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)

Abstract Non-tubercular mycobacteria (NTM) present a serious challenge in managing lung transplant candidates and recipients. Pretransplant NTM isolation has been associated with post-transplant NTM infection and significantly increased mortality risk. Strategies for managing pre-transplant NTM isolation vary widely in clinical practice. We present a 35-year-old lung transplant candidate from a tuberculosis-endemic country with severe pulmonary hypertension and Eisenmenger Syndrome due to unrepaired atrial septal defect, who underwent bilateral lung transplantation. Two years prior to transplant, she was successfully treated for pulmonary tuberculosis with six months of an unknown regimen in her home country. After moving to the U.S., she received M. tuberculosis (MTB) clearance from her state tuberculosis board, with three negative sputum samples six months prior to transplant. During her transplant evaluation, multi-drug-resistant M. fortuitum complex was isolated from one mycobacterial sputum culture. There was no clinical or radiographic evidence of active lung infection, and no targeted therapies were added. Standard peri-transplant antibiotics (vancomycin, cefepime, and caspofungin) were given. The patient received basilixamab for induction immunosuppression, and tacrolimus, mycophenolate mofetil, and prednisone for maintenance immunosuppression. Explant pathology showed necrotizing granuloma in the right upper lobe with acid-fast bacilli (AFB). The differential diagnosis included non-viable MTB, viable MTB despite prior clearance, or M. fortuitum. Three bronchoscopy washings were obtained in the first week post-transplant and returned negative for MTB by PCR, AFB stain, and culture. In collaboration with the Mycobacteriology laboratory, broad-range PCR testing was performed on the formalin-fixed paraffin-embedded samples from the explanted right lung, which was positive for MTB complex DNA. In total, the patient completed six sputum samples within the year pre-transplant and six respiratory samples within a month post-transplant, all of which returned negative for MTB by PCR, AFB stain, and culture. Blood flow cytometric (FC) immunoprofiling with mycobacterial antigens and controls was conducted (Escalante et al. 2015). The patient's FC antigen-specific activated T-cell profiling was consistent with a reduced risk of latent TB infection (FC CD4+ CD25+CD134+ T-cells (RD1-peptides-nil) = 0.19%). T-cell reactivity to MTB300 and PPD antigens suggested prior MTB, NTM, and/or BCG vaccination exposures. She progressed well without any preventive therapy for LTBI. FC immunoprofiling one year after transplantation showed similar results. She continues to have good pulmonary function and quality of life in her second-year post-transplant without evidence of NTM or MTB infection. Escalante P, et al. Combinatorial Immunoprofiling in Latent Tuberculosis Infection. Am J Respir Crit Care Med. 2015;192(5):605-17. PMCID: PMC4595688.

Abstract RATIONALE: Understanding co-isolation patterns between fungi and other potentially pathogenic microorganisms in the airways of bronchiectasis patients is important for uncovering possible microbial interactions and informing treatment. Although numerous organisms have been identified in respiratory cultures, the specific patterns of their co-isolation are underexplored. OBJECTIVES: To examine the patterns of co-isolation between fungi and bacteria or mycobacteria in respiratory samples from patients with bronchiectasis across a large national health system. METHODS: We reviewed 58,170 respiratory culture tests from 8,194 patients with bronchiectasis (identified using ICD-10-CM codes J47.0, J47.1, and J47.9) across Mayo Clinic. These tests were analyzed for fungal, bacterial, and mycobacterial growth, focusing on co-isolation from the same sample. Chi-square statistics were used to compute p-values. RESULTS: Of all 18,983 samples cultured for fungi, 59% were positive. Of these, 72% yielded yeasts and 40% molds. Among the 11,372 samples cultured for both fungi and bacteria, 681 (6%) showed co-isolation, representing 54% of positive bacterial cultures. The odds of bacterial co-isolation with fungi were 1.4 (95% CI: 1.3-1.6; p < 0.01), driven by yeasts (OR: 1.5, 95% CI: 1.3-1.7; p < 0.01), rather than molds (OR: 1.0, 95% CI: 0.9-1.2; p = 0.8). Pseudomonas species, the most common bacterial isolate, had a higher likelihood of co-isolation with fungi (OR: 1.6, 95% CI: 1.3-1.9; p < 0.01), particularly yeasts (OR: 1.6, 95% CI: 1.4-2.0; p < 0.01). Molds, including those from genera such as aspergillus and penicillium, did not show a significant association with the isolation of pseudomonas. On the other hand, among the 15,859 samples cultured for both fungi and mycobacteria, 1352 (9%) showed co-isolation, representing 62% of positive mycobacterial cultures. Odds of co-isolation were 1.7 (95% CI: 1.5-1.8; p < 0.01). Molds showed a stronger association with isolation of mycobacteria (OR: 1.7, 95% CI: 1.5-1.9; p < 0.01) compared to bacteria, while yeasts also had elevated odds (OR: 1.4, 95% CI: 1.2-1.5). CONCLUSIONS: Distinct patterns of fungal co-isolation with bacteria and mycobacteria have been observed in bronchiectasis, which may influence key aspects of the disease, such as inflammation and mucociliary dysfunction. Advanced metagenomic and immunoprofiling techniques could provide deeper insights into these co-isolation patterns while considering other factors like clinical demographics, previous antibiotic exposure, and disease severity. Understanding whether altering the mycobiome could modify these aspects and improve outcomes remains an important avenue for research.

