Native-lung complications following single-lung transplantation for interstitial lung disease: an in-depth analysis.

BACKGROUND: Interstitial lung disease (ILD) represents a heterogeneous group of lung disorders characterized by fibrotic lung tissue changes. In regions with severe donor shortages, single-lung transplantation (SLTx) is often preferred over bilateral lung transplantation for advanced ILD. However, temporal changes and complications in the retained native lung remain poorly understood. METHODS: A retrospective analysis of 149 recipients who had undergone SLTx was conducted, including 34 ILD SLTx recipients. Native-lung volume, radiological alterations, and perfusion were assessed at distinct post-SLTx time points. Statistical analyses compared ILD and non-ILD SLTx groups. RESULTS: Our study revealed a progressive reduction in native-lung volume over time, accompanied by radiographic deterioration and declining perfusion. Complications in the retained native lung were observed, such as pneumothorax (29.4%), pulmonary aspergillosis (11.8%), and acute exacerbation (8.9%). Long-term survival rates were similar between ILD and non-ILD SLTx recipients. CONCLUSIONS: This study illuminates the unique challenges and complications with respect to the native lung following SLTx for ILD. Ongoing monitoring and tailored management are essential. Despite limitations, this research contributes to our understanding of the temporal progression of native-lung complications post-SLTx for ILD, underscoring the need for further investigation.

Morphological Predictors of Primary Lung Cancer among Part-Solid Ground-Grass Nodules on High-Resolution CT.

Recent advancements in computed tomography (CT) scanning have improved the detection rates of peripheral pulmonary nodules, including those with ground-glass opacities (GGOs). This study focuses on part-solid pure ground-glass nodules (GGNs) and aims to identify imaging predictors that can reliably differentiate primary lung cancer from nodules with other diagnoses among part-solid GGNs on high-resolution CT (HRCT). A retrospective study was conducted on 609 patients who underwent surgical treatment or observation for lung nodules. Radiological findings from pre-operative HRCT scans were reviewed and several CT imaging features of part-solid GGNs were examined for their positive predictive value to identify primary lung cancer. The proportions of the nodules with a final diagnosis of primary lung cancer were significantly higher in part-solid GGNs (91.9%) compared with solid nodules (70.3%) or pure GGNs (66.7%). Among CT imaging features of part-solid GGNs that were evaluated, consolidation-to-tumor ratio (CTR) < 0.5 (98.1%), pleural indentation (96.4%), and clear tumor border (96.7%) had high positive predictive value to identify primary lung cancer. When two imaging features were combined, the combination of CTR < 0.5 and a clear tumor border was identified to have 100% positive predictive values with a sensitivity of 40.8%. Thus we conclude that part-solid GGNs with a CTR < 0.5 accompanied by a clear tumor border evaluated by HRCT are very likely to be primary lung cancers with an acceptable sensitivity. Preoperative diagnostic procedures to obtain a pathological diagnosis may potentially be omitted in patients harboring such part-solid GGNs.

Prognostic value of perioperative changes in the prognostic nutritional index in patients with surgically resected non-small cell lung cancer.

PURPOSE: This single-institution retrospective cohort study was conducted to assess the prognostic significance of perioperative changes in the prognostic nutritional index (PNI) in patients who underwent surgery for non-small cell lung cancer (NSCLC). METHODS: Clinicopathological data were collected from 441 patients who underwent lobectomy for NSCLC between 2010 and 2016.The PNI ratio (postoperative PNI/preoperative PNI) was used as an indicator of perioperative PNI changes. Prognostic differences were investigated based on PNI ratios. RESULTS: The optimal cut-off value of the PNI ratio for overall survival (OS) was set at 0.88 using a receiver operating characteristic curve. The PNI ratio was inversely related to a high smoking index, interstitial lung disease, and postoperative pulmonary complications. The 5-year OS rates for the high vs. low PNI ratio groups were 88.2% vs. 68.5%, respectively (hazard ratio [HR]: 3.04, 95% confidence interval [CI]: 1.90-4.86). Multivariable analysis revealed that a low PNI ratio was significantly associated with poor prognosis (HR: 2.94, 95% CI: 1.77-4.87). The PNI ratio was a more sensitive indicator than postoperative PNI status alone for identifying patients at high risk of mortality, particularly those with non-lung cancer causes. CONCLUSION: The perioperative PNI change is a significant prognostic factor for patients with NSCLC.

