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1.
Am J Transplant ; 24(4): 577-590, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37977230

RESUMEN

Growing evidence implicates complement in the pathogenesis of primary graft dysfunction (PGD). We hypothesized that early complement activation postreperfusion could predispose to severe PGD grade 3 (PGD-3) at 72 hours, which is associated with worst posttransplant outcomes. Consecutive lung transplant patients (n = 253) from January 2018 through June 2023 underwent timed open allograft biopsies at the end of cold ischemia (internal control) and 30 minutes postreperfusion. PGD-3 at 72 hours occurred in 14% (35/253) of patients; 17% (44/253) revealed positive C4d staining on postreperfusion allograft biopsy, and no biopsy-related complications were encountered. Significantly more patients with PGD-3 at 72 hours had positive C4d staining at 30 minutes postreperfusion compared with those without (51% vs 12%, P < .001). Conversely, patients with positive C4d staining were significantly more likely to develop PGD-3 at 72 hours (41% vs 8%, P < .001) and experienced worse long-term outcomes. In multivariate logistic regression, positive C4d staining remained highly predictive of PGD-3 (odds ratio 7.92, 95% confidence interval 2.97-21.1, P < .001). Hence, early complement deposition in allografts is highly predictive of PGD-3 at 72 hours. Our data support future studies to evaluate the role of complement inhibition in patients with early postreperfusion complement activation to mitigate PGD and improve transplant outcomes.


Asunto(s)
Trasplante de Pulmón , Disfunción Primaria del Injerto , Humanos , Disfunción Primaria del Injerto/etiología , Complemento C4b , Estudios Retrospectivos , Pulmón , Proteínas del Sistema Complemento , Trasplante de Pulmón/efectos adversos , Aloinjertos , Rechazo de Injerto/etiología , Rechazo de Injerto/patología
2.
J Surg Res ; 299: 129-136, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38754251

RESUMEN

INTRODUCTION: Cytomegalovirus (CMV) infection is associated with a poor prognosis after lung transplantation, and donor and recipient CMV serostatus is a risk factor for reactivation. CMV prophylaxis is commonly administered in the first year following transplantation to reduce CMV infection; however, the risk factors for long-term reactivation remain unclear. We investigated the timing and risk factors of CMV infection after prophylactic administration. METHODS: This study was a retrospective review of the institutional lung transplantation database from June 2014 to June 2022. Data on patient characteristics, pretransplantation laboratory values, postoperative outcomes, and CMV infection were collected. Donor CMV-IgG-positive and recipient CMV-IgG-negative groups were defined as the CMV mismatch group. RESULTS: During the study period, 257 patients underwent lung transplantation and received a prophylactic dose of valganciclovir hydrochloride for up to 1 y. CMV infection was detected in 69 patients (26.8%): 40 of 203 (19.7%) in the non-CMV mismatch group and 29 of 54 (53.7%) in the CMV mismatch group (P < 0.001). CMV infection after prophylaxis occurred at a median of 425 and 455 d in the CMV mismatch and non-CMV mismatch groups, respectively (P = 0.07). Multivariate logistic regression analysis revealed that preoperative albumin level (odds ratio [OR] = 0.39, P = 0.04), CMV mismatch (OR = 15.7, P < 0.001), and donor age (OR = 1.05, P = 0.009) were significantly associated with CMV infection. CONCLUSIONS: CMV mismatch may have increased the risk of CMV infection after lung transplantation, which decreased after prophylaxis. In addition to CMV mismatch, low preoperative albumin level and donor age were independent predictors of CMV infection.


Asunto(s)
Antivirales , Infecciones por Citomegalovirus , Trasplante de Pulmón , Humanos , Infecciones por Citomegalovirus/prevención & control , Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/diagnóstico , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Trasplante de Pulmón/efectos adversos , Adulto , Factores de Riesgo , Antivirales/uso terapéutico , Antivirales/administración & dosificación , Recurrencia , Valganciclovir/uso terapéutico , Valganciclovir/administración & dosificación , Anciano , Citomegalovirus/inmunología , Citomegalovirus/aislamiento & purificación , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología
3.
Artif Organs ; 47(5): 870-881, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36310407

