A case of successful contribution of therapeutic drug monitoring of valganciclovir as the prophylaxis against cytomegalovirus infection in a lung transplant recipient.

BACKGROUND: Ganciclovir and its prodrug, valganciclovir, are first-line agents for cytomegalovirus infection prophylaxis after lung transplantation. Although valganciclovir prophylaxis is known to result in severe leukopenia as an adverse effect, dosage adjustment based on therapeutic drug monitoring (TDM) of ganciclovir concentration is not generally implemented in clinical practice. CASE PRESENTATION: In this report, we describe the case of a female in her fifties after lung transplantation who successfully maintained valganciclovir prophylaxis under TDM with a minimal occurrence of severe leukopenia. Valganciclovir administration was initiated at a conventional dose of 450 mg/day on postoperative day 43 but was reduced to 450 mg/2 days on postoperative day 69 because of a decrease in white blood cell count and an increase in trough ganciclovir concentration. Subsequently, the valganciclovir dose adjustment was switched from label-indicated renal function-guided dosing to TDM-based dosing, targeting a trough level of 300-800 ng/mL. This target range was determined through deliberations with infectious disease specialists and pharmacists based on previously reported data. The TDM-based dose adjustment successfully prevented cytomegalovirus reactivation without causing significant adverse effects. Valganciclovir prophylaxis was completed on postoperative day 256, and the patient was transferred to another hospital for rehabilitation. CONCLUSIONS: The findings of the present case suggest that TDM-based dosing could be helpful for clinicians in optimizing the prophylactic administration of valganciclovir in patients undergoing lung transplantation.

Fan Therapy for Dyspnea in Lung Transplant Recipients in the Intensive Care Unit: A Before-and-After Study.

Introduction Fan therapy has gained attention as a non-pharmacological treatment for alleviating dyspnea in patients receiving palliative care and in those with chronic progressive diseases. However, the effectiveness of fan therapy for dyspnea in critically ill patients in intensive care units (ICUs) remains unclear. This study aimed to investigate the efficacy and safety of fan therapy for lung transplant patients in the ICU. Methods Fan therapy was performed on lung transplant recipients (age >18 years) who experienced dyspnea during their ICU stay. A tabletop portable fan was used to blow air on the patient's face for five minutes providing fan therapy. The intensity of dyspnea before and after the fan therapy was determined, and a statistical analysis was conducted using a paired t-test to evaluate the changes. Results Between May 2023 and February 2024, 16 patients who were admitted to the ICU following lung transplantation were screened, and eight patients received fan therapy. Fan therapy was performed at a median of postoperative day 12. Seven patients (87.5%) received mechanical ventilation via tracheostomy. The mean (±standard deviation) numerical rating scale (NRS) for dyspnea before and after fan therapy was 5.6±2.3 and 4.4±1.5, respectively (p = 0.08). The mean (±standard deviation) respiratory distress observation scale (RDOS) before and after fan therapy was 4.8 ± 2.0 and 3.8 ± 1.7, respectively (p = 0.03). No serious adverse events were observed, and no significant alterations were observed in the respiratory rate, oxygen saturation levels, pulse rate, or blood pressure. Conclusion The findings suggest that fan therapy can be safely used to relieve dyspnea in lung transplant recipients during their ICU stay. Further evaluations in larger trials are required to confirm the results of this study.

Effect of epoprostenol-induced thrombocytopaenia on lung transplantation for pulmonary arterial hypertension.

