Background Lung transplant recipients (LTRs) are at increased risk of genitourinary cancers (GUCs) but do not undergo routine surveillance. This study describes the cumulative incidence and clinical outcomes of GUC among LTRs. Methods This single-center, retrospective cohort study included all adult LTRs transplanted between 2010 and 2020 with histologically confirmed posttransplant bladder or ureteral cancer. The primary outcome was the cumulative incidence (CI) of GUC. We estimated the subdistribution hazard ratio (sHR) for GUC using a competing risks proportional hazards model. Secondary outcomes, including post-diagnosis survival, were analyzed using Kaplan-Meier curves and the log-rank test for comparisons. Statistical significance was set at p<0.05. We also described patient and disease characteristics and treatments. Results Among 835 LTRs, 15 developed posttransplant GUC (13 bladder and 2 ureteral); 11 were diagnosed >5 years post-LT. The CI was 1.8%. The cohort was predominantly male (73.3%) with a median age of 72.5 years (IQR 68–77.8) and substantial tobacco exposure (≥20 pack-years: 93.3%). GUC was diagnosed at a median of 75 months (IQR 52.1-103.6) posttransplant. Mortality was high (73.3% deceased at follow-up) with a median survival of 196 days post-diagnosis. Obstructive lung disease (OLD) was associated with a markedly higher subdistribution hazard of posttransplant GUC (sHR: 4.99 [p=0.0058]), which persisted after multivariable adjustment for age at transplant, sex, and smoking history (adjusted sHR: 5.05 [p=0.007]). Conclusions GUCs were a rare but clinically important late complications after LT, frequently presented with aggressive features, and were associated with poor survival. The association with OLD should be interpreted cautiously given the small number of events and potential confounding by cumulative tobacco exposure. These findings support further study of risk-adapted surveillance strategies in higher-risk LTRs.

BACKGROUND:Lung transplant recipients (LTRs) are susceptible to opportunistic infections, including invasive nocardiosis (IN) and invasive mucormycosis (IM). Polymerase chain reaction (PCR) testing of bronchoalveolar lavage (BAL) fluid offers rapid pathogen detection, but its clinical utility in LTRs is understudied. METHODS:We conducted a single-center, retrospective cohort study of adult LTRs who underwent BAL PCR testing for Nocardia spp. or Mucorales spp. (January 2020-December 2024); samples from both surveillance and "for-cause" bronchoscopies were included. The primary outcome was development of clinical infection within 6 months of PCR testing. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Patient-level analyses were performed for PCR-positive LTRs. Fisher's exact and Mann-Whitney U tests were used for calculating p-values. RESULTS:Of 4279 Nocardia and 3588 Mucorales BAL PCR tests, 1.7% and 1.4% of samples were positive, respectively. Sensitivity, specificity, PPV, and NPV were 92.3%, 98.6%, 16.7%, and 99.98% for Nocardia and 76.2%, 99.1%, 32.0%, and 99.9% for Mucorales. Abnormal chest CT findings and for-cause bronchoscopy increased the PPV to 34.3% for Nocardia and 68.2% for Mucorales. At the patient level, both IN and IM were associated with abnormal imaging and for-cause bronchoscopy. CONCLUSIONS:BAL PCR testing for Nocardia and Mucorales demonstrates excellent specificity and NPV but low PPV. Meaningful PPV was observed primarily in patients undergoing for-cause bronchoscopy with radiographic abnormalities. PCR results can be useful adjuncts in appropriate clinical settings, but have little utility among LTRs with normal imaging undergoing surveillance testing.

