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Introduction. Non-cystic fibrosis bronchiectasis is a complex medical condition with multiple etiologies, characterized by chronic productive cough and radiologic evidence of airway lumen dilation and wall thickening. Associated exacerbations and declining lung function contribute to increasing disability and mortality. There are no data about the prevalence of non-cystic fibrosis bronchiectasis etiologies in the Colombian population.Objective. To investigate non-cystic fibrosis bronchiectasis etiology and clinical characteristics in adults evaluated in the southwest of Colombia.Materials and methods. We conducted a cross-sectional, non-interventional study. Subjects diagnosed with non-cystic fibrosis bronchiectasis were referred to by theirhealthcare providers and then enrolled between October 2018 and April 2021. Medical records and radiological studies were evaluated. Participants underwent laboratory tests, including complete blood count, serum immunoglobulin levels, and, in some cases, additional tests.Results. We included 161 subjects. The average age was 50 years old, and 59% were females. Bronchiectasis etiology was identified in 84.6% of the cases. Postinfectious(34.6%) and immune disorders (25.3%), represented by autoimmunity (13.6%) and immunodeficiency (11.7%), were the leading causes. Gender differences were noted in autoimmune (females: 18.8% versus males: 6.1%, p = 0.021) and immunodeficiency-related bronchiectasis (males: 21.2% versus females 5.2%, p = 0.002). Immunodeficiencies-associated bronchiectases were more frequent in subjects under 50 years of age, while chronic obstructive pulmonary disease-associated bronchiectases were common in subjects over 50 years of age.Discussion. The etiologies of non-cystic fibrosis bronchiectasis in Colombia are diverse, exhibiting notable differences from other global regions. Serum immunoglobulin levels and clinical immunologist consultation should be prioritized in diagnosing patients with unclear bronchiectasis etiology, particularly those with recurrent sinopulmonary infections.

Background: Disparities in postoperative nausea and vomiting and its prophylaxis may exist based on race, ethnicity, and socioeconomic status. The objective was to evaluate whether patients from racial and ethnic minority groups and patients from lower socioeconomic status backgrounds received less appropriate postoperative nausea and vomiting prophylaxis and experienced higher rates of postoperative and postdischarge nausea and vomiting. Methods: This retrospective cohort study included 23,333 adults who underwent major surgeries (total knee arthroplasty, cholecystectomy, hysterectomy, and prostatectomy) from 2017 to 2022 in a single, multistate hospital system. Outcomes included prophylactic antiemetic administration according to consensus guidelines, as well as the occurrence of postoperative and postdischarge nausea and vomiting, with predictors being patient race and ethnicity, payor type, and community-level socioeconomic status. Results: About 45% (n = 10,407) of patients received guideline-recommended postoperative nausea and vomiting prophylaxis. Regression models showed statistically significant differences in appropriate postoperative nausea and vomiting prophylaxis by race and ethnicity, as well as community-level socioeconomic status, with Black (odds ratio, 0.76; 95% CI, 0.63 to 0.92) and Hispanic (odds ratio, 0.82; 95% CI, 0.70 to 0.96) patients having lower odds of receiving appropriate antiemetic prophylaxis compared to non-Hispanic White patients. Approximately 11% of patients (n = 2,522) experienced postoperative nausea and vomiting in the postanesthesia care unit, and about 19.5% of patients (n = 4,540) experienced postdischarge nausea and vomiting. No significant differences in postoperative nausea and vomiting were observed in the postanesthesia care unit among different groups; however, Black, Hispanic, other races and ethnicities, and patients with Medicaid had higher odds of postdischarge nausea and vomiting. Conclusions: The study identified differences in appropriate postoperative nausea and vomiting prophylaxis by race and ethnicity, as well as community-level socioeconomic status. There were no differences in postoperative nausea and vomiting by the predictors, but there were higher odds of postdischarge nausea and vomiting by race and ethnicity and payor. This study underscores the importance of data stratification in quality measures to identify disparities in perioperative care; it can lead to changes in perioperative anesthetic management. Further research should explore these associations in a broader cohort and address potential confounding sources.