The CONUT score is associated with the pathologic grade in non-small cell lung cancer.

PURPOSE: Nutritional scores have been reported to be useful prognostic factors for various cancers. This study evaluated the usefulness of the preoperative controlling nutritional status (CONUT) score as a predictor of recurrence of non-small cell lung cancer (NSCLC). METHODS: The present study included 422 patients with stage I-IIIA NSCLC who underwent complete resection at Tohoku University Hospital between January 2010 and December 2016. The patients were divided into the low-CONUT and high-CONUT groups based on their CONUT scores. Overall survival (OS), recurrence-free survival (RFS), and cumulative recurrence rates in the low- and high-CONUT groups were evaluated retrospectively. RESULTS: One hundred forty-seven patients (34.8%) were assigned to the high-CONUT group. The high-CONUT group had a significantly worse performance status, pleural invasion, vascular invasion, and lung metastasis. In the whole cohort, the low-CONUT group showed better overall survival, recurrence-free survival, and a low cumulative recurrence rate in comparison to the high-CONUT group. There was no significant difference in prognosis or recurrence between the low- and high-CONUT groups after propensity score matching. CONCLUSION: Patients with a high CONUT score may be at high risk of recurrence because of the high frequency of pleural invasion, vascular invasion, and lung metastasis.

Long-term survival and clinical outcomes of delayed chest closure following lung transplantation.

PURPOSES: Delayed chest closure (DCC) is a widely accepted procedure in the context of lung transplantation (LTx); yet there are few reports detailing its long-term survival and clinical outcomes. METHODS: We reviewed the medical records of recipients who underwent deceased-donor lung transplantation (LTx) at Tohoku University Hospital. Long-term survival, including overall survival, freedom from chronic lung allograft dysfunction (CLAD), and CLAD-free survival and the clinical outcomes of graft function and physical performance and constitution were reviewed in recipients with DCC. RESULTS: Between 2009 and 2022, 116 patients underwent LTx, 33 of whom (28.4%) required DCC. The intra-and post-operative courses of the recipients who required DCC were more complicated than those of the recipients who underwent primary chest closure (PCC), with frequent volume reduction surgery and longer periods of invasive mechanical ventilation. Pulmonary vascular disease was considered a risk factor for these complications and DCC. Nonetheless, long-term survival and graft functions were comparable between the DCC and PCC groups. The physical performance and constitution of recipients who required DCC continued to improve, and by 2 years after transplantation, exhibited almost no difference from those who underwent PCC. CONCLUSIONS: In view of the profoundly complicated intra- and post-operative courses, DCC should be performed cautiously and only when clinically indicated, despite which it can result in equivalent long-term survival and acceptable outcomes to PCC.

Therapeutic Drug Monitoring of Blood Sirolimus and Tacrolimus Concentrations for Polypharmacy Management in a Lymphangioleiomyomatosis Patient Taking Two Cytochrome P450 3A Inhibitors.

