RESUMO
Although cytomegalovirus (CMV) viremia/DNAemia has been associated with reduced survival after lung transplantation, its association with chronic lung allograft dysfunction (CLAD) and its phenotypes is unclear. We hypothesized that, in a modern era of CMV prophylaxis, CMV DNAemia would still remain associated with death, but also represent a risk factor for CLAD and specifically restrictive allograft syndrome (RAS)/mixed phenotype. This was a single-center retrospective cohort study of all consecutive adult, first, bilateral-/single-lung transplants done between 2010-2016, consisting of 668 patients. Risks for death/retransplantation, CLAD, or RAS/mixed, were assessed by adjusted cause-specific Cox proportional-hazards models. CMV viral load (VL) was primarily modeled as a categorical variable: undetectable, detectable to 999, 1000 to 9999, and ≥10 000 IU/mL. In multivariable models, CMV VL was significantly associated with death/retransplantation (≥10 000 IU/mL: HR = 2.65 [1.78-3.94]; P < .01), but was not associated with CLAD, whereas CMV serostatus mismatch was (D+R-: HR = 2.04 [1.30-3.21]; P < .01). CMV VL was not associated with RAS/mixed in univariable analysis. Secondary analyses with a 7-level categorical or 4-level ordinal CMV VL confirmed similar results. In conclusion, CMV DNAemia is a significant risk factor for death/retransplantation, but not for CLAD or RAS/mixed. CMV serostatus mismatch may have an impact on CLAD through a pathway independent of DNAemia.
Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Rejeição de Enxerto , Sobrevivência de Enxerto , Transplante de Pulmão , Complicações Pós-Operatórias , Viremia , Humanos , Transplante de Pulmão/efeitos adversos , Infecções por Citomegalovirus/virologia , Infecções por Citomegalovirus/epidemiologia , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Viremia/virologia , Viremia/epidemiologia , Citomegalovirus/isolamento & purificação , Fatores de Risco , Seguimentos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/virologia , Prognóstico , Complicações Pós-Operatórias/virologia , Complicações Pós-Operatórias/epidemiologia , Adulto , Carga Viral , Taxa de Sobrevida , Transplantados/estatística & dados numéricosRESUMO
Over 2.5% of deaths in Canada occur as a result from medical assisting in dying (MAID), and a subset of these deaths result in organ donation. However, detailed outcomes of lung transplant recipients using these donors is lacking. This is a retrospective single center cohort study comparing lung transplantation outcomes after donation using MAID donors compared to neurologically determined death and controlled donation after circulatory death (NDD/cDCD) donors from February 2018 to July 2021. Thirty-three patients received lungs from MAID donors, and 560 patients received lungs from NDD/cDCD donors. The donor diagnoses leading to MAID provision were degenerative neurological diseases (n = 33) and end stage organ failure (n = 5). MAID donors were significantly older than NDD/cDCD donors (56 [IQR 49-64] years vs. 48 [32-59]; p = .0009). Median ventilation period and 30 day mortality were not significantly different between MAID and NDD/cDCD lungs recipients (ventilation: 1 day [1-3] vs 2 days [1-3]; p = .37, deaths 0% [0/33] vs. 2% [11/560], p = .99 respectively). Intermediate-term outcomes were also similar. In summary, for lung transplantation using donors after MAID, recipient outcomes were excellent. Therefore, where this practice is permitted, donation after MAID should be strongly considered for lung transplantation as a way to respect donor wishes while substantially improving outcomes for recipients with end-stage lung disease.