RESUMEN

PURPOSE: Managing acute respiratory distress syndrome (ARDS) patients on venovenous extracorporeal membrane oxygenation (V-V ECMO), without sedation/neuromuscular blockade to allow physical and occupational therapy (PT/OT) participation, is untraditional. Here, we investigate the impact of early PT/OT initiation on discharge functional activity for ARDS patients managed on V-V ECMO. METHODS: This is a retrospective review of 67 ARDS patients managed with V-V ECMO at a single academic center from February 2018 to June 2021. Data collected included patient characteristics, days of V-V ECMO support, day of PT/OT initiation, and ambulation distance and Activity Measure for Post-Acute Care (AMPAC) Six-Clicks score on day of discharge. RESULTS: Patients with >7 days of V-V ECMO support had decreased ambulation and AMPAC scores compared to those with <7 days (70.5 vs. 162.1, p < 0.01 and 12.3 vs. 16.4, p = 0.01, respectively). PT/OT initiation within 7 days after starting V-V ECMO significantly improved ambulation and AMPAC scores (163.5 vs. 59.5, p < 0.001, and 16.6 vs. 11.8, p < 0.01, respectively). Additionally, in patients with >7 days of V-V ECMO support, those who began PT/OT within 8 days of V-V ECMO cannulation had significantly improved ambulation and AMPAC scores (151.8 vs. 44.2, p < 0.01, and 16.5 vs. 11.0, p < 0.01, respectively). CONCLUSION: Early PT/OT initiation in severe ARDS patients managed on V-V ECMO is associated with improved patient functional activity on day of discharge. Our study further supports the use of V-V ECMO in treatment of severe ARDS without sedation/neuromuscular blockade and specifically demonstrates PT/OT should be started early following V-V ECMO cannulation.


Asunto(s)
Oxigenación por Membrana Extracorpórea , Terapia Ocupacional , Síndrome de Dificultad Respiratoria , Humanos , Síndrome de Dificultad Respiratoria/terapia , Estudios Retrospectivos , Modalidades de Fisioterapia
4.
Kyobu Geka ; 75(4): 244-251, 2022 Apr.
Artículo en Japonés | MEDLINE | ID: mdl-35342153

RESUMEN

Lung transplantation has become popular in Japan, showing better survival rate than other countries. However, the results are still not satisfactory compared with other solid organ transplantation. One of the reasons for this might be that knowledge on donor-specific antibodies or antibody-related rejection, which has been attracting attention these days, is less than that of kidney or liver transplantation. Our laboratory has continued basic research in this field using rodent lung transplantation model. We have previously shown that type V collagen is associated in chronic rejection as an autoimmune, and that oral administration of type V collagen induces tolerance. The murine chronic rejection model of the minor antigen mismatch was developed, and involvement of the humoral immunity and role of the complement activation were shown. We are now studying the effects of immune checkpoint molecules, which play a central role in the field of cancer therapy, on rejection after lung transplantation. We are also working to verify the effects of anti-complement drugs and molecular targeted drugs in the future treatment on rejection.


Asunto(s)
Rechazo de Injerto , Trasplante de Pulmón , Animales , Anticuerpos , Reacciones Antígeno-Anticuerpo , Rechazo de Injerto/prevención & control , Humanos , Japón , Ratones
5.
Cancer Immunol Immunother ; 70(5): 1239-1254, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33128583

RESUMEN

Glioblastoma is the most common and aggressive type of brain tumor with high recurrence and fatality rates. Although various therapeutic strategies have been explored, there is currently no effective treatment for glioblastoma. Recently, the number of immunotherapeutic strategies has been tested for malignant brain tumors. Invariant natural killer T (iNKT) cells play an important role in anti-tumor immunity. To address if iNKT cells can target glioblastoma to exert anti-tumor activity, we assessed the expression of CD1d, an antigen-presenting molecule for iNKT cells, on glioblastoma cells. Glioblastoma cells from 10 of 15 patients expressed CD1d, and CD1d-positive glioblastoma cells pulsed with glycolipid ligand induced iNKT cell-mediated cytotoxicity in vitro. Although CD1d expression was low on glioblastoma stem-like cells, retinoic acid, which is the most common differentiating agent, upregulated CD1d expression in these cells and induced iNKT cell-mediated cytotoxicity. Moreover, intracranial administration of human iNKT cells induced tumor regression of CD1d-positive glioblastoma in orthotopic xenografts in NOD/Shi-scid IL-2RγKO (NOG) mice. Thus, CD1d expression represents a novel target for NKT cell-based immunotherapy for glioblastoma patients.


