Core Team Research Articles

289 Evaluation of fecal microbiota transplantation in primiparous sows

Abstract Fifty primiparous (parity 3+) and 25 multiparous sows (DNA 241, DNA, Columbus, NE) were used to evaluate the impacts of fecal microbiota transplantation (FMT) from sows to gilts on piglet scours prevalence, mortality, and fecal microbial diversity. Fresh fecal samples were collected from the primiparous and multiparous sows on approximately d 69 and 89 of gestation. The sows selected for sampling were from the same breed week as the gilts and had a historical record of low piglet mortality with increased litter size and no medical treatment during the current gestation period. The fecal samples from the sows were pooled on an equal weight basis and used for FMT solution preparation. The gilts were randomly assigned to one of two treatments: FMT or placebo (PBO). The FMT solution was administered orally to the 25 FMT gilts on approximately d 70 through 76 and 90 through 96 of gestation, while saline was administered to the 25 PBO gilts on the same days. Fecal samples were collected from all gilts and sows at the time of farrowing and at weaning. Piglets were individually weighed at birth and 5 wk post-weaning to calculate average daily gain (ADG). Scours prevalence was recorded daily from d 0 to 6 of lactation. Fecal samples were collected from two piglets per litter at weaning and 5 wk post-weaning. Pre-wean and nursery piglet mortality and morbidity were recorded. Total DNA from fecal samples and FMT solution from each timepoint were submitted for amplicon sequencing (Illumina MiSeq, Illumina Inc., San Diego, CA) at the Iowa State University DNA Facility (Ames, IA) to evaluate differences in microbial diversity and relative abundances across treatments groups. Data were analyzed using R version 4.3.1 (R Core Team, 2023). The sow and her litter were the experimental unit and results were considered significant if P ≤ 0.05 and a tendency if 0.05 < P ≤ 0.10. The number of piglets after cross-fostering and weaned were similar across treatments (P ≥ 0.721). There was no effect of treatment group on piglet birth weight or ADG (P ≥ 0.198). Scours prevalence was less in sow litters compared with PBO litters (16.7 vs. 52.0%; P = 0.039), while FMT scours prevalence was intermediate. There was no effect of FMT on pre-wean or nursery mortality (P ≥ 0.890). In conclusion, FMT did not impact gilt litter scours prevalence, growth rate, or mortality through the nursery.

31 Effects of dietary standardized ileal digestible (SID) lysine (Lys) levels and dietary SID tryptophan to Lys ratios on growth performance and behavior of late-nursery to finish maternal barrows

Abstract The objective was to determine the effects of dietary standardized ileal digestible (SID) lysine (Lys) levels and SID tryptophan (Trp) to Lys ratios on growth performance and behavior of late-nursery to finish maternal barrows. A total of 2,293 barrows (PIC Camborough, initially 11.9 ± 0.35 kg) were used in this trial with 96 mixed-sex pens and 23 to 25 pigs/pen. There was a total of 6 dietary phases: P1:11.9-29.5 kg; P2:29.5-49.6 kg; P3:49.6-62.6 kg; P4:62.6-80.3 kg; P5:80.3-103.3 kg; and P6:103.3-137.8 kg. Pens were blocked by body weight and randomly allotted to 1 of 6 treatments:T1: 100% Lys (dietary SID Lys levels meet PIC SID Lys recommendation) and 21.0% of SID Trp:Lys ratio; T2: 100% Lys and 18.5% of SID Trp:Lys ratio; T3: 100% Lys and 16.0% of SID Trp:Lys ratio; T4: 80% Lys (dietary SID Lys levels meet 80% of PIC SID Lys recommendation) and 21.0% of SID Trp:Lys ratio; T5: 80% Lys and 18.5% of SID Trp:Lys ratio; and T6: 80% Lys and 16.0% of SID Trp:Lys ratio for P1-P2 and then 100% Lys and 18.5% of SID Trp:Lys ratio for P3-P6. Ear lesion (EL) was monitored during P2-P5. Data were analyzed using a linear mixed model in R Studio (Version 3.5.2, R Core Team; Vienna, Austria). Pigs fed T1 and T2 showed improved average daily gain than T6 (P < 0.05), with other treatments intermediate (Table 1). Pigs fed T2 showed improved average daily feed intake as compared with T6 (P < 0.05), with other treatments intermediate. There was no evidence for significant difference on feed-to-gain ratio or mortality. Removal was significantly greater for pigs fed T6 compared with all other treatments (P < 0.05). Pigs fed T2 had significantly greater hot carcass weight than T4, with other treatments intermediate. There was no evidence for significant differences on carcass yield or lean percentage. Pig fed T6 had significantly greater incidence of EL in P2 than all other treatments (P < 0.05). Pigs fed T4 and T6 had greater incidence of EL in P3 than T1 (P < 0.05), with other treatments intermediate. Pigs fed T5 and T6 had significantly greater incidence of EL in P4 than T1, T2, and T3 (P < 0.05), with T4 intermediate. During P5, pigs fed T4 and T5 had the greatest incidence of EL (P < 0.05), while pigs fed T6 had significant greater incidence of EL than T3 (P < 0.05), with T1 and T2 intermediate. In conclusion, dietary SID Lys and SID Trp:Lys ratio less than PIC recommendation during late-nursery-to-grower phase resulted in compromised overall growth performance of maternal barrows, even with restored dietary SID Lys and SID Trp:Lys levels in finish phase. Dietary SID Lys level and/or SID Trp:Lys ratios lower than PIC recommendation may result in greater incidence of aggression behavior in maternal barrows.

