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Abstract Disclosure: O. Hamidi: Advisory Board Member; Self; Corcept, Neurocrine Biosciences, Amryt Pharma, Recordati Rare Diseases, Lantheus, Xeris. B.H. Salama: None. P. Dogra: None. A.P. Dackiw: None. F. Nwariaku: None. A. Islam: None. A. Mehta: None. S.C. Oltmann: None. S. Mirfakhraee: None. T. McKenzie: None. T.R. Foster: None. M. Lyden: None. B.M. Dy: None. I. Bancos: None. Introduction: Patients with mild autonomous cortisol secretion (MACS) are at risk for adrenal insufficiency (AI) after unilateral adrenalectomy. We aimed to determine the prevalence, predictors, and duration of AI after unilateral adrenalectomy for MACS, and to compare baseline and peak cortisol post cosyntropin stimulation test (CST) in diagnosing AI. Methods: We conducted a dual-center retrospective cohort study of patients with MACS who underwent unilateral adrenalectomy and were evaluated with postoperative cosyntropin stimulation test (CST). AI was diagnosed when postoperative morning cortisol was <10μg/dL and/or CST peak cortisol was <18μg/dL. Baseline and CST peak cortisol levels were considered concordant when both met corresponding cut-offs. Biochemical (BSS) and clinical (CSS) severity scores for hypercortisolism were calculated. Results: In 100 adults with MACS (77% women, median age 56 years, interquartile range [IQR] 48-63), median adenoma size was 2.8 cm (IQR, 2.2-3.7), and 25 (25%) had bilateral nodules. Median BSS was 3 (IQR, 2-5) and median CSS was 4 (IQR, 2-8). After adrenalectomy, AI was diagnosed in 56 (56%) patients. AI was associated with higher BSS, larger tumor size, but not age, sex, BMI, tumor laterality. Baseline and CST peak cortisol levels were concordant in 76% of cases. In 14% of cases morning cortisol was <10μg/dL but CST peak cortisol was ≥18μg/dL, and in 10% of cases morning cortisol was ≥10μg/dL, but CST peak cortisol was <18μg/dL. On a multivariable analysis that included age, sex, BMI, BSS, laterality, and tumor size, only higher BSS (odd ratio [OR] = 1.6 per 1 point) was associated with postoperative baseline cortisol <10μg/dL (P<0.05 for all). Independent predictors of CST peak cortisol <18μg/dL were BSS (OR 1.5 per 1 point) and unilateral adenoma (OR 3.7). During a median postoperative follow up of 13 months, 33 (59%) patients recovered from AI. Median time to recovery was 6.0 months, with AI recovery in 28% of patients by 2 months, 42% by 3 months, 53% by 6 months, and 64% by 12 months. Conclusions: Prevalence of postoperative AI in MACS was 56%. Only 76% of patients had concordant baseline and CST peak cortisol, with peak CST cortisol being more commonly abnormal in patients treated for unilateral MACS. Patients with larger adenomas and higher BSS were at higher risk for AI. Patients with MACS should be counseled about the risk and duration of AI after adrenalectomy. Presentation: 6/3/2024

Background: Targeting interleukin-23 (IL-23) represents a significant therapeutic avenue for treating ulcerative colitis (UC). Study Question: What are the effectiveness and safety of selective inhibitors targeting IL-23p19 and IL-12/23p40 in individuals with moderate-to-severe UC? Data Sources: MEDLINE, Embase, Scopus, and Cochrane databases. Study Design: A systematic search of MEDLINE, Embase, Scopus, and Cochrane databases till January 15, 2024, to identify randomized controlled trials comparing IL-23p19 and IL-12/23p40 inhibitors against placebo or active comparators in UC patients. The primary outcome was clinical remission, with secondary outcomes including clinical response, endoscopic remission, and safety profiles during induction and maintenance phases. Using a fixed-effect model, we pooled dichotomous data with risk ratio (RR) and 95% confidence interval (CI) for analysis. Results: In 5 trials involving 1120 patients with moderate to severe UC, targeting IL-23 showed significant superiority in inducing clinical remission [RR: 2.08, 95% CI, (1.66–2.61)], endoscopic remission [RR: 1.73, 95% CI, (1.39–2.16)], and histologic remission [RR: 1.88, 95% CI, (1.34–2.64)]. Additionally, individuals treated with IL-12/23p40 or IL-23p19 antagonists maintained clinical remission [RR: 1.85, 95% CI, (1.53–2.23)], endoscopic remission [RR: 2.03, 95% CI, (1.60–2.57)], and histologic remission [RR: 1.66, 95% CI, (1.11–2.48)]. Targeting IL-23 was linked with a reduced risk of any adverse events (AE) during both induction [RR: 0.94, 95% CI, (0.86–1.02)] and maintenance phases [RR: 0.93, 95% CI, (0.86–0.99)], any serious AE during the induction phase [RR: 0.53, 95% CI, (0.36–0.78)], and withdrawal due to AEs compared to patients receiving placebo during induction [RR: 0.24, 95% CI (0.14, 0.43)]. Conclusion: Targeting IL-23 demonstrates efficacy and safety for inducing and maintaining clinical and endoscopic remission in moderate-to-severe UC patients.