Asunto(s)
Antígenos CD1d/metabolismo , Neoplasias Encefálicas/inmunología , Vacunas contra el Cáncer/inmunología , Glioblastoma/inmunología , Inmunoterapia Adoptiva/métodos , Células T Asesinas Naturales/metabolismo , Anciano , Animales , Presentación de Antígeno , Neoplasias Encefálicas/terapia , Células Cultivadas , Citotoxicidad Inmunológica , Femenino , Regulación Neoplásica de la Expresión Génica , Glioblastoma/terapia , Humanos , Masculino , Ratones , Ratones SCID , Persona de Mediana Edad , Células T Asesinas Naturales/inmunología , Células T Asesinas Naturales/trasplante , Trasplante de Neoplasias , Tretinoina/metabolismo
6.
Cancer Sci ; 111(1): 288-296, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31677359

RESUMEN

The role of immune checkpoint inhibitors in metastatic lung cancer has been established in recent years and the pretherapeutic profiles of the tumor microenvironment in responders have been increasingly reported. The role of salvage surgery and the immune profiles of the posttherapeutic specimens in patients achieving an objective response have rarely been studied. We report a case of metastatic lung cancer treated by anti-programmed death-1 Ab followed by surgical resection. The immune status of the tumor was assessed, showing germinal center formation, memory B cell infiltration, and a high frequency of interferon gamma -secreting T cells.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/terapia , Receptor de Muerte Celular Programada 1/inmunología , Anciano , Linfocitos B/inmunología , Centro Germinal/inmunología , Humanos , Masculino , Linfocitos T/inmunología , Microambiente Tumoral/inmunología
7.
Cancer Sci ; 111(7): 2223-2233, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32324315

RESUMEN

Invariant natural killer T (iNKT) cells are innate-like CD1d-restricted T cells that express the invariant T cell receptor (TCR) composed of Vα24 and Vß11 in humans. iNKT cells specifically recognize glycolipid antigens such as α-galactosylceramide (αGalCer) presented by CD1d. iNKT cells show direct cytotoxicity toward CD1d-positive tumor cells, especially when CD1d presents glycolipid antigens. However, iNKT cell recognition of CD1d-negative tumor cells is unknown, and direct cytotoxicity of iNKT cells toward CD1d-negative tumor cells remains controversial. Here, we demonstrate that activated iNKT cells recognize leukemia cells in a CD1d-independent manner, however still in a TCR-mediated way. iNKT cells degranulated and released Th1 cytokines toward CD1d-negative leukemia cells (K562, HL-60, REH) as well as αGalCer-loaded CD1d-positive Jurkat cells. The CD1d-independent cytotoxicity was enhanced by natural killer cell-activating receptors such as NKG2D, 2B4, DNAM-1, LFA-1 and CD2, but iNKT cells did not depend on these receptors for the recognition of CD1d-negative leukemia cells. In contrast, TCR was essential for CD1d-independent recognition and cytotoxicity. iNKT cells degranulated toward patient-derived leukemia cells independently of CD1d expression. iNKT cells targeted myeloid malignancies more than acute lymphoblastic leukemia. These findings reveal a novel anti-tumor mechanism of iNKT cells in targeting CD1d-negative tumor cells and indicate the potential of iNKT cells for clinical application to treat leukemia independently of CD1d.


