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Abstract Background: Prostate cancer (PCa) in men is, to date, the number one cause of death from cancer worldwide. PCa has been associated with a large number of lifestyle factors, including unhealthy dietary habits. In particular, diet and nutrition have been shown to play pivotal roles in PCa, and the habitual consumption of certain specific foods like meat cooked at very high temperatures has been implicated. However, this has not been documented among Black men. The aim of this study was to determine the association between dietary patterns and their association with the occurrence of prostate cancer. Method: This is a longitudinal multisite Prostate Cancer Transatlantic Consortium (CaPTC) familial cohort phase 2 study. Participants were Nigerian Black men between 35 and 70 years old who were willing to participate in the study over a 10-year period. For the food variety score, a score of 1 was given for each food item eaten weekly, and the aggregate food variety score was totaled and categorized as ≥54% very good, 45%–53% was good, 36%–44% fair, 18%–35% poor and <18% was very poor. Data were analyzed using descriptive statistics, such as frequency analyses. Chi-square analysis was used to evaluate dichotomous variables to compare groups based on demographic factors and the occurrence of PCa. Multivariate logistic regression was used to determine the specific predictors of the diagnosis of PCa with potential adjustment for the other demographic variables. P-values < 0.05 was set as significant. Results: A total of 780 participants were recruited, with 72.6% reporting no history of cancer. The median age was 47.00 (range: 21-97),16.5% have been diagnosed with Pca, and 1.5% were diagnosed with other Cancers. Age of cancer diagnosis showed that 21% were diagnosed at about 50 years. Participants’ fruit consumption showed that 28.4%, 29%, 39.5%, 23%, 31%, 28.7%, and 39.2, ate apples, mango, citrus, papaya, green banana, tomatoes, and watermelon, weekly, respectively. Fish was the most consumed protein source of animal origin irrespective of the cooking methods categories, such as boiling, frying, grilling, and smoking. The median food variety score was 20 (0-67), with 8.5%, 3.8%,49.3%, and 26.8% classified as good, very good, poor, and very poor, respectively. Multivariate analysis showed that the category of food variety score (P=0.0009), age (P<0.0001), and grilled fish consumption (P=0.0333) were found to be associated with Pca occurrence. Conclusions: The study showed that food variety score, age, and fish consumption were the correlates of prostate cancer occurrence in the population studied. Citation Format: Opeyemi O. Bolajoko, Catherine A. Oladoyinbo, Daniel Lee, Oluwaseyi Toye, Parisa Fathi, Robert Turesky, Ademola Popoola, Iya Bassey, Solomon Rotimi, Paul Jibrin, Chidebere Ogo, Abidemi Omonisi, Adebanji Adeniji, Anthonia Showunmi, Omolara Fatiregun, Ayo Salako, Haruna Nggada, Faruk Mohammed, Ifeoma Okoye, Ernie Kaninjing, Folakemi Odedina. Association between dietary patterns and occurrence of prostate cancer among Nigerian men: The CaPTC Familial Cohort Study [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B055.

ABSTRACT Early COVID-19 convalescent plasma (CCP) transfusion to outpatients with COVID-19 decreases progression to hospitalization, but the mechanism of how CCP reduces severity is unknown. Among 882 COVID-19 participants transfused with CCP or control plasma in a randomized controlled trial, 21 cytokines and chemokines were measured using electrochemiluminescence assays. Wilcoxon rank sum tests were used to evaluate the difference between early (transfused within 5 days of symptom onset) CCP vs early control plasma and late (transfused 6–9 days after symptom onset) CCP vs late control plasma at each visit. Linear mixed-effect models were used to assess the difference in the slope of cytokine change. Median cytokine and chemokine levels were similar between the early CCP and early control groups pre-transfusion. At the day 14 visit, only the median IL-6 ( P = 0.014) and IL-16 ( P = 0.036) levels were lower in the early CCP group compared to the early control group, but these differences were not statistically significant after correcting for multiple comparisons (requiring P < 0.0024). IL-6 levels decreased significantly faster in the early CCP group from screening to the day 14 visit compared to the early control group ( P < 0.001). No difference was observed in the slope of cytokine change from screening to day 90 between early CCP and early control groups. Late control and late CCP arms showed similar cytokine and chemokine levels through study follow-up. One mechanism by which early CCP transfusion reduces hospitalization may be by decreasing IL-6 levels, as the reduction is associated with better recovery from COVID-19. IMPORTANCE This study examined the role that cytokines may have played in the beneficial outcomes found when outpatient individuals infected with SARS-CoV-2 were transfused with COVID-19 convalescent plasma (CCP) early in their infection. We found that the pro-inflammatory cytokine IL-6 decreased significantly faster in patients treated early with CCP. Participants with COVID-19 treated with CCP later in the infection did not have the same effect. This decrease in IL-6 levels after early CCP treatment suggests a possible role of inflammation in COVID-19 progression. The evidence of IL-6 involvement brings insight into the possible mechanisms involved in CCP treatment mitigating SARS-CoV-2 severity.

