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Abstract Disclosure: E.R. Uddenberg: None. N. Safwan: None. G. Cook-Wiens: None. O. Obrutu: None. M. Saadedine: None. M.D. Hurtado: None. S. Faubion: None. M.D. Pisarska: None. S.L. Berga: None. J.E. Manson: None. C.N. Bairey Merz: None. C.L. Shufelt: None. Background: Functional hypothalamic amenorrhea (FHA) occurs in women of reproductive age and is a common form of secondary amenorrhea that results in hypoestrogenemia and hypercortisolemia. The underlying cause of FHA is due to a mismatch between energetic intake and expenditure that often manifests as disordered eating, excessive exercise, and psychosocial stress. Previous research identified that 1 in 3 women with FHA had endothelial dysfunction, a preclinical marker for cardiovascular disease. We sought to evaluate the nutrition content in young women with FHA compared to eumenorrheic controls and further assess the relationship to endothelial dysfunction. Methods: We enrolled 30 women with FHA and 29 eumenorrheic controls, not on hormones. FHA was defined as ≥3 consecutive months of amenorrhea, estradiol <50 pg/mL, FSH<10 mIU/L, and LH<10 mIU/L, and exclusion of polycystic ovary syndrome, hyperprolactinemia, thyroid dysfunction, and pregnancy. Eumenorrheic controls had monthly menses with ovulation (progesterone ≥4 ng/mL). Vascular function was measured using EndoPAT 2000 (Itamar® Medical Ltd) to calculate the reactive hyperemic index (RHI). An RHI ≤1.67 indicates endothelial dysfunction. Nutritional intake was collected using a 3-day food diary and analyzed using ESHA Research Food Processor® Nutrition Analysis. Percent (%) recommendation values for nutrition content comparison were calculated based on height, weight, and age. Statistical analysis included Analysis of Variance and Kruskal Wallis test with nonparametric variables reported as median [IQR]. Results: The mean age and BMI of FHA and controls were 26.4 ± 6.2 yrs and 30.3 ± 3.7 yrs (p=0.008), and 21.6 ± 6.2 and 21.8 ± 2.0 kg/m2 (p=0.16), respectively. The median months of FHA amenorrhea was 12 months [5.0, 34.0]. After adjusting for age, there was no difference in caloric intakes in women with FHA compared to controls (1783.9 [1465, 2011] kcal vs. 1731.9 [1578, 1982] kcal, p=0.73); however FHA has higher intake of grams of protein (84.2 [74, 112] g vs. 74 [59, 92] g, p=0.0036), and higher grams of dietary fiber (30.1 [22, 43] g vs. 17.3 [15, 23] g, p=0.0037), respectively. In women with FHA, endothelial dysfunction was associated with a higher % recommended calories (p=0.0098), calories from fat (p=0.02), grams of saturated fat (p=0.03), and grams of carbohydrates (p=0.049). Conclusions: Our results demonstrate that women with FHA consumed similar daily calories, although more grams of protein and dietary fiber than controls. In women with FHA, higher calories, calories from fat, grams of saturated fat and carbohydrates were associated with endothelial dysfunction. Future studies should aim to identify other factors related to endothelial dysfunction among women with FHA and whether some FHA phenotypes are associated with more endothelial dysfunction than others. Presentation: 6/1/2024

Abstract Disclosure: E.R. Uddenberg: None. N. Safwan: None. G. Cook-Wiens: None. O. Obrutu: None. M. Saadedine: None. M.D. Hurtado: None. S. Faubion: None. M.D. Pisarska: None. S.L. Berga: None. J.E. Manson: None. C.N. Bairey Merz: None. C.L. Shufelt: None. Background: Functional hypothalamic amenorrhea (FHA) occurs in women of reproductive age and is a common form of secondary amenorrhea that results in hypoestrogenemia and hypercortisolemia. The underlying cause of FHA is due to a mismatch between energetic intake and expenditure that often manifests as disordered eating, excessive exercise, and psychosocial stress. Previous research identified that 1 in 3 women with FHA had endothelial dysfunction, a preclinical