Kennedy, Cassie C.

Background Medication nonadherence has been associated with poor outcomes in transplant recipients yet identifying these behaviors pre-transplant remains challenging. The simplified medication adherence questionnaire (SMAQ) is a brief, reliable instrument to assess medication adherence. The aim of this study was to perform SMAQ testing on thoracic organ candidates and examine correlations between these scores and individual patient factors predicting medication nonadherence. Methods Consenting waitlisted lung, heart, and heart-lung transplant candidates from six thoracic transplant centers were mailed a survey that included demographic information and the Simplified Medication Adherence Questionnaire (SMAQ). Univariate logistic regression analysis was performed to assess association between pre-transplant medication adherence and demographic characteristics, psychosocial factors, and mortality. Results Among 298 participants, 60.7% were medication nonadherent. Nonadherence was associated with some college education (OR: 1.73; CI: 1.06, 2.81), lower positive affect (OR: 0.95; CI: 0.92, 0.99), and higher uncertainty (OR: 1.02; CI: 1.01, 1.04). Higher positivity ratio predicted adherence. Conclusion Identifiable patient-specific characteristics associated with medication nonadherence can be screened for during thoracic transplant evaluation. Interventions aimed at improving these factors during the pre-transplant period may improve clinical post-transplant outcomes, however, larger studies are needed to validate these findings.

ABSTRACT Background The impact of psychosocial health and socioeconomic status (SES) on long‐term lung transplant survival remains unclear. Methods We conducted a single‐center, retrospective 2:1 matched case‐control study of adult lung transplant recipients (1999–2019). Cases survived ≥6 years post‐transplant; controls survived <6 years. Matching was based on transplant year (±5 years) and indication. Psychosocial health and SES were assessed using the Psychosocial Assessment of Candidates for Transplant (PACT) score, Mayo Clinic Housing‐Based Socioeconomic Status (HOUSES) index, and Area Deprivation Index (ADI). Secondary covariates included insurance, marital status, employment, caregiver relationship, and proximity to the transplant center. Conditional logistic regression adjusted for age and gender was used. Results Among 189 patients (63 cases, 126 controls), PACT score, HOUSES index, and ADI were not significantly associated with long‐term survival. Patients with non‐family caregivers had lower odds of survival compared to those with a spouse or partner (OR = 0.16, p = 0.022). Regional residents had lower odds of long‐term survival compared to local recipients (OR = 0.55, p = 0.001). Conclusions Pre‐transplant psychosocial and SES measures were not significantly associated with long‐term survival. Caregiver relationships and geographic proximity may have a greater impact on outcomes, highlighting the importance of support systems and access to care.

Abstract Introduction: Over 90% of adolescents (18-24 years) have a social media account. In 2021, an estimated 18.3% of 18-24-year-olds used electronic cigarettes. This age group is more likely to use social media as a health information resource than other sources. The social media platform TikTok is the fastest growing platform among adolescents. There is growing interest in vaping cessation among adolescents, and vaping cessation posts have grown accordingly. Our hypothesis is there are diverse vaping cessation methods described by TikTok users important for clinicians to understand. The use of qualitative methods informed by netnography represents an ideal way to evaluate TikTok videos. Methods: TikTok videos describing at least one vaping cessation method posted in English uploaded after January 1, 2022 were eligible for inclusion. Any post associated with advertising, sponsorship, corporations, or retail entities were excluded. Reposts of any kind were excluded. A total of 200 videos were reviewed in duplicate for eligibility. NVivo Version 14 transcription cloud and coding software was used. Coding was conducted independently by the study team until thematic saturation was reached. This study was deemed exempt by the Mayo Clinic Institutional Review Board as social media data is public domain and no identifiers were collected. Results: A total of 52 videos were included. Included videos had an average of 2.4 million views, 285,000 likes, and 11,000 shares. There were a wide variety of vaping cessation methods described. Some methods, such as hand motions mimicking vaping, limiting exposures, and use of nicotine replacement are supported by cigarette smoking cessation literature. There were also numerous videos outlining methods known to be ineffective or harmful, including instructions to vape continuously until illness occurs, and utilizing negative self-affirmations to “scold” yourself when using electronic cigarettes. Themes of inner strength, motivations, and shame were also discussed, and multiple users described their “wake up call” to quit vaping. Conclusions: Social media platforms are growing in popularity with adolescents and individuals under age 18. The inability for users to discriminate between evidence-based health advice and anecdotal experiences represents a key issue for clinicians to be aware of when counseling patients. Given the age demographics of social media users, this issue will grow as the population ages. Clinicians should engage in conversations with their patients about sources of reputable health information, and future directions may include novel methods such as partnering with influencers or social media companies.