Abstract Background Post-COVID conditions (PCC) are common, and risk factors include older age and female sex. While high interleukin (IL)-6 and C-reactive protein are associated with more severe disease, it is unclear whether other cytokines are associated with PCC. This study was performed to identify factors associated with PCC development. Methods The Convalescent Plasma to Limit SARS-CoV-2 Associated Complications (CSSC-004) trial was a double-blind, multi-center, randomized, controlled trial comparing the use of COVID-19 convalescent plasma (CCP) to control plasma for the prevention of hospitalization among COVID-19 outpatients. Among 882 individuals participating in the trial with available biospecimens and symptom data, the association between early COVID-19 treatment, cytokine levels and PCC was evaluated. Cytokine and chemokine levels were assessed at baseline, day 14 and day 90 using a multiplexed sandwich immuosassay. Presence of any PCC symptom was assessed at day 90. Associations between COVID-19 treatment, cytokine levels and PCC were examined using multivariate logistic regression models. Results Baseline characteristics were similar by trial treatment group (Figure 1). At day 90, 292 (33.1%) participants had PCC. The most common symptoms were fatigue (14.5%), anosmia (14.5%), and ageusia (10.0%). Levels of most cytokines decreased over time (Figure 2). Six pro-inflammatory cytokines especially IL-6 were elevated at baseline among those with PCC (Figure 3). In multivariable analysis, female sex (adjusted odds ratio [AOR]=2.70[1.93-3.81]), age 50 or greater (AOR=1.32[1.17-1.50]), and elevated baseline IL-6 (AOR=1.59[1.02-2.47]) were associated with development of PCC, whereas race, obesity, vaccine status and diabetes were not. Those who received early CCP treatment (&lt;5 days after symptom onset) compared to late CCP treatment had statistically significant lower odds of PCC (AOR=0.60 [0.38-0.95]). Conclusion This study showed high prevalence of PCC symptoms at day 90, particularly among those with higher baseline levels of IL-6 or who did not receive early CCP treatment. The potential utility of IL-6 modulation as a therapeutic intervention among individuals as higher risk for PCC should be studied. Disclosures Kelly Gebo, MD, MPH, Pfizer: Advisor/Consultant|Spark HealthCare: Advisor/Consultant Sonya L. Heath, MD, Pfizer: Data Monitoring Committee/DSMB Shmuel Shoham, MD, adagio: Advisor/Consultant|Adamis: Advisor/Consultant|ansun: Grant/Research Support|Avir Pharma: Honoraria|cidara: Grant/Research Support|F2G: Grant/Research Support|Immunome: Advisor/Consultant|Karius: Honoraria|Scynexis: Advisor/Consultant|zeteo: Grant/Research Support Judith S. Currier, M.D., MSc, Merck and Company: Advisor/Consultant|Merck and Company: Honoraria Moises A. Huaman, MD, MSc, AN2 Therapeutics Inc: Grant/Research Support|Gilead Sciences Inc: Grant/Research Support|Insmed Inc: Grant/Research Support Jay S. Raval, MD, Sanofi Genzyme: Advisor/Consultant Arturo Casadevall, MD, PhD, Ortho Diagnostics: Speakers Bureau|Sabtherapeutics: Advisor/Consultant