marker for cardiovascular disease. We sought to evaluate the nutrition content in young women with FHA compared to eumenorrheic controls and further assess the relationship to endothelial dysfunction. Methods: We enrolled 30 women with FHA and 29 eumenorrheic controls, not on hormones. FHA was defined as ≥3 consecutive months of amenorrhea, estradiol <50 pg/mL, FSH<10 mIU/L, and LH<10 mIU/L, and exclusion of polycystic ovary syndrome, hyperprolactinemia, thyroid dysfunction, and pregnancy. Eumenorrheic controls had monthly menses with ovulation (progesterone ≥4 ng/mL). Vascular function was measured using EndoPAT 2000 (Itamar® Medical Ltd) to calculate the reactive hyperemic index (RHI). An RHI ≤1.67 indicates endothelial dysfunction. Nutritional intake was collected using a 3-day food diary and analyzed using ESHA Research Food Processor® Nutrition Analysis. Percent (%) recommendation values for nutrition content comparison were calculated based on height, weight, and age. Statistical analysis included Analysis of Variance and Kruskal Wallis test with nonparametric variables reported as median [IQR]. Results: The mean age and BMI of FHA and controls were 26.4 ± 6.2 yrs and 30.3 ± 3.7 yrs (p=0.008), and 21.6 ± 6.2 and 21.8 ± 2.0 kg/m2 (p=0.16), respectively. The median months of FHA amenorrhea was 12 months [5.0, 34.0]. After adjusting for age, there was no difference in caloric intakes in women with FHA compared to controls (1783.9 [1465, 2011] kcal vs. 1731.9 [1578, 1982] kcal, p=0.73); however FHA has higher intake of grams of protein (84.2 [74, 112] g vs. 74 [59, 92] g, p=0.0036), and higher grams of dietary fiber (30.1 [22, 43] g vs. 17.3 [15, 23] g, p=0.0037), respectively. In women with FHA, endothelial dysfunction was associated with a higher % recommended calories (p=0.0098), calories from fat (p=0.02), grams of saturated fat (p=0.03), and grams of carbohydrates (p=0.049). Conclusions: Our results demonstrate that women with FHA consumed similar daily calories, although more grams of protein and dietary fiber than controls. In women with FHA, higher calories, calories from fat, grams of saturated fat and carbohydrates were associated with endothelial dysfunction. Future studies should aim to identify other factors related to endothelial dysfunction among women with FHA and whether some FHA phenotypes are associated with more endothelial dysfunction than others. Presentation: 6/1/2024

Background Cerebral sinus venous thrombosis (CSVT) has traditionally been treated medically with systemic anticoagulation. Recent advances in endovascular therapy (EVT) may represent an alternative treatment to medical therapy for CSVT. We conducted a systematic review and meta-analysis to evaluate the use of EVT for CSVT. Methods We conducted a systematic literature review using PubMed, Embase, Scopus, and Web of Science. We included studies that reported outcomes following EVT for CSVT. The primary outcome of interest was rate of modified Rankin Scale (mRS) 0–2. Secondary outcomes of interest were rates of complete, partial, and failed recanalization, mortality, and new or expansion of hematoma. We calculated pooled rates (%) and their corresponding 95% confidence intervals (CIs). Results Thirty-eight studies with 682 patients were included. Rate of mRS 0–2 was 82.6% (95% CI, 75.3%–88.0%). Rate of complete recanalization was 60.9% (95% CI, 49.1%–71.5%), rate of partial recanalization was 34.2% (95% CI, 24.1%–45.9%), and rate of failed recanalization was 5.4% (95% CI, 3.1%–9.2%). Rate of mortality was 6.7% (95% CI, 4.1%–10.8%), and rate of new hematoma or expansion of hematoma was 5.1% (2.9%–8.8%). Conclusions In this systematic review and meta-analysis, EVT for CSVT was associated with favorable rates of mRS 0–2 and recanalization. Furthermore, EVT was associated with a promising safety profile. Future prospective, comparative studies are warranted to assess EVT for CSVT.