ABSTRACT Wound infections, exacerbated by the prevalence of antibiotic-resistant bacterial pathogens, necessitate innovative antimicrobial approaches. Polymicrobial infections, often involving Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA), present challenges due to biofilm formation and antibiotic resistance. Hypochlorous acid (HOCl), a potent antimicrobial agent, holds promise as an alternative therapy. An electrochemical bandage (e-bandage) that generates HOCl in situ via precise polarization controlled by a miniaturized potentiostat was evaluated for the treatment of murine wound biofilm infections containing both P. aeruginosa with “difficult-to-treat” resistance and MRSA. Previously, HOCl-producing e-bandage was shown to reduce murine wound biofilms containing P. aeruginosa alone. Here, in 5-mm excisional skin wounds containing 48-h biofilms comprising MRSA and P. aeruginosa combined, polarized e-bandage treatment reduced MRSA by 1.1 log 10 CFU/g ( P = 0.026) vs non-polarized e-bandage treatment (no HOCl production), and 1.4 log 10 CFU/g (0.0015) vs Tegaderm only controls; P. aeruginosa was similarly reduced by 1.6 log 10 CFU/g ( P = 0.0032) and 1.6 log 10 CFU/g ( P = 0.0015), respectively. For wounds infected with MRSA alone, polarized e-bandage treatment reduced bacterial load by 1.1 log 10 CFU/g ( P = 0.0048) and 1.3 log 10 CFU/g ( P = 0.0048) compared with non-polarized e-bandage and Tegaderm only, respectively. The e-bandage treatment did not negatively impact wound healing or cause tissue toxicity. The addition of systemic antibiotics did not enhance the antimicrobial efficacy of e-bandages. This study provides additional evidence for the HOCl-producing e-bandage as a novel antimicrobial strategy for managing wound infections, including in the context of antibiotic resistance and polymicrobial infections. IMPORTANCE New approaches are needed to combat the rise of antimicrobial-resistant infections. The HOCl-producing electrochemical bandage (e-bandage) leverages in situ generation of HOCl, a natural biocide, for broad-spectrum killing of wound pathogens. Unlike traditional therapies that may exhibit limited activity against biofilms and antimicrobial-resistant organisms, the e-bandage offers a potent, standalone solution that does not contribute to further resistance or require adjunctive antibiotic therapy. Here, we show the ability of the e-bandage to address polymicrobial infection by antimicrobial resistant clinical isolates of Staphylococcus aureus and Pseudomonas aeruginosa , two commonly isolated, co-infecting wound pathogens. Effectiveness of the HOCl-producing e-bandage in reducing pathogen load while minimizing tissue toxicity and avoiding the need for systemic antibiotics underscores its potential as a tool in managing complex wound infections.

SummaryEvidence suggests an association between obesity and the risk for cardiomyopathy development; however, robust evidence is still lacking. In this study we sought to explore the relationship of obesity with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) and possible interactions with sex using large‐scale epidemiological real‐world data. We analysed data from the Nationwide Inpatient Sample of US hospitalisations for the years 2015–2019. There were a total of 46 934 admissions with diagnosis of HCM and 170 924 with DCM. There was a significant interaction between cardiomyopathies' diagnosis with sex and age subgroups; the rates of both DCM and HCM increased with age (p < .001 for both); DCM diagnosis was significantly higher in males compared with females (0.85% vs. 0.35%, p < .001). After adjustment for age, sex, race and presence of arterial hypertension there was a significant stepwise positive association between obesity and the population rates of both cardiomyopathy subtypes. For hospitalised patients with a body mass index (BMI) ≥30 kg/m2 there was an odds ratio (OR) of 1.68 (95% CI: 1.55–1.81, p < .001) for HCM and OR = 1.82 (95% CI: 1.79–1.84, p < .001) for DCM. More importantly, the positive relationship between a cardiomyopathy diagnosis (HCM or DCM) with increasing BMI was driven by the male sex (p < .001 for both) and it was non‐significant in females. The findings from this nationwide observational analysis support a sexual dimorphism in the relationship between obesity and HCM or DCM, which should be further investigated.