140 Response of 6 to 13 kg nursery pigs to increasing SID Arg:Lys

Abstract Newly weaned pigs (n = 480; PIC 337 × 1050; Genus, Hendersonville, TN) with an initial body weight (BW) of 6.20 ± 0.61 kg were used in a dose-response study to evaluate the effects of increasing standardized ileal digestible (SID) Arg:Lys in nursery pigs. At weaning, pigs were placed into 48 pens with five barrows and five gilts per pen and randomly assigned to one of six dietary treatments. The experimental diets were formulated with increasing levels of SID Arg by replacing corn starch, glycine, and L-alanine with L-arginine. Levels of SID Arg:Lys ranged from 45 to 145%. Diets were sub-limiting in SID Lys and exceeded all other essential amino acid requirements. Furthermore, diets were formulated to be isocaloric, isonitrogenous, and met or exceeded NRC (2012) vitamin and mineral recommendations. The experimental diets were fed in two feeding phases from d 0 to 10 and d 10 to 27, with adjustments made to account for the decreasing Lys requirement of the pigs. Pigs were subsequently fed a common diet for the remaining 14 d of the nursery period to determine carryover effects. Pigs and feeders were weighed at the beginning and end of each dietary phase for the calculation of average daily gain (ADG), average daily feed intake (ADFI), and feed efficiency (gain to feed ratio; G:F). The data were fit using linear regression with R version 4.3.1 (R Core Team, 2023). The model included linear and quadratic effects of SID Arg:Lys and initial BW. Pen was the experimental unit, and results were considered significant at P ≤ 0.05 and a tendency at 0.05 < P ≤ 0.10. There was a significant linear and quadratic effect of SID Arg:Lys on BW on d 27 (P ≤ 0.024), where BW was maximized at a SID Arg:Lys 97.09%. From d 0 to 27 there was a linear and quadratic tendency of SID Arg:Lys on ADFI (P = 0.069), where feed intake was maximized at a SID Arg:Lys of 97.00%. Furthermore, there tended to be a linear and quadratic effect of SID Arg:Lys on ADG from d0 to 27 (P ≤ 0.081), where ADG was maximized at a SID Arg:Lys of 95.65%. There was no evidence for an effect of SID Arg:Lys on G:F at any timepoint throughout the trial (P ≥ 0.298). In conclusion, SID Arg:Lys linearly and quadratically impacted ADFI and ADG in 6 to 13 kg nursery pigs, where ADG was maximized at a SID Arg:Lys of 95.65%, but ADFI was maximized at a SID Arg:Lys of 97.00%. Together, these data suggest that the SID Arg:Lys requirement of nursery pigs is greater than NRC (2012) recommendations, and excessive Arg supplementation may have negative consequences on growth performance.

17 Effect of branched-chain amino acids on lactating sow and piglet performance

Abstract Sows (n = 360 PIC 1050 and Genesus) were used to investigate the effect of various branched-chain amino acid (BCAA) levels on sow lactation and litter growth performance. Upon entering the farrowing room, sows were blocked by parity group (P0, P2, P3+) and randomly assigned to one of six dietary treatments containing various levels of BCAA. Experimental diets were formulated to various standardized ileal digestible (SID) leucine, isoleucine, and valine levels by replacing cornstarch with L-leucine, L-isoleucine, and L-valine. Levels of the BCAA were expressed as ratios to SID lysine and were formulated at 114 or 180 for Leu, 56 or 64 for Ile, and 64 or 120 for Val. Diets were formulated to be isocaloric (3.23 Mcal ME/kg) and met or exceeded all other NRC (2012) essential amino acid and vitamin and mineral recommendations. Sow body weight (BW), backfat, and body condition score were recorded at the time of entry into the farrowing room and at the time of weaning. Piglet litter weights were recorded after cross-fostering and at weaning to determine litter growth rate. Data were analyzed using generalized linear mixed models with fixed effects of dietary treatment and parity group and a random effect of lactation group. The models were fit using R version 4.3.1 (R Core Team, 2023). The sow and her litter were the experimental unit, and results were considered significant if P ≤ 0.05 and a tendency if 0.05 < P ≤ 0.10. Sows nursed piglets for 21.3 d (P = 0.998). The mean parity by treatment ranged from 3.8 to 3.9 (P = 0.999). After farrowing, the mean estimated sow BW was 219 kg, with a range between treatments of 216 to 221 kg (P = 0.651). On average, sows gained 2.82% of their BW (P = 0.696) with an average daily feed intake (ADFI) of 8.75 kg/d (P = 0.932). However, as expected, sow Leu, Ile, Val, and total BCAA intakes were different across treatments (P ≤ 0.001). Sows entered the farrowing house with an average of 11.50 mm of backfat (P = 0.919) and lost 6.04% backfat through lactation (P = 0.667). Sows started the trial with an average of 14.1 piglets/sow (P = 0.967) and weaned 12.6 piglets per sow (P = 0.981) with a piglet average daily gain of 0.22 kg/d (P = 0.193) and a daily litter growth rate of 2.89 kg/d (P = 0.291). In conclusion, there was no evidence of an effect of the various leucine, isoleucine, and valine levels evaluated in this study on lactating sow and piglet performance.

Abstract PO5-17-10: PERFORMANCE AND OUTCOMES OF THE 70-GENES SIGNATURE (MAMMAPRINT™) IN A POPULATION WITH MIDDLE INCOME – REAL WORLD STUDY (AGEMA-BRA)