Fungal infections represent a significant global health challenge. Candida albicans is a particularly widespread pathogen, with both molecular and biofilm-based mechanisms making it resistant to or tolerant of available antifungal drugs. This study reports a combination therapy, active against C. albicans, utilizing terbinafine and essential oils incorporated into a gelatin-based nanoemulsion system (T-GNE). Eugenol and methyl eugenol/terbinafine T-GNEs had an additive efficacy, while carvacrol (CT-GNE) worked synergistically with terbinafine, providing effective antifungal treatment with minimal mammalian cell toxicity. Confocal microscopy demonstrated that CT-GNE penetrated the dense C. albicans biofilm and disrupted the fungal cell membrane. Overall, the combination of essential oils with terbinafine in GNE provided a promising treatment for fungal biofilms.

AbstractBackgroundEvidence for abnormal amyloid‐β (Aβ) plaque accumulation is necessary prior to initiating anti‐amyloid therapy in early symptomatic Alzheimer’s disease (AD). While the clinical trials for lecanemab and related drugs utilized positron emission tomography (PET) to demonstrate brain amyloidosis, current appropriate use recommendations for clinical practice consider PET or cerebrospinal fluid (CSF) biomarkers as satisfactory for this purpose. Here, we present four clinical cases where CSF biomarker results were discordant from amyloid PET, with the potential to result in erroneous treatment targeting.MethodPatients were seen at a tertiary care subspecialty clinic in consideration for lecanemab therapy. All patients had office examination, neuropsychological assessment, structural magnetic resonance imaging (MRI), amyloid PET (with either 11C‐Pittsburgh compound B or 18F‐florbetapir), CSF AD biomarkers (Roche Elecsys p‐tau181/Aβ42 and Fujirebio Lumipulse Aβ42/Aβ40 ratios), and apolipoprotein E (APOE) allele testing. Amyloid PET interpretations were made by consensus visual review from experienced readers.ResultAll four patients had clinical diagnoses of mild cognitive impairment or mild dementia (Table 1). Two patients had positive CSF p‐tau181/Aβ42 and Aβ42/40 ratios with negative amyloid PET (indicating sparse to no neuritic plaques). Case 1 displayed aphasia (characterized by anomia and deep dysgraphia) and imaging findings possibly compatible with semantic dementia. Case 2 displayed a gait abnormality and imaging signs of abnormal CSF dynamics. Two other patients had negative CSF p‐tau181/Aβ42 measures with positive amyloid PET (indicating moderate to frequent neuritic plaques). In those instances, the clinical syndrome and imaging studies were strongly supportive of AD and the CSF Aβ42/40 ratio was “likely positive” (Table 1). For one patient (Case 4), tau PET and Lumipulse plasma p‐tau217 concentration were both positive.ConclusionClinicians prescribing anti‐amyloid therapies should be aware of the possibility for CSF biomarkers to be discordant from amyloid PET status in select scenarios. These cases highlight the value of considering PET imaging in the presence of clinically atypical features, concern for mixed etiology, or strong clinical suspicion for AD despite negative CSF biomarkers. Larger series are needed to identify broader patterns contributing to biomarker discordance by assay, modality (PET versus CSF/plasma measures), and medical/neurologic comorbidities.

AbstractBackgroundCross‐modality translation between MRI and PET presents significant challenges due to the distinct mechanisms underlying those modalities. Currently, the leading method for this translation is CycleGAN. Previous studies have proved a strong correlation between BBBMs and brain amyloid status measured by PET. However, the impact of blood‐based biomarkers (BBBMs) on PET image synthesis has not yet been thoroughly evaluated. In this study, we propose Plasma CycleGAN, a generative model based on CycleGAN to synthesize PET images from MRI, while also incorporating BBBMs and other clinical covariates. We show that Plasma CycleGAN outperforms the state‐of‐the‐art CycleGAN for MRI‐to‐PET translation. Our method is the first to integrate BBBMs in a conditional cross modality translation from MRI to PET.MethodOur model was built on CycleGAN architecture, while the backbone was improved by integrating BBBMs as additional conditions in the input domain. To be specific, we introduce a masked perturbation in the MRI image, whose voxel‐level magnitudes are learnable parameters in the neural network. The dataset we used to evaluate our model is downloaded from the ADNI database. The cohort contains 160 subjects with matching BBBM, T1‐weighted MRI images, amyloid PET, and clinical features, including age, sex, weights, etc. The synthesized PET images are compared with the ground truth PET images for performance evaluation using traditional metrics like structural similarity index (SSIM), peak‐signal‐to‐noise ratio (PSNR) and mean square error (MSE). In addition, the Pearson correlation coefficients (PCCs) of the masked SUVR ratios were calculated.ResultWe evaluated the baseline CycleGAN model using MRI input, as well as combined inputs of MRI+BBBM and other clinical features. Our model achieved an SSIM of 0.72±0.16 and PSNR of 22.8±2.3 in PET image synthesis task using MRI+ Aβ42/40, both yielding the best results among all input combinations. MRI+sex achieved the best result using MSE measurement. PCCs of all experimental results ranged from 0.44 to 0.5.ConclusionWe introduce Plasma CycleGAN, the first generative model to integrate BBBMs and clinical features in PET image synthesis from MRI images. In PET image synthesis task, our proposed integrated model outperforms the baseline CycleGAN model.

