Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 3.850
Filter
1.
Article in English | MEDLINE | ID: mdl-39029637

ABSTRACT

Primary graft dysfunction (PGD) is a complication of lung transplantation that continues to cause significant morbidity. The Th2 immune response has been shown to counteract tissue-damaging inflammation. We hypothesized that Th2 cytokines/chemokines in blood would be associated with protection from PGD. Utilizing pre-transplant sera from the multicenter Clinical Trials in Organ Transplantation (CTOT-20) study, we evaluated Th2 cytokines/chemokines in 211 patients. Increased concentrations of Th2 cytokines were associated with freedom from PGD, namely IL-4 (Odds Ratio (OR) 0.66 (95% CI 0.45-0.99), p=0.043), IL-9 (OR 0.68 (95% CI 0.49-0.94), p=0.019), IL-13 (OR 0.73 (95% CI 0.55-0.96), p=0.023), and IL-6 (OR 0.74 (95% CI 0.56-0.98), p=0.036). Multivariable regression performed for each cytokine including clinically relevant covariables confirmed these associations and additionally demonstrated association with IL-5 (OR 0.57 (95% CI 0.36-0.89), p=0.014) and IL-10 (OR 0.55 (95% CI 0.32-0.96), p=0.035). Higher levels of Th2 immune response prior to lung translant appear to have a protective effect against PGD, which parallels the Th2 role in resolving inflammation and tissue injury. Pre-transplant cytokine assessments could be utilized for recipient risk stratification.

2.
J Cardiothorac Surg ; 19(1): 466, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39054519

ABSTRACT

BACKGROUND: Lung transplantation (LT) represents a high-risk procedure for end-stage lung diseases. This study describes the outcomes of patients undergoing LT that require massive transfusions as defined by the universal definition of perioperative bleeding (UDPB). METHODS: Adult patients who underwent bilateral LT at a single academic center were surveyed retrospectively. Patients were grouped by insignificant, mild, or moderate perioperative bleeding (insignificant-to-moderate bleeders) and severe or massive perioperative bleeding (severe-to-massive bleeders) based on the UDPB classification. Outcomes included 1-year survival and primary graft dysfunction (PGD) of grade 3 at 72 h postoperatively. Multivariable models were adjusted for recipient age, sex, body mass index (BMI), Lung allocation score (LAS), preoperative hemoglobin (Hb), preoperative extracorporeal membrane oxygenation (ECMO) status, transplant number, and donor status. An additional multivariable model was created to find preoperative and intraoperative predictors of severe-to-massive bleeding. A p-value less than 0.05 was selected for significance. RESULTS: A total of 528 patients were included, with 357 insignificant-to-moderate bleeders and 171 severe-to-massive bleeders. Postoperatively, severe-to-massive bleeders had higher rates of PGD grade 3 at 72 h, longer hospital stays, higher mortality rates at 30 days and one year, and were less likely to achieve textbook outcomes for LT. They also required postoperative ECMO, reintubation for over 48 h, tracheostomy, reintervention, and dialysis at higher rates. In the multivariate analysis, severe-to-massive bleeding was significantly associated with adverse outcomes after adjusting for recipient and donor factors, with an odds ratio of 7.73 (95% CI: 4.27-14.4, p < 0.001) for PGD3 at 72 h, 4.30 (95% CI: 2.30-8.12, p < 0.001) for 1-year mortality, and 1.75 (95% CI: 1.52-2.01, p < 0.001) for longer hospital stays. Additionally, severe-to-massive bleeders were less likely to achieve textbook outcomes, with an odds ratio of 0.07 (95% CI: 0.02-0.16, p < 0.001). Preoperative and intraoperative predictors of severe/massive bleeding were identified, with White patients having lower odds compared to Black patients (OR: 041, 95% CI: 0.22-0.80, p = 0.008). Each 1-unit increase in BMI decreased the odds of bleeding (OR: 0.89, 95% CI: 0.83-0.95, p < 0.001), while each 1-unit increase in MPAP increased the odds of bleeding (OR: 1.04, 95% CI: 1.02-1.06, p < 0.001). First-time transplant recipients had lower risk (OR: 0.16, 95% CI: 0.06-0.36, p < 0.001), whereas those with DCD donors had a higher risk of severe-to-massive bleeding (OR: 3.09, 95% CI: 1.63-5.87, p = 0.001). CONCLUSION: These results suggest that patients at high risk of massive bleeding require higher utilization of hospital resources. Understanding their outcomes is important, as it may inform future decisions to transplant comparable patients.