Abstract OBJECTIVES To estimate gender disparities among first and last authorships in cardiothoracic randomized controlled trials (RCTs) and association of gender with publications in high-impact journals. METHODS PubMed/MEDLINE database was searched from 1 January 2014 to 31 December 2020 using R statistical software via the ‘easyPubMed’ package to retrieve pertinent data. The ‘gender’ package was utilized to determine gender using the United States Social Security Administration Baby Name Data. The percentage of female first and last authors were computed along with determining the uniqueness of the names. The association of gender and publication in high-impact peer-reviewed journals was delineated. Jonckheere’s trend was computed. RESULTS The database search retrieved a total of 4820 RCTs, of which gender was encoded for the first author in 3247 (67%) RCTs, among which 911 (28%) studies had women as first authors, with a similar trend across 7 years (P = 0.23). Gender was encoded for the last author of 3204 (66%) RCTs, of which 622 (19%) studies had women as last authors, with a similar trend across 7 years (P = 0.45). A total of 627 studies were published in high-impact-factor journals, among which 79 (16%) studies had female first authors and 67 (13%) studies had female last authors. CONCLUSIONS There is an obvious gender disparity of first and last authors in cardiothoracic surgery-related RCTs, with a similar trend across 7 years. However, the post-hoc analysis did demonstrate a positive trend with an increase in the number of female first authors, demonstrating progress.

Objective Peripheral nerve stimulation (PNS) is an emerging neuromodulation modality, yet there remains limited data highlighting its long-term effectiveness. The objective of this study was to report real-world data on pain intensity and opioid consumption after temporary and permanent PNS for chronic pain up to 24 months postimplantation. Methods A retrospective study was conducted on all patients who received PNS implants at a multi-centered enterprise between January 1, 2014 and February 24, 2022. The two co-primary outcomes were: (1) change in pain intensity (11-point Numerical Rating Scale) from baseline to 12 months postimplant; and (2) comparison of the change in pain intensity between temporary and permanent PNS cohorts 12 months postimplant. Results 126 patients were included in this analysis. Pain intensity significantly decreased 12 months postimplant in the overall cohort (mean difference (MD) −3.0 (95% CI −3.5 to −2.4), p<0.0001). No significant difference in this reduction was identified between temporary and permanent PNS cohorts (MD 0.0 (95% CI −1.1 to 1.0), p=1.00) 12 months postimplantation. Pain intensity significantly decreased in the overall, temporary, and permanent cohorts at all secondary time points (3, 6, and 24 months). No change in daily opioid consumption was observed at 6 and 12 months postimplant in the overall cohort. Conclusion This study found that both temporary and permanent PNS may be effective for reducing pain intensity in patients with chronic pain up to 24 months postimplantation, although no changes in opioid consumption were observed. The decrease in pain intensity was comparable between patients receiving temporary versus permanent implants, highlighting that temporary PNS may achieve long-lasting clinical benefits. However, given the substantial loss to follow-up, further large-scale studies are needed to solidify conclusions about the efficacy of PNS.