Abstract INTRODUCTION – Breast cancer remains the most frequent tumor in the female population and the fourth in mortality in the world population (GLOBOCAN 2020). With the aim of reducing mortality and at the same time de-escalating treatment, avoiding overtreatment, individualized therapy is increasingly being applied. The genomic signature of 70-genes, when stratifying patients into high and low risk of relapse, makes it possible to withdraw part of the cases of high clinical risk from chemotherapy treatment. However, the MINDACT study, which validated this signature, was carried out only in the European population, with no data on performance and outcomes in other populations with greater miscegenation. OBJECTIVE – To study the performance and outcomes of the 70-gene genomic signature (MammaPrint™) in a Brazilian population with a high ethnic miscegenation. METHODOLOGY – A retrospective cohort study was conducted in 953 women with breast cancer at high clinical risk, who underwent genomic analysis with the 70-gene platform (MammaPrint™), from January 2016 to December 2020. For the statistical evaluation, a descriptive analysis of the data with absolute and relative frequencies of the variables was performed. To verify the association between qualitative variables, the chi-square test was used. All analyzes were performed in the R 4.1.0 environment (R Core Team, 2021). Study approved by the Research Ethics Committee of the State University of Ponta Grossa (PR) - (CAAE: 12194219.4.0000.0105). RESULTS – The analysis of 955 cases from the AGEMABRA cohort (all at high clinical risk) showed 546 cases (57.2%) with low genomic risk and 409 cases (42.8%) with high genomic risk to MammaPrint™ (MP); when compared with data from the MINDACT study (46.2% low risk and 53.8% high risk) a significant difference was observed in the distribution for high and low risk in the two populations (p.< 0.001). After excluding patients with missing data, 409 cases of low- and high-risk MP were studied. The variables regarding age group, tumor diameter, number of affected lymph nodes, hormone receptors and HER2 overexpression showed no significant difference; within this same analysis, the tumor grade showed a higher incidence of grade 1 in the population with low genomic risk (6.6%) compared to high risk (2.9%) and grade 3 in high risk (13%) compared to low risk (5%) with p.< 0.001 (table 1). With an average follow-up of 40 months, the DMFS (disease metastatic free survival) found was 97.2%, being 97.8% for low risk and 96.2% for high risk (p.0.54). All patients with high-risk MP who progressed had used adjuvant chemotherapy, and all patients with low-risk MP who relapsed received only endocrine therapy. When compared to the MINDACT population, the AGEMA-BRA has more elderly patients, and smaller tumors with a lower histological grade (p.=< 0.001). CONCLUSION – The analysis of the Brazilian population submitted to the 70-gene genomic signature showed a greater proportional number of tumors with low genomic risk than in the test approval study, favoring its application with the aim of de-escalating systemic treatment in this population. Despite the low rate of disease progression in the AGEMA-BRA study, probably determined by the population with the best prognosis disease and the short follow-up, recurrence was similar in the high and low genomic risk groups, demonstrating the adequate selection of systemic therapy following the results of the MP. An increase in the sample size and longer follow-up are necessary to confirm the results found. Table 1. Characteristics of patients and tumor according to risk (AGEMA-BRA) Citation Format: Fabio Mansani, Ruffo Freitas-Junior. PERFORMANCE AND OUTCOMES OF THE 70-GENES SIGNATURE (MAMMAPRINT™) IN A POPULATION WITH MIDDLE INCOME – REAL WORLD STUDY (AGEMA-BRA) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-17-10.

Abstract PO5-08-10: Breast cancer risk prediction performance of polygenic risk score in Taiwanese female with dense breast: A nested case-control study

Abstract Introduction: Breast cancer is the most common cancer among women in Taiwan and the incidence rate of breast cancer has been increasing steadily over the past 30 years. To address this, a nationwide screening program with biennial mammography for women aged 40-69 was implemented in 2004, which has contributed to a significant reduction in breast cancer mortality. Asian women are more likely to have dense breast tissue, and studies have shown a correlation between breast density and the risk of developing breast cancer, with higher breast density values associated with increased risk. Polygenic risk scores (PRS) are calculated based on an individual's genetic information and can estimate their risk of developing a particular disease. Although PRS can identify low-penetrance risk variants, its use in breast cancer risk estimation is typically limited to gene-only models, and integration with breast cancer screening databases is rare. Hence, the aim of this specific study was to evaluate the predictive capacity of PRS in women with dense breast tissue by exploring potential genetic markers and constructing a PRS to investigate the genetic factors associated with clinical characteristics and the risk of developing breast cancer. Methods: The PRS was developed using genetic information from the Taiwan Precision Medicine Initiative genotyping data. A total of 6335 patients were enrolled, and 101 single nucleotide polymorphisms (SNPs) were selected as candidate markers based on the PGS Catalog (PGS000001). Clinical characteristics of the study cohort were summarised using median and range, or frequency and percentage. The distribution of characteristics between breast cancer and controls was estimated using an independent two-sample t-test, chi-square, and Fisher’s exact test. The association of the PRS and related characteristics with breast cancer risk in the study cohort was estimated using univariate and multivariate binomial logistic regression. Harrel’s C-index was reported to demonstrate the predictive performance of PRS in both univariate and multivariate models. All p-values were two-sided, and a p less than .05 is considered statistically significant. All analyses were performed using R 4.1.2 (R core team, 2023) Results: The results showed that breast cancer patients constituted a higher proportion of individuals in PRS Q4 (37.8% vs 24.8% in controls). The model's predictive performance for breast cancer risk increased from 0.565 (95% CI = 0.520-0.611) to 0.699 (95% CI = 0.644-0.755) by adding related clinical characteristics compared to the PRS-only model. Patients characterized with benign breast disease (OR = 0.50, 95% CI = 0.31-0.79, P = 0.004) showed a decreased breast cancer risk, and patients with mastalgia or palpable breast lesion (OR = 6.87, 95% CI = 4.29-10.8, P < 0.001) predicted significant greater breast cancer risk. Subgroup analysis of patients without breast symptoms was conducted as they may be overlooked or underestimated for breast cancer screening. For dense breast patients without symptoms, the high PRS group (Q4) consistently showed a significantly elevated breast cancer risk compared to the low PRS group (Q1-Q3) in both univariate (OR = 2.25, 95% CI = 1.43-3.50, P < 0.001) and multivariate analyses (OR = 2.22, 95% CI = 1.41-3.46, P < 0.001). Conclusion: Breast cancer screening has undergone a shift from a general approach to a personalized, risk-based approach. Besides breast cancer screening using family history as the only risk factor, our proposed model identifies both genetic and clinical risk factors using big data analyses including the EHR, cancer screening, and registry from a single institute. The study suggests that integrating PRS into personalized screening strategies could improve risk prediction for Taiwanese females with dense breasts without prominent symptoms. Table 1. Clinical characteristics of study cohort (n=6335). Table 2. Association of the PRS quartiles in breast cancer risk. Table 3. Predictive performance of PRS for breast cancer risk. Citation Format: Chih Yean Lum, Chih Chiang Hung, Chi-Cheng Huang, Tzu-Hung Hsiao, Sin-Hua Moi. Breast cancer risk prediction performance of polygenic risk score in Taiwanese female with dense breast: A nested case-control study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-08-10.

