outcomes at 2 years in patients with single ventricle heart disease. The current study investigates time-to-event outcomes at 8 years. This cohort enrolled patients with single ventricles who underwent stage 2 or stage 3 palliation from January 2011 to January 2015 at 8 centers in Japan. The primary outcomes were time-dependent CDC treatment effects on death and late complications during 8 years of follow-up, assessed by restricted mean survival time. Among 93 patients enrolled (mean age, 2.3±1.3 years; 56% men), 40 received CDC infusion. Overall survival for CDC-treated versus control patients did not differ at 8 years (hazard ratio [HR], 0.60 [95% CI, 0.21-1.77]; P=0.35). Treatment effect had nonproportional hazards for death favoring CDCs at 4 years (restricted mean survival time difference +0.33 years [95% CI, 0.01-0.66]; P=0.043). In patients with heart failure with reduced ejection fraction, CDC treatment effect on survival was greater over 8 years (restricted mean survival time difference +1.58 years [95% CI, 0.05-3.12]; P=0.043). Compared with control participants, CDC-treated patients showed lower incidences of late failure (HR, 0.45 [95% CI, 0.21-0.93]; P=0.027) and adverse events (subdistribution HR, 0.50 [95% CI, 0.27-0.94]; P=0.036) at 8 years. By 8 years, CDC infusion was associated with lower hazards of late failure and adverse events in single ventricle heart disease. CDC treatment effect on survival was notable by 4 years and showed a durable clinical benefit in patients with heart failure with reduced ejection fraction over 8 years. URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01273857 and NCT01829750.

NIMG-72. VOXEL-WISE, MULTIVARIABLE, COX PROPORTIONAL HAZARD STATISTICAL PARAMETER MAPPING TO INVESTIGATE THE INTERPLAY BETWEEN TUMOR LOCATION, PROGNOSTIC VARIABLES, AND EXPERIMENTAL TREATMENT IN A PHASE 3 TRIAL OF NEWLY-DIAGNOSED GLIOBLASTOMA TREATED WITH CHEMORADIATION WITH OR WITHOUT BEVACIZUMAB

Abstract BACKGROUND Tumor location is known to impact overall survival (OS) in glioblastoma. However, there is a lack of quantitative tools for studying the interplay between tumor location, prognostic variables, and treatments. In the current study we develop a voxel-wise statistical parameter mapping technique using a multivariable Cox regression model to describe the influence of tumor location on treatment effects in newly diagnosed glioblastoma. METHODS 598 newly diagnosed glioblastoma patients from the phase 3 AVAglio trial were studied. Areas of T2/FLAIR hyperintensity and resection cavities on post-surgical MRI scans were segmented and aligned to MNI atlas space. Voxel-wise Cox proportional hazards models for OS were run for each image voxel and included tumor presence in a specific voxel, age, MGMT promoter methylation, baseline tumor volume, and treatment (chemoradiation with or without bevacizumab). Results. After adjusting for other variables, tumor location was an independent predictor of favorable OS for tumors with involvement in the right prefrontal cortex (p&amp;lt;0.05, HR ranging ~0.48–0.65) and a predictor of shorter OS for tumors in the left mesial/basal temporo-occipital areas (p&amp;lt;0.05, HR ~3–6.2) and in the left hemisplenium of the corpus callosum (p&amp;lt;0.05, HR ~2.5–3). Baseline tumor volume (HR ~4–6 x10-6), MGMT status (HR ~0.38–0.41), and age (HR ~1.020–1.025) were significative predictors regardless of location (p&amp;lt;0.05 in all locations). Interestingly, chemoradiation plus bevacizumab treatment showed a favorable OS compared with chemoradiation alone for tumors with involvement in the right corticospinal tract, right motor and sensory cortices, and left hemisplenium of the corpus callosum (p&amp;lt;0.05, HR ~0.82). CONCLUSIONS Tumor involvement in the prefrontal cortex is associated with favorable prognosis, while tumors in mesial/basal temporo-occipital areas or splenium of the corpus callosum are associated with shorter OS. Chemoradiation plus bevacizumab may improve OS for tumors involving eloquent motor areas and the corticospinal tract.

