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.

Efficacy and safety of the SARS-CoV-2 mRNA vaccine in lung transplant recipients: a possible trigger of rejection.

OBJECTIVE: Solid organ transplant recipients have an increased risk of developing severe coronavirus disease 2019 (COVID-19). Although SARS-CoV-2 mRNA vaccination has been strongly recommended for solid organ transplant recipients, its efficacy and safety have remained unknown. METHODS: We performed an observational prospective cohort study in 18 lung transplant recipients who received two doses of SARS-CoV-2 mRNA vaccine, including BNT162b2 (n = 17) or mRNA-1273 (n = 1), between June and October 2021. The titers of IgG antibodies against the SARS-CoV-2 spike protein (S-IgG) were measured in serum samples collected before the prime dose, three weeks after the prime dose, and four weeks after the booster dose. Reactogenicity and adverse events were evaluated after vaccination. RESULTS: There were no recipients with previous SARS-CoV-2 infection prior to vaccination. S-IgG levels were elevated in 2/18 (11.1%) recipients after the prime dose and in 5/18 recipients (27.8%) after the booster dose (31.7 ± 30.6 U/ml). The time from transplantation to vaccination tended to be longer in the seropositive group than the seronegative group [7.5 (3.9-10.2) vs 2.8 (1.9-4.0) years, p = 0.059]. Maintenance dose of mycophenolate mofetil tended to be lower in the seropositive group than in the seronegative group [500 (250-500) vs 1000 (1000-1000) mg/day, p = 0.088]. Regarding the adverse events after vaccination, the development of chronic lung allograft dysfunction (CLAD) or antibody-mediated rejection (AMR) were observed in two seropositive patients. CONCLUSIONS: The antibody response to the SARS-CoV-2 mRNA vaccine was quite poor in lung transplant recipients. We experienced cases that developed clinical CLAD or AMR that was likely related to SARS-CoV-2 vaccination.

Hemothorax resulting from an initially masked aortic perforation caused by penetration of the sharp edge of a fractured rib: A case report.

INTRODUCTION: There are multiple causes of hemothorax in blunt chest trauma. However, a traumatic hemothorax with an uncertain cause is potentially life-threatening without treatment, because an undetected and hidden great vessel injury can remain unknown. Delayed diagnosis can lead to death. PRESENTATION OF CASE: A 77-year-old man was transferred to a local hospital, after experiencing a 3-m fall. Contrast CT of the chest revealed a left clavicle fracture, multiple left rib fractures and hemopneumothorax, but no obvious signs of great vessel injury, such as aortic injury. His condition was stable, owing to the chest tube thoracostomy with 800 ml blood output and intravenous fluid. The patient was then transferred to our hospital for further treatment. However, his condition rapidly deteriorated in the ambulance on the way to our hospital, and he needed a blood transfusion. On arrival, he was in shock, with his vital signs compromised due to blood loss. Emergency open thoracotomy was performed to explore the bleeding point and stop hemorrhaging. Intraoperative findings revealed sharp edges of the fractured fourth and fifth left ribs to be protruding into the chest cavity toward the descending aorta and causing an aortic pinhole injury. Ruptured aorta was repaired with a pledget-armed sutures and the sharp fractured ribs were resected. The patient was discharged, uneventfully, 35 days after the operation. CONCLUSION: This case suggests that even if great vessel injury is not detected on contrast CT at admission, it should always be considered especially in a hemothorax case with multiple rib fractures.

Unilateral antibiotic-induced acute eosinophilic pneumonia on the operative side after surgery for primary lung cancer: a case report.

