Citations

Abstract Introduction Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy through enhancing T-cell-mediated immune responses but have also been associated with immune-related adverse events. Emerging literature suggests a potential association between ICI therapy and the development or reactivation of tuberculous mycobacterial infections. It is unclear whether ICI therapy is also linked to an increased risk of non-tuberculous mycobacterial (NTM) infections, though case reports are rapidly accumulating. We aim to better elucidate the potential association between ICIs and NTM infections through a case series. Case Series This series includes patients at Mayo Clinic who were diagnosed with active NTM infection during or after ICI use from January 1, 2012 to December 31, 2024. Data including demographics, malignancy details, ICI regimen and duration, timing and site of NTM infection, microbiologic findings, antimycobacterial therapy, and clinical outcomes were evaluated. There were seven patients with positive testing for NTM during or after ICI therapy. Two had one colony of M. gordonae on cultures which were determined by Infectious Disease to be contaminants. One case had a reported culture positive for M. franklinii at an outside hospital without further details available and thus was excluded from analysis. Chart review was performed for the remaining four patients with active NTM infection during or after ICI therapy. Two of the patients had underlying chronic obstructive pulmonary disease with a smoking history; these same two had primary lung malignancy. The other two patients had no known underlying lung disease or malignancy lung involvement (primary or metastatic). ICI therapies included PD-1, PD-L1, and CTLA-4 inhibitors. All four NTM infections predominant had lung involvement and were all different species; two were diagnosed while the patient was actively receiving ICI therapy and two were diagnosed several months after ICI discontinuation. Of the two receiving ICI therapy at the time of diagnosis, the ICI was held for 101 days for one patient and the other continued the ICI without interruption. Three received multi-agent therapy while the fourth declined treatment and died of malignancy complications soon after. The other three were alive at one year after NTM diagnosis and completed approximately one year of antimycobacterial therapy. Conclusions Tuberculous and non-tuberculous mycobacterial infections are increasingly seen after immune checkpoint inhibitor therapy. We present a series of four cases of NTM infections after or during ICI therapy for various types of malignancy with good outcomes after approximately one year of treatment. This abstract is funded by: None

ABSTRACT Aims We aimed to examine the association between GLP‐1 RA use and suicidal ideation or behaviours through a systematic review of observational studies. Materials and Methods A comprehensive search of MEDLINE, PubMed, EMBASE, CINAHL and PsycINFO was conducted from database inception through December 11, 2025. Observational studies investigating suicidal ideation, suicide attempts or complete suicide among adults using GLP‐1 RAs were included. Eligibility screening, data extraction and risk of bias assessments were performed independently and in duplicate, with disagreements resolved by a third reviewer. Results Forty‐three studies were included. Findings varied by study design. Some case reports suggested a temporal relationship between GLP‐1 RA use and suicidal ideation. Cross‐sectional studies and case–control studies identified a negative association between GLP‐1 RAs and suicide attempts. Pharmacovigilance and cohort studies showed more mixed results, with some studies identifying a positive association between semaglutide or liraglutide and suicidal ideation, while others paradoxically reported a negative association with suicidal behaviours (i.e., attempts and intentional self‐harm) or completed suicide. Conclusions While evidence does not support GLP ‐1 RAs as a causative agent for suicidality, due to multiple risk factors in this population, clinicians should routinely assess mental health status before and during GLP ‐1 RA treatment regardless of indication. Importantly, a history of concurrent mental health conditions should not preclude use of a GLP ‐1 RA ; rather, individual patient factors should be accounted for when making prescribing decisions.