Subject(s)
Lung Transplantation , Humans , Retrospective Studies , Male , Female , Lung Transplantation/adverse effects , Middle Aged , Adult , Postoperative Hemorrhage/epidemiology , Risk Factors , Blood Transfusion/statistics & numerical data , Treatment Outcome
3.
Am J Transplant ; 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39025302

ABSTRACT

Mycoplasma hominis and Ureaplasma species are urogenital mollicutes that can cause serious donor-derived infections in lung transplant recipients. Best practices for mollicute screening remain unknown. We conducted a single center prospective study analyzing lung transplants performed from 10/5/20 - 9/5/21 whereby donor and recipient bronchoalveolar lavage (BAL) samples obtained at time of transplant underwent mollicute screening via culture and polymerase chain reaction (PCR). Of 115 total lung transplants performed, 99 (86%) donors underwent combined mollicute BAL culture and PCR testing. The study cohort included these 99 donors and their matched recipients. In total, 18 (18%) of 99 donors screened positive via culture or PCR. Among recipients, 92 (93%) of 99 had perioperative BAL screening performed, and only 3 (3%) had positive results. After transplant, 9 (9%) recipients developed mollicute infection. Sensitivity of donor screening in predicting recipient mollicute infection was 67% (6/9) via culture and 56% (5/9) via PCR. Positive predictive value (PPV) for donor culture was 75% (6/8), compared to 33% (5/15) for PCR. Donor screening via culture predicted all serious recipient mollicute infections and had better PPV than PCR; however, neither screening test predicted all mollicute infections. Independent of screening results, clinicians should remain suspicious for post-transplant mollicute infection.

4.
Biochem Biophys Res Commun ; 727: 150308, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-38968769

ABSTRACT

Excessive autophagy may lead to degradation and damage of alveolar epithelial cells after lung transplantation, eventually leading to alveolar epithelial cell loss, affecting the structural integrity and function of alveoli. Glutamine (Gln), a nutritional supplement, regulates autophagy through multiple signaling pathways. In this study, we explored the protective role of Gln on alveolar epithelial cells by inhibiting autophagy. In vivo, a rat orthotopic lung transplant model was carried out to evaluate the therapeutic effect of glutamine. Ischemia/reperfusion (I/R) induced alveolar collapse, edema, epithelial cell apoptosis, and inflammation, which led to a reduction of alveolar physiological function, such as an increase in peak airway pressure, and a decrease in lung compliance and oxygenation index. In comparison, Gln preserved alveolar structure and function by reducing alveolar apoptosis, inflammation, and edema. In vitro, a hypoxia/reoxygenation (H/R) cell model was performed to simulate IR injury on mouse lung epithelial (MLE) cells and human lung bronchus epithelial (Beas-2B) cells. H/R impaired the proliferation of epithelial cells and triggered cell apoptosis. In contrast, Gln normalized cell proliferation and suppressed I/R-induced cell apoptosis. The activation of mTOR and the downregulation of autophagy-related proteins (LC3, Atg5, Beclin1) were observed in Gln-treated lung tissues and alveolar epithelial cells. Both in vivo and in vitro, rapamycin, a classical mTOR inhibitor, reversed the beneficial effects of Gln on alveolar structure and function. Taken together, Glnpreserved alveolar structure and function after lung transplantation by inhibiting autophagy.


Subject(s)
Autophagy , Glutamine , Lung Transplantation , Pulmonary Alveoli , Rats, Sprague-Dawley , Reperfusion Injury , Autophagy/drug effects , Animals , Glutamine/metabolism , Glutamine/pharmacology , Male , Humans , Mice , Rats , Pulmonary Alveoli/metabolism , Pulmonary Alveoli/drug effects , Pulmonary Alveoli/pathology , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Apoptosis/drug effects , Cell Line , Alveolar Epithelial Cells/metabolism , Alveolar Epithelial Cells/drug effects , Alveolar Epithelial Cells/pathology
5.
Article in English | MEDLINE | ID: mdl-38950182