Abstract PO3-11-05: Sexual dysfunction among Brazilian women with early breast cancer on adjuvant endocrine therapy (ET)

Abstract Background: Sexual dysfunction is a common health problem in women, and it can occur during breast cancer treatment and survivorship. This study aims to determine the frequency of sexual disfunction among Brazilian women with early breast cancer on adjuvant endocrine therapy and to explore its relationships with patients’ clinical and social characteristics, adherence to ET, quality of life, return to work and healthcare insurance. Methodology: Women with history of early-stage ER+ invasive carcinoma of the breast on adjuvant endocrine therapy for at least 6 months were invited to participate of this study. Sexual dysfunction was evaluated using the Female Sexual Function Index questionnaire (FSFI). A score of < 26.55 in FSFI indicates sexual dysfunction. We evaluated sexually active patients (women should have at least one sexual intercourse in the previous four weeks). Demographic and medical information, site of treatment (private versus public), degree of education (completed high school vs not) were reviewed from medical records. Quality of life was assessed using EORTC QLQ C30 and BR-23 forms and adherence to ET was assessed by the Morisky Medication Adherence Scale (MMAS-8). Additionally, patients were interviewed about return to work. Data collection was performed using RedCap software and statistical analyzes were performed on the software R (R Core Team (2022). Qualitative variables were compared between groups using the Chi-square or exact Chi-square test and for quantitative variables the non-parametric Mann-Whitney test was used. Multivariable analysis was performed using Poisson regression. P < 0.05 was considered significant. Analyzes were performed in SAS 9.4. Results: From June 2021 to May 2023, a total of 461 women with ER+ early-stage breast cancer from 12 Brazilian institutions were included in this analysis. The mean age was 56.0 years (range 22-93 ), 47.7% were non-white and 38.7% were premenopausal. A total of 233 women (50.6%) had private insurance and the remaining were treated in public institutions. Median duration of ET use was 2.78 years (range 6 months- 9.61 years).Only 249 (54%) out of 461 patients who accepted to participate in this study declared to have sexual intercourse in the previous 4 weeks before evaluation and composes the population of this analysis. Sexual disfunction according results of FSFI questionnaire was found in 113 (53.3%) participants. Age was significantly associated with sexual dysfunction with women > 40 years-old having higher rates (95.3%) compared with versus younger patients (4.71% p=0.0069). Patients without sexual dysfunction had significantly higher EORTC QLQ C30 Global health status, Physical Functioning, Emotional Functioning, Sexual Functioning and Sexual Enjoyment scores than those with sexual dysfunction (p = 0.0060, p = 0.0242, p = 0 .0353, p = 0.0002 and p < 0.0001 respectively). ET duration between 2 and 5 years vs < 2 years, higher vs lower education level, EORTC QLQ-BR23 breast symptom and sexual functioning higher scores were significantly associated with the occurrence of sexual dysfunction in multivariated analysis (p < 0.05). Conclusion: In our study, only 54% of women evaluated had sexual intercourse in the previous four weeks and from those women 53.3% reported sexual dysfunction. Factors related to sexual dysfunction were higher education level, ET duration between 2 and 5 years, breast symptom and sexual functioning higher scores. div style=margin-top:10px; margin-bottom:20px;>Characteristic with adjusted prevalence ratios for the occurrence of sexual disfunction XX XX PR: prevalence ratio, EORTC: European Organisation for Research and Treatment of Cancer Citation Format: Daniele Assad-Suzuki, Fernanda Moura, Danielle Santos, Sulene Oliveira, Cristiano Souza, Heloísa Resende, Andrea Shimada, Anna Luiza Galvão, Bruno Souza, Amanda Castro, Monalisa Andrade, Yuri Beckedorff, Maria Cristina Magalhães, Carlos Paiva, Angelica Rodrigues, Daniela Pereira, Daniela Rosa, Romualdo Barroso-Sousa. Sexual dysfunction among Brazilian women with early breast cancer on adjuvant endocrine therapy (ET) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-11-05.

Abstract PO3-08-06: Challenges in Implementing Genetic Counseling and Genetic Testing for Breast Cancer: Insights from the First 1000 Families Assessed in a Public University Hospital in Argentina