Abstract Purpose This analysis aims to provide a comprehensive overview of lung transplantation trends in the United States from January 1, 1988, through January 31, 2025. By examining key variables such as recipient ABO blood group, donor type (deceased or living), demographic factors, and geographic distribution, the goal is to highlight the evolution and current state of lung transplantation practices. Methods Data were obtained from the Organ Procurement and Transplantation Network (OPTN), encompassing all reported lung transplants during the specified time period. Relevant metrics included the number of transplants per year, recipient characteristics (blood type, race/ethnicity, gender, and age), donor type (deceased versus living), and state-level transplant volumes. Simple descriptive statistics (e.g., frequencies and percentages) were used to identify trends and capture the distribution of transplants among different demographic groups and geographic regions. Results A total of 55,435 lung transplants were performed in the United States between 1988 and early 2025. The vast majority (over 99%) utilized deceased donors, underscoring the limited role of living-donor lobar transplantation, with only 253 procedures reported nationally. Among recipients, ABO blood group O was the most common (∼45%), followed by group A (∼40%), group B (∼11%), and group AB (∼4%). Male recipients represented approximately 57% of transplants, while females accounted for 43%. Regarding race/ethnicity, White non-Hispanic patients constituted roughly 80% of all recipients, with Black non-Hispanic (8%) and Hispanic/Latino (8%) recipients forming smaller but significant proportions. Age distribution data revealed that individuals aged 50 to 64 years received nearly half of all lung transplants, and those over 65 years composed about a quarter of total recipients, reflecting a gradual shift in acceptance criteria favoring older adults. Geographically, California reported the highest volume of lung transplants, attributable to its large population and multiple high-volume transplant centers, while other states such as Florida, Ohio, North Carolina, and Missouri also demonstrated notable activity. Conclusion Lung transplantation in the United States has witnessed substantial expansion in both volume and scope since 1988, with the majority of procedures involving deceased donor lungs. A small number of living-donor lung transplants, while demonstrating innovative clinical possibilities, remains limited. The demographic profile of recipients continues to shift, evidenced by a growing proportion of older adults and a predominance of ABO type O and White, non-Hispanic recipients. Despite these advancements, persistent gaps in access, particularly among underrepresented racial and ethnic groups, highlight the need for further refinement in organ allocation policies and broader support services. This abstract is funded by: None

Abstract Rationale In the early post-lung transplant period, close surveillance is essential to detect allograft dysfunction, infection, or medication toxicity. This requires frequent in-person clinic visits and laboratory testing, creating substantial travel and time burdens for patients and caregivers. Remote patient monitoring (RPM), which uses devices to collect and transmit physiologic and symptom data to the care team, has the potential to reduce geographic barriers and enable earlier detection of changes in patient status. Understanding the feasibility, adherence, and clinical impact of RPM is essential before broader implementation. Methods The Chronic Lung Allograft Monitoring (CLAM) program was launched in August 2024 at our center. Participants were provided a tablet and devices (spirometer, pulse oximeter, scale, and blood pressure cuff) to submit daily physiologic and symptom data. Abnormal parameters triggered review by RPM nurses and escalation to transplant physicians according to protocol. After 12 months of monitoring, patients were transitioned to self-monitoring when clinically appropriate. Demographics, compliance, and escalation characteristics were summarized descriptively. An escalation was defined as any entry triggering an alert to the transplant team. Escalations were categorized by cause and reviewed to determine clinical impact. Results Among 105 enrolled patients, the median