OBJECTIVES: Preoperative intravenous epoprostenol therapy can cause thrombocytopaenia, which may increase the risk of perioperative bleeding during lung transplantation. This study aimed to determine whether lung transplantation can be safely performed in patients with epoprostenol-induced thrombocytopaenia. METHODS: From June 2008 to July 2022, we performed 37 lung transplants in patients with pulmonary arterial hypertension (PAH), including idiopathic PAH (n = 26), congenital heart disease-associated PAH (n = 7), pulmonary veno-occlusive disease (n = 3) and peripheral pulmonary artery stenosis (n = 1) at our institution. Of these, 26 patients received intravenous epoprostenol therapy (EPO group), whereas 11 patients were treated with no epoprostenol (no-EPO group). We retrospectively analysed the preoperative and postoperative platelet counts and post-transplant outcomes in each group. RESULTS: Preoperative platelet counts were relatively lower in the EPO group than in the no-EPO group (median EPO: 127 000 vs no-EPO: 176 000/µl). However, blood loss during surgery was similar between the 2 groups (EPO: 2473 ml vs no-EPO: 2615 ml). The platelet counts significantly increased over 1 month after surgery, and both groups showed similar platelet counts (EPO: 298 000 vs no-EPO: 284 000/µl). In-hospital mortality (EPO: 3.9% vs no-EPO: 18.2%) and the 3-year survival rate (EPO: 91.4% vs no-EPO: 80.8%) were similar between the 2 groups. CONCLUSIONS: Patients with PAH treated with intravenous epoprostenol showed relatively lower platelet counts, which improved after lung transplantation with good post-transplant outcomes.

Pulmonary cyst newly formed after lobectomy in various underlying lung conditions.

BACKGROUND: It has been recently recognized that pulmonary cyst may develop after pulmonary resection, causing various symptoms. Most previously reported cases were after upper lobectomy in patients with chronic obstructive lung disease (COPD). CASE PRESENTATION: Case 1 was a man in his 70 s with interstitial pneumonia (IP). Right lower lobectomy was performed for metastatic lung tumor using video-assisted thoracoscopic surgery (VATS). On postoperative day (POD) 19, computed tomography (CT) revealed a large cyst at the upper interlobular surface of the middle lobe, with pneumoderma and pneumomediastinum. The cyst was incised, polyglycolic acid (PGA) sheet and fibrin glue were applied, and the cyst was sutured. The sutured line was covered again with PGA sheet and fibrin glue. Case 2 was a man in his 70 s with COPD. Right upper lobectomy for primary lung cancer was performed using VATS. On POD 17, CT revealed a large pulmonary cyst at the apex of S6 and massive air leakage was observed. The same surgical procedure as that used in case 1 was performed. Cases 3 and 4 were healthy donors for living-donor lung transplantation. Two months after the right lower lobectomy in Case 3 and 3 months after the left lower lobectomy in Case 4, the patients had respiratory symptoms such as dyspnea and hemosputum. CT revealed a large cyst on the diaphragmatic surface of the right middle lobe in Case 3 and on the posterior mediastinal surface of the left upper lobe in Case 4. Cyst incision, soft coagulation, and application of PGA sheet with fibrin glue were performed in both cases. CT performed 1 year after surgery showed no development of a pulmonary cyst or air space in these four cases. CONCLUSIONS: Pulmonary cysts newly formed after lobectomy can develop not only in COPD or IP but also in healthy lungs. Our findings suggest that incision of the cyst and application of fibrin glue and PGA sheet with or without suturing the cyst wall is effective for management.

Comparison of the safety and cost-effectiveness of nebulized liposomal amphotericin B and amphotericin B deoxycholate for antifungal prophylaxis after lung transplantation.

INTRODUCTION: Fungal infection after lung transplantation can lead to poor clinical outcome, for which lung transplant recipients require prophylaxis. One of the antifungal agents used after lung transplantation is nebulized amphotericin B (AMB). Nebulized AMB causes adverse events such as dyspnea and airway irritation, and long-term use leads to high economic costs. So far, prophylactic regimens employing AMB deoxycholate (AMB-d) and liposomal AMB (L-AMB) have been developed. This study compared the efficacy, safety, and cost of AMB-d and L-AMB. PATIENTS AND METHODS: Patients who underwent lung transplantation at Kyoto University Hospital from January 2021 to May 2023 were included in this study. Thirty-three patients received nebulized AMB-d, whereas 29 received nebulized L-AMB. RESULTS: Both regimens maintained comparable prophylactic efficacy regarding the development of fungal infection in the AMB-d and L-AMB groups (3.0% vs. 3.4%, P = 0.877). Patients treated with nebulized L-AMB experienced fewer respiratory-related adverse reactions than those treated with nebulized AMB-d (6.9% vs. 30.3%, P < 0.05), leading to a longer treatment duration with L-AMB than with AMB-d. Additionally, the daily cost of administering L-AMB was lower than that of administering AMB-d (3609 Japanese yen vs. 1792.3 Japanese yen, P < 0.05). DISCUSSION: These results suggest that nebulized L-AMB is safer and more cost-effective than nebulized AMB-d, with comparable efficacy.