Assuntos
Transplante de Pulmão , Obtenção de Tecidos e Órgãos , Estudos de Coortes , Morte , Sobrevivência de Enxerto , Humanos , Assistência Médica , América do Norte , Estudos Retrospectivos , Doadores de TecidosRESUMO
Definitions for chronic lung allograft dysfunction (CLAD) phenotypes were recently revised (2019 ISHLT consensus). Post-CLAD onset phenotype transition may occur as a result of change in obstruction, restriction, or RAS-like opacities (RLO). We aimed to assess the prevalence and prognostic implications of these transitions. This was a single-center, retrospective cohort study of bilateral lung transplants performed in 2009-2015. CLAD phenotypes were determined per ISHLT guidelines. CLAD phenotype transition was defined as a sustained change in obstruction, restriction or RLO. We specifically focused on phenotype changes based on RLO emergence. Association of RLO development with time to death or retransplant were assessed using Kaplan-Meier and Cox proportional hazards models. Among 211 patients with CLAD, 47 (22.2%) experienced a phenotype transition. Nineteen patients developed RLO. Development of RLO phenotype after CLAD onset was associated with a shorter time to death/retransplant when considering the entire CLAD patient cohort (HR = 4.00, CI 2.74-5.83, P < 0.001) and also when restricting the analysis to only patients with a Non-RLO phenotype at CLAD onset (HR 9.64, CI 5.52-16.84, P < 0.0001). CLAD phenotype change based on emergence of RAS-like opacities implies a worse outcome. This highlights the clinical importance of imaging follow-up to monitor for phenotype transitions after CLAD onset.
Assuntos
Transplante de Pulmão , Disfunção Primária do Enxerto , Aloenxertos , Humanos , Pulmão , Transplante de Pulmão/efeitos adversos , Fenótipo , Disfunção Primária do Enxerto/epidemiologia , Disfunção Primária do Enxerto/etiologia , Estudos RetrospectivosRESUMO
BACKGROUND: This study aimed to analyze cause-specific mortality in lung cancer patients over 80 years old undergoing surgery. METHODS: This retrospective, multi-institutional analysis included patients aged ≥ 80 years who underwent radical surgery for primary lung cancer from January 1998 to December 2015. Preoperative clinical data, surgical results, survival, and cause of death were evaluated. Competing risk analysis for cause-specific mortality was performed. RESULTS: Of the 337 patients (median age 82 years) enrolled and analyzed, 68.1% were male. There were 52 and 44 cancer-specific and non-cancer-specific deaths, respectively. On competing risk regression analysis, non-cancer-specific deaths were significantly associated with male sex (hazard ratio [HR]: 3.06, 95% confidence interval [CI]: 1.02-9.12, p = 0.046), coronary artery disease (HR: 2.49, 95% CI: 2.49 [1.14-5.47], p = 0.02), interstitial pneumonia (HR: 3.58, 95% CI: 1.73-7.40, p < 0.001), and pathological stage III (HR: 3.83, 95% CI: 1.44-10.13, p = 0.007). In contrast, cancer-specific deaths were significantly associated with limited resection (HR: 1.99, 95% CI: 1.02-3.89, p = 0.04) and pathological stage III (HR: 3.13, 95% CI: 1.44-6.80, p = 0.004). The 5-year cumulative incidences of lung cancer-specific and non-cancer-specific deaths were 18.0% and 15.9%, respectively. CONCLUSIONS: Prognostic factors for non-cancer-specific death were different from those of cancer-specific death, except for pathological stage. Each prognostic factor should be considered when deciding surgical indication and procedure and monitoring for pulmonary events during outpatient follow-up.
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Causas de Morte , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/cirurgia , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/mortalidade , Feminino , Humanos , Doenças Pulmonares Intersticiais/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de Neoplasias , Pneumonectomia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco/métodos , Fatores SexuaisRESUMO
PURPOSE: The azygoesophageal recess (AER) is known as a possible cause of bulla formation in patients with spontaneous pneumothorax. However, there has been little focus on the depth of the AER. We evaluated the relationship between the depth of the AER and pneumothorax development. METHODS: We conducted a retrospective study of 80 spontaneous pneumothorax patients who underwent surgery at our institution. We evaluated the depth of the AER on preoperative computed tomography scans. RESULTS: Ruptured bullae at the AER were found in 12 patients (52.2%) with secondary spontaneous pneumothorax (SSP) and 8 patients (14.0%) with primary spontaneous pneumothorax (PSP) (p < 0.001). In patients with ruptured bullae at the AER, 10 SSP patients (83.3%) had a deep AER while only 2 PSP patients (25%) had a deep AER (p = 0.015). CONCLUSIONS: A deep AER was more frequently associated with SSP than with PSP. A deep AER may contributes to bulla formation and rupture in SSP patients.