ABSTRACT

OBJECTIVES: With increased lung transplantation in those aged 70 and older, limited literature addresses risk factors affecting their survival. Our study aims to identify independent factors impacting mid- and long-term mortality in this elderly population. METHODS: This study analyzed lung transplant patients over 70 from May 2005 to December 2022 using United Network for Organ Sharing data. The 3- or 5-year cohort excluded multi-organ, secondary transplantation and loss to follow-up. Univariable Cox analysis was conducted to assess recipient, donor and transplant factors. Factors with a significance level of P < 0.2 were subsequently included in a multivariable Cox model to identify correlations with 3- and 5-year mortality in patients aged over 70. RESULTS: Multivariable analysis has identified key factors affecting 3- and 5-year mortality in elderly lung transplant patients over 70. Common notable factors include recipient total bilirubin, intensive care unit status at the time of transplantation, donor diabetes, Cytomegalovirus (CMV) mismatch and single lung transplantation. Additionally, Hispanic/Latino patients and ischaemia time of the transplant significantly impact the 3-year mortality, while recipient age, diabetes, nitric oxide use before transplantation and creatinine were identified as unique independent risk factors affecting the 5-year morality. CONCLUSIONS: The study identified several independent risk factors that impact the mid- and long-term survival of lung transplantation for individuals over 70 years. These findings can contribute to the optimization of lung transplant treatment strategies and perioperative management in elderly patients, thereby enhancing the survival rate of this age group.

6.
J Thorac Dis ; 16(6): 3636-3643, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38983139

ABSTRACT

Background: As an important supplementary approach to clinical in orthotopic lung transplantation (LTx), lobar LTx currently lacks a stable animal model and in the orthotopic left LTx model, the right lung of the donor mouse is completely removed and discarded. We introduce a novel mouse lobar LTx model that potentially provides a mouse model for clinical lobar LTx and increase the utilization rate of the experimental donor. Methods: Lobar and orthotopic left LTx were performed in syngeneic strain combinations. We performed micro-computed tomography and tested arterial blood gases to assess the graft function 28 days after transplantation. Hematoxylin-eosin and Masson's trichrome staining were used to evaluate pathological changes. Results: We performed ten lobar LTx with an operation success rate of 90%, accompanied by ten orthotopic left LTx from the same donors with an operation success rate of 100%. The graft preparation for lobar LTx was longer than that of the orthotopic left LTx (42.11±3.79 vs. 30.10±3.14 minutes, P<0.001). The recipient procedure for lobar LTx was nearly equivalent to the orthotopic left LTx. The graft function and histopathological changes for lobar LTx were comparable to those of orthotopic left LTx 28 days after transplantation. Conclusions: We describe a lobar LTx model in the mouse, which potentially provides a model for clinical lobar LTx and effectively addresses the issue of resource wastage in the orthotopic left LTx model.

7.
J Thorac Dis ; 16(6): 3685-3695, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38983135

ABSTRACT

Background: Size matching between donors and recipients is a major issue in lung transplantation (LTx), especially in patients with restrictive lung disease (RLD). This study aims to evaluate computed tomography (CT) as an additional method for defining the total lung capacity (TLC) in patients with end-stage interstitial disease awaiting LTx. Methods: Clinical data and CT scans from patients who underwent a first LTx from January 2014 to July 2018 in Bichat Hospital, Paris, were prospectively included in a database. CT TLC (ctTLC) was retrospectively calculated after semi-automatic contouring of the parenchyma and compared with measured TLC (mTLC) and predicted TLC (pTLC) values. Results: The study group included 89 patients (male:female =68:21; mean age, 59.5±10.0 years). The time between pulmonary function tests (PFTs) and CT scan was 162±270 days [median, 67 days; interquartile range (IQR), 0-233 days]. ctTLC was inferior to mTLC and pTLC (respectively 2,979±1,001 mL, 3,530±1,077 and 6,381±955 mL, P<0.001). The relative difference between CT lung volume (ctLV) and measured lung volume (mLV) was higher on the left than on the right side (25.4% vs. 16.3%, respectively, P=0.11). After exclusion of two outliers, we found a significant correlation between ctTLC and mTLC (r=0.762, P<0.001). Conclusions: CT volume is a feasible method to assess TLC in patients with end-stage interstitial disease awaiting LTx. This study highlights potential size-mismatch for graft selection before LTx and opens the perspective of a prospective trial evaluating impact of size-matching by donor-recipient (D-R) ctTLC ratio on postoperative outcomes.