age was 64 (IQR 58-68) years, 66 (63%) were male. 70 (67%) remain enrolled, 22 (21%) graduated, and 13 (12%) discontinued monitoring prematurely. reasons for discontinuation included death (n = 7; 7%), patient preference (n = 3; 3%), and non-adherence (n = 3; 3%), yielding an overall dropout rate of 5.7%. Completion rates were 64% for vital sign and spirometry submissions and 91% for symptom questionnaires.There were 395 escalations, with a median of 3 per patient (IQR 1-6); 82 patients (78%) experienced at least one escalation. Causes of escalations are summarized in Figure 1. Of all escalations, 282 (71%) were managed with continued monitoring, while 113 (29%) resulted in changes in care. Seven escalations (1.8%) led to emergency department evaluation and 2 (0.5%) resulted in direct hospital admission. Among non-emergent escalations, 35 (8.8%) prompted expedited clinic visits; of the remainder, 42 (10.6%) led to diagnostic testing orders and 32 (8.0%) resulted in medication initiation or adjustment. Conclusions RPM after lung transplantation was feasible, well accepted, and frequently informed clinical decision-making. The CLAM program demonstrates high engagement and clinical utility, supporting further prospective evaluation of RPM in lung transplant care. This abstract is funded by: None

Abstract Rationale Acute cellular rejection (ACR) within first-year post-lung transplantation has important implications for prognosis. Calcineurin inhibitors (CNI), including tacrolimus or cyclosporine, along with cell cycle inhibitors (CCI) and steroids, remain the standard immunosuppression regimen post-transplant. Although tacrolimus is used as the primary CNI, target therapeutic levels vary across recipients due to adverse effects and tolerability, sometimes requiring switching over to Cyclosporine. We hypothesized that ACR within the first year is associated with switching CNI from Tacrolimus to Cyclosporine. Methods We performed a cross-sectional study of 255 adult lung transplant recipients between June 2019 to November 2024 at Mayo Clinic, Florida. Demographics, induction regimens, CNI type and their levels (average low and high levels) were compared between the 2 groups. The institutional maintenance immunosuppression regimen is Tacrolimus, Mycophenolate Mofetil (MMF) and prednisone, but could be switched to Cyclosporine if the previous regimen is not tolerated. The primary outcome was ACR <1 year diagnosed based on biopsy and/or clinical criteria. Comparisons between groups were performed using Chi-Square test for categorical variables and t-test or Wilcoxon Rank sum test for continuous variables. Multivariable regression analysis was performed with ACR <1 year as the outcome to adjust for the confounders. Results Our cohort included 255 lung transplant recipients with median age of 63 years, 61% Male, 84% Caucasians, 88% bilateral lung transplant (Further details elucidated in Table 1). A total of 173 (67%) out of 255 patients had ACR <1 year. The group with ACR < 1 year had higher proportion of Interstitial Lung Disease (ILD) (81% vs 68%, p = 0.044), use of Basiliximab for induction (70% vs 55%, p = 0.018), and cyclosporine instead of tacrolimus (23% vs 11%, p = 0.027). Group with ACR <1 year also had higher Antibody Mediated Rejection (AMR) < 1year (15% vs 6.1%, p = 0.041) and higher CLAD (BOS 0p-3: 43% vs 25.6%, p = 0.033) compared to the group without ACR < 1 year (Table 1.1). Multivariate regression analysis showed ILD (adjusted odds ratio, aOR 2.84, 95% CI 1.31 - 6.27, p = 0.008) and use of cyclosporine (aOR 2.55, 95% CI 1.07 - 6.78, p = 0.034) as independent predictors of ACR < 1 year (Table 2). Conclusions The presence of ACR < 1 year was associated with the use of Cyclosporine over Tacrolimus as a maintenance regimen. Also, ACR < 1year was associated with higher AMR and CLAD. Further prospective studies are needed to study this long-term given its significant prognostic implications. This abstract is funded by: Not Applicable

