Citations

Abstract Introduction Central sleep apnea (CSA) may occur as an adverse effect of sodium oxybates, a medication commonly used to treat narcolepsy with cataplexy. Management is challenging, as sodium oxybates remain essential for symptom control in many patients, yet untreated CSA poses substantial respiratory risk. We present a rare case of sodium-oxybate–associated CSA successfully treated with adaptive servo ventilation (ASV), representing, to our knowledge, the first documented use of ASV for this indication. Methods A 49-year-old woman with longstanding narcolepsy with cataplexy presented with worsening daytime sleepiness despite stable use of sodium oxybate. She had been receiving a very high dose prescribed by an outside provider (6.75 g twice nightly), exceeding the recommended maximum of 4.5 g twice nightly, and her dose was subsequently adjusted to 4.5 g twice nightly. An in-lab polysomnogram revealed moderate central sleep apnea (AHI 21; RDI 23) with predominantly central events. Because the patient did not wish to wean or discontinue sodium oxybate—reporting that it remained the only therapy that consistently improved her sleep and cataplexy—adaptive servo ventilation (ASV) titration was pursued as the next step in management. She had previously failed multiple stimulants, wake-promoting agents, and SSRIs due to either limited efficacy or intolerable side effects. Her BMI was 18 kg/m2, she was not taking any CNS depressant medications, and her echocardiogram demonstrated a normal ejection fraction. Results The patient tolerated ASV well. Final settings included an EPAP of 5 cm H₂O with a pressure support range of 3–15 cm H₂O and minimal leak. Her adherence was excellent, with more than 93% of nights exceeding four hours of use. Residual AHI improved to 4.6 events per hour, accompanied by noticeable improvement in daytime alertness. She continued sodium oxybate without any respiratory complications. Conclusion ASV may be an effective and well-tolerated therapy for sodium-oxybate–induced CSA in patients who must continue the medication. Sodium oxybate can induce CSA by acting on GABA-B receptors in the Kölliker–Fuse and pre-Bötzinger complex, suppressing respiratory drive and depressing hypoglossal motor output. This case highlights the successful use of ASV in treating CSA secondary to oxybates when the medication cannot be weaned or discontinued. Support (if any)

Abstract Introduction Hypoglossal nerve stimulators (HGNS) are used in patients with moderate-to-severe obstructive sleep apnea (OSA) who are unable to tolerate or do not respond to continuous positive airway pressure (CPAP) therapy. However, a subgroup of patients fail to achieve resolution of OSA with HGNS alone. Previous studies have shown that lower BMI, lower nadir oxygenation, decreased sleep latency, and higher VOTE score on drug-induced sleep endoscopy (DISE) predict better treatment outcome. We hypothesize that baseline diagnostic polysomnography (PSG) may further predict which patients will achieve successful therapeutic outcome with HGNS therapy. Methods We conducted a retrospective analysis of all adult patients who underwent HGNS implantation at Mayo Clinic Arizona between 2019-2025 and had a pre-implantation diagnostic PSG available for review. Treatment success was defined by Sher Criteria: >50% reduction in post-treatment apnea hypopnea index (AHI) to a final AHI of < 20/hr. Responders met Sher criteria and non-responders did not meet Sher criteria. Demographics, sleep questionnaire results, PSG variables, and VOTE score on DISE were collected and analyzed using Spearman’s rank correlation of reduction in AHI. Results Twenty-three patients (11M/12F, median age: 69[IQR:64,75] years) met inclusion criteria. Median baseline AHI was 24[IQR:19,37]/hr. Median post-implant AHI was 8 [IQR:3, 14]/hr. Responders (n=15, 65%) and non-responders (n=8, 35%) demonstrated median post-implant AHI of 4.5[IQR:2.3,7.3]/hr and 15.7[IQR:12.3,28.5]/hr, respectively. Treatment response was associated with less time with SpO2 < 88% (T88%) (21min [IQR:3,64] vs. 73[IQR:36,105mins]; p=0.023) and higher central apnea index (CAI) (1[IQR:0.1,3] vs. 0[IQR:0,1], p=0.03) on pre-implantation PSG. Conclusion In this small cohort of OSA patients, less nocturnal hypoxemia as defined by T88% and higher baseline central apnea index were predictors of better treatment response to HGNS therapy as measured by Sher criteria. We hypothesize that greater nocturnal hypoxemia likely reflects more severe airway obstruction during sleep. Our analysis also showed that responders had higher baseline CAI than non-responders, however we believe this association is not clinically significant and likely driven by one outlier (CAI 13/hr). Further analysis in a larger HGNS cohort is needed to confirm these findings. Data enrichment efforts and more sophisticated analyses are underway. Support (if any)

