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1.
J Clin Invest ; 134(6)2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38488011

RESUMEN

Ischemia/reperfusion injury-mediated (IRI-mediated) primary graft dysfunction (PGD) adversely affects both short- and long-term outcomes after lung transplantation, a procedure that remains the only treatment option for patients suffering from end-stage respiratory failure. While B cells are known to regulate adaptive immune responses, their role in lung IRI is not well understood. Here, we demonstrated by intravital imaging that B cells are rapidly recruited to injured lungs, where they extravasate into the parenchyma. Using hilar clamping and transplant models, we observed that lung-infiltrating B cells produce the monocyte chemokine CCL7 in a TLR4-TRIF-dependent fashion, a critical step contributing to classical monocyte (CM) recruitment and subsequent neutrophil extravasation, resulting in worse lung function. We found that synergistic BCR-TLR4 activation on B cells is required for the recruitment of CMs to the injured lung. Finally, we corroborated our findings in reperfused human lungs, in which we observed a correlation between B cell infiltration and CM recruitment after transplantation. This study describes a role for B cells as critical orchestrators of lung IRI. As B cells can be depleted with currently available agents, our study provides a rationale for clinical trials investigating B cell-targeting therapies.


Asunto(s)
Monocitos , Daño por Reperfusión , Humanos , Receptor Toll-Like 4/genética , Pulmón , Isquemia , Receptores de Antígenos de Linfocitos B
2.
Artículo en Inglés | MEDLINE | ID: mdl-39226995

RESUMEN

OBJECTIVE: There is a critical shortage of donor lungs for transplantation. We previously developed a parsimonious, highly discriminatory nine-variable Lung Donor (LUNDON) acceptability score. We assess the utility of this score as a tool to improve lung recovery rates for transplantation. METHODS: We examined all brain-dead donors between 2014-2020 from three US organ procurement organizations and validated the score's predictive performance. We examined the trajectory of donors with low (<40) and high (>60) initial LUNDON scores, their corresponding lung recovery rates, factors contributing to score improvement using multivariable regression models, and one-year post-transplant recipient survival. RESULTS: Overall lung recovery was 32.4% (1410/4351). Validation of the LUNDON score in our cohort revealed a C statistic of 0.904 but required intercept calibration. Low initial LUNDON donors that improved to a high final score had an increase in lung recovery rate from 29.3% (1100/3765) to 86.8% (441/508), associated with lower BMI, management in specialized donor care facilities (SDCF), and more bronchoscopies. Donors with high initial and final LUNDON scores had lung recovery rate of 85.2% (98/115), associated with shorter lengths of stay. One-year survival was similar between recipients of low-to-high versus high-to-high LUNDON score donors (0.89 vs 0.84, p=0.2). CONCLUSIONS: The LUNDON score performs well as a predictor of lung recovery in a contemporary cohort but may require OPO-specific calibration. SDCF use, more bronchoscopies, and expediting time from brain death to organ procurement may improve lung utilization. The LUNDON score can be used to guide donor management to expand the donor pool.

3.
J Thorac Dis ; 15(4): 2233-2239, 2023 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-37197524

RESUMEN

Background: Appropriate size matching between donor and recipient is critical for successful pulmonary transplantation. Although surrogate measurements such as height and gender are often utilized to approximate predicted lung volume, these methods provide only a gross estimation with wide variability and poor predictive value. Case Description: A single center exploratory study was conducted in which four patients underwent lung transplantation (LT) with pre-operative computed tomography (CT) volumetry obtained in both the donor and recipient to facilitate decision making regarding organ size and suitability. In four cases in which CT volumetry was used, the lung volumes calculated using surrogate measurements significantly overestimated both donor and recipient lung volumes quantified by CT volumetric analysis. All recipients underwent successful LT without necessary graft downsizing. Conclusions: This is an initial report of prospectively utilizing CT volumetry as an adjunct to decision-making regarding suitability of donor lungs. In these cases, CT volumetry facilitated the confident acceptance of donor lungs that were initially predicted to be oversized based on other clinical measures.

4.
Magy Seb ; 74(4): 142-147, 2021 Nov 25.
Artículo en Húngaro | MEDLINE | ID: mdl-34821584

RESUMEN

Introduction: Not only atraumatic surgical technique, precise bleeding control, removal foreign materials from the abdomen, but also avoiding desiccation or mechanical damage of peritoneal surface at abdominal surgery mean today evidence based expectation. Peritoneum with its extensive surface and special histological structure represents an important factor in normal physiological processes, furthermore as "Guard of abdomen" it has an important role to localise inflammatory reactions, useful as dialysing surface and provides also possibility for hyperthermic abdominal chemotherapy in tumour treatment. Largest part of peritoneal sac covers small intestine and colon. To prevent postoperative complications it is necessary to avoid desiccation of intestinal tract at laparoscopic and at open procedures as well ­ consequently "rehyration" is a routine recommendation today. Desiccation of intestinal tract results postoperative adhesions, furthermore damage of serosa will increase permeability of intestine wall and can result perforation. All the surgical recommendations suggest keeping intestine moist, whereas there are only a few real studies in surgical literature to support or to deny this theory. Our study reviews the pathophysiological and surgical respects of this situation and summarizes the results of latest researches of combined functions of peritoneum.


Asunto(s)
Laparoscopía , Peritoneo , Humanos , Complicaciones Posoperatorias
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