Patients with lymphangioleiomyomatosis (LAM) and lung transplantations are treated with multiple drugs, such as tacrolimus, mycophenolate mofetil, prednisolone, and itraconazole, for long-term suppression of rejection response and prevention of infection. Additional drugs are required when lung transplant recipients develop graft complications. Therefore, managing polypharmacy is critical because of drug-drug interactions caused by various factors, including drug-metabolizing enzymes such as cytochrome P450 3A (CYP3A). The patient was a 48-year-old woman (height 144.9 cm and weight 38.4 kg) who underwent lung transplantation for LAM. Mycophenolate mofetil, tacrolimus (target blood concentration, 4.0-8.0 ng/mL), and prednisolone were administered for immunosuppression, and itraconazole and clarithromycin were administered to manage graft infection. The patient developed unilateral lymphedema, predominantly in the left leg; therefore, sirolimus was initiated with a target blood concentration of 3.0-5.0 ng/mL. In addition to 1.0 mg/day of sirolimus, tacrolimus (0.3 mg/day), itraconazole (100 mg/day), and clarithromycin (800 mg/day) were added. Blood sirolimus concentrations ranged from 18.8 to 36.9 ng/mL on days 6 to 9; thus, treatment with sirolimus was stopped because of over-target blood concentrations. Blood concentrations of sirolimus and tacrolimus were successfully managed without adverse events using therapeutic drug monitoring (TDM) and azole anti-fungal substitution of azithromycin instead of clarithromycin although sirolimus concentration was relatively lower compared to the target range. Thereby, frequent TDM, management of polypharmacy that influences CYP3A activity, and possibly CYP3A genotyping should be appropriately conducted for personalized medicine.

Efficacy and safety of mRNA SARS-CoV-2 vaccines in lung transplant recipients.

BACKGROUND: To date, reports addressing the antibody response following mRNA SARS-CoV-2 vaccination in lung transplant (LTX) recipients are limited. Thus, the aim of this clinical study was to investigate the efficacy and safety of the vaccines in LTX recipients compared to controls. METHODS: An open-label, nonrandomized prospective study was conducted at Tohoku University Hospital. LTX recipients and controls who received either the BNT162b2 vaccine or the mRNA-1273 vaccine were recruited, and SARS-CoV-2 IgG was measured before and after vaccination. The adverse events were reviewed. Predictors of negative serology after vaccination were evaluated with logistic regression. RESULTS: Forty-one LTX recipients and 24 controls were analyzed. Although all controls had a positive antibody response to a SARS-CoV-2 mRNA vaccine, antibody response was found in 24.4% of LTX recipients (p < .0001). The amount of SARS-CoV-2 IgG following the 2nd dose significantly climbed to 6557 AU/mL in controls, whereas the increase in IgG in LTX recipients was 8.3 AU/mL (p < .0001). Fewer LTX recipients developed systemic fever than controls (p < .0001) despite equivalent overall adverse event percentages in both groups. A higher plasma concentration of mycophenolate was a significant predictor of negative serology (p = .032). CONCLUSIONS: An impaired antibody response to mRNA vaccines was significantly found in LTX recipients compared to controls and was associated with the plasma concentration of mycophenolate. While repeating mRNA vaccination may be one of the strategies to improve antibody response given the safety of the vaccines, emerging data on humoral immune responses based on immunosuppression regimens in LTX recipients should be studied (jRCT1021210009).

Treatment outcomes of nontuberculous mycobacterial pulmonary disease in lung transplant recipients.

BACKGROUND: Lung transplant (LTX) recipients are at risk miscellaneous infections, among whom the clinical significance of nontuberculous mycobacteria (NTM) is increasingly recognized. Despite anti-mycobacterial therapy becoming standardized worldwide, there is a lack of data on treatment outcomes in LTX recipients who develop NTM-pulmonary disease (PD). We aimed to review the treatment outcomes of NTM-PD among LTX recipients in our center. METHODS: Patients who underwent LTX from January 2013 to December 2014 were consecutively enrolled in the retrospective cohort, with follow-up of data retrieved to December 2017. Clinical and radiological improvement and culture conversion after anti-mycobacterial therapy were reviewed in those who developed post-transplant NTM-PD. RESULTS: Sixteen of 230 LTX recipients developed post-transplant NTM-PD. Ten of 16 patients with post-transplant NTM-PD were treated with macrolide-containing anti-mycobacterial therapy, leading to clinical improvement in 5/10 (50%), radiological improvement in 5/10 (50%) and culture conversion in 6/10 (60%) patients. CONCLUSION: Anti-mycobacterial therapy may relieve pulmonary symptoms and reduce microbial load among individuals with post-transplant NTM-PD.

Outcome and prognostic factors after lung transplantation for bronchiectasis other than cystic fibrosis.