Asunto(s)
Antígenos CD1d/metabolismo , Leucemia/inmunología , Leucemia/metabolismo , Activación de Linfocitos/inmunología , Células T Asesinas Naturales/inmunología , Células T Asesinas Naturales/metabolismo , Animales , Antígenos CD1d/genética , Biomarcadores , Degranulación de la Célula , Línea Celular Tumoral , Receptores Coestimuladores e Inhibidores de Linfocitos T/metabolismo , Citocinas/metabolismo , Citotoxicidad Inmunológica , Modelos Animales de Enfermedad , Femenino , Edición Génica , Xenoinjertos , Humanos , Inmunofenotipificación , Leucemia/genética , Leucemia/patología , Activación de Linfocitos/genética , Ratones , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/metabolismo , Receptores Gatillantes de la Citotoxidad Natural/metabolismo
8.
Gen Thorac Cardiovasc Surg ; 72(3): 176-182, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37474741

RESUMEN

PURPOSE: The impact of the modified frailty index (mFI) on postoperative complications after lung cancer surgery was investigated. METHODS: Patients who underwent lung cancer surgery in 2017 were included. 30-day postoperative mortality and morbidity were evaluated according to their Clavien-Dindo classification. mFI values are presented as the sum of values of 11 included items. Logistic regression was used to assess the effect of mFI on postoperative severe complication incidence. RESULTS: Among 190 patients considered, severe postoperative complications (Grade 3 or more) were observed in 30 (16%). No patients died within 30 days of surgery. The incidence of severe complications was 3.6% in patients with mFI of 0, 16.2% in patients with mFI of 1, 23.4% in patients with mFI of 2, and 31.6% in patients with mFI of 3 or more, and was correlated with the grade of mFI. Univariate and multivariate analyses showed that the high mFI was significantly predictive of postoperative complications. Frail patients of mFI ≥ 2 were at 3.0-fold greater risk of severe complications than non-frail patients of mFI 0 or 1. CONCLUSION: mFI was associated with morbidity after lung cancer surgery. Preoperative frailty assessment and appropriate intervention to frail patients would be required to improve postoperative outcomes.


Asunto(s)
Fragilidad , Neoplasias Pulmonares , Humanos , Fragilidad/complicaciones , Fragilidad/diagnóstico , Fragilidad/epidemiología , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/complicaciones , Complicaciones Posoperatorias/etiología , Morbilidad , Incidencia , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo
9.
J Thorac Dis ; 16(2): 989-996, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38505039

RESUMEN

Background: Home oxygen therapy (HOT) is used to treat chronic respiratory diseases and is sometimes required in patients with lung cancer after radical surgery. We aimed to identify the risk factors for postoperative home-based oxygen therapy in patients with lung cancer. Methods: Patients who underwent surgery for primary lung cancer at Chiba University Hospital between January 2019 and March 2021 were included. Patients who did not undergo complete resection, died in hospital after surgery, or used oxygen therapy preoperatively were excluded. Eligible patients were divided into HOT and non-HOT groups. They were retrospectively analyzed for risk factors for postoperative HOT using medical records in a multivariate analysis. Results: A total of 410 patients were included in this study, 24 (5.9%) of whom required HOT after surgery. The HOT group comprised significantly more men, heavy smokers, and patients with pulmonary comorbidities, low percent forced expiratory volume, percent forced vital capacity, predicted postoperative forced expiratory volume in 1 s, and postoperative pulmonary complications on univariate analysis. In a multivariate analysis, independent risk factors for postoperative HOT were pulmonary comorbidities [odds ratio (OR): 5.94; 95% confidence interval (CI): 1.64-21.5; P=0.002) and postoperative pulmonary complications (OR: 5.39; 95% CI: 2.14-13.5; P<0.001). The postoperative HOT application rate was calculated according to a formula developed for this purpose. Conclusions: Comorbid pulmonary diseases and postoperative pulmonary complications were significantly associated with postoperative HOT in patients with lung cancer.