8.
Diagnostics (Basel) ; 14(13)2024 Jun 24.
Article in English | MEDLINE | ID: mdl-39001230

ABSTRACT

Lung transplantation (LT) constitutes the last therapeutic option for selected patients with end-stage respiratory disease. Primary graft dysfunction (PGD) is a form of severe lung injury, occurring in the first 72 h following LT and constitutes the most common cause of early death after LT. The presence of pulmonary hypertension (PH) has been reported to favor PGD development, with a negative impact on patients' outcomes while complicating medical management. Although several studies have suggested a potential association between pre-LT left ventricular diastolic dysfunction (LVDD) and PGD occurrence, the underlying mechanisms of such an association remain elusive. Importantly, the heterogeneity of the study protocols and the various inclusion criteria used to define the diastolic dysfunction in those patients prevents solid conclusions from being drawn. In this review, we aim at summarizing PGD mechanisms, risk factors, and diagnostic criteria, with a further focus on the interplay between LVDD and PGD development. Finally, we explore the predictive value of several diastolic dysfunction diagnostic parameters to predict PGD occurrence and severity.

9.
Article in English | MEDLINE | ID: mdl-39004267

ABSTRACT

OBJECTIVES: Concomitant heart and lung recovery can result in increased operative complexity, ischemic time, and competition for resources and anatomic territory. Dual thoracic recovery from circulatory death donors (DCD) may have additional risks that are not fully understood. We investigated the effects of dual heart and lung recovery from DCD donors on thoracic transplant outcomes. METHODS: Using the United Network for Organ Sharing database, we categorized all adult thoracic DCD transplants 2019-2023 by whether the donor heart, lung, or both (dual donors) were recovered. Heart and lung transplant outcomes were compared between dual recovery donors and heart-only or lung-only donors, respectively, using multivariable analyses. RESULTS: Of the 2,513 donors included, 42.9% were heart-only,45.0% were lung-only, and 12.0% were dual donors. Recipients of dual versus heart-only donors had similar likelihood of post-transplant dialysis (18.9% vs. 18.3%, p=0.84), likelihood of stroke (2.9% vs. 4.7%, p=0.34), and 2-year risk of mortality (aHR 1.15 [95% CI: 0.90-1.47], p=0.26), but lower likelihood of acute rejection (10.2% vs. 16.1%, p=0.04). Recipients of dual and lung-only donors had similar likelihood of pre-discharge acute rejection (7.6% vs. 8.5%, p=0.70), intubation at 72 hours (38.9% vs. 45.1%, p=0.13), and ECMO at 72 hours (13.1% vs. 18.1%, p=0.11), as well as 2-year risk of mortality (aHR 1.16 [95% CI: 0.74-1.82], p=0.52). CONCLUSIONS: Recovering both the heart and lungs from a DCD donor does not negatively impact transplant outcomes. Outcomes in this population should continue to be investigated as more data and longer-term follow up become available.

10.
J Med Virol ; 96(7): e29770, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38949200

ABSTRACT

Donor and recipient human cytomegalovirus (HCMV) seropositive (D+R+) lung transplant recipients (LTRs) often harbor multiple strains of HCMV, likely due to transmitted donor (D) strains and reactivated recipient (R) strains. To date, the extent and timely occurrence of each likely source in shaping the post-transplantation (post-Tx) strain population is unknown. Here, we deciphered the D and R origin of the post-Tx HCMV strain composition in blood, bronchoalveolar lavage (BAL), and CD45+ BAL cell subsets. We investigated either D and/or R formalin-fixed paraffin-embedded blocks or fresh D lung tissue from four D+R+ LTRs obtained before transplantation. HCMV strains were characterized by short amplicon deep sequencing. In two LTRs, we show that the transplanted lung is reseeded by R strains within the first 6 months after transplantation, likely by infiltrating CD14+ CD163+/- alveolar macrophages. In three LTRs, we demonstrate both rapid D-strain dissemination and persistence in the transplanted lung for >1 year post-Tx. Broad inter-host diversity contrasts with intra-host genotype sequence stability upon transmission, during follow-up and across compartments. In D+R+ LTRs, HCMV strains of both, D and R origin can emerge first and dominate long-term in subsequent episodes of infection, indicating replication of both sources despite pre-existing immunity.