BACKGROUND: While lung transplant (LTX) can be an effective therapy to provide the survival benefit in selected populations, post-transplant outcome in LTX recipients with bronchiectasis other than cystic fibrosis (CF) has been less studied. Pseudomonas aeruginosa, often associated with exacerbations in bronchiectasis, is the most common micro-organism isolated from LTX recipients. We aimed to see the outcomes of patients with bronchiectasis other than CF after LTX and seek the risk factors associated with pre- and post-transplant Pseudomonas status. METHODS: Patients who underwent LTX at Tohoku University Hospital between January 2000 and December 2020 were consecutively included into the retrospective cohort study. Pre- and post-transplant prevalence of Pseudomonas colonization between bronchiectasis and other diseases was reviewed. Post-transplant outcomes (mortality and the development of chronic lung allograft dysfunction (CLAD)) were assessed using a Cox proportional hazards and time-to-event outcomes were estimated using the Kaplan-Meier method. RESULTS: LTX recipients with bronchiectasis experienced a high rate of pre- and post-transplant Pseudomonas colonization compared to other diseases with statistical significance (p < 0.001 and p < 0.001, respectively). Nevertheless, long-term survival in bronchiectasis was as great as non-bronchiectasis (Log-rank p = 0.522), and the bronchiectasis was not a trigger for death (HR 1.62, 95% CI 0.63-4.19). On the other hand, the chance of CLAD onset in bronchiectasis was comparable to non-bronchiectasis (Log-rank p = 0.221), and bronchiectasis was not a predictor of the development of CLAD (HR 1.88, 95% CI 0.65-5.40). CONCLUSIONS: Despite high prevalence of pre- and post-transplant Pseudomonas colonization, the outcome in LTX recipients with bronchiectasis other than CF was comparable to those without bronchiectasis.

Waiting time and mortality rate on lung transplant candidates in Japan: a single-center retrospective cohort study.

BACKGROUND: As lung transplantation (LTX) is a valuable treatment procedure for end-stage pulmonary disease, delayed referral to a transplant center should be avoided. We aimed to conduct a single-center analysis of the survival time after listing for LTX and waitlist mortality in each disease category in a Japanese population. METHODS: We included patients listed for LTX at Tohoku University Hospital from January 2007 to December 2020 who were followed up until March 2021. Pulmonary disease was categorized into the Obstructive, Vascular, Suppurative, Fibrosis, and Allogeneic groups. Risk factors for waitlist mortality were assessed using a Cox proportional hazards model. The Kaplan-Meier method was used to model time to death. RESULTS: We included 269 LTX candidates. Of those, 100, 72, and 97 patients were transplanted, waiting, and dead, respectively. The median time to LTX and time to death were 796 days (interquartile range [IQR] 579-1056) and 323 days (IQR 129-528), respectively. The Fibrosis group showed the highest mortality (50.9%; p < .001), followed by the Allogeneic (35.0%), Suppurative (33.3%), Vascular (32.1%), and Obstructive (13.1%) groups. The Fibrosis group showed a remarkable risk for waitlist mortality (hazard ratio 3.32, 95% CI 2.11-4.85). CONCLUSIONS: In Japan, the waiting time is extremely long and candidates with Fibrosis have high mortality. There is a need to document outcomes based on the underlying disease for listed LTX candidates to help determine the optimal timing for listing patients based on the estimated local waiting time.

Recovery of physical function in lung transplant recipients with sarcopenia.