Abstract Introduction Positive airway pressure (PAP) therapy is the standard treatment for obstructive sleep apnea (OSA); however, its use may be contraindicated in patients with recurrent pneumothorax, particularly in the presence of emphysematous lung disease and bleb formation. Hypoglossal nerve stimulation (HGNS) offers a non–positive-pressure alternative for appropriately selected patients. We describe what is, to our knowledge, the first reported case of successful HGNS therapy in an older adult with severe OSA and multiple recurrent pneumothoraces. Methods An 87-year-old man with severe OSA (baseline AHI 38, predominantly obstructive events) experienced multiple right-sided pneumothoraces beginning in December 2022, several of which were temporally associated with BiPAP use at 17/9 cm H₂O. His episodes required repeated interventions, including chest tubes, thoracoscopy with apical bleb resection and pleurodesis, and several pigtail catheter placements. Chest CT imaging demonstrated emphysema with multiple blebs, raising concern for the safety of continued PAP therapy. A mandibular advancement device was deemed inappropriate due to disease severity. The patient’s BMI was 27 kg/m2. HGNS was considered a suitable alternative. Results HGNS implantation was completed without complications. At activation, both the sensation and functional thresholds measured 0.8 V, with excellent tongue protrusion and waveform quality. The device was programmed to 0.8–1.8 V with a 30-minute start delay, 12-hour nightly duration, and 15-minute pause. On follow-up, the patient demonstrated excellent adherence (average 70 hours/week), progressed to level 8 (1.6 V), and reported significant clinical improvement with resolution of snoring and apneas. Functional threshold and waveform analysis at 1.6 V remained optimal. Importantly, the patient tolerated HGNS well without any further episodes of pneumothorax following implantation. Conclusion HGNS may represent a safe and effective alternative to PAP therapy in patients at risk for pneumothorax. While positive pressure ventilation can theoretically worsen pneumothorax by increasing pleural pressure, HGNS operates through an entirely different mechanism: it maintains upper airway patency without altering intrathoracic pressure dynamics, making it a potentially safer option for select high-risk OSA patients. Support (if any)

Background: Premedications used to prevent paclitaxel-associated infusion hypersensitivity reactions (iHSRs) can cause undesirable toxicities, such as sleep disturbance and weight gain. Although phase II data suggest that discontinuing premedications after paclitaxel-associated iHSRs may be safe and feasible in select patients without prior iHSRs, no prospective randomized trials have evaluated this approach. Patients and Methods: This randomized clinical trial enrolled patients with breast cancer receiving paclitaxel chemotherapy. Those who experienced no iHSRs with the first 2 doses of paclitaxel were randomized to either continue standard premedications (control arm) or to discontinue all premedications (investigational arm). Both arms were followed longitudinally for any subsequent iHSRs requiring parenteral rescue medications. Additionally, changes in weight, drug-related side effects, and quality of life were assessed. Results: A total of 98 patients were randomized; 89 were evaluable (46 in the control arm and 43 in the investigational arm). Only 1 (2.3%) patient in the investigational arm experienced an iHSR, which resolved with rescue medications. No iHSRs occurred in the control arm. The estimated proportion of subjects who experienced a hypersensitivity reaction (exact binomial 95% CI) was 2.3% (95% CI, 0.1%–12.3%) in the investigational arm and 0.0% (95% CI, 0.0%–7.7%) in the control arm. Patients in the investigational arm reported significantly less sleep disruption (0.5 vs 1.7; P =.002) and unwanted appetite increases (1.0 vs 2.5; P =.0018). Conclusions: Discontinuation of premedications after 2 uneventful paclitaxel doses was not associated with a high rate of subsequent iHSRs and resulted in fewer steroid-related side effects. This strategy may reduce unnecessary medication exposure, improve patient experience, and streamline clinical workflows. For patients who do not experience iHSRs during the first 2 paclitaxel treatments, discontinuing premedications appears safe and may improve tolerability.