Abstract RATIONALE: Long-term survival after lung transplantation is challenging, with limited research on risk and protective factors. Clinical factors such as younger age, female sex, fewer acute rejection hospitalizations, and double lung transplants are associated with better outcomes. However, the role of psychosocial health and socioeconomic status (SES) remains underexplored. This study aimed to assess the influence of pre-transplant psychosocial health and SES on long-term survival in adult lung transplant recipients. METHODS: We conducted a single-center, retrospective case-control study using the Mayo Clinic Rochester lung transplant registry. Cases (survivors ≥ 6 years) and controls (survivors &lt;6 years) were matched by transplant date (+/- 5 years) and indication for transplant, resulting in 190 subjects (63 cases, 127 controls). We assessed the impact of pre-transplant psychosocial health and SES on long-term survival using initial PACT scores (&lt;2), the HOUSES index, and the national/state area deprivation index (ADI). Additional factors included proximity to the transplant center, insurance type, marital status, primary caregiver status, and employment status. Statistical analyses used the paired Wilcoxon rank-sum test for continuous variables and McNemar's test for categorical variables, with results reported as median (IQR) or percentages. RESULTS: Donor characteristics (age, sex, smoking history, risk criteria, cause of death) and recipient characteristics (age at transplant, sex, BMI, medical condition, functional status, type of transplant) were similar between cases and controls, with no statistically significant differences (all p&gt;0.05). CMV mismatch, waitlist time, and transplant hospital length of stay were also comparable (all p&gt;0.05). Psychosocial health indicators, including proximity to the transplant center, pre-transplant initial PACT score, insurance type, marital status, primary caregiver, and employment status, did not differ significantly between groups (all p&gt;0.05). The HOUSES index was similar between cases and controls (p=0.179). However, long-term survivors had significantly higher national and state ADI scores than controls (national ADI: p=0.029; state ADI: p=0.019). CONCLUSIONS: Pre-transplant psychosocial health indicators, including proximity to the transplant center, initial PACT score, and caregiver support, did not differ significantly between long-term lung transplant survivors and those with shorter survival. Although SES measured by the HOUSES index was not associated with long-term survival, higher national and state ADI scores were linked to increased long-term survival, suggesting unique protective factors for patients from socioeconomically deprived areas. These findings highlight the complex role of socioeconomic factors in lung transplant outcomes and underscore the need for further research into how specific socioeconomic and environmental factors influence long-term survival.

ABSTRACTItraconazole and posaconazole are frequently prescribed following transplantation to prevent and treat fungal infections. Navigating drug interactions is challenging due to these agents’ potent CYP3A4 inhibition, and literature describing concurrent apixaban, a CYP3A4 substrate, is limited. This retrospective study of cardiothoracic transplant recipients evaluates the impact of itraconazole and posaconazole on apixaban exposure and reports clinical outcomes from routine apixaban dose reduction. Institutional practice reduces apixaban to 2.5 mg twice daily with itraconazole or posaconazole and obtains apixaban therapeutic drug monitoring (TDM), expected range 34–230 ng/mL. Eighteen levels collected in 15 patients on itraconazole displayed a median [IQR] apixaban trough of 143 ng/mL [95–195]. Fifteen levels collected in 13 patients on posaconazole displayed a median [IQR] apixaban trough of 124 ng/mL [93–174]. Two major bleed events, three VTE, two stroke, and eight instances of clot resolution were identified. Reduced‐dose apixaban resulted in apixaban exposure similar to normal dosing in the general population. Apixaban TDM is encouraged for individualized dosing when administered with itraconazole and posaconazole.

