Citations

Abstract Introduction Emerging evidence suggests that positive airway pressure (PAP) treatment for moderate-to-severe obstructive sleep apnea (OSA) in elderly patients does not improve daytime sleepiness, or quality of life outcomes, despite improving apnea-hypopnea index (AHI). While oral appliance therapy (OAT) is known to be an effective treatment for mild-to-moderate OSA, its efficacy in treatment of elderly patients with severe OSA is unknown. Methods Retrospective chart review of patients ≥ 65 years old with diagnosis of OSA, treated with OAT, who underwent subsequent follow-up sleep testing and clinical assessments, including Epworth Sleepiness Scale (ESS), a measure of daytime sleepiness. Results We studied 66 elderly patients with OSA (31 women, 35 men), including 58 with mild-to-moderate OSA (AHI < 30) and 8 with severe OSA (AHI ≥ 30) treated with OAT. At baseline, patients with mild-to-moderate OSA had a median AHI of 11.6 compared to 41.3 in patients with severe OSA (p < 0.0001). There was no difference in ESS score between patients with mild-to-moderate OSA (median ESS = 8; IQR = 4-12) and severe OSA (median ESS = 6; IQR = 3-9). Following their OSA diagnosis, OAT was offered due to PAP intolerance (n = 32), patient preference (n = 28), or as an alternative treatment option (n = 4). After initiation of OAT, 42 patients with mild-to-moderate and 7 with severe OSA underwent follow-up assessment with home sleep testing (n = 32), oximetry (n = 15), or polysomnography (n = 2). At follow-up assessment, ESS was decreased in patients with mild-to-moderate OSA (median ESS = 5; IQR = 3-8) and severe OSA (median ESS = 5; IQR = 3-7), indicating reduction in daytime sleepiness in response to OAT in both groups. Moreover, 50% of patients with mild-to-moderate OSA and 50% of severe OSA patients saw ≥ 50% reduction in AHI. Conclusion Our study findings suggest that treatment with OAT in mild-to-moderate and severe OSA is tolerable and effective in elderly patients who do not have contraindication for this treatment. OAT should be considered as an alternative treatment specifically for elderly adults with severe OSA not tolerating or improving with PAP therapy. Support (if any)

Background: The number of multiply revised anterior cruciate ligament reconstructions (rrACLRs) performed each year continues to increase. The most reliable graft type and surgical technique in the young, active patient remains to be determined. Purpose: To determine the outcomes of rrACLR using quadriceps tendon (QT) autograft with lateral extra-articular tenodesis (LET). Study Design: Case series; Level of evidence, 4. Methods: A retrospective review was performed of all competitive athletes undergoing rrACLR with QT autograft and LET at a single institution with a minimum follow-up of 2 years. Patient demographics, physical examination, and radiological findings, and previous surgical details were documented. Patient outcomes were noted, including the International Knee Documentation Committee (IKDC) and Lysholm scores, ability to return to sport and return at the same level of play, retear rate, and other complications. Results: A total of 19 rrACLRs were performed and met inclusion criteria in the 10-year study period. All participants were high school, collegiate, or professional athletes with a mean age of 22 years, and 63.2% were female. The mean follow-up was 42.3 months, and IKDC scores increased from 51.6 preoperatively to 74.7 at the final follow-up ( P < .001). Likewise, the Lysholm score increased significantly from a preoperative value of 53.6 to 76.8 at the final follow-up ( P < .001). Return to play was possible in 52.6% of the patients at a mean of 11.5 months, with 31.6% returning to the same or higher level of play. One (5.3%) patient experienced a recurrent ACL tear, and 2 (10.5%) experienced a contralateral tear. Arthrofibrosis requiring surgical intervention occurred in 26.3% of the athletes. Conclusion: Short- to midterm results demonstrated that competitive athletes who received an rrACLR using a QT autograft with LET had statistically significant improvements in both IKDC and Lysholm scores, with more than half of patients being able to return to sport and nearly a third returning at the same or higher level of play. In the setting of a third ACL reconstruction, quadriceps tendon autograft with LET is a reasonable option even in high-risk patients.