10.
Eur J Cancer ; 201: 113951, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38417299

RESUMEN

OBJECTIVES: To clarify the impact of central nervous system (CNS) metastasis on performance status (PS) at relapse, on subsequent treatment(s), and on survival of patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutation. METHODS: We conducted the multicenter real-world database study for patients with radical resections for lung adenocarcinomas between 2015 and 2018 at 21 centers in Japan. EGFR mutational status was examined at each center. RESULTS: Of 4181 patients enrolled, 1431 underwent complete anatomical resection for lung adenocarcinoma harboring common EGFR mutations. Three-hundred-and-twenty patients experienced disease relapse, and 78 (24%) had CNS metastasis. CNS metastasis was significantly more frequent in patients with conventional adjuvant chemotherapy than those without (30% vs. 20%, P = 0.036). Adjuvant chemotherapy did not significantly improve relapse-free survival at any pathological stage (adjusted hazard ratio for stage IA2-3, IB, and II-III was 1.363, 1.287, and 1.004, respectively). CNS metastasis did not affect PS at relapse. Subsequent treatment, mainly consisting of EGFR-tyrosine kinase inhibitors (TKIs), could be equally given in patients with or without CNS metastasis (96% vs. 94%). Overall survival after relapse was equivalent between patients with and without CNS metastasis. CONCLUSION: The efficacy of conventional adjuvant chemotherapy may be limited in patients with lung adenocarcinoma harboring EGFR mutations. CNS metastasis is likely to be found in practice before deterioration in PS, and may have little negative impact on compliance with subsequent EGFR-TKIs and survival after relapse. In this era of adjuvant TKI therapy, further prospective observational studies are desirable to elucidate the optimal management of CNS metastasis.


Asunto(s)
Adenocarcinoma del Pulmón , Antineoplásicos , Neoplasias del Sistema Nervioso Central , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Japón , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/cirugía , Adenocarcinoma del Pulmón/tratamiento farmacológico , Receptores ErbB/genética , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/cirugía , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Mutación , Recurrencia , Sistema Nervioso Central/patología , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios Retrospectivos
11.
J Thorac Dis ; 15(2): 399-409, 2023 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-36910052

RESUMEN

Background: Primary graft dysfunction is a major cause of early mortality following lung transplantation. The International Society for Heart and Lung Transplantation subdivides it into 4 grades of increasing severity. Methods: A retrospective review of the institutional lung transplant database from March 2018 to September 2021 was performed. Patients were stratified into three groups: primary graft dysfunction grade 0 patients, grade 1 or 2 patients, and grade 3 patients. Recipient, donor, and surgical variables were analyzed by logistic regression analysis to identify risk factors for primary graft dysfunction grade 1 or 2 and grade 3. Results: Primary graft dysfunction grade 1 to 3 occurred in 45.0% of the cohort (n=68) of whom 33.3% (n=23) had primary graft dysfunction grade 3. Longer operative time was more common in primary graft dysfunction grade 1 to 3 patients (P<0.001). The 1-year survival of the patients with primary graft dysfunction grade 3 was lower than the others (grade 0-2 vs. 3, 93.7% vs. 65.2%, P=0.0006). Univariate analysis showed that acute respiratory distress syndrome, operative time, and intraoperative veno-arterial extracorporeal membrane oxygenation use were risk factors for primary graft dysfunction grades 1 or 2 and grade 3. Multivariate analysis identified that intraoperative veno-arterial extracorporeal membrane oxygenation use was an independent risk factor of primary graft dysfunction grade 1 or 2. Patients with an operative time of more than 8.18 hours had significantly higher incidence of primary graft dysfunction grade 3, acute kidney injury, and digital ischemia. Conclusions: The calculated predictors of primary graft dysfunction grade 1 or 2 were similar to those of primary graft dysfunction grade 3.

12.
J Thorac Dis ; 15(4): 1640-1647, 2023 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-37197533

RESUMEN

Background: In the surgical treatment of chest wall tumors requiring large chest wall resection, reconstruction of the chest wall defect is required using various autologous tissues or artificial materials. However, no appropriate method has been reported to evaluate whether each reconstruction is successful or not. Therefore, we performed lung volumetry before and after surgery to evaluate the negative effects of chest wall surgery on lung expansion. Methods: Twenty-three patients with chest wall tumors who underwent surgery were included in this study. Lung volume (LV) before and after surgery was measured using SYNAPSE VINSENT (FUJIFILM, Tokyo, Japan). The rate of change in LV was calculated as the postoperative and preoperative LV of the operative side × preoperative/postoperative LV of the opposite side. The excised chest wall area was calculated as vertical diameter × horizontal diameter of the tissue specimen. Results: Reconstruction methods included rigid reconstruction (a combination of titanium mesh and extended polytetrafluoroethylene sheet) in four patients, non-rigid reconstruction (extended polytetrafluoroethylene sheet only) in 11, no reconstruction in five, and no chest wall resection in three. Changes in LV were generally well preserved, regardless of the resected area. In addition, LVs were well maintained in most patients who underwent chest wall reconstruction. However, in some cases, decreased lung expansion was observed with migration and deflection of the reconstructive material into the thorax due to postoperative lung inflammation and shrinking. Conclusions: Lung volumetry can be used to evaluate the effectiveness of chest wall surgery.