Abstract Introduction: Integrating genetic testing into breast cancer patients care is crucial for personalized treatment recommendations, risk reduction strategies, and family members evaluation. However, Argentina faces several concerns in implementing these services. Objective: This study aims to explore the challenges encountered in implementing genetic testing for breast cancer, drawing insights from the assessment of the first 1000 patients at a public university hospital in Argentina. Methods: We conducted a retrospective analysis of patients who underwent genetic counseling in our institution from January 2015 to June 2023. We also analyzed patients who underwent surgery from June 2022 to May 2023. Results: 1032 patients were evaluated in our unit. 836 patients (81%) met the National Comprehensive Cancer Network (NCCN) criteria for genetic testing. Genetic testing was requested for 575 patients (68.7%) Only 44% of patients were able to access the test, with 60% receiving only the BRCA1/2 test (see Table 1 and 2 for details). In the analysis of breast cancer surgeries (n=246), 62% (n=154) met the NCCN criteria for genetic testing. However, only 56% of these patients underwent genetic counseling prior to their surgery and only 15 (9.86%) received their results before primary treatment. Discussion Unfortunately, only 9.8% of patients have the results of genetic testing prior to their primary treatment, indicating a critical need for timely referrals and mainstream genetic testing. To counteract, our university hospital's breast cancer unit has taken proactive measures since January 2015. Genetic counseling has been established as a standard of care for all patients, and a streamlined workflow has been implemented to optimize referrals. Trained professionals, including a genetic counselor, psycho-oncologist, and geneticist, have been integrated into core teams. Additionally, healthcare professional continued education has played a pivotal role in improving referrals. Additionally, we have introduced an easy workflow to optimize referrals to genetic counseling. Completion rate of requested genetic tests is concerning, with 56% of tests not being completed, and 60% of the completed tests limited to BRCA1/2. Improving access to genetic testing is imperative. Currently, comprehensive genetic testing is inaccessible to patients without medical coverage, and even those with coverage face difficulties in testing access. Moreover, patient education plays a vital role in promoting the importance of genetic testing and its impact on patient care and their families. In collaboration with the Argentinean Breast Pathology Society, we have developed two informative videos that reinforce knowledge provided by primary care physicians and breast surgeons. Conclusion, Our study is the first in Argentina to analyze the numerous challenges faced in conducting genetic testing for breast cancer in a public hospital. By addressing these challenges collectively, we can facilitate the effective integration of genetic counseling and testing into routine practice for breast cancer patients in Argentina. Table 1: Breast Cancer Genetic Counseling Unit Patients (2015-2023) Table 2: Breast Cancer Genetic Counseling Unit Patients studies (2015-2023) Citation Format: Dolores Mansilla, Diana Bequelman, Jorgelina Cavallero, Hernan Ursino, Berman Gaston, Ipiña Martin, Eduardo Armanasco, Andrea Aguilar, Valeria Caceres, Eugenia Azar. Challenges in Implementing Genetic Counseling and Genetic Testing for Breast Cancer: Insights from the First 1000 Families Assessed in a Public University Hospital in Argentina [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-08-06.

Abstract PO5-17-11: STRATIFICATION OF HIGH GENOMIC RISK IN THE GENETIC SIGNATURE OF 70 GENES (MAMMAPRINT™) IN REAL WORLD ANALYSIS (AGEMA-BRA)

Abstract INTRODUCTION – Although genetic signatures for breast cancer are used to de-escalate chemotherapy treatment, around half of the patients, according to several analyses, present high genomic risk and are conducted in the same way, regardless of the risk score found. The stratification into high risk 1 and high risk 2, proposed in the ISKY-2 cohort, sought to verify the possibility of selecting women with breast cancer who need to escalate the systemic treatment according to the score measured by the MammaPrint™ (MP). OBJECTIVE – To evaluate the outcomes of the AGMA-BRA cohort population (Mammaprint™ genetic signature in the brazilian population), analyzing the characteristics and behavior of patients stratified into high risk 1 (H1) and high risk 2 (H2) by the 70-gene genetic signature. METHODOLOGY – Retrospective study in the AGEMA-BRA cohort with high clinical and genomic risk. They were divided into high risk 1 (H1) with MP score between 0 and > -0.57 and high risk 2 (H2) with MP score ≤ -0.57; analyzing the epidemiological, anatomopathological, immunohistochemical (IHC) profiles and outcomes in the two populations. For the statistical evaluation, a descriptive analysis of the data with absolute and relative frequencies of the variables was performed. To verify the association between qualitative variables, the chi-square test was used. All analyzes were performed in the R 4.1.0 environment (R Core Team, 2021). The AGEMA-BRA study was approved by the ethics and research committee of the State University of Ponta Grossa (CAAE: 12194219.4.0000.0105). RESULTS – The AGEMA-BRA cohort comprises 953 patients with high clinical risk luminal breast cancer, of which 407 (42.7%) are at high genomic risk. After excluding cases that did not contain the necessary information, 176 records were analyzed, with an average follow-up of 40 months. The age group, tumor diameter and number of affected lymph nodes were similar. Statistical significance was observed when evaluating the histological grade where grade 3 was more frequent in cases with the highest risk MP score (H2) with 60% of the records (p. =0.039) (Table 1). As for the IHC analysis, the positivity of estrogen and progesterone receptors, and HER2 did not show statistical significance in the comparison between H1 and H2. In the Ki67 analysis, the comparison with expression >20% was more frequent in population H2 (76.4%) compared to H1 (48.2%) with p.=0.002. Metastasis-free survival (DMFS) was 96.4% for H1 and 95% for H2 (p.=0.269). CONCLUSIONS – The dichotomization of cases with MP score at high risk H1 and high risk H2 in the AGEMA-BRA cohort showed no difference in DMFS, inferring that this classification does not help in the management of these patients. The sample size and short follow-up for a disease that relapses later may have interfered with the result. More robust analysis of these two populations needs to be performed to confirm the presented data. Table 1 - Profile of high genomic risk AGEMA-BRA Citation Format: Fabio Mansani, Ruffo Freitas-Junior. STRATIFICATION OF HIGH GENOMIC RISK IN THE GENETIC SIGNATURE OF 70 GENES (MAMMAPRINT™) IN REAL WORLD ANALYSIS (AGEMA-BRA) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-17-11.

Listening to patients, for the patients: The COVAD Study-Vision, organizational structure, and challenges.

The pandemic presented unique challenges for individuals with autoimmune and rheumatic diseases (AIRDs) due to their underlying condition, the effects of immunosuppressive treatments, and increased vaccine hesitancy. The COVID-19 vaccination in autoimmune diseases (COVAD) study, a series of ongoing, patient self-reported surveys were conceived with the vision of being a unique tool to gather patient perspectives on AIRDs. It involved a multinational, multicenter collaborative effort amidst a global lockdown. Leveraging social media as a research tool, COVAD collected data using validated patient-reported outcomes (PROs). The study, comprising a core team, steering committee, and global collaborators, facilitated data collection and analysis. A pilot-tested, validated survey, featuring questions regarding COVID-19 infection, vaccination and outcomes, patient demographics, and PROs was circulated to patients with AIRDs and healthy controls (HCs). We present the challenges encountered during this international collaborative project, including coordination, data management, funding constraints, language barriers, and authorship concerns, while highlighting the measures taken to address them. Collaborative virtual models offer a dynamic new frontier in medical research and are vital to studying rare diseases. The COVAD study demonstrates the potential of online platforms for conducting large-scale, patient-focused research and underscores the importance of integrating patient perspective into clinical care. Care of patients is our central motivation, and it is essential to recognize their voices as equal stakeholders and valued partners in the study of the conditions that affect them.