Abstract Rationale Fungal infections remain a major cause of morbidity and mortality post lung transplant due to unique exposure of the allograft to the external environment and the intensity of immunosuppression. Single-center studies have described variable rates of fungal infections. Contemporary population-level data with temporal trends, pathogen distribution, and associated outcomes are limited. Leveraging a large multicenter real-world dataset, we aimed to characterize incidence, prevalence and clinical outcomes of fungal infections among adult lung-transplant recipients. Methods Data were obtained from the TriNetX Global Collaborative Network (160 HCOs). Adult lung-transplant recipients (≥18 years) were identified between 2005 and 2024, using ICD and CPT procedure codes. Patients with solid organ transplants other than lung, combined-organ transplant or stem-cell transplant and HIV patients were excluded. Patients with pre transplant fungal infections were also excluded. Pre-transplant characteristics included demographics, comorbidities within a year, laboratory values within seven days, and medication within 90 days before transplantation. Post-transplant fungal infections were identified using ICD-10 codes for Aspergillus, Candida, Cryptococcus, Mucorales, Histoplasma, Blastomyces, Coccidioides, and Pneumocystis. TriNetX platform was utilized for statistical analysis. Incidence and prevalence of infections, all-cause mortality and transplant rejection were analyzed. Results A total of 12,857 adult lung-transplant recipients were identified. The mean age at transplantation was 57.6 ± 13.4 years, with a male predominance of (57%) and majority were white (65%). Average BMI was 26.8 ± 5.7 kg/m². The most common pulmonary conditions were COPD (15%), pulmonary fibrosis (17%), pulmonary hypertension (9%), bronchiectasis (3%), and cystic fibrosis (3%). Pre-transplant fungal and viral screening assays were rarely available (<1%). Medication exposure within 90 days prior to transplant demonstrated prednisone prescription (17%) methylprednisolone (7%), tacrolimus (6%), and mycophenolate mofetil (7%). Azathioprine and basiliximab were used in 2% each. Systemic antifungals (voriconazole, posaconazole, or fluconazole) in approximately 1% each.The overall incidence of post-transplant fungal infection was 3 % across full study period, rising to 7% in the modern era (2015-2024). Most frequently identified pathogens were Candida spp. (4.8%) and Aspergillus spp. (2.9%), followed by Pneumocystis Jirovecii (0.5%). Infection rates increased from 22 per 1,000 (2005-2014) to 75 per 1,000 (2015-2024) suggestive of improved diagnostic sensitivity and data capture, and longer post-transplant survival. All-cause mortality 5-year post transplant was 22.1%, and rejection rate was 22.5%. Conclusion Our study highlights a rising burden of fungal infections among lung-transplant recipients with potential implications for early post-transplant surveillance and antifungal prophylaxis strategies. This abstract is funded by: None

Abstract Rationale Fungal infections are common after lung transplantation and may adversely affect graft function and survival, but long-term outcomes remain incompletely defined. Using a large multicenter real-world dataset, we aimed to study the impact of post-transplant fungal infections on clinical outcomes of lung transplant recipients. Methods We conducted a retrospective, cohort study using the TriNetX Global Collaborative Network, which aggregates de-identified electronic health records from >160 healthcare organizations across North America, Europe, and Asia. Adult lung transplant recipients (≥18 years) between 2005 and 2024 were identified using ICD-10 and CPT codes. Patients with post-transplant fungal infection (aspergillosis, candidiasis, mucormycosis, histoplasmosis, coccidioidomycosis, blastomycosis) and matched controls without fungal infection within one year before or any time after transplant were identified. The index date was the date of transplantation. Propensity-score matching was performed on demographics, comorbidities, laboratory values, procedures and immunosuppressive medications. Outcomes included all-cause mortality (primary), allograft rejection, and chronic lung allograft dysfunction (CLAD) at 6 months, 1 year, 3 years, and 5 years. Kaplan-Meier and Cox proportional hazards models were used to estimate risk ratios (RRs), hazard ratios (HRs), and 95% confidence intervals (CIs). Analyses were conducted in TriNetX Analytics (v25.0, Cambridge, MA). Results A total of 3,083 patients with post-transplant fungal infection and 11,625 patients without infection were identified. Mean age was 58 ± 13 years, and 56% were male. The most common pulmonary comorbidities were chronic obstructive pulmonary disease, unspecified pulmonary fibrosis, idiopathic pulmonary fibrosis and bronchiectasis. Immunosuppression exposure was similar across groups. After propensity score matching across 56 clinical variables, both groups (1,790 per group) were well balanced. Mortality was higher in the fungal infection cohort at all follow-up points: 13.