INTRODUCTION: There is an urgent need for effective and safe treatment of gastroparesis. Metopimazine, a selective, peripherally restricted dopamine D 2 receptor antagonist, is used in France for the symptomatic treatment of nausea and vomiting and chemotherapy-induced nausea and vomiting. The aim of this study is to assess the safety and efficacy of oral NG101, the mesylate salt of metopimazine, for the treatment of gastroparesis. METHODS: We conducted a 12-week phase 2 multicenter trial with NG101 5, 10, and 20 mg 4 times a day versus placebo. The primary end point was the change in mean nausea severity from the Diabetic and Idiopathic Gastroparesis Symptoms Daily Diary (DIGS-DD) during weeks 7–12 of the Treatment Period from baseline. The DIGS-DD measured nausea, abdominal pain, early satiety, postprandial fullness, and vomiting at their worst in the past 24 hours using a 0-10 point numeric rating scale. Patient Global Impression of Change questionnaires, including nausea, were assessed weekly using a 7-point balanced ordinal score. RESULTS: Of 161 randomized participants (45.3% diabetic and 54.7% idiopathic), mean DIGS-DD nausea severity scores decreased from baseline during weeks 7–12 in all treatment groups, but these improvements were not statistically significant compared with placebo. However, there were statistically significant improvements in nausea Patient Global Impression of Change during weeks 1–12 for all treatment groups compared with placebo. Trends in safety and efficacy favored patients with idiopathic gastroparesis compared with those with diabetic gastroparesis. DISCUSSION: While NG101 did not meet statistical significance in its primary end point for reducing nausea severity, it demonstrated a favorable safety profile and significant improvement in some secondary end points. Further study is needed to determine whether NG101 is an effective treatment for patients with idiopathic gastroparesis.

AbstractINTRODUCTIONCerebral microhemorrhages (CMHs) are detectable by magnetic resonance imaging (MRI). CMHs in deep brain regions are linked to hypertensive vasculopathy, while those in lobar regions with amyloid beta (Aβ) deposition in blood vessels. This study aims to determine the association between anti‐thrombotic treatment and CMH prevalence among cognitively asymptomatic adults, and to assess the role of Aβ markers, apolipoprotein E (APOE) ε4 carrier status, and cardiovascular risk factors in CMH development.METHODSUsing baseline data from the Anti‐Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) studies, we examined CMH presence via 3T MRI, along with medication use, APOE ε4 carrier status, medical history, and blood pressure.RESULTSOur analysis showed a significantly higher prevalence of CMHs in the A4 cohort (17.3%) compared to the LEARN cohort (2.6%).DISCUSSIONFactors such as male sex, age, Aβ markers, and APOE ε4 status were significantly associated with higher CMH prevalence in the A4 cohort. However, anti‐thrombotic treatment did not show association with overall CMHs.Highlights Male sex, age > 75, amyloid beta (Aβ) burden, and apolipoprotein E (APOE) ε4 homozygosity are significantly associated with higher prevalence of CMHs (cerebral microhemorrhages) in a cohort of cognitively asymptomatic individuals. Male sex, age > 75, Aβ burden, and APOE ε4 homozygosity are significantly associated with higher prevalence of lobar CMHs in a cohort of cognitively asymptomatic individuals. Anti‐platelet or anti‐coagulant usage were not associated with an increased prevalence of CMHs in either brain location or overall, in a cohort of cognitively asymptomatic individuals. History of a lipid disorder is associated with a higher prevalence of lobar CMHs in a cohort of cognitively asymptomatic individuals.

Abstract Antifungal susceptibility testing among 1740 Candida parapsilosis blood isolates submitted to a United States reference laboratory (2015–2024) revealed a significant increase in fluconazole resistance from 8.2% to 20.3% (odds ratio [OR] per year, 1.13 [95% confidence interval {CI}, 1.06–1.20]; P &lt; .001), with notable acceleration since 2021. Voriconazole resistance remained stable over this period. Micafungin resistance was rare, but intermediate susceptibility significantly increased, especially after 2021 (OR per year, 1.42 [95% CI, 1.25–1.63]; P &lt; .001). These findings highlight important recent shifts in antifungal susceptibility among C parapsilosis isolates, emphasizing the need for ongoing surveillance and stewardship.