Background The efficacy of spinal cord stimulation (SCS) in chronic pain studies is traditionally assessed by pain scores, which do not reflect the multidimensional nature of pain perception. Despite the evidence of SCS’s influence on emotional functioning comprehensive assessments of its effect remain lacking. Objective To assess changes in emotional and psychosocial functioning in patients who underwent SCS implantation for chronic pain. Evidence review Ovid MEDLINE, EMBASE, PsychINFO, Cochrane CENTRAL and Scopus databases were searched for original peer-reviewed publications reporting emotional functioning after SCS. The primary outcomes were a pooled mean difference (MD) in anxiety, depression, global functioning, mental well-being and pain catastrophizing at 12 months. The Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) was used to determine the quality of evidence. Findings Thirty-two studies were included in the primary analysis. Statistically significant improvements were observed in anxiety (MD −2.16; 95% CI −2.84 to −1.49; p<0.001), depression (MD −4.66; 95% CI −6.26 to −3.06; p<0.001), global functioning (MD 20.30; 95% CI 14.69 to 25.90; p<0.001), mental well-being (MD 4.95; 95% CI 3.60 to 6.31; p<0.001), and pain catastrophizing (MD −12.09; 95% CI −14.94 to −9.23; p<0.001). Subgroup analyses revealed differences in Global Assessment of Functioning and mental well-being based on study design and in depression based on waveform paradigm. Conclusion The results highlight the statistically and clinically significant improvements in emotional and psychosocial outcomes in patients with chronic pain undergoing SCS therapy. However, these results need to be interpreted with caution due to the very low certainty of evidence per the GRADE criteria. PROSPERO registration CRD42023446326.

9000 Background: Despite IMGs accounting for up to one-third of all practicing oncologists in the United States, little is known about their contributions to presentations at international oncology meetings, such as the American Society of Clinical Oncology (ASCO). Therefore, we investigated the representation of IMGs in invited faculty roles at ASCO Annual Meetings. Methods: Speaker presentation details at ASCO 2022 and 2023 Annual Meetings were collected using publicly available program guides. We collected presentation-level variables of invited faculty roles (discussant, moderator, chairmanship, session topic presenter) and original research type (oral abstract, poster discussion, plenary session). Speaker-level variables comprised presumed gender, academic rank, and institution. Speakers were categorized into the following groups - American Medical Graduate (AMG): currently affiliated with a US institution, completed medical school in the US; IMG: affiliated with a US institution, completed medical school outside the US; non-US based speakers: affiliated with an institution outside the US; non-MD speakers. Univariable and multivariable analyses were employed to assess factors associated with the selection of presenters for invited faculty roles. Results: A total of 3337 presentations (1649 from 2022, 1688 from 2023) were included. 71.6% of the speakers were US-based, 56.6% were male and 40.5% were full professors. The highest proportion of podium presentations was by AMGs (48.5%), followed by non-US based (28.3%), IMGs (14.1%), and non-MD (9.1%) speakers. 57% of IMG presentations consisted of original research compared to 48.7% for AMGs (Table). Notably, compared to AMGs, IMGs were significantly less likely to be included in invited faculty roles (odds ratio [OR] 0.72 [95% CI 0.58 – 0.88], p <0.01), a finding that remained significant after accounting for gender and academic rank (adjusted OR 0.75 [0.61 – 0.94], p= 0.01). Conclusions: Relative to IMGs’ original research output, IMGs appear to receive less invitations for ASCO Annual Meeting invited faculty roles compared to AMGs. Our findings suggest potential under-representation and under-recognition of IMGs in these roles, despite their contributions to the oncology workforce in the US. [Table: see text]