Assuntos
Diafragma/anormalidades , Esôfago/anormalidades , Mediastino/anormalidades , Pleura/anormalidades , Pneumotórax/etiologia , Pneumotórax/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Vesícula/etiologia , Diafragma/diagnóstico por imagem , Esôfago/diagnóstico por imagem , Feminino , Humanos , Masculino , Mediastino/diagnóstico por imagem , Pessoa de Meia-Idade , Pleura/diagnóstico por imagem , Estudos Retrospectivos , Risco , Procedimentos Cirúrgicos Torácicos , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
After median sternotomy, the sternum is commonly closed using metal wires, which sometimes cause complications because they are permanent foreign bodies. As an alternative, we used a combination of absorbable sutures and pins for full median sternotomy in 24 adult general thoracic surgery patients. There were three cases of sternal dehiscence detectable by computed tomography, none of which required re-operation. Two of these patients had diabetes mellitus (DM) and the third patient was on corticosteroid therapy. In an appropriately selected patient population that excludes patients with DM or who are undergoing corticosteroid therapy, we have not observed any sternal complications. We concluded that our technique is clinically feasible with appropriate patient selection.
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Implantes Absorvíveis , Pinos Ortopédicos , Esternotomia , Esterno/cirurgia , Suturas , Técnicas de Fechamento de Ferimentos/instrumentação , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Deiscência da Ferida Operatória/prevenção & controleRESUMO
A 64-year-old woman with a mediastinal tumor incidentally found on computed tomography( CT) was referred to our hospital. CT and magnetic resonance imaging( MRI) showed the tumor had a clear border and was located on the right side of the 12th thoracic vertebra, spanning the thoracic and abdominal cavities. She was suspected of having a benign neurogenic tumor of the mediastinum. She underwent tumor resection through the tenth intercostal space via a posterolateral thoracotomy. We easily resected the tumor using this approach. Pathological examination revealed a benign schwannoma of the mediastinum. Although this approach is rarely chosen by thoracic surgery, it is sometimes useful for the resection of mediastinal tumors near the diaphragm.
Assuntos
Neoplasias do Mediastino/cirurgia , Neurilemoma/cirurgia , Toracotomia/métodos , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Baseline lung allograft dysfunction (BLAD) refers to a condition in which a lung transplant recipient does not achieve normal pulmonary function (i.e., forced expiratory volume in 1 s or forced vital capacity of <80% of predicted values). Although BLAD is reportedly associated with a poor prognosis, the condition has not been examined in Japanese patients. METHODS: In this study, we retrospectively examined 38 Japanese adults who underwent bilateral lung transplantation from 2015 to 2022 in a single center. RESULTS: Twenty-one (55%) patients met the criteria for BLAD. No significant differences were found in recipient or donor factors between the BLAD and non-BLAD groups, but the donor-recipient ratio of the predicted vital capacity was lower in the BLAD group (p = 0.009). The intensive care unit length of stay, ventilator duration, and blood loss during transplant surgery were significantly higher in the BLAD group (p < 0.05). No significant difference was found in survival. The median observation period was significantly shorter in the BLAD than non-BLAD group (744 vs.1192 days, respectively; p = 0.031). The time to reach the normal threshold of pulmonary function after lung transplantation varied among the patients, ranging from 6 months to 4 years. CONCLUSIONS: The characteristics of these Japanese patients with BLAD were similar to those of other patients in previous reports. The effects of the observation period and donor-recipient age discrepancy on BLAD require further exploration.