BACKGROUND:Pleural space infections (PSI) are a common complication after lung transplantation (LT) and have historically been linked to impaired allograft function and decreased survival, though contemporary outcome data are limited. METHODS:This retrospective cohort included adult LT recipients (LTRs) who underwent pleural effusion drainage ≤ 90 days posttransplant from June 2013 to December 2023. Pulmonary function tests (PFTs; FEV1 and FVC percent predicted) and 1-year survival were compared between LTRs with and without culture-proven PSI using linear mixed-effects models. Survival was analyzed using an adjusted Cox proportional hazards model controlling for restrictive lung disease, with Kaplan-Meier curves to visualize survival trajectories. PSI diagnosis, microbiology, and management considerations were also described. RESULTS:Among 1005 LTRs, 7% developed PSI (n = 72) and 30% had sterile effusions (n = 304). A pleural neutrophil percentage > 21% predicted infection with 71% sensitivity and 76% specificity. Gram-positive bacteria and Candida comprised 80% of isolates. Median antimicrobial treatment was 4 weeks, combined with pleural drainage. Surgical intervention within 30 days of nonoperative drainage was more frequent in PSI patients (22% vs. 7%, p < 0.001; two-thirds VATS procedures). PSI was associated with modest early pulmonary impairment (∼4%-7% lower PFTs), primarily reflecting stable (non-improving) values from Months 1 to Month 2. However, both groups showed similar trajectories thereafter, with >10% absolute PFT improvement from Month 1 to Month 12. One-year survival was 93% (PSI) versus 94% (non-PSI) (HR: 1.23, 95% CI: 0.44-4.43, p = 0.69). CONCLUSION:PSI remains frequent post-LT but with contemporary management-including drainage, antimicrobials, and early surgical intervention-may no longer carry excess risk for sustained allograft dysfunction or death relative to pleural effusions without associated infection.

Kaposi sarcoma-associated herpesvirus (KSHV) infection is the cause of Kaposi sarcoma (KS), certain lymphoproliferative disorders, and the inflammatory condition Kaposi sarcoma-associated herpesvirus inflammatory cytokine syndrome (KICS). In solid organ transplant recipients, KSHV-related complications can result from reactivation of latent infection, new posttransplant infection, or transmission of virus from the transplanted organ. However, testing of donors and recipients is not routinely performed. During January 2021-September 2025, after transplantation of 185 organs into 153 recipients, 46 deceased donors were identified whose transplanted organs were suspected of having transmitted KSHV, approximately five times the number of such donors (nine) reported during 2016-2020. As of February 2026, a posttransplantation KSHV infection has been identified among 74 (48%) of these 153 transplant recipients. Among the 74 recipients with KSHV infection, 45 (61%) developed KS; 10 (14%) of these recipients with KS also developed a lymphoproliferative disorder (multicentric Castleman disease [eight], posttransplant lymphoproliferative disorder [one], and primary effusion lymphoma [one]) and six (8%) developed KICS; four (5%) recipients developed a lymphoproliferative disorder alone (primary effusion lymphoma [one] and posttransplant lymphoproliferative disorder [three]); and one (1%) developed KICS alone. To date, 25 (16%) of the 153 transplant recipients have died. Most donors and recipients were HIV-negative, and nonmedical drug use was common among donors. Clinicians should maintain a high index of suspicion for KSHV in transplant recipients, particularly when donors have risk factors including nonmedical drug use, or when another recipient from the same donor is found to be infected. Development and implementation of effective testing strategies and timely reporting could guide clinical management, reduce risk for KSHV-related complications, and improve transplant safety.

BACKGROUND:Lung transplant recipients (LTRs) can develop donor-specific antibodies (DSAs), which are associated with antibody-mediated rejection (AMR). LTRs at our center undergo regular DSA surveillance in the first year after lung transplant (LT), and LTRs that develop DSAs are treated, even in the absence of allograft dysfunction. We compared the clinical outcomes of LTRs without DSAs to those of LTRs that developed DSAs early after LT (< 3 months) or late after LT (3-12 months). METHODS:We retrospectively analyzed 428 LTRs transplanted at our center between February 2017 and June 2022. Of these, 94 were included in the no-DSA group (mean fluorescence intensity [MFI] < 500) and 143 were included in the DSA groups (MFI ≥ 2000), with 131 in the early-DSA group and 12 in the late-DSA group. We compared the groups using Fisher's exact test, the median test, and Kaplan-Meier and Cox regression survival analyses. RESULTS:There was no statistically significant difference in 1- and 3-year survival between the 3 groups; however, 3-year survival in the late-DSA group was 33%, with AMR as the cause of death in 2 of the 4 deceased LTRs. DSAs declined in the majority of patients in both the early and late groups. There were no significant differences in infectious complications between the groups (p = 0.332). CONCLUSION:LTRs with early DSAs and preemptive treatment have a good prognosis, with post-LT overall survival and chronic lung allograft dysfunction (CLAD)-free survival comparable to that of LTRs without DSAs. LTRs with late DSAs may have worse long-term and CLAD-free survival; however, larger studies are needed.