7542 Background: Teclistamab, a novel bispecific monoclonal antibody targeting CD3 and BCMA, exhibits promising effects for patients with relapsed and refractory multiple myeloma (MM). However, rates of acute kidney injury (AKI) associated with this therapy remains inadequately characterized. Methods: This was a retrospective observational cohort study of patients with relapsed refractory MM who received teclistamab or Chimeric Antigen Receptor T-cell Therapy (CAR-T) therapy at Mayo Clinic between 12/1/2022-5/15/2023 and who were not in kidney failure at the time of treatment. The primary endpoint was incidence of AKI during follow-up; secondary endpoints included treatment and recovery from AKI. AKI was defined based on Kidney Disease Improving Global Outcomes criteria as an increase of serum creatinine levels > 1.5 times their baseline value after starting therapy. Cumulative incidences and Cox proportional hazard regression models were used to evaluate time to event data. Results: A total of 64 patients met inclusion criteria for the study (30 received CAR-T and 34 received teclistamab therapy). There were 14 AKI events occurring during follow-up (10 teclistamab [n = 6 stage 1, n = 3 stage 2 and n = 1 stage 3] and 4 CAR-T [n = 3 stage 1 and n = 1 stage 2]). Cumulative incidence estimates of AKI at 120 days after treatment were 32% (95% CI: 14%-47%) for teclistamab patients and 10% (95% CI: 0%-21%) for CAR-T patients. While patients receiving teclistamab were found to be at increased risk of an incident AKI event compared to patients receiving CAR-T therapy, results were not statistically significant (HR (95% CI): 3.38 (0.93-12.31), p = 0.065). Median time to development of AKI was 30 days (IQR 16, 73) in teclistamab and 59 days (IQR 9, 146) in CAR-T patients. Among the 10 patients in the teclistamab group with an AKI event, 4 (40%) had complete renal recovery and 4 (40%) had partial recovery, while among the 4 patients with CAR-T with an AKI event, 2 (50%) experienced complete renal recovery and 2 (50%) experienced partial recovery. Conclusions: Our study showed that almost one third of patients receiving teclistamab therapy for relapsed and refractory multiple myeloma experienced an incident AKI event during follow-up. This finding underscores the importance of monitoring for kidney function in these patients.

3520 Background: In patients with metastatic colorectal cancer (CRC) and deficient DNA mismatch repair (dMMR), we previously found transcriptomic signatures reflecting stromal compartment composition and proliferative capacity that can predict the efficacy of immune checkpoint blockade (ICB). To identify proteomic markers of response and/or resistance to ICB, we performed spatially resolved proteomic analysis of the tumor microenvironment. Methods: Patients with surgically resected, primary dMMR metastatic CRCs received pembrolizumab (Mayo Clinic, N=30). In FFPE tissues, Digital Spatial Profiling of 71 proteins was performed using panels covering immune cells, immune activation, cell death, PI3/AKT signaling, MAPK signaling, and pan-tumor markers (GeoMx nCounter). In ten regions of interest/slide (~600 µm2) at the tumor invasive margin, protein expression was determined in four cellular compartments: epithelium (panCK+), immune cells (CD45+; leucocyte common antigen), stroma (panCK-), and nonimmune stroma (panCK-/CD45-). After normalization, protein abundance per compartment was analyzed by response (RECIST 1.1) [OmicVerse Python]. Differentially expressed proteins (binary) were examined by progression-free survival (PFS) using multivariable Cox regression with covariate adjustment (Lifelines Python). Results: Pre-treatment panels including 71 proteins were analyzed by treatment response and PFS after PD-1 inhibition. Proteins found to be significantly associated with response (p< 0.01) and PFS are described. Across all compartments, responders showed upregulation of NK cells and T cell subsets (CD3+, CD4+, CD8+), and ICOS; strongest association was found for CD4+: HRadj: 0.16; 95%CI: 0.08-0.31; p< 0.001. Nonresponders showed higher phospho-JNK (HRadj: 2.09; 95%CI: 1.28-3.42; p=0.003) and SMA. In the epithelial compartment, upregulation of the Treg marker CD25 and reduced caspase-9 were observed in responders. Among responders, the stromal compartment was highly enriched in HLA-DR, dendritic cells (CD11c), PD-L1, immune activation markers (CD40, CD44, CD80, CD27), CD95/Fas, and GZMB. In the stromal compartment, downregulation of BCL6 and phospho-GSK3B was observed in responders. The immune compartment of responders showed increased beta2-microglobulin and Ki-67, while the non-immune stromal compartment showed increase in the macrophage marker CD68. Importantly, proteins found to be upregulated in responders were significantly and independently associated with longer PFS whereas the opposite was true for nonresponders. Conclusions: In metastatic dMMR CRCs, spatially defined protein markers were significantly associated with anti-PD-1 response, and independently associated with patient PFS (strongest predictive utility for CD4 in immune stroma and phospho-JNK in epithelium).