13.
Crit Care Explor ; 5(9): e0965, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37693304

RESUMEN

Transfer of select, medically refractory acute respiratory distress syndrome patients to lung transplant centers requires extensive resources. Here, we report 270 consecutive lung transplant patient referrals to our center for medically refractory ARDS from June 2021 to April 2022, following the implementation of clinical care pathways for intake of these patients. Eighty-seven of 270 patients (32.2%) met screening criteria and were evaluated for transfer within a median of 12 days, during which 38 of 87 patients (43.7%) died and 12 of 87 patients (13.8%) transferred elsewhere. Thirty-seven of 87 patients (42.5%) were accepted for transfer of which 16 of 37 patients (43.2%) successfully transferred to our center with a median transfer waiting period of 12 days. Because of resource constraints, 21 of 37 accepted patients (56.8%) could not be transferred of which 9 of 21 patients (42.9%) died while waiting. Nine of 16 transferred patients (56.2%) eventually underwent lung transplantation with over 80% 6-month survival. ARDS patients referred for transplantation have high risk of mortality and, therefore, require well-described pathways for evaluation and transfer.

14.
J Thorac Dis ; 15(7): 3751-3763, 2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37559611

RESUMEN

Background: Primary graft dysfunction (PGD) and acute kidney injury (AKI) are major early complications of lung transplantation and are associated with increased mortality. Lung injury after PGD can contribute to renal dysfunction; however, the association between PGD and AKI severity has not been thoroughly investigated. We analyzed the association between PGD grading and AKI staging, and the impact of AKI on subsequent changes to chronic kidney disease (CKD), including glomerular filtration rate (GFR), over time. Methods: This was a retrospective review of a single-center lung transplantation database between January 2018 and June 2022. AKI and GFR categories were classified according to the Kidney Disease: Improving Global Outcomes criteria. Spearman's and Kaplan-Meier tests were used to compare disease severity and assess survival. Results: In a total of 206 patients: 119 (57.8%), 25 (12.1%), 34 (16.5%), and 28 (13.6%) had PGD grades 0, 1, 2, and 3, respectively; 96 (46.6%), 47 (22.8%), 27 (13.1%), and 36 (17.5%) had AKI stages 0, 1, 2, and 3, respectively. Twenty-one of the 28 patients (75.0%) with PGD grade 3 had AKI stage 3. There was a significant correlation between PGD grade and AKI stage (P<0.001). There was also a significant correlation between AKI stage and GFR category of CKD at 3, 6, 9, and 12 months after lung transplantation (all P<0.001). For all AKI stages, GFR categories worsened with postoperative time. Conclusions: PGD grade was significantly correlated with AKI stage, and AKI stage was correlated with GFR categories of CKD.