BIOM-72. INTEGRATION OF ULTRASENSITIVE ELECTROLUMINESCENT IMMUNOASSAY AND CELL-FREE DNAMETHYLATION ANALYSIS FOR NON-INVASIVE MONITORING OF ADULT DIFFUSE GLIOMAS

Abstract Gliomas are highly aggressive brain tumors with nearly universal recurrence rate. Despite this, the ability to accurately predict and identify tumor recurrence relies solely on serial MRI imaging, which is marred by treatment effects such as radiation necrosis, and necessarily identifies progression retrospectively. It is believe that tumor undergo molecular changes upon tumor progression, however the resampling of tumors upon recurrence imposes significant risks. This highlights the need for novel non-invasive biomarkers capable of identifying tumor recurrence. Due to the low accuracies of individual biomarkers, we have proposed the use of an integrated, multi-platform approach to biomarker discovery. A cohort of 107 glioma plasma samples, including 30 pairs, underwent plasma proteomic analysis, consisting of a panel of serum proteins (FABP4, GFAP, NFL, Tau and MMP3,4 &amp;7) quantified through ultrasensitive electrochemiluminescence multiplexed immunoassays, and plasma DNA methylation analysis, captured through cell-free methylated DNA immunoprecipitation and high-throughput sequencing. Unsupervised hierarchal clustering revealed robust separation of primary and recurrent tumors through plasma proteomics, associated with a distinct plasma methylation signature. NFL, Tau and MMP3 levels differed between primary and recurrent samples; pair-wise analysis revealed increased in NFL and Tau concentrations upon recurrence. Tau levels predicted outcome independent of WHO Grade and IDH status. A predictive generalized linear regression model created through the integration of the proteomic and methylation signatures allowed for the discrimination of primary and recurrent samples in 83% of cases. This work suggests that the combination of DNA methylation and plasma proteomics may improve the ability of these techniques for the serial monitoring of gliomas patients.

Magnetic resonance imaging techniques for monitoring glioma response to chemoradiotherapy.

Treatment response assessment for gliomas currently uses changes in tumour size as measured with T1- and T2-weighted MRI. However, changes in tumour size may occur many weeks after therapy completion and are confounded by radiation treatment effects. Advanced MRI techniques sensitive to tumour physiology may provide complementary information to evaluate tumour response at early timepoints during therapy. The objective of this review is to provide a summary of the history and current knowledge regarding advanced MRI techniques for early treatment response evaluation in glioma. The literature survey included perfusion MRI, diffusion-weighted imaging, quantitative magnetization transfer imaging, and chemical exchange transfer MRI. Select articles spanning the history of each technique as applied to treatment response evaluation in glioma were chosen. This report is a narrative review, not formally systematic. Chemical exchange saturation transfer imaging potentially offers the earliest method to detect tumour response due to changes in metabolism. Diffusion-weighted imaging is sensitive to changes in tumour cellularity later during radiotherapy and is prognostic for progression-free and overall survival. Substantial evidence suggests that perfusion MRI can differentiate between tumour recurrence and treatment effect, but consensus regarding acquisition, processing, and interpretation is still lacking. Magnetization transfer imaging shows promise for detecting subtle white matter damage which could indicate tumour invasion, but more research in this area is needed. Advanced MRI techniques show potential for early treatment response assessment, but each technique alone lacks specificity. Multiparametric imaging may be necessary to aid biological interpretation and enable treatment guidance.

The cerebral and cognitive changes after intermittent theta burst stimulation (iTBS) treatment for depression: study protocol for a randomized double-blind sham-controlled trial.