Ward-based in situ simulation: lessons learnt from a UK District General Hospital

IntroductionIn situ simulation (ISS) enables multiprofessional healthcare teams to train for real emergencies in their own working environment and identify latent patient safety threats. This study aimed to determine ISS...

Sociological research of the men’s androgenic alopecia problem

Diseases of the skin and its appendages currently occupy one of the leading places in terms of prevalence. In addition, today the relationship between dermatopathologies and the psychoemotional state of people and vice versa is clearly monitored. Psychodermatology is engaged in the study of exactly this regularity. One of the most common trichological diseases is androgenic alopecia, which is characterized by excessive hair loss under the influence of androgens in individuals with a hereditary predisposition. Androgenic alopecia is often accompanied by secondary mental disorders, which significantly impair the quality of people’s life. It is relevant to conduct sociological research of this problem among men of all age groups. Such research will reveal the level of influence of androgenic alopecia on the psychoemotional state of men who may be potential consumers of medicines and dermatocosmetics. The aim of the work was to conduct a sociological study to establish the impact of androgenic alopecia on the psychoemotional state of men and their readiness for pharmacotherapy. Materials and methods. Sociological research was conducted from 01.03.2019 to 31.08.2019 by surveying 150 men aged 18 to 66. Respondents were visitors to pharmacies in the Ivano-Frankivsk and Chernivtsi regions of Ukraine, who gave written consent to participate in the survey. Only persons with visible manifestations of androgenic alopecia according to the Norwood scale were included in the survey. All respondents were divided into the following age groups: from 18 to 20 years old, from 21 to 30 years old, from 31 to 40 years old, from 41 to 50 years old, from 51 to 60 years old, from 61 years old and older. The distribution was carried out to segment the target market. The results of the study were displayed as percentages with 95 % confidence intervals. Statistical analysis was performed using R version 4.1.2 (R Core Team (2021). The results. According to the results of the sociological study, 48.7 % of interviewed men consider that androgenic alopecia is a problem which can affect the emotional state and, so, the quality of life. As a result, about 90 % of the respondents indicated that they need to expand the assortment of effective remedies to solve this problem on the pharmaceutical market of Ukraine, of which 36.7 % are ready to pay for a course of effective pharmacotherapy from 200 to 500 hryvnias. Conclusions. The obtained results confirm that androgenic alopecia has a negative effect on the psychoemotional state of men and worsens their quality of life. To solve the problem of androgenic alopecia, men are interested in using effective medicinal or dermatocosmetic products

P188 Frailty and its impact on patient-reported outcomes in polymyalgia rheumatica

Abstract Background/Aims Frailty is an increasingly important construct in the field of rheumatology, aiding the identification of individuals with increased vulnerability to accelerated clinical decline, and overall worse disease outcomes. The aim of this research was to explore the prevalence of frailty and its potential associated impact on patient reported outcomes (PROs) in a cohort of patients with polymyalgia rheumatica (PMR). Methods Patients with a diagnosis of PMR (fulfilling the 2012 EULAR/ACR Provisional Classification Criteria), who were in clinical remission and on active treatment with glucocorticoids were recruited from two centres. Patients were >3 months and <12 months from diagnosis. Frailty was defined by the 5 criteria of the widely validated Fried Phenotypic Frailty Index. Patient-reported outcomes included anxiety, using the Generalised Anxiety Disorder Assessment (GAD-7), mood using the Patient Health Questionnaire (PHQ-9), fatigue using the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F), pain using the visual analogue scale (VAS) and overall health related quality of life using the Health Assessment Questionnaire-Disability Index (HAQ-DI). The associations between categorical variables were compared using the -test or Fishers exact test. The association between continuous variables and categorical variables was assessed using the Kruskal-Wallis test. Correlations were calculated using Pearson’s r. All analyses were conducted using R (R Core Team, 2022). A p-value of < 0.05 was considered as statistically significant. Results 51 consecutive patients were recruited, of which 56.9% (n = 29) were female. Using the Fried Phenotypic Index, 64.7% (n = 33) were classified as robust, 27.5% (n = 14) as pre-frail and 7.8% (n = 4) as frail. All patients classified as frail were female and had a statistically significantly higher BMI (p = 0.040) than those in the robust and pre-frail categories. Compared to robust individuals, those who were frail had statistically significant higher median GAD-7 (p = 0.003), PHQ-9 (p = 0.001), VAS (p = <0.001) and HAQ-DI (p = <0.001) scores. FACIT-F scores were also worse in those who were frail versus robust (p = 0.001). Conclusion Over one third of patients with PMR in this cohort were classified as pre-frail or frail. Increased frailty status was significantly correlated with worse PROs, including mood, pain, fatigue and overall quality of life. As frailty is a potentially reversible state, accurately identifying frailty, and implementing appropriate interventions is of utmost importance to ensure improved clinical outcomes in those with PMR. Disclosure P. Harkins: Grants/research support; British Society for Rheumatology. S. Cowley: None. R. Harrington: None. D. Kane: None. R. Conway: None.