Assuntos
Transplante de Pulmão , Humanos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Japão , Adulto , Aloenxertos , Capacidade Vital , Volume Expiratório Forçado , Tempo de Internação , Fatores de Tempo , Idoso , Pulmão/fisiopatologia , Disfunção Primária do Enxerto/etiologia , Disfunção Primária do Enxerto/fisiopatologia , Doadores de TecidosRESUMO
OBJECTIVES: Dual-lumen cannulas for veno-venous (VV) extracorporeal membrane oxygenation (ECMO) support are typically inserted in the right internal jugular vein (RIJV); however, some scenarios can make this venous route inaccessible. This multicentre case series aims to evaluate if single-site cannulation using an alternative venous access is safe and feasible in patients with an inaccessible RIJV. METHODS: We performed a multi-institutional retrospective analysis including high-volume ECMO centres with substantial experience in dual-lumen cannulation (DLC) (defined as >10 DLC per year). Three centres [Freiburg (Germany), Toronto (Canada) and Vienna (Austria)] agreed to share their data, including baseline characteristics, technical ECMO and cannulation data as well as complications related to ECMO cannulation and outcome. RESULTS: A total of 20 patients received alternative DLC for respiratory failure. Cannula insertion sites included the left internal jugular vein (n = 5), the right (n = 7) or left (n = 3) subclavian vein and the right (n = 4) or left (n = 1) femoral vein. The median cannula size was 26 (19-28) French. The median initial target ECMO flow was 2.9 (1.8-3.1) l/min and corresponded with used cannula size and estimated cardiac output. No procedural complications were reported during cannulation and median ECMO runtime was 15 (9-22) days. Ten patients were successfully bridged to lung transplantation (n = 5) or lung recovery (n = 5). Ten patients died during or after ECMO support. CONCLUSIONS: Alternative venous access sites for single-site dual-lumen catheters are a safe and feasible option to provide veno-venous ECMO support to patients with inaccessible RIJV.
RESUMO
Significant frequency of ruptured bullae at the azygoesophageal recess (AER) in secondary pneumothorax patients was reported recently. In normal anatomy, the AER usually exists only in the right thorax. We herein report a case of secondary spontaneous pneumothorax due to a ruptured bulla at a leftsided AER-like structure in a patient with right aortic arch. The case was a 70-year-old man who developed left spontaneous pneumothorax secondary to pulmonary emphysema. He was initially treated by thoracic drainage, but in vain, and finally referred to our department because of prolonged air leakage. Preoperative computed tomography demonstrated a bulla formation at a recess between the rightsided descending aorta and thoracic vertebrae. In thoracoscopic surgery, we confirmed air leakage from the bulla at the recess and the bulla was subsequently ligated. To the best of our knowledge bulla formation at a left-sided AER-like structure has never been reported. Local overinflation of the lung parenchyma may have been a cause of bulla formation in this case.
Assuntos
Aorta Torácica/anormalidades , Veia Ázigos/anormalidades , Vesícula/complicações , Esôfago/anormalidades , Pneumotórax/etiologia , Idoso , Vesícula/cirurgia , Humanos , Masculino , Ruptura Espontânea , ToracoscopiaRESUMO
BACKGROUND: Airway epithelial injury is thought to be a key event in the pathogenesis of chronic lung allograft dysfunction (CLAD). We investigated whether markers of epithelial activity and injury in bronchoalveolar lavage fluid (BAL) correlate with CLAD diagnosis and major CLAD phenotypes: bronchiolitis obliterans syndrome (BOS) vs restrictive allograft syndrome (RAS)-related phenotypes (including RAS, mixed phenotype, and all other patients with RAS-like opacities). METHODS: CLAD status and phenotypes were retrospectively determined in a cohort of all consecutive adult, first, bilateral lung transplants performed 2010-2015, with available BAL samples. All patients with RAS-related phenotypes were included and 1:1 matched with BOS patients based on the time from transplant to CLAD-onset. Subjects who were CLAD-free for a minimum of 3 years post-transplant were 1:1 matched to CLAD patients and included as controls. Proteins that maintain the barrier function of the airway epithelial mucosa (club cell secretory protein, surfactant protein-D and epithelial mucins: MUC1, MUC5AC, MUC5B, MUC16), as well as epithelial cell death markers (M30&M65 representing epithelial cell apoptosis and overall death, respectively), were measured in BAL obtained within 6-months post CLAD onset using a double-sandwich ELISA or a multiplex bead assay. Protein levels were compared using Mann-Whitney-U-test. Association between protein levels and graft survival was assessed using Cox proportional hazards models, adjusted for CMV serology mismatch status and CLAD phenotype. RESULTS: Fifty-four CLAD (27 BOS, 11 RAS, 7 mixed, 9 others with RAS-like opacities) patients and 23 CLAD-free controls were included. Median BAL levels were significantly higher in patients with CLAD compared to CLAD-free controls for M30 (124.5 vs 88.7 U/L), MUC1 (6.8 vs 3.2 pg/mL), and MUC16 (121.0 vs 30.1 pg/mL). When comparing CLAD phenotypes, M30 was significantly higher in patients with RAS-related phenotypes than BOS (160.9 vs 114.6 U/L). In multivariable models, higher M30 and MUC5B levels were associated with decreased allograft survival after CLAD onset independent of phenotype (p < 0.05 for all). CONCLUSIONS: Airway epithelial mucins and cell death markers are enhanced in the BAL of patients with CLAD and can assist in differentiating between CLAD phenotypes and post-CLAD outcomes. Abnormal airway mucin expression and epithelial cell death may be involved in the pathogenesis of CLAD, and therefore their detection may aid in future selection of targeted therapies.