Energy drinks are a commonly consumed beverage, and studies suggest a possible performance-enhancing effect. A Google Scholar search using the keywords “energy drinks” and “exercise” yields numerous results, underscoring the voluminous research on this topic. However, there are questions regarding the effectiveness and safety of energy drinks. These questions include, but are not limited to: (1) What are the main active ingredients in energy drinks? (2) Do energy drinks assist in weight management? (3) Do energy drinks enhance aerobic performance? (4) Do energy drinks enhance athletic speed? (5) Do energy drinks improve reaction time? (6) Do energy drinks enhance lean tissue mass? (7) Can energy drinks improve cognitive performance? (8) Does the acute consumption of energy drinks elevate resting energy expenditure? (9) Is there any evidence to suggest that energy drinks are more effective than an identical serving of caffeine alone? (10) Are there sex differences in the response to energy drink consumption? (11) Do energy drinks affect sleep or sleepiness? (12) Should pregnant women avoid energy drinks? (13) Do energy drinks adversely affect cardiovascular function? (14) Does consuming energy drinks cause brain damage? (15) What are other safety considerations regarding energy drinks? (16) Is there any evidence to suggest that energy drinks are more effective than an identical serving of caffeine alone? (17) If caffeine is the main active ingredient in energy drinks and coffee, why is there a discrepancy in the adverse events reported for each? To address these questions, we performed an evidence-based scientific evaluation of the literature on energy drink supplementation.