P183 Cognitive function in polymyalgia rheumatica

Abstract Background/Aims Over the past decade our understanding of the prevalence, and indeed impact, of cognitive impairment in rheumatic diseases has increased. An aging population coupled with systemic inflammation have been postulated as key drivers of increased cognitive decline in these conditions. Intact cognitive function is imperative not only for quality of life and maintenance of one’s functional capacity, but also for the successful therapeutic management of disease, namely the adherence to treatment regimens. The prevalence of cognitive impairment in community dwelling adults above the age of 65 in Ireland has been estimated at 13%.1 To date, the prevalence of cognitive impairment in PMR has not been studied. The aim of this research is therefore to explore the prevalence and potential associated factors of cognitive impairment in those with PMR. Methods Patients with a diagnosis of PMR (fulfilling the 2012 EULAR/ACR Provisional Classification Criteria) who were in clinical remission and on active treatment with glucocorticoids were recruited from two centres. Patients were >3 months and <12 months from diagnosis. Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA) test which was conducted by trained interviewers. Cognitive impairment was defined by the previously validated MoCA cut-off score of < 26. Demographics, clinical and laboratory data, in addition to patient reported outcomes (PROs) were collected. PROs included anxiety using the Generalised Anxiety Disorder Assessment (GAD-7), mood using the Patient Health Questionnaire (PHQ-9), fatigue using the Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F), pain using the visual analogue scale (VAS) and overall health-related quality of life using the Health Assessment Questionnaire-Disability Index (HAQ-DI). The associations between categorical variables were compared using the -test or Fishers exact test. The association between continuous variables and categorical variables were assessed using the Kruskal-Wallis test. Correlations were calculated using Pearson’s r. All analyses were conducted using R (R Core Team, 2022). A p-value of < 0.05 was considered as statistically significant. Results 51 consecutive patients with PMR were recruited, of which 56.9% (n = 29) were female. 70.6% (n = 36) of patients were cognitively impaired, with visuo-spatial, delayed recall and abstraction the most commonly affected cognitive domains. Interestingly, those with cognitive impairment had a younger age, versus those without (p = 0.514). Although not statistically significant, median BMI, anxiety, depression and pain scores were all higher in those who were cognitively impaired. Moreover, median fatigue scores were also worse in the cognitively impaired group. No statistically significant difference in serum markers was observed. Conclusion This study demonstrates that the burden of cognitive impairment in PMR is significant, and is markedly higher than that observed usually at population level. Future studies exploring specific etiologic contributors are needed. Disclosure P. Harkins: Grants/research support; British Society for Rheumatology. S. Cowley: None. R. Harrington: None. D. Kane: None. R. Conway: None.

ALARMING PREVALENCE OF POOR SLEEP AND ANXIETY IN MEDICAL STUDENTS

Objective: Anxiety and sleep disorders have been reported to be common in medical students. This study aimed to determine the frequency of poor sleep quality and anxiety symptoms in medical students. Moreover, to reveal the relationship between sociodemographic characteristics, lifestyle data, perceptions of professional future, academic performance with anxiety, and sleep quality. Material and Methods: A total of 225 participants enrolled in the first through fifth years of education in Kafkas University’s Faculty of Medicine in the 2022-23 academic year participated in the study. Participants were asked to complete a questionnaire encompassed sociodemographic data, lifestyle information that may affect sleep, the Pittsburgh Sleep Quality Index (PSQI), Generalized Anxiety Disorder-7 (GAD-7) scale. Statistical analyses were performed with R Statistical Software (v4.2.2; R Core Team 2022). Results: It was found that 76% of the participants had poor sleep quality according to the PSQI, while 31.56% of the participants had GAD-7 scores of 10 or above. There was a relationship between the poor sleep quality and anxiety of the participants (p

P060 Multi-targeted therapy better in achieving a complete response in Lupus Nephritis: A systematic review and meta-analysis

Abstract Background/Aims Overall management of SLE and Lupus Nephritis (LN) has significantly improved over the last four decades. Recently great therapeutic strides have been made in management of LN using newer agents alone or combination of older therapies. With the availability of increased number of options choosing the optimal treatment regimen for LN has become challenging. Identifying the treatment regimen most effective in achieving complete response while minimizing adverse events is crucial for improving patient outcomes. We performed a systematic review and meta-analysis of clinical trials to explore optimal treatment regimen for LN. Methods The systematic review and meta-analysis were performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The literature search was conducted using public databases, such as the Cochrane Library, Web of Science and PubMed. Only randomized controlled clinical trials with either active comparator or placebo arms were included. Studies were excluded if they were retrospective, with no comparative drug arm, or less than 20 subjects per treatment response arm. Due to lack of agreed upon outcome measures, complete response (CR) and partial response (PR) criteria were determined as per the definition used by individual studies. Severe adverse reaction (SAE) frequencies were determined for each study for safety evaluation. Publication bias was detected by using funnel plots. Forest plots were used to summarize data, generate frequencies, odds ratio (OR), relative risks (RR) and corresponding 95% confidence intervals (CI) for each subgroup. Heterogeneity was evaluated using the I2 statistic, and labelled as low (25%), moderate (50%) and high (75%). All analyses were performed using R Statistical Software meta package (v4.2.1; R Core Team 2022). Results 31 eligible studies comprising 5495 SLE patients were included in analyses, the study characteristic features are shown in Table 1. Overall significant OR for achieving CR was reported by 10 studies (Figure 1). The highest effect was reported from study by Bao et.al using a combination of tacrolimus(TAC) and mycophenolate mofetil (MMF) compared to cyclophosphamide (CYC) (OR = 10.5, 95% CI 2.27; 48.76), another study using TAC+MMF combo reported OR = 2.49, 95% CI 1.59;3.88. The study by Ginzler et.al reported OR = 5.06 (95% CI 1.6:16.02) in favor of using MMF. Studies using CYC, voclosporin + MMF, and belimumab also reported significant OR for achieving CR. Data for the frequency of SAE were available in 22 studies. The frequency of SAE was not significantly different between treatments arms (OR: 1.07, 95%CI: 0.93-1.23, p > 0.05) Conclusion Our meta-analysis suggests multi-target treatment strategies, by adding calcineurin inhibitors to MMF may be better for achieving complete response in LN. Furthermore, using this combination treatment did not seem to increase the risk of side effects. Heterogenous treatment response criteria and variable comparator arms were major limiting factors of this study. Disclosure O. Pamuk: None. B. Shaikh: None. S. Khan: None. S. Abi Doumeth: None. S. Hasni: None.