Assuntos
Síndrome de Bronquiolite Obliterante , Bronquiolite Obliterante , Transplante de Pulmão , Humanos , Estudos Retrospectivos , Bronquiolite Obliterante/etiologia , Pulmão , Transplante de Pulmão/efeitos adversos , Fenótipo , AloenxertosRESUMO
CASE: The patient was a 17-year-old girl. She underwent treatment for osteosarcoma when she was around 10 ~ 11 years old. A follow-up chest computed tomography(CT) revealed one small pulmonary nodule 6 years later. The orthopedist thought it was metastasis. The patient was referred to our division and treated with thoracoscopic partial resection. The final pathological diagnosis was a primary lung adenocarcinoma. CONCLUSION: This case is unique because the patient is juvenile and had a history of another cancer, i.e., osteosarcoma. Her primary lung cancer is a 2nd malignancy. The incidence of 2nd malignant neoplasm is one of the significant late effects of pediatric cancer treatment. When pulmonary lesions are detected in young patient with histories of neoplasms, primary lung cancer as a 2nd malignant neoplasm as well as pulmonary metastasis from 1st neoplasm, should be considered as differential diagnosis.
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Adenocarcinoma/patologia , Neoplasias Ósseas/patologia , Neoplasias Pulmonares/patologia , Segunda Neoplasia Primária/patologia , Osteossarcoma/patologia , Adolescente , Feminino , HumanosRESUMO
BACKGROUND: Our recent work has challenged 4°C as an optimal lung preservation temperature by showing storage at 10°C to allow for the extension of preservation periods. Despite these findings, the impact of 10°C storage has not been evaluated in the setting of injured donor lungs. METHODS: Aspiration injury was created through bronchoscopic delivery of gastric juice (pH: 1.8). Injured donor lungs (n = 5/group) were then procured and blindly randomized to storage at 4°C (on ice) or at 10°C (in a thermoelectric cooler) for 12 hours. A third group included immediate transplantation. A left lung transplant was performed thereafter followed by 4 hours of graft evaluation. RESULTS: After transplantation, lungs stored at 10°C showed significantly better oxygenation when compared to 4°C group (343 ± 43 mm Hg vs 128 ± 76 mm Hg, p = 0.03). Active metabolism occurred during the 12 hours storage period at 10°C, producing cytoprotective metabolites within the graft. When compared to lungs undergoing immediate transplant, lungs preserved at 10°C tended to have lower peak airway pressures (p = 0.15) and higher dynamic lung compliances (p = 0.09). Circulating cell-free mitochondrial DNA within the recipient plasma was significantly lower for lungs stored at 10°C in comparison to those underwent immediate transplant (p = 0.048), alongside a tendency of lower levels of tissue apoptotic cell death (p = 0.075). CONCLUSIONS: We demonstrate 10°C as a potentially superior storage temperature for injured donor lungs in a pig model when compared to the current clinical standard (4°C) and immediate transplantation. Continuing protective metabolism at 10°C for donor lungs may result in better transplant outcomes.