BACKGROUND: Lung transplant (LTX) can provide a survival benefit and improve physical function for selected patients with advanced pulmonary disease. Sarcopenia is a systemic muscle-failure that can be found in a variety of life stages and disabilities. In this study, we follow the evolution of each variable defined in sarcopenia and the outcomes in LTX recipients with post-transplant sarcopenia. METHODS: Patients who underwent LTX at Tohoku University Hospital between 2013 and 2018 were consecutively included in the retrospective cohort study, with follow-up to 2019. Sarcopenia was defined by low muscle mass (the cross-sectional area (CSA) of erector spinae muscle (ESM) in thoracic CT with a threshold < 17.24 cm2/m2) and either low muscle strength (hand-grip with a threshold of < 26 kg in males and of < 18 kg in females) or physical performance (6-min walk distance with a threshold < 46.5% of predicted distance). RESULTS: Fifty-five recipients were included into the study, of whom 19 patients were defined as sarcopenic and 36 as non-sarcopenic. The muscle mass improved after transplant in both sarcopenic and non-sarcopenic individuals: the median ESM-CSA enlarged from 17.25 cm2/m2 in 2 months post-LTX to 18.55 cm2/m2 in 12 months (p < 0.001) and 17.63 cm2/m2 in 36 months (p < 0.001) in non-sarcopenic individuals, while in sarcopenic patients it improved from 13.36 cm2/m2 in 2 months to 16.31 cm2/m2 in 12 months (p < 0.005) and 18.01 cm2/m2 in 36 months (p < 0.001). The muscle mass in sarcopenia substantially recovered to close to non-sarcopenic conditions within 36-months (p < 0.001 in 2 months and p = 0.951 in 36 months). Accordingly, muscle strength and physical performance in both groups improved over time. No difference in survival was seen in both groups (Log-rank p = 0.096), and sarcopenia was not associated with an overall hazard of death (p = 0.147). There was no difference in the cumulative incidence of chronic lung allograft dysfunction between patients with or without sarcopenia (Log-rank p = 0.529). CONCLUSIONS: Even patients with post-transplant sarcopenia have a chance to recover physical function to levels close to those without sarcopenia several years post LTX.

[Anterior Mediastinal Cholesterin Granuloma Associated with Bilateral Pleurisy and Pericarditis].

The patient was a 41-year-old man. He was diagnosed with pleurisy and came to our hospital. The pleural effusion and pleurisy remained even after administration of sufficient doses of antibiotics. A thorough examination revealed an anterior mediastinal tumor. Six months later, pericarditis also developed. Autoimmune diseases, infections, and malignant diseases were suspected, but a definitive diagnosis could not be made. In order to confirm the diagnosis, anterior mediastinal tumor resection and pleural biopsy were performed. The anterior mediastinal tumor was diagnosed as cholesterin granuloma pathollogically. Cholesterin granuloma is a granuloma formed by deposition of cholesterin crystals and cholesterin granuloma occurring in the mediastinum is extremely rare.

[Assessment of Computed Tomography Sagittal Images for Early Diagnosis of Pulmonary Torsion after Lung Resection].

The incidence of postoperative pulmonary torsion is not frequent but it has a high mortality rate once it occurs, and prompt diagnosis and treatment are required. From past reports, it is considered effective to point out disruption of pulmonary blood flow by contrast-enhanced computed tomography (CT) examination for diagnosis. However, the comparison of pre- and post-operative plain CT images is considered to be useful in diagnosing lung torsion, and postoperative CT lung window setting sagittal images were examined in three cases of postoperative lung torsion. Results indicate that pulmonary torsion of the middle lobe after right lower lobectomy and the middle lobe after right upper lobectomy can be diagnosed by the present method.

[Ingenuity for Completion of Thoracoscopic Pulmonary Resection after Esophageal Cancer Treatment].

In recent years, with the improvement of diagnostic techniques and treatment outcomes, the number of lung cancer cases after esophageal cancer treatment has been increasing. In general, severe adhesions are expected in the right lung, during lung resection after esophageal cancer surgery. In this study, we reviewed intraoperative findings of lung resection with respect to the influence of different treatment methods for esophageal cancer, the site of adhesion formation for each lobe, and the techniques and precautions for lung resection. There were no difficulty in the left upper major segmentectomy. During the left lower lobectomy, the inflammation around the inferior pulmonary vein was noted. The adhesions between the reconstructed gastric tube and the inferior pulmonary vein were found during the right lower lobectomy. During the right upper lobectomy, severe adhesions between the lung and the superior vena cava as well as the gastric tube in the posterior mediastinum were observed, which should be paid much attention.

Plasma mycophenolic acid concentration and the clinical outcome after lung transplantation.