15.
Gen Thorac Cardiovasc Surg ; 70(12): 1032-1041, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35767165

RESUMEN

OBJECTIVE: Antibody-mediated rejection (AMR) could induce acute or chronic graft failure during organ transplantation. Several reports have shown that anti-C5 antibodies are effective against AMR after kidney transplantation. However, few reports have assessed the efficacy of anti-C5 antibodies against AMR after lung transplantation. Therefore, this study aimed to evaluate the efficacy of this novel therapy against AMR after lung transplantation. METHODS: BALB/c and C57BL/6 mice were used as donors and recipients. One group was pre-sensitized (PS) by skin transplantation 14 days before lung transplantation. The other group was non-sensitized (NS). Orthotopic left-lung transplantation was performed in both groups. Animals were killed at 2 or 7 days after lung transplantation and evaluated for histopathology, C4d immunostaining, and serum donor-specific antibodies (DSAs) (n = 5 per group). Isograft (IS) models with C57BL/6 mice were used as controls. To evaluate the efficacy of C5 inhibition, other animals, which received similar treatments to those in the PS group, were treated with anti-C5 antibodies, cyclosporine/methylprednisolone, anti-C5 antibodies/cyclosporine/methylprednisolone, or isotype-matched irrelevant control monoclonal antibodies (n = 5 per group). RESULTS: Two days after lung transplantation, the NS group exhibited mild, localized graft-rejection features (rejection score: 0.45 ± 0.08, p = 0.107). The PS group exhibited AMR features with a significantly higher rejection score (2.29 ± 0.42, p = 0.001), C4d vascular-endothelium deposition, and substantial presence of serum DSA. On day 7 after lung transplantation, both groups showed extensive graft alveolar wall destruction, and high acute-rejection scores. Mice receiving anti-C5 antibodies or anti-C5/antibodies/cyclosporine/methylprednisolone demonstrated significantly lower acute-rejection scores (0.63 ± 0.23, p = 0.002; 0.59 ± 0.22, p = 0.001, respectively) than those receiving isotype control antibodies. CONCLUSIONS: Murine orthotopic allograft lung transplant models met the clinical diagnosis and pathogenesis classification criteria of AMR. In these models, anti-C5 antibodies suppressed AMR. Therefore, anti-C5 therapy may be effective against AMR after lung transplantation.


Asunto(s)
Ciclosporinas , Trasplante de Pulmón , Ratones , Animales , Trasplante de Piel , Ratones Endogámicos C57BL , Rechazo de Injerto/etiología , Anticuerpos/farmacología , Trasplante de Pulmón/efectos adversos , Donantes de Tejidos , Metilprednisolona
16.
Ann Thorac Surg ; 2022 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-36521520

RESUMEN

BACKGROUND: Primary graft dysfunction is a risk factor of early mortality after lung transplant. Models identifying patients at high risk for primary graft dysfunction are limited. We hypothesize high postreperfusion systolic pulmonary artery pressure is a clinical marker for primary graft dysfunction. METHODS: This is a retrospective review of 158 consecutive lung transplants performed at a single academic center from January 2020 through July 2022. Only bilateral lung transplants were included and patients with pretransplant extracorporeal life support were excluded. RESULTS: Primary graft dysfunction occurred in 42.3% (n = 30). Patients with primary graft dysfunction had higher postreperfusion systolic pulmonary artery pressure (41 ± 9.1 mm Hg) than those without (31.5 ± 8.8 mm Hg) (P < .001). Logistic regression showed postreperfusion systolic pulmonary artery pressure is a predictor for primary graft dysfunction (odds ratio 1.14, 95% CI 1.06-1.24, P < .001). Postreperfusion systolic pulmonary artery pressure of 37 mm Hg was optimal for predicting primary graft dysfunction by Youden index. The receiver operating characteristic curve of postreperfusion systolic pulmonary artery pressure at 37 mm Hg (sensitivity 0.77, specificity 0.78, area under the curve 0.81), was superior to the prereperfusion pressure curve at 36 mm Hg (sensitivity 0.77, specificity 0.39, area under the curve 0.57) (P < .01). CONCLUSIONS: Elevated postreperfusion systolic pulmonary artery pressure after lung transplant is predictive of primary graft dysfunction. Postreperfusion systolic pulmonary artery pressure is more indicative of primary graft dysfunction than prereperfusion systolic pulmonary artery pressure. Using postreperfusion systolic pulmonary artery pressure as a positive signal of primary graft dysfunction allows earlier intervention, which could improve outcomes.

17.
Respir Med Case Rep ; 40: 101762, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36340866

RESUMEN

Primary racemose hemangioma of the bronchial artery (RHBA) is one of the causes of massive hemoptysis. A 72-year-old woman was admitted to our hospital with recurrent hemoptysis. Bronchoscopy showed an endobronchial lesion, and the angiography of the right bronchial arteries indicated RHBA. Bronchial arterial embolization (BAE) was performed to prevent hemoptysis. Although the endobronchial lesion shrank after the first BAE, the lesion re-increased and caused massive hemoptysis. A thoracoscopic right upper lobectomy was performed, and hemoptysis did not recur. Therefore, in cases of RHBA where there is recurrent hemoptysis and the endobronchial lesions that remain after BAE, additional treatments should be considered.