% vs 9% at 6 months (RR 1.45, 95% CI 1.2-1.75, p = 0.001), 17.8% vs 13% at 1 year (RR 1.36, p = 0.0001), 27.7% vs 21% at 3 years (RR 1.28, p < 0.0001), and 33 % vs 25% at 5 years (RR 1.32, p < 0.0001). Allograft rejection remained consistently higher (46-61% vs 22-34%), while CLAD occurred two- to three-fold more frequently (1.8-5.7% vs 0.7-2%). Conclusion Post-transplant fungal infection is independently associated with significantly increased mortality, acute rejection, and CLAD following lung transplantation. These findings underscore the need for early fungal surveillance, optimized antifungal prophylaxis, and individualized immunosuppression strategies to improve long-term patient outcomes. This abstract is funded by: None

Abstract Rationale Pulmonary hypertension (PH) is a major determinant of peri- and post-transplant outcomes in liver-transplant recipients. While baseline mean pulmonary artery pressure (mPAP) is routinely assessed, the prognostic value of dynamic hemodynamic improvement during the transplant hospitalization remains poorly defined. This study evaluated whether changes in mPAP (ΔmPAP) independently predict one-year mortality after liver transplantation. Methods This retrospective study utilized data obtained from the Medical Information Mart for Intensive Care (MIMIC-IV) database to identify patients who underwent allogenic liver transplant (ICD-10-PCS code 0FY00Z0) between 2008 and 2019. Patients were excluded if they did not have invasive pulmonary hemodynamics data available through the database. The primary outcome of interest was one year mortality. Among 278 patients who underwent allogenic liver transplant in the given timeframe, 195 liver-transplant were included in the final analysis. Pulmonary pressures were extracted longitudinally and summarized as the first (baseline) and last mPAP values; ΔmPAP was defined as (first − last). The primary outcome was one-year all-cause mortality. Logistic regression models evaluated associations between ΔmPAP (continuous), baseline mPAP, age, and Charlson Comorbidity Index (CCI). Results The cohort included 195 patients (mean age 56 ± 9 years), of whom 62% were male. The mean baseline mPAP was 27 ± 8 mm Hg, and the average ΔmPAP was −8 ± 6 mm Hg. Compared with survivors, non-survivors had higher baseline mean mPAP (29 ± 9 mm Hg vs. 26 ± 7 mm Hg, p = 0.02) and smaller ΔmPAP improvement (−6 ± 5 mm Hg vs. −9 ± 6 mm Hg, p = 0.01). Age and CCI were similar between groups (p > 0.1 for both). On univariate analysis, both higher baseline mPAP (OR 1.09 per mm Hg, p = 0.011) and greater ΔmPAP reduction (OR 0.92 per mm Hg, p = 0.013) predicted one-year mortality. In the multivariable model including ΔmPAP, baseline mPAP, age, and CCI, we noted that ΔmPAP remained the only independent predictor (OR 0.90 per mm Hg, 95 % CI 0.83-0.97, p = 0.009) for 1 year mortality. Increase in baseline mPAP, age and CCI demonstrated non-significant trend towards 1-year mortality risk. Conclusions Greater reduction in mean pulmonary artery pressure during hospitalization independently predicted improved one-year survival after liver transplantation. These findings highlight hemodynamic reversibility being as a key determinant of post-transplant outcomes. Further large scale prospective studies are warranted to evaluate the prognostic utility of hemodynamic parameters in liver transplant patients. This abstract is funded by: None