Spinal cord epidural electrical stimulation (EES) has been successfully employed to treat chronic pain and to restore lost functions after spinal cord injury. Yet, the efficacy of this approach is largely challenged by the suboptimal spatial distribution of the electrode contacts across anatomical targets, limiting the spatial selectivity of stimulation. In this study, we exploited different ESS paradigms, designed as either Spatial-Selective Stimulation (SSES) or Orientation-Selective Epidural Stimulation (OSES), and compared them to Conventional Monopolar Epidural Stimulation (CMES). SSES, OSES, and CMES were delivered with a 3- or 4-contact electrode array. Amplitudes and latencies of the Spinally Evoked Motor Potentials (SEMPs) were evaluated with different EES modalities. The results demonstrate that the amplitudes of SEMPs in hindlimb muscles depend on the orientation of the electrical field and vary between stimulation modalities. These findings show that the electric field applied with SSES or OSES provides more selective control of amplitudes of the SEMPs as compared to CMES. We demonstrate that spinal cord epidural stimulation applied with SSES or OSES paradigms in the rodent model could be tailored to the functional spinal cord neuroanatomy and can be tuned to specific target fibers and their orientation, optimizing the effect of neuromodulation.

Abstract Introduction Sexual well-being is an important quality of life component to women throughout life, and during menopausal transition and beyond. Female sexual response cycle includes desire, arousal, orgasm, and resolution phases. Female sexual dysfunction (FSD) encompasses all phases of sexual response cycle and can lead to distress for both the woman and her partner and warrant further investigation. Research has indicated both positive and negative associations between alcohol consumption and sexual health, our review goal is to further explore the relationship between alcohol consumption and sexual function in perimenopausal women. Objective We aim to review the current literature regarding the influence of alcohol use on sexual health during the menopausal transition and beyond. Methods The examination of alcohol consumption and its effects on sexual health in menopausal women was performed through reviewing existing literature. The literature search was completed in the Ovid MEDLINE database (1946- Present) in August 2023. 16 articles were identified in the initial search. 12 articles met our inclusion criteria and were independently reviewed by the authors. Results from these articles were summarized. The search was limited to the English language and the last 20 years (2003-current). Keywords included: menopause, pre-menopause, post menopause, perimenopause, alcohol use, alcohol related disorder, and sexual function. Results Seven out of 16 articles reviewed linked a negative association between alcohol consumption and female sexual function. Seven indicated a positive association between alcohol use and sexual function and 2 articles did not reveal an association. The findings of our review indicate a complex relationship of alcohol on women's sexual function. Studies indicating a positive association between mild alcohol consumption (equal or less than 0.21 FL oz. alcohol/day) and improved sexual function. This effect was theorized due to alcohol increasing endogenous estrogen or due to behavioral changes such as disinhibition, influencing sexual activities influenced by alcohol or subjective arousal due to drinking. Additionally, a positive association was seen between increased alcohol consumption and Female Sexual Function Index (FSFI) scores. However no significant influence on Female Sexual Distress Scale scoring was identified which is a key component to FSD. Other studies showed that excessive or prolonged alcohol consumption (more than 1.00 FL oz. alcohol per day) found to be associated with worsening sexual function and can impact all 6 domains on the FSFI (which include: desire, arousal, lubrication, orgasm, satisfaction, and pain) even after abstinence. These findings were reflected in another study that showed women (however not exclusively menopausal) who were seeking treatment for alcohol dependency diagnosis experienced low sexual desire, inability to achieve orgasm and less satisfaction. Initiating alcohol consumption at a younger age, along with an extended and more intense period of dependency, was correlated with a higher likelihood of experiencing increased sexual dysfunction. A meta-Analysis of 7 studies showed increased odds of sexual dysfunction with alcohol consumption. Another study showed that moderate alcohol consumption was found to be an independent risk factor for FSD and Genitourinary syndrome of menopause (GSM) which can lead to FSD. Conclusions The impact of alcohol on sexual health in postmenopausal women is multifaceted, based on varying levels of consumption influencing various aspects of sexual function. This relationship can also be influenced by other factors such as pre-existing sexual problems and the utilization of alcohol as a coping mechanism to reduce anxiety, release stress or to increase sexual behavior through enhancing arousal. A study indicated that menopausal symptoms may trigger a craving for alcohol, leading to increased alcohol consumption. Further research is essential to elucidate the direct and indirect effects of alcohol consumption on sexual dysfunction. In addition, the impact of abstinence from alcohol on sexual dysfunction in postmenopausal women needs to be further explored. Understanding the impact of alcohol consumption on sexual function of postmenopausal women is critical for healthcare professionals, to provide appropriate guidance and interventions. These findings highlight the need for further research and increased awareness regarding the impact of alcohol use on sexual health during in pre-menopausal, peri and postmenopausal women. Disclosure No.