18.
Surg Case Rep ; 7(1): 8, 2021 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-33409601

RESUMEN

BACKGROUND: Knowledge of anatomical abnormalities and variations in pulmonary vessels and bronchi is critical for patients requiring a lung segmentectomy. To the best of our knowledge, this is the first case of a tumor existing in the lower lobe in conjunction with a displaced B1+2 in which the B1+2 was not accidentally cut during surgery. CASE PRESENTATION: A 71-year-old woman was referred to our hospital after a part-solid lung cancer was found in the superior segment of her left lung on chest computed tomography. Preoperative three-dimensional computed tomography revealed a displaced anomalous left B1+2 arising from the left main bronchus and anomalous V1+2 returning to the inferior pulmonary vein. We identified these anomalies during surgery and performed a left superior segmentectomy. After an unremarkable recovery, the patient was discharged from the hospital on the eighth day postoperative. CONCLUSIONS: We used a three-dimensional construction system during the preoperative planning of the pulmonary segmentectomy to better understand the bronchovascular structures. When performing surgery where anatomical abnormalities are present, there is the possibility of misidentification. Using the three-dimensional construction system, it was possible to perform safer surgery, as the surgeons were able to preoperatively prepare for any abnormalities.

19.
Sci Rep ; 11(1): 13526, 2021 06 29.
Artículo en Inglés | MEDLINE | ID: mdl-34188146

RESUMEN

Tumor spread through air spaces (STAS) in non-small-cell lung cancer (NSCLC) is known to influence a poor patient outcome, even in patients presenting with early-stage disease. However, the pre-operative diagnosis of STAS remains challenging. With the progress of radiomics-based analyses several attempts have been made to predict STAS based on radiological findings. In the present study, patients with NSCLC which is located peripherally and tumors ≤ 2 cm in size on computed tomography (CT) that were potential candidates for sublobar resection were enrolled in this study. The radiologic features of the targeted tumors on thin-section CT were extracted using the PyRadiomics v3.0 software package, and a predictive model for STAS was built using the t-test and XGBoost. Thirty-five out of 226 patients had a STAS histology. The predictive model of STAS indicated an area under the receiver-operator characteristic curve (AUC) of 0.77. There was no significant difference in the overall survival (OS) for lobectomy between the predicted-STAS (+) and (-) groups (p = 0.19), but an unfavorable OS for sublobar resection was indicated in the predicted-STAS (+) group (p < 0.01). These results suggest that radiomics with machine-learning helped to develop a favorable model of STAS (+) NSCLC, which might be useful for the proper selection of candidates who should undergo sublobar resection.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Femenino , Humanos , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias
20.
J Thorac Dis ; 12(5): 2635-2643, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32642171

RESUMEN

BACKGROUND: Tumor seeding, whereby malignant cells are deposited along the needle tract, is considered to be a potential hazard of needle biopsies. The aim of this study is to elucidate the relationship between needle biopsies for lung tumor, such as a preoperative computed tomography-guided needle biopsy (PCTGNB) or an intraoperative fine-needle aspiration biopsy (IFNAB), and ipsilateral pleural recurrence (PR) after lung cancer surgery. METHODS: Between 2008 and 2017, 1,047 patients with non-small cell lung cancer (NSCLC) underwent curative lung resection in our institution. They were divided into two groups: those in whom the first recurrent site was the ipsilateral pleural cavity (PR group) and the others (control group). Risk factors of PR were investigated retrospectively. RESULTS: Recurrence was observed in 191 patients (18.2%), 25 of whom were categorized to the PR group (17 malignant effusion, 10 dissemination). Pathological tumor [2-4], lymph nodes [1-2], pleural, lymphatic and vascular invasion (each ≥1) factors and patients who underwent PCTGNB were more frequently observed in the PR group than in the control group (each P<0.01) whereas the proportion of patients who underwent IFNAB was not significant. A multivariate analysis identified pathological lymph node factor and the frequency of PCTGNB as independent risk factors for PR with hazard ratios of 7.33 (95% CI, 2.93-19.8; P<0.01) and 6.92 (95% CI, 2.25-17.8; P<0.01), respectively. CONCLUSIONS: PCTGNB is a risk factor of PR but IFNAB is not. Indications for PCTGNB should be carefully determined.

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