Fibrotic progression from acute cellular rejection is dependent on secondary lymphoid organs in a mouse model of chronic lung allograft dysfunction.

Chronic lung allograft dysfunction (CLAD) remains one of the major limitations to long-term survival after lung transplantation. We modified a murine model of CLAD and transplanted left lungs from BALB/c donors into B6 recipients that were treated with intermittent cyclosporine and methylprednisolone postoperatively. In this model, the lung allograft developed acute cellular rejection on day 15 which, by day 30 after transplantation, progressed to severe pleural and peribronchovascular fibrosis, reminiscent of changes observed in restrictive allograft syndrome. Lung transplantation into splenectomized B6 alymphoplastic (aly/aly) or splenectomized B6 lymphotoxin-ß receptor-deficient mice demonstrated that recipient secondary lymphoid organs, such as spleen and lymph nodes, are necessary for progression from acute cellular rejection to allograft fibrosis in this model. Our work uncovered a critical role for recipient secondary lymphoid organs in the development of CLAD after pulmonary transplantation and may provide mechanistic insights into the pathogenesis of this complication.

Various combinations of living and deceased donors for lung retransplantation-a single institutional retrospective study.

OBJECTIVES: Lung retransplantation has been performed as a treatment option mainly for chronic lung allograft dysfunction; however, the outcomes of lung retransplantation have been reported to be worse than those of primary lung transplantation. Because of the scarcity of deceased donors in our country, our lung transplant experience includes both living and deceased donors. Therefore, we have experienced lung retransplantation cases with various combinations of living and deceased donors. The aim of this study was to explore technical pitfalls and outcomes of lung retransplantation in this unique environment. METHODS: We performed 311 lung transplantation procedures between April 2002 and October 2022. Eight lung retransplantation cases (2.6%) were analysed retrospectively. RESULTS: At lung retransplantation, the age of the recipient patients ranged from 11 to 61 years (median, 33 years). The combinations of donor sources (primary lung transplantation/lung retransplantation) were as follows: 2 living/living, 2 deceased/living, 3 living/deceased and 1 deceased/deceased. Seven of 8 patients received lung retransplantation for chronic lung allograft dysfunction. Hospital death occurred in 2 patients (25.0%). The 1-, 3- and 5-year survival rates after lung retransplantation (n = 8) were 75.0%, 75.0% and 75.0%, respectively, while those after primary lung transplantation (n = 303) were 92.8%, 83.4% and 76.4%, respectively (P = 0.162). CONCLUSIONS: Lung retransplantation with various combinations of living and deceased donors is a technically difficult but feasible procedure with acceptable outcomes.

Favorable effect of CD26/DPP-4 inhibitors on postoperative outcomes after lung transplantation: A propensity-weighted analysis.

BACKGROUND: We have shown the efficacy of CD26/dipeptidyl peptidase 4 (CD26/DPP-4) inhibitors, antidiabetic agents, in allograft protection after experimental lung transplantation (LTx). We aimed to elucidate whether CD26/DPP-4 inhibitors effectively improve postoperative outcomes after clinical LTx. METHODS: We retrospectively reviewed the records of patients undergoing LTx at our institution between 2010 and 2021 and extracted records of patients with diabetes mellitus (DM) at 6 months post-LTx. The patient characteristics and postoperative outcomes were analyzed. We established 6 months post-LTx as the landmark point for predicting overall survival (OS) and chronic lung allograft dysfunction (CLAD)-free survival. Hazard ratios were estimated by Cox regression after propensity score weighting, using CD26/DPP-4 inhibitor treatment up to 6 months post-LTx as the exposure variable. We evaluated CLAD samples pathologically, including for CD26/DPP-4 immunohistochemistry. RESULTS: Of 102 LTx patients with DM, 29 and 73 were treated with and without CD26/DPP-4 inhibitors, respectively. Based on propensity score adjustment using standardized mortality ratio weighting, the 5-year OS rates were 77.0% and 44.3%, and the 5-year CLAD-free survival rates 77.8% and 49.1%, in patients treated with and without CD26/DPP-4 inhibitors, respectively. The hazard ratio for CD26/DPP-4 inhibitor use was 0.34 (95% confidence interval (CI) 0.14-0.82, p = 0.017) for OS and 0.47 (95% CI 0.22-1.01, p = 0.054) for CLAD-free survival. We detected CD26/DPP-4 expression in the CLAD grafts of patients without CD26/DPP-4 inhibitors. CONCLUSIONS: Analysis using propensity score weighting showed that CD26/DPP-4 inhibitors positively affected the postoperative prognosis of LTx patients with DM.