The therapeutic use of intermittent theta burst stimulation (iTBS) delivered to the left dorsolateral prefrontal cortex (LDLPFC) is a relatively new but promising treatment option for depression. There is a need for more knowledge on the mechanisms involved in its antidepressant effects. This is a single-centre, prospective, randomized, double-blind, placebo-controlled trial with two arms, iTBS and sham iTBS. Adult outpatients with unipolar major depressive disorder of at least moderate severity will undergo cognitive assessment with an N-back task (0-back and 2-back), functional and structural magnetic resonance imaging and assessment of depression severity before and after brain stimulation. Neuronavigated iTBS or sham stimulation will be targeted at the LDPFC once a day for 10 consecutive workdays. ITBS will be delivered with the parameters 120% of resting motor threshold, triplet 50Hz bursts repeated at 5Hz; 2s on and 8s off, 600 pulses per session with a total duration of 3min 9s. The severity of depression will be measured with the Montogomery Aasberg Depression Rating Scale and the Beck Depression Inventory - second edition. In the iTBS group relative to sham, we expect significant antidepressant effects and improved N-back performance, associated with increased integrity in white matter tracts functionally connected with the LDLPFC and emotion regulation areas within the rostral anterior cingulate cortices, alongside potential increases in cortical thickness in these regions. On functional imaging, we expect to observe increased brain activity in the LDPFC during the performance of the N-back condition with higher cognitive load (2-back) in the iTBS group relative to sham. iTBS is a promising, time-efficient, and considered a safe treatment option for depression according to existing evidence. This trial aims to assess the neurocognitive impact of a 2-week, once-daily iTBS compared to sham iTBS, targeting the LDLPFC in depressed adult outpatients. The study investigates the relationships between changes in cerebral measures and cognitive performance on an N-back task in relation to the antidepressant effect following iTBS. This trial delves into the neurocognitive mechanisms of iTBS in depression, potentially offering novel scientific insights into its treatment effects and mechanisms of action. ClinicalTrials.gov NCT06534684. Retrospectively registered on August 1st 2024.

Impact of lenalidomide-bortezomib-dexamethasone induction on patients with newly diagnosed multiple myeloma and renal impairment: Results from the Connect® MM Registry.

Limited data exist on the effects of induction treatment in patients with newly diagnosed multiple myeloma (NDMM) and renal impairment (RI), who may also be ineligible for autologous stem cell transplant. This analysis investigated the impact of lenalidomide-bortezomib-dexamethasone (RVd) induction on renal function in patients from the Connect® MM Registry based on transplant status. Eligible patients were aged ≥18 years with symptomatic MM diagnosed ≤2 months before enrollment. Patients in this analysis received front-line RVd for ≥3 cycles and were grouped by transplant status and baseline renal function. As of August 4, 2021, 344 transplanted and 289 non-transplanted patients had received RVd for ≥3 cycles at induction. Improved renal function was observed at 3, 6, and 12 months in patients with all severities of RI at baseline. In patients with >60 and ≤60 creatinine clearance mL/min at baseline, median progression-free survival was 49.4 months and 47.6 months in transplanted patients and 35.7 months and 29.1 months in non-transplanted patients, respectively. These results provide real-world evidence that patients with NDMM and RI who receive front-line RVd for ≥3 cycles may have improved renal function regardless of transplant status, with renal function no longer affecting the long-term outcome. Clinical trial information: NCT01081028.

Effect of Electrofriction Treatment on Microstructure, Corrosion Resistance and Wear Resistance of Cladding Coatings

In recent years, the issue of increasing the wear resistance of the working bodies of agricultural machinery designed for cutting and breaking the soil has received special attention. The surface layers of working bodies of agricultural machinery during operation are subjected to intensive abrasive wear, which leads to rapid wear of equipment and a reduction in its service life. The induction cladding method using materials such as Sormait-1 is widely used to increase the wear resistance of tool working surfaces. However, after coating, additional heat treatment is required to improve the physical and mechanical properties of the material and increase its durability. In electrofriction technology (EFT) hardening, the surfaces of the parts are subjected to melting under the influence of electric arcs. In this work, three types of surface treatment of L53 steel have been investigated: induction cladding using Sormait-1, electrofriction treatment, and a combination of induction cladding followed by electrofriction treatment. The microstructure was analyzed using optical microscopy and scanning electron microscopy. Erosion and abrasion tests were carried out in accordance with ASTM G65 and ASTM G76-04 international standards to evaluate the wear resistance of the materials under mechanical stress. A dendritic structure was formed after the induction cladding of the Sormait-1 material, but subsequent electrofriction treatment resulted in a reduction of this dendritic structure, which contributed to an increase in the hardness of the material. However, the highest hardness, reaching 965 HV, was recorded after electrofriction treatment of L53 steel. This is explained by needle martensite in the structure, which is formed as a result of quenching. Further, the influence of structural characteristics and hardness on erosion and abrasion wear resistance was examined. The analysis showed that the material microstructure and hardness have a decisive influence on the improvement of wear resistance, especially under conditions of intensive erosion and abrasive friction.