Abstract Background Lung transplantation remains the accepted treatment modality of choice for life-threatening advanced lung disease due to established benefits of improving survival and functional status of the patients. However, the annual mortality of lung waitlist candidates remains high, reflecting ongoing donor-recipient mismatches and prolonged wait times. Modalities such as extracorporeal membrane oxygenation (ECMO) have been effectively used as a “bridge to transplant” (BTT) in high-risk patients on waitlist. Objective To evaluate trends in ECMO utilization, waitlist dynamics, and outcomes among lung transplant candidates between 2018 and 2024, with emphasis on the use of ECMO as a bridge to transplantation. Methods We conducted a retrospective chart review of all ECMO runs performed between 2018 to 2024 at the Mayo Clinic Florida Hospital. Among these, patients who underwent evaluation for lung transplantation were identified, and their waitlisting patterns, transplant outcomes, and peri-transplant ECMO status were described. Results Between 2018 and 2024, a total of 348 ECMO runs were recorded among 293 patients. Annual ECMO runs increased steadily from 17 in 2018 to 83 in 2024 (2019: 33, 2020: 30, 2021: 61, 2022: 56, 2023: 68, 2024: 83). Out of these patients, 142 underwent evaluation for lung transplantation and 133 (93.67%) were placed on the waitlist. Among waitlisted patients, 105 (78.9%) were listed before ECMO initiation, 23 (17.3%) during ECMO, and 5 (3.8%) after decannulation. Waitlist outcomes included 116 (87.2%) transplanted, 16 (12.0%) deaths before transplant, and 1 (0.8%) clinical improvement precluding transplant. Among 116 transplanted patients, 36 patients (31.03%) received ECMO as a bridge to lung transplantation. The annual patients bridged with ECMO demonstrated a progressive rise: 1 (2019), 3 (2020), 9 (2021), 6 (2022), 9 (2023), and 8 (2024). Among these 36 patients, 29 (80.56%) remained on ECMO support in the immediate post-transplant period. At the latest follow-up, mortality among BTT recipients was 9 (25%). Conclusion ECMO utilization has expanded substantially over the past several years reflecting its expanding role in supporting critically ill patients. There has been increased utilization of ECMO as a bridge to lung transplantation in order to support high risk candidates awaiting donor organs. The post-transplant mortality among BTT recipients was 25%, which highlights the importance of peri-transplant management to optimize long-term outcomes in this high-risk cohort. This abstract is funded by: None

Abstract Introduction Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by the accumulation of surfactant-derived lipoproteinaceous material within the alveoli, resulting in impaired gas exchange. While most cases are autoimmune, caused by anti-GM-CSF antibodies, secondary PAP results from macrophage dysfunction due to malignancy, infection, or inhalational toxins. E-cigarette or vaping product use-associated lung injury (EVALI) is an emerging clinical entity, but its potential to trigger secondary PAP remains poorly defined. We report a unique, treatment resistant case of vaping-induced secondary PAP, expanding the clinical spectrum of EVALI. Description A 28-year-old male with a 9-year history of daily nicotine vaping and frequent cannabis wax inhalation presented with progressive exertional dyspnea, hypoxemia, and digital clubbing. Chest CT showed diffuse ground-glass opacities and interlobular septal thickening, characteristic of the classic “crazy paving” pattern. BAL revealed PAS-positive lipoproteinaceous material, and lung biopsy confirmed intra-alveolar surfactant accumulation and foamy macrophages, consistent with PAP. Negative anti-GM-CSF antibodies excluded autoimmune PAP. Despite vaping cessation and aggressive management, including 5 months of systemic corticosteroids, a 7-day trial of inhaled GM-CSF (sargramostim), and empiric antibiotics, his condition progressed to respiratory failure requiring high-flow oxygen (FiO2 70%). Whole-lung lavage was deferred due to refractory hypoxemia. Ultimately, he underwent bilateral lung transplantation, highlighting the profound severity and irreversible nature of the disease. Discussion This case underscores an urgent public health concern as vaping use surges among young adults. Chronic inhalation of nicotine and cannabis aerosols may result in irreversible alveolar macrophage dysfunction, culminating in secondary PAP. The patient’s lack of response to standard therapies and progression to end-stage respiratory failure emphasizes the seriousness of vaping-related lung injury. Clinicians should maintain a high index of suspicion for PAP in young patients with unexplained respiratory symptoms and a history of vaping. Public health efforts must prioritize regulation and education to reduce vaping-related lung disease. This abstract is funded by: None