Impact of perioperative airway pathogens on living-donor lobar lung transplantation outcomes.

PURPOSE: To elucidate the clinical impact of pathogenic organism (PO) positivity early after transplantation, we evaluated the impact of perioperative airway POs on outcomes after living-donor lobar lung transplantation (LDLLT), where the graft airway is supposed to be sterile from a healthy donor. METHOD: A retrospective review of 67 adult LDLLT procedures involving 132 living donors was performed. Presence of POs in the recipients' airways was evaluated preoperatively and postoperatively in intensive-care units. RESULTS: POs were detected preoperatively in 13 (19.4%) recipients. No POs were isolated from the donor airways at transplantation. POs were detected in 39 (58.2%) recipients postoperatively; most were different from the POs isolated preoperatively. Postoperative PO isolation was not associated with short-term outcomes other than prolonged postoperative ventilation. The 5-year overall survival was significantly better in the PO-negative group than in the PO-positive group (89.1% vs. 63.7%, P = 0.014). In the multivariate analysis, advanced age (hazard ratio [HR]: 1.041 per 1-year increase, P = 0.033) and posttransplant PO positivity in the airway (HR: 3.684, P = 0.019) significantly affected the survival. CONCLUSIONS: The airways of the living-donor grafts were microbiologically sterile. PO positivity in the airway early after transplantation negatively impacted long-term outcomes.

Evaluation of Bone Mineral Density in Lung Transplant Recipients by Chest Computed Tomography.

INTRODUCTION: Lung transplantation (LT) recipients are at risk of bone mineral density (BMD) loss. Pre- and post-LT BMD loss has been reported in some cross-sectional studies; however, there are limited studies regarding the serial BMD change in LT recipients. The aim of this study was to investigate the serial BMD changes and the clinical characteristics associated with BMD decline. METHODS: This was a single-center, retrospective observational study. BMD was serially measured in thoracic vertebral bodies (Th4, 7, 10) using computed tomography (CT) before and 3 and 12 months after LT. The frequency of osteoporosis and factors associated with pre-LT osteoporosis and post-LT BMD loss were evaluated. The frequency of post-LT compression fracture and its associated factors were also analyzed. RESULTS: This study included 128 adult LT recipients. LT recipients had decreased BMD (151.8 ± 42.2 mg/mL) before LT compared with age-, sex-, and smoking index-matched controls (176.2 ± 35.7 mg/mL). The diagnosis of COPD was associated with pre-LT osteoporosis. LT recipients experience further BMD decline after transplantation, and the percentage of recipients classified as exhibiting osteoporosis increased from 20% at baseline to 43% at 12 months. Recipients who had been taking no or small doses of glucocorticoids before LT had rapid BMD loss after LT. Early bisphosphonate use (within 3 months) after LT attenuated BMD loss and decreased new-onset compression fracture. CONCLUSION: LT recipients are at high risk for BMD loss and compression fracture after LT. Early bisphosphonate use may decrease BMD loss and compression fracture.

Novel intrathoracic irrigation using ultrafine ozone bubbles in a rat empyema model.