Introduction: Telomere biology disorders (TBD) are multisystemic accelerated aging syndromes due to abnormal telomere length (TL) shortening and increased cancer risk. Pediatric-onset TBD is characterized by severely shortened TL and specific associations with germline pathogenic variants mainly in DKC1, TINF2, PARN genes and characteristic clinical features [bone marrow failure (BMF), abnormal nail/skin/oral mucosa]. Adult-onset TBD is genetically distinct (predominantly, TERT, TERC, and RTEL1 mutations) with varied organ involvement [interstitial lung disease (ILD), BMF, cirrhosis, or bone disease] and heterogenous outcomes. In our previous study of predominantly adult patients with short telomeres, multiple organ involvement (Mangaonkar A et al. Blood Cancer J 2021) predicted poor overall survival (OS). We sought to validate these findings in a larger, well annotated adult cohort of TBD patients. Methods: Patients with suspected TBD underwent comprehensive clinical and molecular evaluation through our TBD-dedicated clinic after regulatory approval. TL was assessed through clinical flow cytometry fluorescence in-situ hybridization (FlowFISH).Clinical and laboratory features, including pulmonary imaging, lung volumes/function testing, hepatic imaging (MR elastography/fibroscan) and bone density assessments were retrospectively abstracted. Germline and somatic genetic testing was performed on peripheral blood through targeted panels for known TBD and myeloid genes respectively. Cox proportional hazard model was used to identify significant variables that also retained independent prognostic impact. Results: Overall, 122 patients met criteria for TBD as defined by lymphocyte TL (LTL) &lt;=10th percentile and/or a presence of a germline-TBD variant; 34 patients LTL &lt;1st percentile, 84 1st and the 10th percentile (27 with TBD-germline variants) and 4 with only TBD-germline variants. Median age at diagnosis was 56 (18-77) years, with 72 (59%) males. Clinical features included presence of ILD (n=81, 66%), BMF (n=39, 32%), cirrhosis/hepatic fibrosis (n=19, 38%), bone disease osteopenia/osteoporosis/fractures, n=53, 70%), MDS/AML (n=11, 9%), non-hematological cancer (n=38, 31%), and head and neck cancer (n=2). Germline pathogenic variants were detected in 22 (18%), most frequently in TERT (n=10), RTEL1 (n=7) and TERC (n=2), while variants of uncertain significance (VUS) were seen in 35 (29%) patients, especially in TERT (n=20), TERC/RTEL1(n=6), NAF1 (n=4). Somatic variants in hematopoietic cells were detected in 37 (30%) patients with frequent alterations seen in DNA damage response and repair (PPM1D/TP53, n=11), and splicing component (U2AF1/SF3B1/ZRSR2, n=9) genes. At last follow-up [median of 3 (0-18) years], there were 26 (21%) deaths (most commonly, progressive ILD-18, cancer of lung/breast/pancreas-3, transplant-related complications-2). After censoring patients at the time of any transplantation (lung transplant-26, liver transplant-5, bone marrow transplant-8), the Kaplan-Meier estimate of median OS was not reached. Univariate survival analysis found adverse OS predicted by older age at diagnosis (P=0.006), presence of ILD (P=0.0002), hepatic fibrosis/cirrhosis (P=0.02), and somatic DNA repair variants (P=0.03). Multivariate model analysis found that only presence of ILD retained independent prognostic impact (HR=2, P=0.02). Among radiographic ILD subtypes, UIP was the most common (51%), followed by NSIP (10%), and others (6%), with median FEV1 of 2L (range: 0.5-4.6), FVC 2.4L (0.7-6.2), and TLC 4L (1.9-7.4). TBD-ILD patients were older (P&lt;0.0001) with a male preponderance (P=0.03), 52 (64%) with multi-organ involvement, and had a less severe hematological phenotype [lower incidence of BMF (P&lt;0.0001) and fetal hemoglobin elevation (P=0.01)], more frequent bone disease (P=0.0009), relatively longer telomeres in lymphocytes (P=0.04), and no particular association with any germline or somatic genetic alterations. Conclusions: Presence of ILD is an independent and significant predictor of adverse survival in adult TBD. Within adult TBD, patients with ILD represent a unique clinical subtype without any obvious genetic or pathologic correlates. Focusing on definitive therapeutic measures in this subgroup of adult TBD has the best chance to alter natural history and improve outcomes.

ABSTRACTCellular senescence is a biological mechanism of aging and age‐related diseases. The aim of this study was to examine whether senescence biomarkers are associated with frailty and physical function trajectories in patients undergoing kidney transplantation (KT). We also discussed the relationship between senescence biomarkers and KT function. In this multicenter study, we prospectively assessed plasma levels of senescence biomarkers, frailty as measured by the Physical Frailty Phenotype, and physical function as measured by the Short Physical Performance Battery prior to KT. Frailty, physical function, and KT function were also measured 1 year after KT. Variable associations were assessed using Cox and relaxed least absolute shrinkage and selection operation regression. The cohort consisted of 197 participants (mean age 53 ± 13 years, 61.4% male, and 80.2% White race). Higher pre‐KT levels of macrophage‐derived chemokine (MDC/CCL22) and growth differentiation factor‐15 (GDF‐15) were independently associated with less improvement in frailty and/or physical function during the first year after KT. Higher pre‐KT levels tumor necrosis factor receptor superfamily member 6 (FAS) and MMP‐9 levels were independently associated with lower KT function one year after KT. Pre‐KT cellular senescence may contribute to frailty, physical function, and kidney function trajectories during the first year after KT.