AbstractBackgroundMayo Test DRIVE (MTD): Test Development through Rapid Iteration, Validation and Expansion, is a web‐based multi‐device (smartphone, tablet, personal computer) platform optimized for remote self‐administered cognitive assessment that includes a computer‐adaptive word list memory test (Stricker Learning Span; SLS), a measure of processing speed/executive functioning (Symbols Test) and a score combining both the memory and processing speed/executive functioning measures (MTD Composite). We aimed to determine the reliability of MTD measures across follow‐up sessions.MethodIndividuals participating in this ancillary study who completed at least two and up to four complete MTD sessions were included, resulting in 1,293 participants (mean age = 70.6, SD = 11.6; mean education = 15.6, SD = 2.3; 48.6% male; 96.9% White; 99.1% non‐Hispanic; 97.1% cognitively unimpaired) from parent studies (see Table 1). MTD raw scores were winsorized at 1% and 99% to minimize the impact of outliers. Test‐retest reliability was assessed using single‐rating, absolute‐agreement, and two‐way mixed ICCs and results are described using descriptives from Koo et al. (2016). ICCs for in‐person‐administered traditional neuropsychological measures are also reported alongside MTD for a subset of participants newly enrolled into the MCSA (to ensure participants were test naïve to both MTD and in‐person tests).ResultReliability was good for the MTD Composite raw [total ICC = 0.78; see Table 2 for session‐to‐session ICCs and 95% CIs], and moderate‐to‐good for the primary outcome variables for each subtest [total ICC = 0.74 for both SLS and Symbols]. Weighting by accuracy negatively impacted reliability of Symbols and the Composite; without this weighting, MTD Composite and Symbols variables showed higher reliability (MTD Composite z total ICC = 0.80; Symbols response time total ICC = 0.84; see Table 2). Alternative methods of defining response time on Symbols showed nearly identical reliability values. SLS sum of trials (primary variable) had subtly higher reliability than separate measures of learning (1‐5 correct, max span) or delay. Reliability of remote MTD and in‐person‐administered measures and select comparisons are provided in Table 3.ConclusionMTD showed moderate to good reliability, similar to in‐person‐administered traditional neuropsychological tests. Future work will examine the effect of demographics, device type, and session interference on reliability.

AbstractBackgroundCharacterizing stress can inform our understanding of direct and indirect pathways impacting mental and physical health outcomes, including age‐related cognitive decline. Chronic stress has been strongly associated with increased risk for cognitive decline, and hair cortisol concentration (HCC) has emerged as a viable neuroendocrine biomarker for its quantification. Cognitive appraisal of stress (CAS) provides key insight into the cognitive framework for responding to a given stressor. We implemented a multi‐pronged approach to evaluate chronic stress and examined its relation to cognition in older adults.MethodParticipants were 22 cognitively normal individuals (x̄ MMSE = 29.33, 0.92; x̄ age: 67.3 ± 8.8 years old, 17.0 ± 2.9 years of education, 54.5% female, 92.6% Non‐Hispanic White). Participants completed the Stress and Adversity Inventory (STRAIN) assessing lifetime stressor exposure and the Primary and Secondary Cognitive Appraisal Scale (PSCAS). HCC was used as a neuroendocrine biomarker of chronic stress. A brief cognitive battery assessing episodic memory and executive functions (Digit Span, HVLT‐R, Trail Making Test, Letter Fluency) and mood/anxiety measures were completed. To correct for skewness, log‐transformed HCC values were used for Pearson and partial correlation analyses controlling for age and education.ResultLifetime stressor exposure and CAS were not significantly related to cognitive performance (all ps > 0.05). There was a marginally significant association between HCC and executive functions (r = ‐0.41, p = 0.08). Total lifetime stressor count, chronicity, and severity were unrelated to symptoms of depression and anxiety (all ps > 0.05). Although lifetime stressor exposure and mood were not significantly related to HCC, higher HCC was associated with higher perceived control of stress (r = 0.45, p = 0.03).ConclusionHCC may be more sensitive to CAS rather than to objective stressor exposure. This highlights the potential of interventions targeted at improving coping in those with chronic stress. Results are preliminary, and the present study will explore impact of social and structural determinants of health on chronic stressor exposure, appraisal, and cognition.

