Vadiyala, Mounika Reddy

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: Impaired left ventricular (LV) global longitudinal strain (GLS) is associated with worse outcomes in patients with severe aortic stenosis (AS). However, its prognostic value in patients with moderate AS is still unknown. The aim of this study is to investigate the impact of LV GLS on outcomes of patients with moderate AS. Methods: PubMed/Medline, Scopus, and Google Scholar databases were systematically reviewed to find relevant studies through June 2023 reporting data on the relationship between the LV GLS and long-term mortality in patients with moderate AS. Binary random effects models were used to estimate pooled odds ratios (OR) and 95% confidence intervals (CI). I2 statistics were used to interpret heterogeneity, with I2>75% indicating substantial inter-study variation. Leave-one-out meta-analysis was performed to evaluate the effect of each study on the overall estimate. A p<0.05 was considered statistically significant. Results: A total of 172 studies were reviewed, and 4 studies between 2000-2023 were included in our meta-analysis with a median follow-up of 48.5 months and GLS cut-off varying from 11% to 16%. The pooled univariate analysis revealed a significant association between LV GLS and long-term mortality in patients with moderate AS with a pooled OR of 2.02 (95CI 1.04-3.93) p=0.04, I2=94.25%. The multivariate analysis, after adjusting for overall modifiable risk factors, yielded significant results, with an adjusted odds ratio (aOR) of 1.56 (95CI 1.21-2.01) p<0.01, I2=89.48%. Sensitivity analysis, using leave-one-out method, demonstrated robustness and stability of the results with aOR 1.56 (95CI 1.21-2.01) p<0.01. Conclusions: In patients with moderate AS, impaired LV GLS is associated with an increased risk for all-cause mortality. If further randomized studies confirm the prognostic ability of impaired GLS, moderate AS can be redefined, and GLS can be considered in determining the optimal timing for aortic valve intervention.

Abstract Background Biomarkers that predict the patients most likely to develop progressive NTM-LD are urgently needed. We hypothesize flow cytometric (FC) detection of T cell markers after ex vivo antigen challenge in PBMC can differentiate patients with progressive vs. nonprogressive NTM-LD. We also measured the serum anti-glycopeptidolipid core IgA antibody by commercial ELISA kit and compared with FC immunoprofiling results. Methods PBMCs were isolated from patients with NTM-LD and stimulated with purified protein derivative (PPD), mycobacteria-specific peptide pools (MTB300, RD1-peptides). We have performed ELISA and FC T-cell phenotypic assays to measure diagnostic accuracy of these assays by ROC and non-parametric statistics analysis. Results A total of 29 NTM-LD patients were studied and classified into 15 non-progressive and 14 progressive NTM-LD based on radiological and clinical evaluation. Patients with progressive NTM-LD showed a statistically significantly higher frequency of PPD-specific CD3+/CD8+ IFN-γ+HLA-DR+ subsets and high diagnostic accuracy compared with non-progressors: Sensitivity = 80% specificity = 71.4% with the ROC of 0.72. There were no other statistically significant differences in other antigen-stimulated T-cell subsets but a trend was observed with HLA-DR+TNF-α+, CD25+CD134+ and CD25+PDL1+ T-cell subsets in progressors. The anti-GPL IgA levels did not show a significant difference and might not be useful in distinguishing progressive from non-progressive NTM-LD. Conclusion Our study findings suggest that PPD-specific CD8+ IFN-γ+HLA-DR+ can distinguish progressive and nonprogressive NTM-LD patients, which can identify those patients at risk of disease progression.

TB remains a leading cause of morbidity and mortality worldwide. However, most infected immunocompetent individuals are asymptomatic and only 5–10% of these will eventually develop active TB during their lifetime (typically within 2 years after exposure). Therefore, rapid diagnosis and efficient management of asymptomatic infected individuals who are at the highest risk of progression and transmission remain major clinical and public health challenges. In recent years, there has been important scientific progress in our understanding of the spectrum of asymptomatic Mycobacterium tuberculosis (Mtb) infections that not only includes the dynamic state of latent TB infection (LTBI), but also the preclinical state of incipient and subclinical TB. The latter is possibly as prevalent as symptomatically active TB and potentially contributes to global Mtb transmission in various settings. We summarize the latest developments and current challenges of the existing testing tools for LTBI and describe promising biomarkers and diagnostics for the spectrum of asymptomatic TB. Following the negative results of a recent clinical trial for a biomarker-guided preventive therapy approach, we also suggest some treatment options for incipient TB.

Abstract Introduction Interstitial lung disease (ILD) is a heterogenous group of parenchymal lung disorders with multiple etiologies. ILD often affects the quality of life and survival of patients. OSA is commonly diagnosed among ILD patients with reported prevalences of 50-90%, and a prevalence of moderate to severe OSA as high as 65%. There is also concern that patients with ILD may be less tolerant of PAP therapies. We aim to identify differences in PAP treatment response and adherence in patients with ILD and OSA compared with a group of matched OSA controls. Methods A retrospective cohort analysis was conducted on patients ≥ 18 years-old that were evaluated at Mayo Clinic Center for Sleep Medicine between July 2012 to June 2022. Inclusion criteria were patients with a diagnosis of ILD per ATS criteria also diagnosed with OSA by HSAT or PSG. Control OSA patients were matched to ILD/OSA patients by age, BMI, and AHI ranges. Exclusion criteria included comorbid conditions of asthma or COPD. Patients with early non-adherence to CPAP or those who didn't have sleep follow up were also excluded. Follow-up sleep visits were assessed to determine CPAP adherence, change in PAP pressure, addition of oxygen, and change in Epworth sleepiness scale. Results We compared 51 patients with ILD/OSA and 51 OSA matched-controls. Twenty-five ILD/OSA patients were diagnosed by PSG and 26 by HSAT. Median treatment follow-up for the ILD group was 7 months (IQR of 3 to 18 months). Baseline characteristics, including oxygen desaturation index (ODI), oxygen saturation, time spent below 89% during overnight oximetry, and baseline Epworth scale, were similar between ILD/OSA and non-ILD OSA patients. Importantly, there was no statistically significant difference in PAP adherence, median PAP levels, PAP pressure change, residual AHI, or change in Epworth after treatment Conclusion There was no significant difference in baseline OSA characteristics, treatment response, and PAP adherence in ILD patients with OSA compared with matched non-ILD OSA controls. Outcome assessment may be limited by sample size and the shorter follow-up period. Future studies should include longer-term follow-up with a larger ILD cohort to assess the impact of ILD progression on PAP adherence over time. Support (if any)