Dissolved ozone is generally used for sanitization, but it has not been used for thoracic cavity sanitization because of its short half-life (< 20 min) and possible toxicity. We developed a novel solution containing ultrafine ozone bubbles (ozone-UFB) with a fivefold longer half-life than non-UFB ozone. Using an in vitro model, Staphylococcus aureus colonies were counted after exposure to ozone-UFB or non-UFB ozone at the same ozone concentration (0.4 mg/L). The colony count was significantly lower in the ozone-UFB group than in the non-UFB ozone group (p = 0.034). The effect of repeated pleural irrigation using ozone-UFB and saline was compared in a rat empyema model of S. aureus infection. The bacterial count in the pleural effusion was decreased by at least fivefold following intrathoracic lavage with ozone-UFB (3 mg/L). To examine the safety of ozone-UFB for intrathoracic use, ozone-UFB with a higher ozone concentration (10 mg/L) was injected into the thoracic cavities of normal rats. The treatment did not result in any specific pleural damage or elevated serum interleukin-6 concentrations. The findings highlighted the efficacy and safety of ozone-UFB for intrathoracic sanitization, but further studies are needed to determine the optimal therapeutic ozone concentration with appropriate safety margins.

M2-like tumor-associated macrophages promote epithelial-mesenchymal transition through the transforming growth factor ß/Smad/zinc finger e-box binding homeobox pathway with increased metastatic potential and tumor cell proliferation in lung squamous cell carcinoma.

Epithelial-mesenchymal transition (EMT) promotes primary tumor progression toward a metastatic state. The role of tumor-associated macrophages (TAMs) in inducing EMT in lung squamous cell carcinoma (LUSC) remains unclear. We aimed to clarify the significance of TAMs in relation to EMT in LUSC. We collected 221 LUSC specimens from patients who had undergone surgery. Immunohistochemistry was performed to evaluate M1-like and M2-like TAM distribution and EMT by E-cadherin and vimentin staining. Human LUSC cell lines (H226 and EBC-1) and a human monocyte cell line (THP-1) were used for in vitro experiments. M2-like polarization of TAMs and EMT marker expression in LUSC cells were evaluated by western blotting. The biological behavior of LUSC cells was evaluated by migration, invasion, and cell proliferation assays. Immunohistochemical analysis showed that 166 (75.1%) tumors were E-cadherin-positive and 44 (19.9%) were vimentin-positive. M2-like TAM density in the tumor stroma was significantly associated with vimentin positivity and worse overall survival. Western blotting demonstrated higher levels of CD163, CD206, vascular endothelial growth factor, and transforming growth factor beta 1 (TGF-ß1) in TAMs versus unstimulated macrophages. Furthermore, increased TGF-ß1 secretion from TAMs was confirmed by ELISA. TAM-co-cultured H226 and EBC-1 cells exhibited EMT (decreased E-cadherin, increased vimentin). Regarding EMT-activating transcriptional factors, phosphorylated Smad3 and ZEB-family proteins were higher in TAM-co-cultured LUSC cells than in parental cells. TAM-co-cultured H226 and EBC-1 cells demonstrated enhanced migration and invasion capabilities and improved proliferation. Overall, the present study suggests that TAMs can induce EMT with increased metastatic potential and tumor cell proliferation in LUSC.

Prognosis of patients with systemic sclerosis-related interstitial lung disease on the lung transplant waiting list: a retrospective study.

Advanced systemic sclerosis-associated interstitial lung disease (SSc-ILD) can be treated with lung transplantation. There is limited data on lung transplantation outcomes in patients with SSc-ILD, in non-Western populations.We assessed survival data of patients with SSc-ILD, on the lung transplant (LT) waiting list, and evaluated post-transplant outcomes in patients from an Asian LT center. In this single-center retrospective study, 29 patients with SSc-ILD, registered for deceased LT at Kyoto University Hospital, between 2010 and 2022, were identified. We investigated post-transplant outcomes in recipients who underwent LT for SSc-ILD, between February 2002 and April 2022. Ten patients received deceased-donor LT (34%), two received living-donor LT (7%), seven died waiting for LT (24%), and ten survived on the waiting list (34%). Median duration from registration to deceased-donor LT was 28.9 months and that from registration to living-donor LT or death was 6.5 months. Analysis of 15 recipients showed improved forced vital capacity with a median of 55.1% at baseline, 65.8% at 6 months, and 80.3% at 12 months post-transplant. The 5-year survival rate for post-transplant patients with SSc-ILD was 86.2%. The higher post-transplant survival rate at our institute than previously reported suggests that lung transplantation is acceptable in Asian patients with SSc-ILD.