AbstractBackgroundHearing loss occurs commonly with age and is more prevalent among adults with Mild Cognitive Impairment (MCI) or Alzheimer’s Disease and related dementias (ADRD) than among older adults with typical cognitive abilities. Over‐the‐counter (OTC) hearing aids are a recently approved, lower‐cost method of hearing treatment which can be accessed directly by patients. However, there are almost no data which can guide whether to recommend this treatment for adults with MCI or ADRD. OTC aids also have technology constraints that may limit their benefit for wearers with ADRD, who have specific communication and rehabilitation needs.MethodParticipants in this randomized clinical trial will be recruited at the time of diagnosis of either MCI or early ADRD. The trial design embeds a brief hearing assessment within the structure of a memory assessment at Geriatrics and Neurology clinics, in both urban (Madison, WI) and rural (La Crosse, WI) settings. Trial participants will be randomized to receive either OTC aids or communication strategies tailored for adults with cognitive decline. To maximize access for patients (including patients from rural or underserved areas), treatment will be delivered via telehealth. Outcomes will be measured at baseline and after one month of use of the OTC hearing aids or communication strategies. The primary outcome is subjective assessment of dyadic communication by the listener’s primary communication partner. Additional outcomes include hearing‐related quality of life and a novel assessment of communication ability using structured conversation analysis.ResultThis presentation will describe the trial design, expertise and roles of the multidisciplinary study team, mechanism of treatment delivery via telehealth, and planned outcome measurements.ConclusionResults of this trial will provide important evidence to guide treatment recommendations in community‐dwelling older adults with MCI or early ADRD. This project will also establish feasibility of conducting hearing assessment as part of a memory assessment.

AbstractBackgroundThe Institute on Methods and Protocols for Advancement of Clinical Trials in Alzheimer’s Disease and Alzheimer’s Disease Related Dementias (AD/ADRD) (IMPACT‐AD) is a novel multi‐disciplinary training program funded by the National Institute on Aging (NIA) and the Alzheimer’s Association for individuals seeking expertise in designing and conducting AD/ADRD trials. IMPACT‐AD offers a Professionals Track for investigators in a variety of trial roles and a Fellowship Track for future AD/ADRD clinical trial principal investigators.MethodTo evaluate long‐term training outcomes, alumni‐scholars from the 2020‐2022 courses (n = 109) were surveyed via REDCap in January 2024. Measured constructs encompassed alumni‐scholar retention in AD/ADRD trials, promotions received, project funding, and the status of the protocol developed during the course, including whether it had been funded, conducted, and published (Fellowship Track). Alumni‐scholars rated the extent to which the course facilitated their achievements (not at all, somewhat, very much).ResultOf the 63 (58%) of alumni‐scholars who responded (48% Professional Track, 69% Fellowship Track), 44 (70%) were female. 21 (33%) identified as African American/Black, Asian, Multiracial or of another race; 7 (11%) self‐identified as Hispanic/Latino ethnicity. 5 (8%) identified as LGBTQ+. 12 (19%) indicated being first in their families to attend college.Since program completion, 87% of survey participants maintained a career in ADRD clinical trials. A majority (63%) experienced a promotion or career advancement, with all indicating that IMPACT‐AD “somewhat” or “very much” contributed. Less than half of scholars (43%) had received project funding since IMPACT‐AD, but 74% of those had credited IMPACT‐AD at least somewhat for this achievement. Among the 34 Fellowship Track respondents, 15 (44%) indicated that the trial proposed at IMPACT‐AD had received funding, 14 (41%) reported its completion, and 5 (15%) had published its results. Nearly all respondents (%) reported assuming additional roles and responsibilities within their current title. In total, 92% of surveyed participants reported at least one positive change across all measured categories.ConclusionIMPACT‐AD is effectively fulfilling its goals of training, nurturing, and diversifying a next generation of AD/ADRD trialists.