This cross-sectional study evaluates the prevalence of and characteristics associated with discontinuation of cancer treatment among patients who received a diagnosis of COVID-19 during their treatment planning.

Background: Gastrointestinal (GI) disorders like chronic constipation are more prevalent with aging. Aging GI tract becomes stiffer and exhibits delayed GI transit. Smooth muscle cells (SMCs) are involved in controlling GI transit and show reduced contractility with age. Piezo1 is a mechanically activated ion channel that responds to membrane tension by opening its pore to allow flow of ions such as calcium (Ca2+) and regulates various cellular processes through Ca2+-calcineurin signaling pathway. We wondered GI stiffness changes might control SMC contractile to non-contractile phenotype through Piezo1. Objective: To determine how substrate stiffness regulates GI SMC contractile phenotype through Piezo1. Hypothesis: SMC Piezo1 senses GI tissue stiffness changes and alters SMC phenotype. Methods: Pathway analysis on human colon single cell sequencing data was performed using Gene Set Enrichment Analysis (GSEA) pre-ranked module with publicly available gene-sets from Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Immortalized human jejunal SMCs (HuSMCs) and freshly dissociated SMCs from control (CTRL, Myh11-creERT2) and SMC specific Piezo1 knockout [Myh11-creERT2xPiezo1 Flox (Piezo1-KO)] mouse colons (primary SMCs) were cultured on soft (1kPa) and stiff (50kPa) substrates to model age-dependent shifts in intestinal stiffness for 48 hours either in the presence/absence of Piezo1 siRNA, Piezo1 agonist (Yoda1, 1μM), and calcineurin blocker (Cyclosporin A, CsA, 1μM) and used for Ca2+ imaging, RT-qPCR and immunostaining. Results: GSEA showed Piezo1+ve SMCs were significantly enriched in pathways involved in the regulation of Ca2+ signaling compared to Piezo1−ve SMCs (p<0.05). HuSMCs and primary SMCs showed increased Piezo1 expression (HuSMCs:1.1±0.2-fold, n=8, p<0.05; primary SMCs:2.1±0.1-fold, n=3, p<0.05) and cytoplasmic Ca2+ (3.6-fold, n=10, p<0.05) in response to Yoda1 on stiff substrates compared to soft. HuSMCs on stiff substrate showed decreased expression of contractile SMC markers smoothelin ( SMTN:0.7±0.2-fold, n=7, p<0.05) and transgelin ( TAGLN:0.6±0.1-fold, n=7, p<0.05) which was rescued by Piezo1 siRNA treatment ( SMTN:1.2±0.1-fold, n=2-7, p<0.05; TAGLN:1.15±0.02-fold, n=2-7, p<0.05) (Piezo1 is necessary). Stimulation by Yoda1 of HuSMCs on the soft substrate resulted in decreased expression of SMTN (0.7±0.3-fold, n=2-7, p<0.05) and TAGLN (0.7±0.1-fold, n=2-7, p<0.05) (Piezo1 is suffcient). CTRL primary SMCs on stiff substrate showed decreased expression of Smtn (0.4±0.1-fold, n=3, p<0.05) and Tagln (0.3±0.2-fold, n=3, p<0.05) compared to SMCs on soft substrate which was reversed when SMCs from Piezo1-KO mice were cultured on these substrates ( Smtn:1.8±0.5-fold, n=3, p<0.05; Tagln:2.4±0.07-fold, n=3, p<0.05). Treatment of CsA in HuSMCs cultured on stiff substrate also rescued from loss of SMTN (1.3±0.1-fold, n=3, p<0.05) and TAGLN (1.7±0.3-fold, n=3, p<0.05) expression and prevented nuclear factor of activated T cells (NFAT) nuclear translocation. Summary and Conclusion: GI SMC Piezo1 senses stiffness changes and regulates SMC phenotype through Ca2+-calcineurin signaling pathway. Targeting Piezo1 might be protective from age induced reduced GI SMC contractility. NIH DK052766, DK123549. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.