Abstract Background Empiric antibiotic selection in outpatient care often relies on inpatient antibiograms which may not accurately reflect ambulatory susceptibility rates. To address this, Novant Health (NH) and Labcorp analyzed urine culture results from North Carolina (NC) to create an ambulatory antibiogram and assess temporal and regional differences. Methods Cross-sectional study of urine culture data collected 1/1/20-12/31/21 from ambulatory sites in NC. Testing and antibiogram preparation were performed at Labcorp (Burlington, NC) based on CLSI guidelines (M100 S28). Pediatric and adult data were compiled separately. NH and state-wide data were analyzed using the chi-square or Fisher exact test with Bonferroni correction for multiple comparisons. Results In 2021, Escherichia coli was the most common isolate for NH (n=18937 adult, n=624 pediatric) and state-wide (n=87,226 adult; n=2696 pediatric). E. coli was ≥ 80% susceptible to all tested antibiotics except ampicillin; Klebsiella pneumoniae was ≥ 80% susceptible to all except nitrofurantoin; and Proteus mirabilis/penneri was ≥ 80% susceptible to all antibiotics tested. Susceptibility rates were similar between NH and state-wide data except for lower susceptibility to ceftriaxone (94% vs 95%; p&lt; .001). Compared to 2020, state-wide adult E. coli isolates from 2021 had increased susceptibility for amoxicillin/clavulanic acid (86% vs 85%), ampicillin (60% vs 59%), cephalosporins (84-93% vs 82-92%), and quinolones (87% vs 86%) (p&lt; .001 all). NH isolates did not show significant changes. Susceptibility rates by region were similar, except for lower susceptibility to cefuroxime among adult E. coli isolates in the Triad region relative to state-wide (82% vs 84%; p&lt; .001). No significant temporal or regional differences in susceptibility were observed for K. pneumoniae, Proteus spp., P. aeruginosa, and among pediatric samples. Conclusion Susceptibility data were largely similar in NH vs. state-wide data, and between regions. Small but statistically significant temporal changes were found in state-wide data. Overall, our results support use of a state-wide antibiogram to inform treatment choices across all regions and within specific healthcare systems. Disclosures Dusica Curanovic, PhD, Labcorp: employed by labcorp during study|Labcorp: Stocks/Bonds Chris Garcia, MD, Labcorp: Prior employee|Labcorp: Stocks/Bonds Catherine Wright, PhD, Labcorp: Employee|Labcorp: Stocks/Bonds Rita Stainback, MS, MT (ASCP) SM, DLM, Labcorp: Employee|Labcorp: Stocks/Bonds Melissa Martin, BS, Labcorp: Employee Samia Naccache, PhD, D(ABMM), Labcorp: Employee|Labcorp: Stocks/Bonds Kristen Smith, PhD, bioMerieux: Employee|Labcorp: Stocks/Bonds Howard Engler, PhD, D(ABMM), Labcorp: Employee|Labcorp: Stocks/Bonds

Slow, deep breathing (SDB) is thought to lead to reductions in blood pressure by decreasing vascular‐sympathetic coupling. Venous Occlusion Plethysmography (VOP) is used to assess forearm blood flow (FBF) (ml/min/100 dl tissue). We used this technique to determine the vasodilatory effect of device‐guided (DG) vs self‐paced (SP) slow, deep breathing. We hypothesized that SP would lead to a larger vasodilation response than DG due to a more profound reduction in vascular‐sympathetic coupling, and that this would be correlated with psychological evaluations. Young, healthy male subjects (Mean age: 20 yr; DG: n=10; SP: n=11) rested supine for 20 minutes (baseline), followed by 20 minutes of SP or DG slow, deep breathing, then completed 20 minutes of endogenous breathing (recovery). At baseline, there was no difference in breathing rate between SP and DG (14.36±1.03 vs 15.39±1.29 breaths per minute, p=0.27) and respiratory rate was reduced to 8.36±0.74 breaths per minute (BPM) in the SP group (p<0.01 compared to baseline) and to 6.37±0.10 BPM in the DG group (p<0.01 compared to baseline). Respiratory rates between the two groups differed significantly during SDB (p<0.01 between groups). There was a significant increase in SP FBF compared to baseline at the end of the 20 minute intervention (p<0.05),while the DG group saw no significant increases. In DG, there was a strong negative correlation with the cognitive interference scores to VOP responsiveness (−0.77; R2=0.591), as well as between the cognitive failure score and VOP responsiveness (−0.61; R2=0.3693). In contrast, the SP groups had positive correlations when comparing VOP responsiveness to cognitive interference (0.1; R2=0.093) or cognitive failure (0.30; R2=0.011). For subjects in either breathing group, those who had an increase in FBF in response to SDB also had reductions in STAI anxiety score after the intervention whereas those with a decrease in FBF to SDB had an increase in anxiety score during the slow breathing (p=0.04). Overall, male subjects have a variable vasodilator responses to two types of SDB practices related to underlying psychological metrics. Our data underscores the importance of psychological metrics in physiological outcomes related to SDB practices.