Introduction Cutis laxa (CL) is an inherited or acquired connective tissue disorder characterized by hypoelastic, loose skin due to a deficiency of dermal elastic fibers or reduced elastin synthesis by fibroblasts. Patients with CL can have systemic disease manifestations with loss of tissue support in the lungs, gastrointestinal (GI) tract, heart, vasculature, and urogenital system. Pulmonary manifestations include bronchiectasis and emphysema leading to advanced lung disease, and a literature review revealed a case of successful bilateral lung transplantation (LT) for juvenile emphysema associated with CL. We report a suspected case of CL-associated end-stage emphysema in a young adult and describe the implications of extrapulmonary disease on LT candidacy. Case Report A 34-year-old male never-smoker with advanced obstructive lung disease, skin laxity leading to older appearance, hiatal and ventral hernia repair, and bilateral foot drop was transferred to our center for LT evaluation. His chest CT showed severe panacinar bilateral emphysema with a large left basilar bulla, an umbilical hernia, and a hiatal hernia. An echocardiogram showed a normal left and right ventricular fraction, and no structural valvular disease. His GI evaluation was notable for gastroparesis, impaired swallow with laryngeal penetration of thin liquids, and a large right-sided 1.4 cm Killian Jamieson and 2.3 cm Zenker's diverticula. A CT of the soft tissue of his neck with contrast showed symmetric outpouchings emanating from the lower pharynx and the proximal cervical esophagus, and an abdominal CT was notable for colonic enlargement with a diameter of 6 cm. After a careful multidisciplinary board review, the patient was deemed an LT candidate, but would require prolonged tube feeding to prevent aspiration associated with esophageal diverticula and hiatal hernia. The patient elected to pursue hospice care to avoid feeding tube dependence. Discussion Although LT can be considered in patients with CL-associated pulmonary disease, the deficiency of elastic fiber can lead to thin and fragile bronchial cartilage that can contribute to post-LT airway complications. Additionally, extrapulmonary disease manifestations may lead to increased post-LT morbidity and mortality due to GI, cardiac, and vascular complications. Lastly, although surgical interventions are generally uncomplicated for patients with CL, outcomes are often temporary and relapse is common, as noted in our patient with recurrent GI hernias and prominent diverticula.

BACKGROUND:Heparin induced thrombocytopenia (HIT) is often suspected among lung transplant recipients (LTRs) due to a high prevalence of thrombocytopenia and frequent heparin use. This study explores the utility of the 4Ts score in stratifying HIT risk among adult LTRs. METHODS:LTRs from a single large transplant center with post-transplant platelet factor 4 (PF4) antibody testing between January 2020 and June 2024 were included in the analysis. The 4Ts score was calculated retrospectively, and the risk of HIT was classified as low (4Ts score ≤3), intermediate (4-5), or high (≥6). The 4Ts risk classification was correlated with HIT laboratory testing results, with a positive serotonin release assay (SRA) representing confirmed HIT. RESULTS:A total of 205 LTRs were included. The median 4Ts score was 2 (IQR 2-4), 153 patients (74.6%) were classified as low risk, and 52 (25.4%) were intermediate or high risk. Among low-risk patients, none had confirmed HIT. In contrast, among intermediate or high-risk patients, six had HIT (11.5%), representing an overall incidence of 2.9%. Using a low 4Ts score to rule out HIT would have averted 153 PF4 tests (75% of total), 17 SRA tests (50% of total), and nine orders for direct thrombin inhibitors (53% of total). CONCLUSION:A low 4Ts score ruled out HIT among LTRs at our large transplant center. Incorporating the 4Ts clinical risk assessment into the diagnostic process may help avoid unnecessary HIT testing and use of alternative anticoagulation.