This multicenter, single-arm, phase 1/2 study evaluated the safety and efficacy of CD19-directed allogeneic chimeric-antigen-receptor (CAR) immunotherapy CTX110 in adult patients with relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (NHL). Patients received 1 or 2 treatment courses: standard lymphodepletion, followed by 1 CTX110 infusion at dose levels (DLs) 1-4 (3-60 × 107 CAR T-cells; dose escalation, N=32), or 2 infusions at DL4 on days 1 and 35 (cohort expansion, N=31). Primary endpoints in dose escalation and cohort expansion were incidence of dose-limiting toxicities and objective response rate, respectively. CTX110 was administered to 63 heavily pretreated patients: 59% primary refractory, 43% with ≥3 prior treatment lines. Among 57 patients whose first infusion was DL≥3, rates of objective and complete response (CR) were 65% and 39%, respectively. Among 22 patients achieving CR, 5 (23%) had ongoing CR at data cutoff, with 15-50 (median 34) months follow-up. The 2-infusion regimen appeared to prolong response duration compared to 1 infusion (hazard ratio 0.65). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were reported in 54% and 13% of treated patients, respectively, including 2 grade ≥3 cases each. The most common grade ≥3 adverse events were neutropenia (59%), and anemia and thrombocytopenia (35% each). Serious adverse events occurred in 32% of treated patients, including CRS (14%), ICANS (8%), and febrile neutropenia (6%). In this r/r NHL population, CTX110 was well-tolerated, resulting in clinically meaningful responses at DL≥3, with a second infusion demonstrating evidence of further clinical benefit. This trial (NCT04035434) was registered at www.clinicaltrials.gov.

Abstract Background: Bria-IMT™ is an allogeneic whole cell immunotherapy expressing tumor associated antigens and GM-CSF, designed to stimulate adaptive and innate immune responses. The ongoing multicenter phase 3 Bria-ABC trial (NCT06072612) evaluates Bria-IMT + Retifanlimab vs physician’s choice in pts with metastatic breast cancer who have exhausted standard therapies. Quality of life characterization in this advanced disease setting is clinically relevant yet underreported. Methods: QOL was assessed using the European Organization for Research and Treatment of Cancer QOL Questionnaire Core 30 (EORTC QLQ-C30) at baseline (BL) and treatment visits. Raw item responses (scale: 1 - 4 for functional/symptom items; 1 - 7 for global health ; lower scores = better functional/symptom outcomes; higher scores = better global health) were aggregated into domain scores. Changes from BL were quantified as absolute point differences on response scales and domain level scores are the median of constituent items. Changes from BL assessed using Wilcoxon matched-pairs signed-rank tests. ECOG status assessed at BL and each treatment visit. TEAEs graded per CTCAE. Missing QOL data handled using observed cases approach. We report QoL outcomes at visits (V) BL, 3, 6, and 9 to characterize pt experience during treatment. Results: As of data cut date, 235 pts have been screened, 169 randomized,129 treated. Median age: 60. 74% Caucasian; 18% other; 8% not reported; median 6 prior lines (2-15); ECOG 2: 7%, intracranial mets: 11%. 51% of pts HR+, 37% TNBC, 10% HER2+, 2% not reported. mPFS 2.9 mo (95% CI, 2.3 - 3.7), median of 5 QoL assessments per pt. Of 127 pts who completed ≥2 EORTC QLQ-C30 assessments, 67 (52%), 21 (17%), and 7 (6%) had paired data available at V3, 6, and 9, respectively. Global health status remained stable (median: BL 5.0, V3 5.0, V6 5.0, V9 4.5; 63% of pts reported maintenance or improvement at V3 [p=0.7], V6: 62%, V9: 71%). Functional domains: physical (median: BL 1.0, V3 2.0, V6 2.0, V9 2.0; 68.7% , 47.6% [p=0.03], 71.4% maintenance), role (BL 1.5, V3 2.0, V6 2.0, V9 2.0; 62.7% [p=0.02], 52.4%, 71.4% maintenance), emotional (BL 1.5, V3 1.5, V6 1.5, V9 1.5; 75.8% [p=0.9], 81.0%, 85.7% maintenance), cognitive (BL 1.5, V3 1.5, V6 1.5, V9 1.5; 63.6% [p=0.2], 61.9%, 85.7% maintenance), and social functioning (BL 1.5, V3 1.5, V6 2.0, V9 2.5; 58.5% [p=0.06], 75.0%, 57.1% maintenance). Symptoms: fatigue (median 2.0 at all timepoints; 61%, 67%, 71% maintenance), nausea/vomiting (1.0 throughout; 73% maintenance at V3 [p=0.8], V6 86% , V9 86%), and pain (1.5 at BL and V3, increasing to 2.0 at V6 and V9, w/ 57% maintenance at V3 [p=0.03], V6 62% [p=0.9], and V9 86%. ECOG status remained stable in 78% (n = 99) of pts during treatment. Most common TEAEs were fatigue, nausea, anemia, and constipation; w/ 45% Grade 3 or 4; 84% < grade 3. QoL trends consistent w/ observed ECOG status and AE profiles. Conclusion: Heavily pretreated metastatic breast cancer pts demonstrated stability in overall health status and key functional domains during treatment. These findings are encouraging w/ a meaningful QOL in a population with advanced disease and limited therapeutic options. These observations and AE profile support decentralized clinical trial initiatives including home self-administration. Ongoing follow up will further characterize the durability of pt reported outcomes and their relationship w/ clinical status. Citation Format: Saranya Chumsri, Chaitali Nangia, Adriana Kahn, Lawrence Negret, Carmen Calfa, Blaise Bayer, Giuseppe Del Priore, Tamar Aghajanian, William Williams, Kelly McCann. QOL outcomes in Bria-ABC late stage metastatic phase 3 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT137.

