Aspergillus colonization after lung transplantation may increase the risk for bronchiolitis obliterans syndrome (BOS), a disease of small airways. We hypothesized that colonization with small conidia Aspergillus species would be associated with a greater risk of BOS, based upon an increased likelihood of deposition in small airways. We studied adult primary lung recipients from two large centers; 298 recipients at University of California, Los Angeles and 482 recipients at Duke University Medical Center. We grouped Aspergillus species by conidia diameter ≤3.5μm. We assessed the relationship of colonization with outcomes in Cox models. Pre-BOS colonization with small conidia Aspergillus species, but not large, was a risk factor for BOS (P = 0.002, HR 1.44, 95% CI 1.14–1.82), along with acute rejection, single lung, and Pseudomonas. Colonization with small conidia species also associated with risk of death (P = 0.03, HR 1.30, 95% CI 1.03–1.64). Although other virulence traits besides conidia size may be important, we have demonstrated in two large independent cohorts that colonization with small conidia Aspergillus species increases the risk of BOS and death. Prospective evaluation of strategies to prevent Aspergillus colonization of small airways is warranted, with the goal of preserving lung allograft function as long as possible.

Objectives Depression is an important precursor to dementia, but less is known about the role dementia plays in altering the course of depression. We examined whether depression prevalence, incidence, and severity are higher in those with dementia versus those with mild cognitive impairment (MCI), or normal cognition. Design Prospective cohort study using the longitudinal Uniform Data Set of the National Alzheimer's Coordinating Center (2005–2013). Setting 34 Alzheimer Disease research centers. Participants 27,776 subjects with dementia, MCI, or normal cognition. Measurements Depression status was determined by a clinical diagnosis of depression within the prior 2 years and by a Geriatric Depression Scale-Short Form score >5. Results Rates of depression were significantly higher in subjects with MCI and dementia compared with those with normal cognition at index visit. Controlling for demographics and common chronic conditions, logistic regression analysis revealed elevated depression in those with MCI (OR: 2.40 [95% CI: 2.25, 2.56]) or dementia (OR: 2.64 [95% CI: 2.43, 2.86]) relative to those with normal cognition. In the subjects without depression at the index visit (N = 18,842), those with MCI and dementia had higher probabilities of depression diagnosis 2 years post index visit than those with normal cognition: MCI = 21.7%, dementia 24.7%, normal cognition = 10.5%. Conclusion MCI and dementia were associated with significantly higher rates of depression in concurrent as well as prospective analyses. These findings suggest that efforts to effectively engage and treat older adults with dementia will need also to address co-occurring depression.

Rationale: Cytomegalovirus (CMV), which is one of the most common infections after lung transplantation, is associated with chronic lung allograft dysfunction and worse post-transplantation survival. Current approaches for at-risk patients include a fixed duration of antiviral prophylaxis despite the associated cost and side effects.Objectives: We sought to identify a specific immunologic signature that predicted protection from subsequent CMV.Methods: CMV-seropositive lung transplantation recipients were included in the discovery (n = 43) and validation (n = 28) cohorts. Polyfunctional CMV-specific immunity was assessed by stimulating peripheral blood mononuclear cells with CMV pp65 or IE-1 peptide pools and then by measuring T-cell expression of CD107a, IFN-g, tumor necrosis factor-a (TNF-a), and IL-2. Recipients were prospectively monitored for subsequent viremia. A Cox proportional hazards regression model that considered cytokine responses individually and in combination was used to create a predictive model for protection from CMV reactivation. This model was then applied to the validation cohort.Measurements and Main Results: Using the discovery cohort, we identified a specific combination of polyfunctional T-cell subsets to pp65 that predicted protection from subsequent CMV viremia (concordance index 0.88 [SE, 0.087]

Objective The challenges posed by people living with multiple chronic conditions are unique for people with dementia and other significant cognitive impairment. There have been recent calls to action to review the existing literature on co-occurring chronic conditions and dementia in order to better understand the effect of cognitive impairment on disease management, mobility, and mortality. Methods This systematic literature review searched PubMed databases through 2011 (updated in 2016) using key constructs of older adults, moderate-to-severe cognitive impairment (both diagnosed and undiagnosed dementia), and chronic conditions. Reviewers assessed papers for eligibility and extracted key data from each included manuscript. An independent expert panel rated the strength and quality of evidence and prioritized gaps for future study. Results Four thousand thirty-three articles were identified, of which 147 met criteria for review. We found that moderate-to-severe cognitive impairment increased risks of mortality, was associated with prolonged institutional stays, and decreased function in persons with multiple chronic conditions. There was no relationship between significant cognitive impairment and use of cardiovascular or hypertensive medications for persons with these comorbidities. Prioritized areas for future research include hospitalizations, disease-specific outcomes, diabetes, chronic pain, cardiovascular disease, depression, falls, stroke, and multiple chronic conditions. Conclusions This review summarizes that living with significant cognitive impairment or dementia negatively impacts mortality, institutionalization, and functional outcomes for people living with multiple chronic conditions. Our findings suggest that chronic-disease management interventions will need to address co-occurring cognitive impairment.

ORCID IDs: 0000-0002-5459-9579 (D.M.V.); 0000-0002-4186-5698 (M.T.D.). AbstractRationale: Lung transplantation is an accepted and increasingly employed treatment for advanced lung diseases, but the anticipated survival benefit of lung transplantation is poorly understood.Objectives: To determine whether and for which patients lung transplantation confers a survival benefit in the modern era of U.S. lung allocation.Methods: Data on 13,040 adults listed for lung transplantation between May 2005 and September 2011 were obtained from the United Network for Organ Sharing. A structural nested accelerated failure time model was used to model the survival benefit of lung transplantation over time. The effects of patient, donor, and transplant center characteristics on the relative survival benefit of transplantation were examined.Measurements and Main Results: Overall, 73.8% of transplant recipients were predicted to achieve a 2-year survival benefit with lung transplantation. The survival benefit of transplantation varied by native disease group (P = 0.062), with 2-year expected benefit in 39.2 and 98.9% of transplants occurring in those with obstructive lung disease and cystic fibrosis, respectively, and by lung allocation score at the time of transplantation (P , 0.001), with net 2-year benefit in only 6.8% of transplants occurring for lung allocation score less than 32.5 and in 99.9% of transplants for lung allocation score exceeding 40.Conclusions: A majority of adults undergoing transplantation experience a survival benefit, with the greatest potential benefit in those with higher lung allocation scores or restrictive native lung disease or cystic fibrosis. These results provide novel information to assess the expected benefit of lung transplantation at an individual level and to enhance lung allocation policy.