Abstract Background Pleural space infections (PSI) represent a known complication of lung transplantation (LT) in the early posttransplant period. Within the historical literature, PSIs, and empyemas in particular, have been associated with an increased risk for death, with 29-43% 1-year mortality. However, these studies were small and conducted prior to advances in anti-infective prophylaxis and treatment strategies. Therefore, the purpose of this investigation was to characterize the microbial profile and outcomes of early PSI among lung transplant recipients (LTRs) within the modern era.Figure 1.Isolated organisms from pleural fluid of lung transplant recipients from present study (Panel A, 66 isolates, 2017-2022 transplants) and historical literature (Panel B, 4 studies, 55 isolates, 1983-2005 transplants) Methods This study was approved by the Institutional Review Board of St. Joseph’s Hospital and Medical Center (SJHMC). Included LTRs were transplanted between 2017-2022 at SJHMC with ≥ 1 pleural fluid culture positive for an organism within 90 days of LT. LTRs at SJHMC received cefepime, vancomycin, and levofloxacin in the immediate postoperative period, or targeted antibiotic therapy based on donor and recipient airway cultures. During the index transplant hospitalization, LTRs received prophylaxis with inhaled amphotericin and tobramycin. Additional opportunistic infection prophylaxis throughout the study period included valganciclovir, itraconazole, and trimethoprim/sulfamethoxazole. Results Among 554 total LTRs, 250 (45%) had pleural effusion cultures, and 54 (54/250, 22%) had ≥ 1 pleural culture positive for an organism (Table 1). Over 95% of effusions were exudative and 53% were neutrophil predominant. Of the 66 organisms isolated (Figure 1), 40 (61%) were Gram-positive bacteria, 21 (32%) were fungi (15 Candida species, 6 molds), 4 (6%) were Gram-negative bacteria, and 1 (2%) was unspeciated acid-fast bacilli. Infection was typically managed via effusion drainage and 4-6 weeks of pathogen-directed antimicrobial therapy. All-cause 1-year mortality was 7.4%, lower than national LTR 1-year mortality rates over the study period (∼10-12%). Conclusion In a large investigation of LTRs with early posttransplant PSIs, Gram-positive bacteria were isolated most frequently, with isolation of Candida also common. Gram-negative bacteria comprised a smaller proportion of infections than reported in prior literature. PSIs did not appear to predispose LTRs to poor posttransplant survival. Disclosures Michael D. Nailor, Pharm.D., InflaRx: Advisor/Consultant|Shionogi: Advisor/Consultant

Purpose:To investigate the relationship between Public Health Service (PHS) increased-risk donors and post-lung transplant (LT) Kaposi sarcoma (KS). Methods:This retrospective cohort study included LT recipients (April 1, 2019-April 1, 2024) who had PHS increased-risk donors at our institution. Data were abstracted from UNOS and electronic medical records. Published post-LT KS cases were also reviewed. Descriptive statistics and Kaplan-Meier estimates were used. Results:Of 467 LT recipients, 90 (23.9%) had PHS increased-risk donors, including 13 [14.4%] men who have sex with men (MSM). Four of these 13 (30.8%) recipients developed KS (median time to diagnosis, 365 days [IQR 276-502]). Basiliximab was the most common induction agent; all 4 patients were on standard 3-drug immunosuppression. All 4 recipients had pulmonary KS without extrapulmonary involvement and positive human herpes virus 8 (HHV-8) immunohistochemistry results. Pulmonary nodules were incidentally noted on chest CT in 3 asymptomatic patients; 1 patient presented with dyspnea and central airway obstruction. Immunosuppression was reduced and mTOR inhibitors were initiated for all 4 patients; 1 patient underwent stenting of the left main bronchus and radiation, and 1 was treated with liposomal doxorubicin. Three recipients improved, and 1 is awaiting follow-up imaging (median follow-up, 276 days [IQR 177-433]). In our data pooled with 15 published cases, mean survival time was lower in patients with disseminated KS (182 vs. 563 days, p=0.011). Conclusion:LT recipients with MSM donors may be at an increased risk for post-LT KS from donor-derived HHV-8. Larger, more definitive, multicenter studies are needed.