One-year change in the health status predicts the subsequent hospitalization and mortality in patients waitlisted for lung transplantation in Japan.

BACKGROUND: Poor health-related quality of life (HRQL) at the registration for lung transplantation is related to waitlist mortality. We investigated the relationship between 1-year change in HRQL and subsequent outcomes in patients waitlisted for lung transplantation. METHODS: In a 5-year longitudinal study, we analyzed the factors related to waitlist mortality in 197 lung transplant patients registered on the Japan Organ Transplant Network. HRQL was assessed using St. George's Respiratory Questionnaire (SGRQ), and factors related to changes in SGRQ scores were evaluated after 1 year. We assessed the relationship between the 1-year change in SGRQ score and subsequent mortality or hospitalization. RESULTS: Among 197 patients, 108 remained waitlisted during the first-year assessment. During the median follow-up period of 469 d, 28 patients died, and 54 underwent lung transplantation. Univariate Cox proportional hazards analysis revealed that the changes in all components and total score of the SGRQ after 1 year were associated with waitlist mortality (p < 0.05). Stepwise multivariate analysis revealed that the 1-year changes in SGRQ scores were significantly related to waitlist mortality. Forty-three patients with worsened HRQL after 1 year had higher likelihoods of hospitalization (p = 0.038) and mortality (p = 0.026) after 1 and 4 years of follow-up, respectively, than 61 patients without worsened HRQL. CONCLUSIONS: Patients with worsened health status during the first year after registration had higher likelihoods of hospitalization and mortality after 1 and 4 years of follow-up, respectively, than those without worsened HRQL. Strategies to improve health status while waiting are needed to reduce waitlist hospitalization or mortality.

Dedifferentiated liposarcoma lung metastases with different FDG-PET/CT findings.

BACKGROUND: Dedifferentiated liposarcoma (DDLPS) is a rare tumor and generally shows poor prognosis with the lung frequent metastatic site. 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is used for staging or metastatic evaluation of this disease. We report a case of bilateral lung metastases of DDLPS showing uncommon imaging on FDG-PET/CT with completely different FDG uptake, which made preoperative diagnosis difficult. CASE PRESENTATION: The patient was a male in his 60 s and bilateral lung nodules were noted after proton beam therapy for retroperitoneal DDLPS. FDG-PET/CT showed high FDG uptake in the left S3 15-mm nodule but no uptake in the right S8 10-mm nodule. Thoracoscopic wedge resection for the left nodule was performed, and the pathology revealed metastasis of dedifferentiated liposarcoma. After resection of the left nodule, the right S8 nodule enlarged without FDG uptake. Thoracoscopic right S8 segmentectomy was performed, and metastasis of dedifferentiated liposarcoma was diagnosed. The 2 tumors showed completely different appearances on FDG-PET/CT with similar histopathological findings. CONCLUSIONS: We encountered a case of multiple pulmonary metastases of DDLPS which did not follow the same imaging appearance on FDG-PET/CT. Appropriate timing of surgical resection for pathological diagnosis should be determined carefully.

The first successful case of ABO-incompatible living-donor lobar lung transplantation following desensitization therapy.

ABO-incompatible (ABO-I) living-donor lobar lung transplantation (LDLLT) was successfully performed in a 14-year-old girl who suffered from bronchiolitis obliterans due to graft-versus-host disease following hematopoietic stem cell transplantation. In the ABO-I LDLLT procedure, the blood type O patient received a right lower lobe donated from her blood type B father and a left lower lobe donated from her blood type O mother. Desensitization therapy, using rituximab, immunosuppressants, and plasmapheresis, was implemented for 3 weeks prior to transplantation to reduce the production of anti-B antibodies in the recipient and prevent acute antibody-mediated rejection after ABO-I LDLLT.