BACKGROUND: The therapeutic drug monitoring of mycophenolic acid (MPA) has been investigated for renal and heart transplantations; however, its usefulness in lung transplantation is unclear. METHODS: The MPA area under the plasma concentration-time curve (AUC) was calculated in 59 adult lung transplant recipients. The MPA AUC0-12 s were compared among the three groups determined by the presence of adverse events (no events, infection, and chronic lung allograft dysfunction [CLAD]). Next, MPA AUC0-12 thresholds for the adverse events were identified by receiver operating characteristic analysis. Cumulative occurrence rate of the adverse events was compared between two groups (adequate and inadequate groups) according to the thresholds. RESULTS: The MPA AUC0-12 s in the no event, infection, and CLAD groups were 30.3 ± 6.5, 36.8 ± 10.7, and 20.6 ± 9.6 µg·h/mL, respectively (P = .0027), while the tacrolimus trough levels were similarly controlled in the groups. The thresholds of MPA AUC0-12 for the occurrence of infection and CLAD were 40.5 and 22.8 µg·h/mL, respectively. The cumulative occurrence rate of adverse events of adequate group (15.3%) was significantly lower than that of inadequate group (56.0%) (P = .0050). CONCLUSIONS: The MPA AUC0-12 may affect the occurrence of adverse events in lung transplant recipients.

The fraction of sensitization among lung transplant recipients in a transplant center in Japan.

BACKGROUND: Anti-human leukocyte antigen (HLA) antibody testing was approved by the Japanese government in 2018. As such, there was no longitudinal data regarding the HLA-sensitization of lung transplant (LTX) patients in Japan. We therefore set out to measure anti-HLA antibodies from all our LTX patients during their annual follow-up to characterize the sensitization status in the Japanese population. METHODS: The cross-sectional study was conducted for consecutive LTX recipients who underwent transplantation from January 2000 to January 2020 at Tohoku University Hospital (TUH). The serum from the recipients was screened for anti-HLA antibody with the panel-reactive assay (PRA) and the donor-specific antibodies (DSA). RESULTS: Sensitization was reviewed in 93 LTX recipients, showing 23 positive (24.7%) and 70 negative (75.3%) PRA. More sensitized recipients were found in recent transplantations (60.9% (14/23), ≤5 years post LTX) than in older transplantations (17.4% (4/23), 5-10 years or 21.7% (5/23), ≥10 years post LTX) (p = 0.04). Even fewer recipients had DSA (5.4%, 5/93), among whom 4/5 (80%) were recently transplanted. CONCLUSION: The rate of PRA positive LTX recipients in our population was lower compared with those in previous reports from US and Europe. More sensitized LTRs were found in recent transplantations than the older cohort, and DSA was identified primarily in the recent recipients. Due to several limitations, it is still unclear whether the sensitization would be related the development of CLAD or survival, yet this study would be fundamental to the future anti-HLA body study in Japanese population.

Radiologic types of Mycobacterium xenopi pulmonary disease: different patients with similar short-term outcomes.

Mycobacterium xenopi pulmonary disease (Mxe-PD) is common among nontuberculous mycobacterial infections in Europe and Canada. Associations between radiological pattern and clinical features and outcomes are inadequately studied in Mxe-PD. We sought to investigate clinical characteristics and outcomes according to the dominant radiological pattern among patients with Mxe-PD. We retrospectively studied patients with Mxe-PD seen in our clinic, categorizing their predominant CT pattern as nodular bronchiectasis, fibrocavitary, or unclassifiable, and compared clinical characteristics, treatment, and outcomes between radiologic groups. Of 94 patients with Mxe-PD, CT patterns comprised nodular bronchiectasis (40/94, 42.6%), fibrocavitary (37/94, 39.4%), and unclassifiable (17/94, 18.1%). Compared with fibrocavitation, patients with nodular bronchiectasis were female dominant, less often had COPD, less often had AFB smear-positive sputum, and more frequently had co-isolation of Pseudomonas. Patients with nodular bronchiectasis were less often treated (65% versus 91.9%) and when treated, they received fewer anti-mycobacterial drugs (on average 3 versus 4). Outcomes did not differ significantly by radiological pattern. Nodular bronchiectasis was common among Mxe-PD patients in our clinic. Compared with fibrocavitary disease, patients with nodular bronchiectasis had features suggestive of milder disease and were less often treated. Among treated patients, outcomes did not differ by radiologic pattern.