BACKGROUND: Acute eosinophilic pneumonia (AEP) is a rare idiopathic lung disease characterized by pulmonary eosinophilia. The epidemiology of AEP remains understudied; however, past reports have reported that AEP can be caused by an allergic reaction to medications, such as antibiotics or inhaled antigens, such as tobacco smoke. AEP usually occurs bilaterally. However, we encountered an unusual case of antibiotic-induced eosinophilic pneumonia showing unilateral consolidation just on the operative side, which was initially diagnosed as postoperative bacterial pneumonia and treated with antibiotic therapy. The prescribed antibiotics paradoxically provoked AEP and worsened the patient's condition. Here, we report this antibiotic-induced AEP case showing unilateral consolidation only on the operative side which could be triggered by surgery for primary lung cancer. CASE PRESENTATION: A 74-year-old man underwent right upper lobectomy for lung adenocarcinoma. On postoperative day (POD) 9, an interstitial shadow appeared in the right lower lung field of the chest radiographs, along with a fever of 38.5 °C, dyspnea needing oxygen supplementation, and increased purulent sputum production, suggesting postoperative bacterial pneumonia. Despite administration of the broad-spectrum antibiotic, meropenem, the fever did not improve, and pulmonary opacity gradually worsened. Blood analysis showed increased peripheral eosinophils at 1182/mm3. The meropenem treatment was discontinued and bronchoscopy was performed for further evaluation, and the bronchoalveolar lavage fluid assessment showed a remarkable increase in the eosinophil population (51%). The drug lymphocyte stimulation test (DLST) for meropenem was positive. We diagnosed the patient with antibiotic-induced unilateral AEP, after which corticosteroid treatment was initiated. The patient subsequently improved and the infiltration in the right lower lung field completely disappeared. The patient was discharged on POD 43 without oxygen supplementation and is doing well without tumor recurrence 16 months after the surgery. CONCLUSIONS: Unilateral drug-induced AEP is rare. Nonetheless, it should be recognized as a differential diagnosis of postoperative pneumonia even in cases of a unilateral radiographic infiltration, because the lung operation itself could trigger this type of AEP.

Late-onset chest wall abscess due to a biodegradable rib pin infection after lung transplantation.

A 55-year-old man with end-stage emphysema underwent a right single-lung transplantation through a posterolateral thoracotomy. The fifth rib was divided and fused back using a biodegradable pin made of polylactide acid and hydroxyapatite. Two weeks postoperatively, he suffered from central vein catheter-related sepsis due to methicillin-sensitive Staphylococcus aureus. After being successfully treated for sepsis, he was discharged. However, 3 months later, computed tomography revealed multiple loculated abscesses in the chest wall and the right pleural space. Reoperative thoracotomy revealed abscesses mainly located around the fifth rib, where the pin was inserted. Both cultures of the abscess and the fifth rib were positive for methicillin-sensitive S. aureus, which suggested that the rib pin was the cause of the secondary infection. This case suggests the rib pins, even if they are biodegradable, could have a risk of infections side effect especially for the immunosuppressed patients.

Inverted Lobes Have Satisfactory Functions Compared With Noninverted Lobes in Lung Transplantation.

BACKGROUND: To overcome the problem of small-for-size grafts in standard living-donor lobar lung transplantation (LDLLT), we developed inverted LDLLT, in which a right lower lobe from 1 donor is implanted as a right graft and another right lower lobe from another donor is implanted as a left graft. We retrospectively analyzed the functions of inverted grafts vs noninverted grafts. METHODS: Between 2008 and 2015, 64 LDLLTs were performed. Included were 35 LDLLTs whose recipients were adults and monitored for more than 6 months without developing chronic lung allograft dysfunction. Among them, 65 implanted lobes were eligible for this analysis. There were 31 right lower lobes implanted as right grafts (right-to-right group), 7 right lower lobes as inverted left grafts (right-to-left group), and 27 left lower lobes as left grafts (left-to-left group). We evaluated the graft forced vital capacity (G-FVC) and graft volume of the 65 lobes before and 6 months after LDLLT and compared them among the three groups. RESULTS: Preoperatively, G-FVC in the right-to-left group (1,050 mL) was comparable to that in the right-to-right group (1,177 mL) and better than that in the left-to-left group (791 mL, p < 0.01). Six months after LDLLT, G-FVC in the right-to-left group (1,015 mL) remained comparable to that in the right-to-right group (1,001 mL) and better than that in the left-to-left group (713 mL, p = 0.047). The ratio of graft volume 6 months after LDLLT to the preoperative value was comparable. CONCLUSIONS: The functions of inverted grafts in inverted LDLLTs were satisfactory compared with those of noninverted grafts.