[Anti-MDA5 antibody-positive rapidly progressive interstitial lung disease after allogeneic hematopoietic cell transplantation successfully treated with triple immunosuppressive therapy].

A 34-year-old man with KMT2A-MLLT1 acute myeloid leukemia in first complete remission underwent allogeneic peripheral blood stem cell transplantation from his HLA-matched sister after conditioning with busulfan/cyclophosphamide. He did not have severe graft-versus-host disease, but he developed interstitial pneumonia six months after transplantation when his oral cyclosporine A (CsA) dose was reduced to 10 mg/day. He was given prednisolone (PSL), which temporarily improved his respiratory condition, but he quickly deteriorated when PSL was reduced. Anti-MDA5 antibody was found to be positive after additional testing, and a three-drug combination of intravenous cyclophosphamide+PSL+CsA was initiated for anti-MDA5 antibody positive rapidly progressive interstitial lung disease, which was effective for interstitial pneumonia. He received a successful living-donor lung transplant from his younger brother and sister. We present a case of rapidly progressive anti-MDA5 antibody positive interstitial lung disease in which the patient's respiratory condition improved after triple therapy and subsequent living-donor lung transplantation.

A case of vasculogenic mesenchymal tumor in the mediastinum: whole-exome sequencing reveals origin from pre-existing germ cell tumor.

Vasculogenic mesenchymal tumor (VMT), a primitive mesenchymal neoplasm enriched by various-sized atypical vessels, is a new entity that develops in mediastinal germ cell tumors (GCTs) with yolk sac tumor (YST) components after chemotherapy. Notably, patients with VMT in the residual GCT have increased risk of developing sarcomas or hematopoietic malignancies. Here, we report a late-teenage male patient with residual teratoma and high-grade VMT after chemotherapy for a mediastinal mixed GCT, including YST. Whole-exome sequencing revealed biallelic inactivation of TP53 and extensive copy number alterations that suggested whole-genome doubling. The biopsy tissue of the mixed GCT before chemotherapy exhibited overlapping genetic alterations to those in the VMT. Immunohistochemical analyses of the VMT showed that the abnormal vessels were positive for cytokeratin, glypican 3, EZH2, and IMP3. The findings that VMT inherits the genetic alterations of pre-existing mixed GCT and exhibits a partly YST-like immunophenotype might contribute to its clinical aggressiveness.

Impact of Spousal Donation on Postoperative Outcomes of Living-donor Lobar Lung Transplantation.

BACKGROUND: The effect of human leukocyte antigen mismatches between donors and recipients on postoperative outcomes of lung transplantation remains controversial. We retrospectively reviewed adult recipients receiving living-donor lobar lung transplantation (LDLLT) to examine the difference in de novo donor-specific antibody (dnDSA) development and clinically diagnosed unilateral chronic lung allograft dysfunction per graft (unilateral CLAD) between lung grafts donated by spouses (nonblood relatives) and nonspouses (relatives within the third degree). We also investigated the difference in prognoses between recipients undergoing LDLLTs including spouse donors (spousal LDLLTs) and not including spouse donors (nonspousal LDLLTs). METHODS: In this study, 63 adult recipients undergoing LDLLTs (61 bilateral and 2 unilateral LDLLTs from 124 living donors) between 2008 and 2020 were enrolled. The cumulative incidence of dnDSAs per lung graft was calculated, and prognoses were compared between recipients undergoing spousal and nonspousal LDLLTs. RESULTS: The cumulative incidence of both dnDSAs and unilateral CLAD in grafts donated by spouses was significantly higher than that in grafts donated by nonspouses (5-y incidence of dnDSAs: 18.7% versus 6.4%, P = 0.038; 5-y incidence of unilateral CLAD: 45.6% versus 19.4%, P = 0.011). However, there were no significant differences in the overall survival or chronic lung allograft dysfunction-free survival between recipients undergoing spousal and nonspousal LDLLTs ( P > 0.99 and P = 0.434, respectively). CONCLUSIONS: Although there were no significant differences in prognoses between spousal and nonspousal LDLLTs, more attention should be paid to spousal LDLLTs because of the higher development rate of dnDSAs and unilateral CLAD.