Abstract Background: Leukocyte immunoglobulin-like receptor B2 (LILRB2) suppresses immune cell activation, particularly within myeloid cells in the tumor microenvironment (TME), while the PD-1/PD-L1 axis serves as a key immune checkpoint that inhibits T-cell function. SPX-303 is a novel bispecific antibody designed to simultaneously block LILRB2 and PD-L1, thereby revitalizing antitumor immune responses. Here, we present initial findings from the ongoing first-in-human Phase 1 trial of SPX-303 in patients with advanced solid tumors, including safety, pharmacokinetics (PK), and receptor occupancy (RO). Methods: This is an open-label, multicenter Phase 1 study for patients with advanced solid malignancies with 3+3 dose-escalation design, followed by an expansion cohort at the recommended Phase 2 dose (RP2D). SPX-303 is administered intravenously every three weeks and safety is assessed through CTCAE v5.0 criteria. Primary Objectives of this study are to determine the safety, tolerability, and RP2D of SPX-303. Secondary endpoints include antitumor activity as well as characterization of the PK and PD of SPX-303. This study is currently open and enrolling in escalation cohorts. Citation Format: Justin Moser, Hao Xie, Yujie Zhao, Yousef Zakharia, Dongdong Li, Brandon William, Dinh-Duc Nguyen, Jack Hovey, Tiffany Li, Robert Cai, Jichun Ma, Jingdong Qin, Martin Siekierzycki, Anthony Haight, Hua Jin, Weiwei Mao, Kevin Bin Li, Gui-Dong Zhu. A first-in-human phase 1 study on the safety, PK, receptor occupancy, and pharmacodynamic markers of SPX-303, a first-in-class LILRB2×PD-L1 bispecific antibody [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT116.

Background Studies suggest that plasma Alzheimer's disease (AD) biomarkers may aid in the overall diagnosis of AD, but their utility among patients with atypical clinical presentations of AD are unknown. Objective The main objective of this study was to determine the relationship between amyloid-β (Aβ) and tau plasma biomarkers and PET measures of both Aβ and tau in atypical AD. The secondary objective was to determine if plasma biomarkers could differentiate patients with different atypical AD phenotypes and whether they were related to measures of disease severity. Methods We assessed whether plasma p-tau 181 and Aβ 42/40 were associated with Aβ and tau PET uptake, clinical phenotype and severity in 77 patients with PET biomarker-confirmed atypical AD. Results Plasma Aβ 42/40 ratio showed positive associations with tau PET uptake, with higher (more normal) Aβ 42/40 ratio associated with higher tau uptake; the ratio was not associated with Aβ PET. No associations were noted with plasma p-tau 181. Plasma Aβ 42/40 ratio and p-tau 181 concentrations were not associated with AD phenotype or cognitive severity. Conclusion Plasma Aβ 42/40 ratio and p-tau 181 concentrations are not associated with amyloid or tau PET or with clinical severity among individuals presenting with atypical AD.

Abstract A hallmark of GBM is its highly-immunosuppressive tumor microenvironment (TME). GBM stem-like cells (GSCs) can evade immune surveillance to allow for continued tumor growth and propagation. GSCs regulate the immune TME through recruitment and production of immunosuppressive cells and factors via tumor cell-intrinsic mechanisms. Blocking these cell-intrinsic immunosuppressive mechanisms is widely viewed as a way to enhance the effects of current immune therapies. We recently showed that TGFβ type II receptor (TGFBR2) promotes a mesenchymal transition in GBM cells characterized by high expression levels of immunosuppressive genes NT5E (CD73), ENTPD1 (CD73), LGALS1 (galectin-1), CD274 (PD-L1), PDCD1LG2 (PD-L2), and TGFB1. miRNA network analysis identified miR-16-5p and miR-124-3p as high-confidence candidates to block the expression of these immunosuppressive signaling axis in GBM cells. Transgenic miR-16-5p and miR-124-3p simultaneously reduced expression of CD274, ENTPD1, NT5E, TGFB1, and LGALS1 and increased tumor cell killing of PBMC-derived CD4+ and CD8+ T cells. We also measured an increase in drivers of the CD8+ effector state and a decrease in expression of exhaustion marker PD1 in PBMC-derived CD8+ T cells. In addition to the effects on CD4+ and CD8+ T cell activation and function, miRNA-mediated knock-down of this immunosuppressive gene signature in tumor cells also resulted in a decrease in CD206 expression and reduced release of anti-inflammatory chemokines in THP1 cells. These findings demonstrate that miRNA-based gene inhibition can block cell-intrinsic immunosuppressive pathways to enhance anti-tumor immune cell function in vitro and predicts that delivering these miRNAs using advanced nanocarriers will cooperate with current immunotherapies in vivo. Citation Format: TC Taylor, Amanda Johnson, Harmon Khela, Jack Korleski, Sophie Sall, Bachchu Lal, Karen Smith-Connor, Hernando Lopez-Bertoni. miR-16-5p and miR-124-3p block the immunosuppressive phenotype of GBM cells in vitro. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1357.