Importance Transcatheter tricuspid valve replacement (TTVR) demonstrated superior outcomes over medical therapy in patients with severe tricuspid regurgitation (TR) in the Edwards EVOQUE Transcatheter Tricuspid Valve Replacement: Pivotal Clinical Investigation of Safety and Clinical Efficacy Using a Novel Device II (TRISCEND II) randomized clinical trial, and received regulatory approval in the US in 2024. Contemporary real-world data on its effectiveness and safety remain limited. Objective To evaluate 30-day clinical, echocardiographic, and health status outcomes of TTVR in real-world use. Design, Setting, and Population Retrospective cohort study of all consecutive patients who underwent TTVR in the US from February 2024 through March 2025 in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. Patients had symptomatic, severe TR despite optimal medical therapy and TTVR was deemed appropriate by a heart team. Statistical analysis was conducted from September 2025 to February 2026. Exposure Device-enabled TTVR. Main Outcomes and Measures Thirty-day event rates (all-cause death, stroke, bleeding, new cardiac implantable electronic device [CIED] implantation, heart failure hospitalizations), TR reduction, and changes in health status (New York Heart Association [NYHA] functional class and Kansas City Cardiomyopathy Questionnaire Overall Summary [KCCQ-OS] score) are reported. Subgroup analyses examined the impact of baseline CIED status on outcomes. Results Among 1034 attempted procedures at 82 centers (mean [SD] age, 77.1 [10.6] years; 69.1% female; 73.2% NYHA functional class III/IV), a valve was successfully implanted in 1017 patients (98.4%). Mild or less TR was achieved in 98.4% of patients post procedure and in 97.7% at 30 days. At 30 days, all-cause mortality was 3.1%; stroke, 0.2%; bleeding, 7.9%; new CIED, 15.9% in CIED-naive patients; and heart failure hospitalization, 3.1%. There were significant improvements in NYHA functional class (class I/II, 82.7%; P < .001) and mean KCCQ-OS score (22.4 points; P < .001) from baseline to 30 days. There were no significant differences in 30-day mortality ( P = .47), heart failure hospitalization ( P > .99), and functional outcomes ( P = .55) when patients were stratified by baseline CIED status. Conclusions and Relevance Early US real-world experience with TTVR confirms safety and effectiveness in patients with severe TR. Thirty-day outcomes are consistent with the TRISCEND II pivotal trial, demonstrating acceptable safety, near-complete TR elimination, and significant health status improvements in an older, comorbid population. Rates of new CIED implantation and bleeding were lower than randomized clinical trial experience.

Substance use disorders (SUD) remain a significant source of morbidity and mortality in the United States, and access to treatment continues to be inadequate. Primary Care Clinicians (PCCs) are well-positioned to provide long-term SUD care for patients. However, multiple provider-level barriers exist. Collaborative Care Management (CoCM) has proven successful in supporting PCCs in treating psychiatric conditions, such as depression. Our group proposes an addiction-focused modified CoCM that leverages telemedicine and an electronic platform (Senyo) into primary care. This study assesses PCCs’ attitudes toward this proposed model and their likelihood (with support) of prescribing medications for alcohol and opioid use disorder. To achieve this, an anonymized and confidential electronic survey was deployed to all 489 of our institutions’ PCCs. Eighty-five completed the survey (17.4% response); the majority (94%) agreed that digital CoCM for SUD will be helpful for their practice, and 85% expressed agreement that such a model will increase their confidence and likelihood to prescribe anti-craving medications. Additionally, we found that PCCs’ comfort level in addressing SUD with patients is not associated with years in practice, clinician type (attending physicians, resident/fellow physicians, nurse practitioner or physician assistant), or their perception of currently available SUD treatment resources. Future work to evaluate practice changes, including rates of anti-craving medication prescribing and SUD-treatment outcomes after implementation of our digital CoCM will prove useful in determining the effectiveness of this model.

ABSTRACT HLA‐A*02:1040:02 differs from HLA‐A*02:01:01:01 by a single nucleotide substitution in codon 283 (CCC>TCC) in exon 5.