Abstract Aims Obesity is causally related to the development of heart failure with preserved ejection fraction (HFpEF) but complicates the diagnosis and treatment of this disorder. We aimed to determine the relationship between severity of obesity and clinical, echocardiographic and haemodynamic parameters in a large cohort of patients with documented HFpEF. Methods and results The REDUCE LAP-HF II trial randomized 626 patients with ejection fraction ≥40% and exercise pulmonary capillary wedge pressure (PCWP) ≥25 mmHg to atrial shunt or sham procedure. We tested for associations between body mass index (BMI), clinical characteristics, cardiac structural and functional abnormalities, physical limitations, quality of life and outcomes with atrial shunt therapy. Overall, 60.9% of patients had BMI ≥30 kg/m2. As the severity of obesity increased, symptoms (Kansas City Cardiomyopathy Questionnaire score) and 6-min walk distance worsened. More severe obesity was associated with lower natriuretic peptide levels despite more cardiac remodelling, higher cardiac filling pressures, and higher cardiac output. Lower cut points for E/e′ were needed to identify elevated PCWP in more obese patients. Strain measurements in all four chambers were maintained as BMI increased. Pulmonary vascular resistance at rest and exercise decreased with higher BMI. Obesity was associated with more first and recurrent heart failure events. However, there was no significant interaction between obesity and treatment effects of the atrial shunt. Conclusions Increasing severity of obesity was associated with greater cardiac remodelling, higher right and left ventricular filling pressures, higher cardiac output and increased subsequent heart failure events. Despite significant obesity, many HFpEF patients have preserved right heart and pulmonary vascular function and thus, may be appropriate candidates for atrial shunt therapy.

AimsPatients with Crohn's disease (CrD) have an elevated risk for the development of small bowel adenocarcinomas (SBAs). Actionable isocitrate dehydrogenase 1 (IDH1) mutations have been reported to be more frequent in CrD‐SBAs than in sporadic SBAs. The present study aimed to investigate the clinicopathological and immunophenotypical features, as well as methylation profiles, of IDH1‐mutated CrD‐SBAs.Methods and resultsAn international multicentre series of surgically resected CrD‐SBAs was tested for IDH1 mutation. Clinicopathological features, immunophenotypical marker expression and O6‐methylguanine‐DNA methyltransferase (MGMT) and long interspersed nuclear element‐1 (LINE‐1) methylation were compared between IDH1‐mutated and IDH1 wild‐type CrD‐SBAs. Ten (20%) of the 49 CrD‐SBAs examined harboured an IDH1 mutation and all the mutated cancers harboured the R132C variant. Compared to IDH1 wild‐type cases, IDH1‐mutated CrD‐SBAs showed significantly lower rates of cytokeratin 7 expression (P = 0.005) and higher rates of p53 overexpression (P = 0.012) and MGMT methylation (P = 0.012). All three dysplastic growths associated with IDH1‐mutated SBAs harboured the same IDH1 variant (R132C) of the corresponding invasive cancer, and all were of non‐conventional subtype (two serrated dysplastic lesions and one goblet cell‐deficient dysplasia). In particular, non‐conventional serrated dysplasia was significantly associated with IDH1‐mutated CrD‐SBAs (P = 0.029). No significant cancer‐specific survival difference between IDH1‐mutated CrD‐SBA patients and IDH1 wild‐type CrD‐SBA patients was found (hazard ratio = 0.55, 95% confidence interval = 0.16–1.89; P = 0.313).ConclusionsIDH1‐mutated CrD‐SBAs, which represent approximately one‐fifth of total cases, are characterised by distinctive immunophenotypical features and methylation profiles, with potential therapeutic implications. Moreover, IDH1‐mutated non‐conventional, serrated dysplasia is likely to represent a precursor lesion to such CrD‐SBAs.

Background Inconsistent nomenclature and anatomical descriptions of regional anesthetic techniques hinder scientific communication and engender confusion; this in turn has implications for research, education and clinical implementation of regional anesthesia. Having produced standardized nomenclature for abdominal wall, paraspinal and chest wall regional anesthetic techniques, we aimed to similarly do so for upper and lower limb peripheral nerve blocks. Methods We performed a three-round Delphi international consensus study to generate standardized names and anatomical descriptions of upper and lower limb regional anesthetic techniques. A long list of names and anatomical description of blocks of upper and lower extremities was produced by the members of the steering committee. Subsequently, two rounds of anonymized voting and commenting were followed by a third virtual round table to secure consensus for items that remained outstanding after the first and second rounds. As with previous methodology, strong consensus was defined as ≥75% agreement and weak consensus as 50%–74% agreement. Results A total of 94, 91 and 65 collaborators participated in the first, second and third rounds, respectively. We achieved strong consensus for 38 names and 33 anatomical descriptions, and weak consensus for five anatomical descriptions. We agreed on a template for naming peripheral nerve blocks based on the name of the nerve and the anatomical location of the blockade and identified several areas for future research. Conclusions We achieved consensus on nomenclature and anatomical descriptions of regional anesthetic techniques for upper and lower limb nerve blocks, and recommend using this framework in clinical and academic practice. This should improve research, teaching and learning of regional anesthesia to eventually improve patient care.