Epstein-Barr virus-associated smooth muscle tumors after lung transplantation.

BACKGROUND: Recipients of solid organ transplants are prone to various complications that are seldom encountered in immunocompetent individuals. Post-transplant lymphoproliferative disorder (PTLD) is the best known and commonest Epstein-Barr Virus (EBV)-associated malignancy post solid organ transplant. EBV-associated smooth muscle tumors (EBV-SMT) including leiomyomas and leiomyosarcomas are rare and much less studied than PTLD. We recently encountered two cases of EBV-SMT post lung transplantation and here we summarize their clinical features and course together with a literature review. METHOD: Clinical data and treatment details of two patients who developed EBV-SMT were reviewed and retrieved up to December 31, 2017. English literature was searched through the PubMed database from 1965 to 2017 for studies of the association between lung transplant and EBV-SMT. RESULTS: The incidence of PTLD is higher among lung transplant recipients compared to kidney transplant recipients, an observation that has been attributed to stronger immune suppression in the lung patients. EBV-SMT showed a higher incidence among kidney recipients than among lung recipients, suggesting that the degree of immunosuppression may be a less important factor in the development of EBV-SMT. EBV-SMT has most often been seen among lung transplant recipients with EBV mismatch. CONCLUSIONS: Because EBV-SMT is a rare tumor, its incidence, risk factors, and optimal management have not been well-defined and further study is needed.

Phosphatidylserine dictates the assembly and dynamics of caveolae in the plasma membrane.

Caveolae are bulb-shaped nanodomains of the plasma membrane that are enriched in cholesterol and sphingolipids. They have many physiological functions, including endocytic transport, mechanosensing, and regulation of membrane and lipid transport. Caveola formation relies on integral membrane proteins termed caveolins (Cavs) and the cavin family of peripheral proteins. Both protein families bind anionic phospholipids, but the precise roles of these lipids are unknown. Here, we studied the effects of phosphatidylserine (PtdSer), phosphatidylinositol 4-phosphate (PtdIns4P), and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) on caveolar formation and dynamics. Using live-cell, single-particle tracking of GFP-labeled Cav1 and ultrastructural analyses, we compared the effect of PtdSer disruption or phosphoinositide depletion with caveola disassembly caused by cavin1 loss. We found that PtdSer plays a crucial role in both caveola formation and stability. Sequestration or depletion of PtdSer decreased the number of detectable Cav1-GFP puncta and the number of caveolae visualized by electron microscopy. Under PtdSer-limiting conditions, the co-localization of Cav1 and cavin1 was diminished, and cavin1 degradation was increased. Using rapamycin-recruitable phosphatases, we also found that the acute depletion of PtdIns4P and PtdIns(4,5)P2 has minimal impact on caveola assembly but results in decreased lateral confinement. Finally, we show in a model of phospholipid scrambling, a feature of apoptotic cells, that caveola stability is acutely affected by the scrambling. We conclude that the predominant plasmalemmal anionic lipid PtdSer is essential for proper Cav clustering, caveola formation, and caveola dynamics and that membrane scrambling can perturb caveolar stability.

Mycobacterium xenopi Genotype Associated with Clinical Phenotype in Lung Disease.

Mycobacterium xenopi is responsible for pulmonary disease (PD) in Europe and Canada. Despite its high prevalence and increasing clinical importance, little is known about the genetic diversity of M. xenopi. Through a prospective study for M. xenopi strain type and the relation to clinical phenotype, 39 patients with M. xenopi PD were analyzed. Our study demonstrated that sequence type (ST) 5 was dominant in Ontario among 15 distinct STs and caused PD in people even without underlying lung disease, whereas disease due to non-ST5 was found almost exclusively in patients with underlying lung disease.