Assuntos
Transplante de Pulmão , Traumatismo por Reperfusão , Animais , Modelos Animais de Doenças , Pulmão/metabolismo , Preservação de Órgãos , Traumatismo por Reperfusão/metabolismo , Suínos , TemperaturaRESUMO
BACKGROUND: Phenotyping chronic lung allograft dysfunction (CLAD) in single lung transplant (SLTX) is challenging, due to the native lung contribution to pulmonary function test (PFT). We aimed to assess the applicability and prognostic performance of International Society for Heart and Lung Transplantation (ISHLT) classification in SLTX. METHODS: In this retrospective study of adult, first, SLTX performed 2009-2017, patients with persistent drop in FEV1≥20% were assessed by 2 independent adjudicators to determine CLAD status and phenotype. Interobserver agreement (IOA) was calculated (Cohen's Kappa) for CLAD, phenotype and presence of RAS (resttrictive allograft syndrome)-like opacities (RLO). Association of CLAD phenotypes with time to death or retransplant (ReTx), adjusted for age at SLTX, sex, CMV mismatch and native lung condition, were assessed using Cox proportional hazards models. RESULTS: Of 172 SLTX recipients, 92 experienced a persistent drop in FEV1>20%. Following adjudication, 67 were diagnosed with CLAD. We noted a moderate IOA for CLAD diagnosis (Kappa 0.69) and poor IOA for phenotype adjudication (Kappa 0.52). The final phenotype adjudication was 31 bronchiolitis obliterans syndrome (BOS) (46.3%), 13 RAS (19.4%), 2 mixed (3%), 2 Undefined (3%), and 19 remained Unclassified (28.3%). Using these adjudicated phenotypes, RAS was significantly associated with a higher risk of death/ReTx compared to other groups (HR 2.98, 95%CI [1.39-6.4]). The adjudication of RLO had the best IOA (Kappa 0.73). The presence of RLO was a strong predictor of death or ReTx (HR 2.37, 95%CI [1.2-4.5]), regardless of the final phenotype. CONCLUSIONS: PFT interpretation is challenging in SLTX. A classification essentially relying on imaging, which harbored good IOA, obtained better prognostic performance than a classification using published physiological cut-offs.
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Bronquiolite Obliterante , Transplante de Pulmão , Disfunção Primária do Enxerto , Aloenxertos , Bronquiolite Obliterante/diagnóstico , Seguimentos , Humanos , Pulmão , Disfunção Primária do Enxerto/diagnóstico , Prognóstico , Estudos Retrospectivos , Fatores de Risco , SíndromeRESUMO
BACKGROUND: Cold static preservation (CSP) at higher temperatures (10°C) has been recently shown as an optimal strategy up to 24-36h of preservation. Here, we hypothesized that alternating 10°C static storage with cycles of normothermic ex vivo lung perfusion (EVLP) would provide conditions for cellular "recharge", allowing for multi-day lung preservation. METHODS: Donor lungs from male Yorkshire pigs were preserved using 10°C CSP with two cycles of 4h EVLP. After a total of 3 days of preservation, a left lung transplant was performed followed by 4h of graft evaluation. As controls, 2 lungs were preserved solely with continuous 10°C preservation for 3 days and transplanted. FINDINGS: For animals receiving lungs preserved using a cyclic EVLP protocol, lung function and histological structures were stable and the recipient systemic partial pressure of oxygen/fraction of inspired oxygen (P/F Ratio) after excluding the contralateral lung was 422 ± 61 mmHg. In contrast, lungs preserved solely in continuous cold static storage at 10°C for 72h developed massive lung failure, resulting in recipient death. Metabolomic analysis revealed that EVLP plays a critical role in the re-vitalization of key central carbon energy metabolites (Glucose, Succinate, N-Acetyl Aspartate) and reducing the expression of the inflammasome activation marker CASP1. INTERPRETATION: In conclusion, we demonstrate for the first time the feasibility of 3-day lung preservation leading to excellent early post-transplant outcomes. The thoughtful combination of cold storage (10°C) and intermittent EVLP can open new opportunities in organ transplantation. FUNDING: This work was supported by the UHN Foundation (Grant#1013612).
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Inflamassomos , Preservação de Órgãos , Animais , Carbono , Glucose , Pulmão/patologia , Masculino , Preservação de Órgãos/métodos , Oxigênio , Perfusão/métodos , Succinatos , SuínosRESUMO
BACKGROUND: Micronodular thymoma with lymphoid stroma (MNT) is a rare subtype of thymic neoplasms. Therefore, clinical guidelines, histopathological diagnostic criteria, prognostic factors, and therapeutic regimens have not been established. CASE PRESENTATION: A 69-year-old woman was admitted to our hospital because of an abnormal shadow detected by chest radiography. Further imaging revealed an anterior mediastinal tumor measuring 65×28×15 mm. We performed thymectomy for diagnosis and treatment. Histopathological examination revealed spindle cells comprised multiple micronodules separated by abundant interstitial lymphocytes and lymphoid follicles. Immunohistochemical staining showed that the tumor was positive for cell adhesion molecule (CAM), cytokeratin (CK) 5/6, and terminal deoxynucleotidyl transferase. The histopathological diagnosis was MNT and the stage was I by the World Health Organization classification. The patient remained free of recurrence for seven years after surgery. CONCLUSION: When the lesion is completely resected, MNT has a good prognosis. Therefore, MNT is considered to be a borderline tumor with good prognosis and no reports of recurrences, distant metastasis, or tumor-related deaths exist thus far. However, preoperative diagnosis is difficult in most cases. Hence, complete surgical resection is recommended for suspicious mediastinal masses, if feasible, for both accurate diagnosis and to ensure long-term survival.