“STEPS”: A Simulation Tool to Enhance Psychological Safety

BackgroundCreating and maintaining a psychologically safe and welcoming environment is an essential element in simulation-based teaching. The purpose of this project was to describe a novel tool the authors developed to visually enhance psychological safety. Using constructs related to psychological safety, the tool was designed and named “Simulation Tool to Enhance Psychological Safety” (STEPS). MethodsSTEPS was designed by a core team of simulation education specialists and then evaluated by a convenience sample of prelicensure (n = 5) and advanced practice (n = 3) nursing simulation educator experts. Using open-ended responses, thes reviewers gave feedback and suggestions for improvement. ResultsFindings revealed that STEPS was positively evaluated as a visual aid to promote psychological safety. Reviewers offered suggestions for improving design features such as making it more inclusive of other disciplines and adding inspirational quotes. The reviewers unanimously agreed that STEPS would be a successful adjunct for promoting psychological safety in simulation. ConclusionsSTEPS is an innovative visual aid to promote a psychologically safe learning environment. We plan to use the tool in simulations across nursing programs.

Evaluation of elite rice lines for resistance to Kenya blast fungus (Magnapothe Oryzae)

Blast resistance tends to often break down, these necessitate search-resistant genes. The screen house experiment was conducted in 2019 and 2020. A total of 56 rice genotypes, (Elite lines, monogenic lines, and local), were screened against ten Kenya isolates of Mangnaporthe oryzae. The establishment was by direct seeding of previously sprouted seeds. A completely Randomized Design (CRD) with two replicates was adopted. Inoculation was done 21 days after planting. Plants were maintained in the moist chamber (26–28 0C) for 48 hrs, then moved into an incubation chamber (25 ◦C ± 2). Disease assessment commenced 48 hours after inoculation until 21 days to full infection. Disease evaluations were performed according to the Standard Evaluation System of IRRI. Polymerase Chain Reactions (PCR) were carried out, blast resistant loci were identified using varied genetic markers that co-segregate with specific resistant loci Analysis was implemented in R version 3.3.2 (R Core Team, 2016). BLUPs were computed, in a mixed model to estimate the random effect of the genotypes. The data was subjected to analysis of variance and means separated by Tukey’s test at P < 0.05. Cluster analyses were performed in JMP software version 11.2 for Windows. Seven genotypes (IR12A311, IR10M210, IR74, 1R02A127, IR09A130, R66 and IR10N230) were more susceptible, IR13N152 and IR14F711 were more resistant to all Isolates. The monogenic lines IRBLsh-B and IRBLkh-K3 which carry blast-resistant genes, were susceptible to at least seven Kenya isolates. The local checks (Basmati 370, BAS 270 (pi9), BW196, and BAS370 (pi9) were highly susceptible. The genotype IR12F711 was consistently resistant to all Kenya Isolates.

Unveiling blood donation knowledge, attitude, and practices among 12,606 university students: a cross-sectional study across 16 countries

We assessed university students’ knowledge, attitude, and practice toward blood donation and identified the factors that promote or hinder their willingness to donate. We employed a multicenter cross-sectional design, collecting data from August to October 2022 through self-administered questionnaires available in Arabic and English. Both online (Google Forms) and paper surveys were utilized. Data were analyzed using R Statistical Software (v4.1.3; R Core Team 2022). A total of 12,606 university students (7966 females and 4640 males) from 16 countries completed the questionnaire; of them, 28.5% had a good knowledge level regarding blood donation, and 22.7% had donated blood at least once. Students in health science colleges had significantly more awareness of blood donation (p-value < 0.001), but there were no significant differences in practice (p-value = 0.8). Barriers to donation included not being asked (37%), medical ineligibility (33%), fear of pain or infection (18%), concerns about negative health effects (18%), difficulty accessing donation centers (15%), and medical mistrust (14%). Individuals aged > 20 years had significantly higher odds of possessing a high knowledge level (adjusted odds ratio [aOR] 1.77, p < 0.001). Private and international university enrollment was associated with increased knowledge (aOR 1.19, p-value < 0.001 and aOR 1.44, p-value = 0.003), while non-health science college students had lower odds (aOR 0.36, p < 0.001). Regarding blood donation status, participants > 20 years old were more likely to donate (aOR 2.21, p < 0.001). Conversely, being female, having congenital or chronic diseases, and possessing low knowledge levels were associated with decreased odds of blood donation (all p < 0.05). University students show insufficient knowledge about blood donation, with health science students displaying higher awareness levels. Despite their positive attitudes, blood donation rates remain low across all disciplines. It is imperative to enhance education and accessibility to foster a culture of blood donation among students.

A Customizable Digital Cognitive Aid for Neonatal Resuscitation: A Simulation-Based Randomized Controlled Trial.

Adherence to the International Liaison Committee on Resuscitation (ILCOR) algorithm optimizes the initial management of critically ill neonates. In this randomized controlled trial, we assessed the impact of a customizable sequential digital cognitive aid (DCA), adapted from the 2020 ILCOR recommendations, compared with a poster cognitive aid (standard of care [SOC]), on technical and nontechnical performance of junior trainees during a simulated critical neonatal event at birth. For this prospective, bicentric video-recorded study, students were recruited on a voluntary basis, and randomized into groups of 3 composed of a pediatric resident and two midwife students. They encountered a simulated cardiac arrest at birth either (1) with DCA use and ILCOR algorithm poster displayed on the wall (intervention group) or (2) with sole ILCOR algorithm poster (poster cognitive aid [SOC]). Technical and nontechnical skills (NTS) between the two groups were assessed using a standardized scoring of videotaped performances. A neonate specific NTS score was created from the adult Team score. 108 students (36 groups of three) attended the study, 20 groups of 3 in the intervention group and 16 groups of 3 in the poster cognitive aid (SOC) group. The intervention group showed a significant improvement in the technical score ( P < 0.001) with an average of 24/27 points (24.0 [23.5-25.0]) versus 20.8/27 (20.8 [19.9-22.5]) in poster cognitive aid (SOC) group. No nontechnical score difference was observed. Feedback on the application was positive. During a simulated critical neonatal event, use of a DCA was associated with higher technical scores in junior trainees, compared with the sole use of ILCOR poster algorithm.