BACKGROUND:Lung transplant recipients (LTRs) frequently receive off-label inhaled tobramycin. However, LTRs differ pharmacokinetically from cystic fibrosis (CF) patients for whom the drug is approved and may be at increased risk for toxic systemic concentrations. This study characterized the incidence and predictors of detectable serum tobramycin concentrations among LTRs without underlying CF. METHODS:This retrospective, single-center cohort study included LTRs receiving inhaled tobramycin (without intravenous/intramuscular tobramycin) with serum concentration testing July 2015 to June 2025. Logistic regression identified predictors of elevated concentrations (tobramycin ≥ 1 µg/mL), and analysis of covariance evaluated the dose/concentration relationship controlled for timing. Acute kidney injury (AKI) was defined as ≥ 0.3 mg/dL or a 1.5× increase in serum creatinine. RESULTS:Forty-four LTRs (median age 69 years [IQR: 63-72]) contributed 56 tobramycin concentrations; 93% were inpatients, and 9% required renal replacement therapy (RRT). Inhaled tobramycin was dosed 160 mg (59%) or 300 mg (41%) twice daily. Detectable tobramycin serum concentrations occurred in 80% of patients (median 0.4 µg/mL [IQR: 0.3-0.8]); 8 (18%) had concentrations ≥ 1 µg/mL, and 3 (7%) ≥ 2 µg/mL. The 300 mg dose was associated with elevated concentrations (OR 7.2, 95% CI: 1.1-49.2, p = 0.043), including after adjusting for concentration timing (p < 0.001). Among non-RRT patients, 55% developed new AKI a median of 3 days after concentration sampling, with tobramycin concentrations significantly higher in the AKI group (0.4 µg/mL vs. 0.2 µg/mL, p = 0.035). CONCLUSION:LTRs without CF commonly had systemic tobramycin exposure during inhaled therapy. The 300 mg dose was linked to higher serum concentrations, supporting reduced dosing and active serum concentration monitoring to enhance safety.

Introduction: We present a case of recurrent diffuse large B-cell lymphoma (DLBCL) in a lung transplant recipient. Case Report: A 62 year-old man underwent bilateral lung transplantation for chronic obstructive pulmonary disease; both donor and recipient were seropositive for Epstein Barr virus (EBV). The patient's posttransplant course was significant for heparin-associated thrombocytopenia, drug-induced leucopenia, steroid-induced diabetes, chronic nephropathy, and COVID, parainfluenza, and respiratory syncytial viral infections. Six years seven months later, the patient was given 2 doses of rituximab due to de-novo donor-specific antibodies. A few weeks later, he presented with bright red painless rectal bleeding; colonoscopy revealed an ulcerative mass in the cecum and ascending colon. Histopathology showed monomorphic EBV-negative DLBCL with a proliferation index of 80%; PET-CT showed no distant metastasis. The patient initially received 4 cycles of rituximab only chemotherapy; however, the patient reported progressively worsening right flank pain with poor oral intake and failure to thrive eight months after initial presentation; exam showed a mildly tender right mid-abdominal firm mobile mass without hepatosplenomegaly. CT demonstrated thick-walled cecum dilated to 9.5 cm with enlarging tumor infiltrating into the lateral abdominal wall. The patient underwent a robotic right colectomy with en-bloc resection of abdominal wall and end-ileostomy. Surgical pathology showed negative margins, 3 of 5 local lymph nodes were positive for lymphoma. A month later, the patient was admitted for shortness of breath and chest pain; exam showed a tender soft mass in the right mid-abdomen. Non-contrast CT was performed due to chronic kidney disease and showed a soft tissue collection in the same area suspicious for surgical site hematoma. Despite interruption of anticoagulation, the mass persisted and the patient continued to have dyspnea and failure to thrive. Contrast MRI was performed and showed right lateral abnormal wall heterogeneous enhancing lobulated mass extending into the extra-peritoneal and peritoneal space, suspicious for locally recurrent lymphoma. After extensive discussion with Oncology teams regarding the poor prognosis, the patient elected to pursue hospice care. Summary: EBV-negative posttransplant lymphoproliferative disorders, such as diffuse large B-cell lymphoma, are biologically distinct from their EBV+ counterparts, tend to occur much later after lung transplantation, frequently involve the gastrointestinal tract, and are more likely to be monomorphic. Modification of conventional chemotherapy is often needed given associated comorbidities. Despite aggressive and definitive therapy, early recurrence can occur and timely detection requires low threshold of clinical suspicion.