Introduction Linvoseltamab is an investigational, BCMA×CD3 bispecific antibody designed for the treatment of RRMM. High objective response rates (ORR) to linvoseltamab 200 mg in the LINKER-MM1 trial (NCT03761108) were demonstrated across high-risk subgroups, including patients aged ≥75 years, patients with high-risk cytogenetics, and patients with penta-class refractory status. The aim of this study was to compare ORR, overall and in key subgroups, between patients in Phase 2 of the LINKER-MM1 trial and patients in an international RW SOC external control arm (ECA). Methods The ECA was derived from a chart review of 16 academic sites across 10 countries that are part of the International Myeloma Foundation (IMF)-International Myeloma Working Group (IMWG) and 2 US electronic health record databases (COTA and Guardian Research Network [GRN]). Included patients initiated ≥1 anti-MM treatment after meeting key eligibility criteria of LINKER-MM1. Weighted random sampling and inverse probability of treatment weighting (IPTW) were used to select 1 line of therapy (LOT) per patient and balance the overall ECA and trial populations on prespecified prognostic factors (Kumar S, et al. IMS 2023). For ORR assessment, LINKER-MM1 and IMF-IMWG used independent central review committees per IMWG criteria, COTA used algorithmic assessment based on IMWG criteria, and GRN used physician-assessed responses. Prior to conducting comparative analyses, an independent committee of epidemiology and oncology experts reviewed the comparability of the cohorts and endpoint assessments, and approved study continuation. ORR among patients in LINKER-MM1 and patients in the ECA was compared overall and across prespecified subgroups (≥10 patients per subgroup), including age, race, cytogenetic risk score, international Staging System (ISS), presence of extramedullary plasmacytoma (EMP), refractory class, bone marrow plasma cell (BMPC) proportion, and number of prior LOTs. Results Median duration of follow-up was 14.3 months (data cut-off: January 6, 2024) for patients receiving linvoseltamab (n=105) and 13.6 months for the ECA (n=307; n=194, n=72, and n=41 from IMF-IMWG, COTA, and GRN, respectively). Following IPTW, 13 prognostic factors with <30% missingness were balanced between cohorts, with an effective sample size in the ECA of 197. After adjustment, ORR was significantly higher in patients who received linvoseltamab compared with patients in the ECA (69.5% vs 45.7%, odds ratio [OR] 2.5 [95% confidence interval (CI) 1.6-4.1]) and in key subgroups with age 65-74 years (76.9% vs 48.3%, OR 3.6 [1.6-8.6]), age ≥75 years (72.4% vs 48.5%, OR 2.8 [1.1-7.4]), Black or African American race (82.4% vs 25.0%, OR 14.0 [3.0-85.4]), White race (68.9% vs 49.7%, OR 2.2 [1.3-4.0]), standard cytogenetic risk (72.3% vs 51.3%, OR 2.5 [1.3-4.8]), ISS stage III (58.8% vs 19.7%, OR 5.8 [1.5-25.2]), absence of EMP (71.6% vs 49.3%, OR 2.6 [1.5-4.6]), triple-class refractory status (68.2% vs 45.7%, OR 2.6 [1.5-4.4]), quadruple-class refractory status (66.7% vs 45.9%, OR 2.4 [1.3-4.3]), 4-5 prior LOTs (65.1% vs 40.4%, OR 2.8 [1.3-6.0]), and >5 prior LOTs (75.7% vs 36.1%, OR 5.5 [2.4-13.6]). Numerically higher (not statistically significant) or similar ORR was observed for patients receiving linvoseltamab compared with patients in the ECA with age <65 years (59.5% vs 46.8%, OR 1.7 [0.79-3.6]), high-risk cytogenetics (65.0% vs 63.1%, OR 1.1 [0.41-2.9]), ISS stage I (73.3% vs 64.6%, OR 1.5 [0.62-3.7]), ISS stage II (67.6% vs 53.5%, OR 1.8 [0.72-4.7]), presence of EMP (58.8% vs 56.9%, OR 1.1 [0.32-3.8]), penta-class refractory status (64.3% vs 48.5%, OR 1.9 [0.78-4.8]), BMPC <50% (77.0% vs 67.2%, OR 1.6 [0.61-4.3]), BMPC ≥50% (41.7% vs 36.0%, OR 1.3 [0.36-4.7]), and ≤3 prior LOTs (68.0% vs 66.4%, OR 1.1 [0.43-2.9]). Separate findings will be presented for IMF-IMWG and COTA/GRN data at the congress. Conclusions Linvoseltamab induced better ORR vs RW SOC treatments overall, and better or similar ORR in the key subgroups assessed, highlighting its therapeutic value across a range of patients with RRMM with heterogeneous risk profiles and levels of disease burden.

Abstract Objective The presence of comorbidities can substantially affect patients’ quality of life, but data regarding their impact on idiopathic inflammatory myopathies (IIMs) are limited. Methods We examined the prevalence of comorbidities in IIM patients, other autoimmune rheumatic diseases (oAIRDs) and healthy controls (HCs), using data from the self-reported COVAD-2 survey. We defined basic multimorbidity (BM) as the presence of ≥2 non-rheumatic chronic conditions and complex multimorbidity (CM) as the presence of ≥3 non-rheumatic chronic conditions affecting ≥3 organ systems. Hierarchical clustering on principal components was performed for grouping. Results Among the COVAD respondents, 1558 IIMs, 4591 oAIRDs and 3652 HCs were analysed. IIMs exhibited a high burden of comorbidities (odds ratio [OR]: 1.62 vs oAIRDs and 2.95 vs HCs, P < 0.01), BM (OR: 1.66 vs oAIRDs and 3.52 vs HCs, P < 0.01), CM (OR: 1.69 vs AIRDs and 6.23 vs HCs, P < 0.01) and mental health disorders (MHDs) (OR: 1.33 vs oAIRDs and 2.63 vs HCs, P < 0.01). Among the IIM patients, those with comorbidities or MHDs had lower PROMIS Global Physical (PGP), PROMIS Global Mental (PGM), and PROMIS Physical Function (SF10) scores, and higher fatigue (F4a) scores (all P < 0.001). PGP, PGM, SF10a and F4a were influenced by age, active disease, BM and MHDs. Four distinct clusters were identified among the IIMs according to comorbidities and PROMIS scores. Conclusion Patients with IIMs have a higher burden of comorbidities that influence physical and mental health, identifiable as clinical clusters for optimized and holistic management approaches.