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Neoplasias do Mediastino , Timoma , Neoplasias do Timo , Idoso , Feminino , Humanos , Recidiva Local de Neoplasia , Timoma/diagnóstico por imagem , Timoma/cirurgia , Neoplasias do Timo/diagnóstico por imagem , Neoplasias do Timo/cirurgiaRESUMO
Effective treatment of respiratory infections continues to be a major challenge. In high doses (≥160 ppm), inhaled Nitric Oxide (iNO) has been shown to act as a broad-spectrum antimicrobial agent, including its efficacy in vitro for coronavirus family. However, the safety of prolonged in vivo implementation of high-dose iNO therapy has not been studied. Herein we aim to explore the feasibility and safety of delivering continuous high-dose iNO over an extended period of time using an in vivo animal model. Yorkshire pigs were randomized to one of the following two groups: group 1, standard ventilation; and group 2, standard ventilation + continuous iNO 160 ppm + methylene blue (MB) as intravenous bolus, whenever required, to maintain metHb <6%. Both groups were ventilated continuously for 6 hours, then the animals were weaned from sedation, mechanical ventilation and followed for 3 days. During treatment, and on the third post-operative day, physiologic assessments were performed to monitor lung function and other significative markers were assessed for potential pulmonary or systemic injury. No significant change in lung function, or inflammatory markers were observed during the study period. Both gas exchange function, lung tissue cytokine analysis and histology were similar between treated and control animals. During treatment, levels of metHb were maintained <6% by administration of MB, and NO2 remained <5 ppm. Additionally, considering extrapulmonary effects, no significant changes were observed in biochemistry markers. Our findings showed that high-dose iNO delivered continuously over 6 hours with adjuvant MB is clinically feasible and safe. These findings support the development of investigations of continuous high-dose iNO treatment of respiratory tract infections, including SARS-CoV-2.
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Anti-Infecciosos , Óxido Nítrico , Animais , Masculino , Administração por Inalação , Anti-Infecciosos/administração & dosagem , Citocinas/análise , Citocinas/sangue , Avaliação Pré-Clínica de Medicamentos , Hemodinâmica , Hemoglobina A/análise , Pulmão/metabolismo , Pulmão/patologia , Metemoglobina/análise , Azul de Metileno/administração & dosagem , Modelos Animais , Nitratos/análise , Óxido Nítrico/administração & dosagem , Nitritos/análise , SuínosRESUMO
Long-term survival after lung transplantation remains suboptimal due to chronic lung allograft dysfunction (CLAD), a progressive scarring process affecting the graft. Although anti-donor alloimmunity is central to the pathogenesis of CLAD, its underlying mechanisms are not fully elucidated and it is neither preventable nor treatable using currently available immunosuppression. Recent evidence has shown that innate immune stimuli are fundamental to the development of CLAD. Here, we examine long-standing assumptions and new concepts linking innate immune activation to late lung allograft fibrosis.
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A red rash developed on both hands of a 54-year-old man. At age 56, he was admitted to our hospital because of an abnormal shadow detected by chest roentgenogram. A detailed examination revealed an anterior mediastinal tumor and dermatomyositis. Thymectomy was performed, and pathologic examination revealed thymic carcinoma. After the surgery, the dermatomyositis symptoms improved. Although dermatomyositis associated with thymic carcinoma is extremely rare, we should account for the possibility of thymic carcinoma-associated dermatomyositis. This will allow for early identification and treatment of malignant tumors, and symptom severity may reflect the degree disease control.