Abstract Introduction Bronchiectasis (BE) is characterized by recurrent infections and dilated airways and has been associated with recurrent exacerbations and hospitalizations affecting quality of life. Approximately 40-60% of patients with BE have concomitant OSA, with an increased AHI (apnea-hypopnea index) in BE patients with Pseudomonas infections. We hypothesize that patients with BE are less tolerant of PAP therapies, contributing to worsening quality of life related to either condition. We aim to determine differences in PAP adherence and treatment response in patients with BE and OSA compared with a matched OSA-control group. Methods A retrospective cohort analysis was conducted on adult patients evaluated at Mayo Clinic Center for Sleep Medicine between January 2000 to December 2020. Inclusion criteria were patients greater than 18 years old diagnosed with BE and OSA per current guidelines and were prescribed PAP therapy. Control OSA patients were matched to BE/OSA patients by gender, BMI, and AHI severity. Exclusion criteria included cystic fibrosis, hospice enrollment, active lung transplant evaluation, and lack of sleep clinic follow-up. Follow-up visits determined PAP compliance and change in quality-of-life metrics over 3 years. Results We compared 50 patients with BE/OSA with 74 OSA matched controls. The etiology of BE in these cases included COPD (32%) or other etiologies (34%). Baseline characteristics were not statistically different in gender, BMI, and AHI severity across groups. Median treatment follow-up for the BE/OSA group was 3 years [IQR 2 to 4]. Importantly, there was no statistically significant difference in PAP adherence in patients with BE/OSA compared to OSA controls regardless of etiology of BE, but these patients more often required supplemental oxygen therapy. Interestingly, there was a statistically significant increase in MRC and decrease in FEV1 over time in BE patients compliant to therapy. Conclusion There was no significant difference in baseline OSA characteristics, treatment response, and PAP adherence, except for need of oxygen supplementation in BE patients with OSA compared with matched non-BE OSA controls. FEV1 values decreased, and dyspnea score increased in BE patients compliant to PAP therapy; however, future larger studies should include longer-term follow-up to further assess the impact of PAP therapy on BE progression and outcomes. Support (if any)

Abstract Introduction Several studies have shown a positive association between Obstructive Sleep Apnea (OSA) and malignancies such as lung cancer. However, the effects of intermittent hypoxemia in cancer-free survival following curative therapy are not known. We propose that OSA-related episodic hypoxemia and hypoxic burden are independent risk factors for accelerated lung cancer reoccurrence (< 2 years). Methods We performed a retrospective record review of patients 18 years and older from January 2016 to September 2023 with history of non-small cell lung cancer who received an overnight oximetry study (OXY) within three years prior to undergoing curative malignancy treatment. Subjects with history of central sleep apnea, baseline oxygen saturation (SpO2) below 90%, receiving supplemental oxygen or treatment for OSA were excluded. Results 403 patients met inclusion criteria (52% female vs 48% males; median age 74 y). The most common histologic subtypes were adenocarcinoma (68%) followed by squamous cell carcinoma (22%). Most patients fell into Stage IA1 (35%) followed by IA2 (24.1%) and IB (19%) as per TNM 8th edition classification. Over this period, 68 patients (22%) had lung cancer recurrence (median 19 months). A 4% oxygen desaturation index (ODI) of >15 and time spent in desaturation events were found to be a risk factor for cancer reappearance in less than 2 years (p< 0.001). Measures of hypoxic burden such as time spent below 89% SpO2, average SpO2 value below 89%, and single nadir oxygen levels, showed a similar association (p< 0.001). This was irrespective of histologic subtype, stage at diagnosis, and all studied demographic variables. Basal SpO2 demonstrated no correlation. A multivariate proportional hazard survival model showed that ODI>15 was no longer significant, however average SpO2 below 89% and single minimum oxygen level remained strongly correlated with accelerated recurrence. Conclusion This study showed a strong, positive association between accelerated lung cancer recurrence and OSA-related episodic hypoxemia and hypoxic burden on our univariate analysis. The multivariate model demonstrated correlation with hypoxic load measures only, suggesting the need for a larger sample to elucidate the involvement of this highly treatable risk factor. To our knowledge, this is the first study revealing this potential link. Support (if any)