Subject(s)
Cytomegalovirus Infections , Cytomegalovirus , Lung Transplantation , Tissue Donors , Transplant Recipients , Humans , Lung Transplantation/adverse effects , Cytomegalovirus/genetics , Cytomegalovirus/classification , Cytomegalovirus Infections/virology , Male , Middle Aged , Female , Adult , Genotype , Lung/virology , Bronchoalveolar Lavage Fluid/virology
11.
Pediatr Pulmonol ; 2024 07 11.
Article in English | MEDLINE | ID: mdl-38990104

ABSTRACT

BACKGROUND: Racial and ethnic disparities in pediatric lung transplantation (LTx) related to the shifting cystic fibrosis (CF) population receiving highly effective modulator therapy (HEMT) has not been well investigated. METHODS: The UNOS Registry was queried for patients age 1-25 years undergoing bilateral LTx between 1 January 2012 and 31 December 2021. Race and ethnicity were classified as non-Hispanic White, non-Hispanic Black, Hispanic, or none of the above. The primary outcome was posttransplant mortality. Trends in the association between race/ethnicity and mortality were examined using transplant year as a continuous variable and stratifying year based on introduction of HEMT (triple combination therapy) in November 2019. RESULTS: In the study sample (N = 941), 7% of patients were non-Hispanic Black, 15% were Hispanic, and 2% were some other racial or ethnic group. One hundred (11%) received LTx after approval of triple combination therapy, and 407 (43%) died during follow-up. We identified a statistically significant disparity in mortality hazard (hazard ratio: 1.91; 95% confidence interval: 1.31, 2.80) in non-Hispanic Black compared to non-Hispanic White patients in the pre-triple combination therapy era. CONCLUSIONS: We found higher mortality hazard among non-Hispanic Black compared to non-Hispanic White children undergoing LTx in the United States. Further monitoring of LTx outcomes to identify and address disparities is needed in the current era of triple combination therapy for CF.

12.
Surg Case Rep ; 10(1): 169, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38987504

ABSTRACT

BACKGROUND: Pulmonary Langerhans cell histiocytosis (PLCH) is a rare disorder characterized by the proliferation of Langerhans cells along the small airways, which causes nodular and cystic changes in the lung parenchyma. Lung transplantation can be a life-saving option for patients with severe respiratory failure or pulmonary hypertension. Herein, we present a case of successful lung transplantation in a patient with PLCH who developed unusually large thrombi in the central pulmonary artery. CASE PRESENTATION: A 47-year-old woman with 16-year history of PLCH with rapidly developing respiratory failure was admitted to our hospital for the evaluation of a lung transplant. Enhanced computed tomography revealed large thrombi in dilated central pulmonary arteries. Right heart catheterization revealed severe pulmonary hypertension, with a mean pulmonary artery pressure of 48 mmHg. The thrombi shrank markedly after 3 months of anticoagulation therapy. However, the respiratory status of the patient did not improve. We performed bilateral living-donor lobar lung transplantation with thrombectomy under extracorporeal membrane oxygenation for the remaining thrombi in the main pulmonary arteries. The dilated main pulmonary arteries of the recipient required direct plication for size mismatch. The patient survived in good condition for more than 2 years with no recurrence of thrombosis. CONCLUSION: Preoperative anticoagulation therapy for massive thrombi in the pulmonary arteries was effective and led to safe lung transplantation.

13.
Respir Investig ; 62(5): 804-810, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-39002293

ABSTRACT

BACKGROUND: Since lung transplant recipients (LTRs) exhibit low immunogenicity after two doses of SARS-CoV-2 mRNA vaccines, optimal vaccine strategies for SARS-CoV-2 are required in LTRs. This study aimed to investigate the efficacy and safety of the third and fourth doses of the SARS-CoV-2 mRNA vaccines in LTRs. METHODS: We conducted a single-center study of 73 LTRs and 23 healthy controls (HCs). Participants received two-to-four doses of SARS-CoV-2 mRNA vaccines. The LTRs were divided into three groups based on the number of vaccine dose. IgG titers against SARS-CoV-2 spike protein were measured, and adverse events were assessed. Factors associated with humoral response were analyzed using univariate and multivariate analyses. RESULTS: The Dose 4 group (n = 27) had a higher humoral response rate (P = 0.018) and higher levels of anti-SARS-CoV-2 IgG antibody (P = 0.04) than the Dose 2 group (n = 14). The Dose 3 group (n = 32) had lower humoral response rates (P = 0.005) and levels of anti-SARS-CoV-2 IgG antibody (P = 0.0005) than the HCs (n = 23) even after the same dose. Systemic adverse events were milder in the LTRs than in the HCs (P < 0.05). Increased number of vaccine dose was identified as a predictor of positive humoral response (P = 0.021). CONCLUSION: Booster doses of SARS-CoV-2 mRNA vaccines may enhance humoral response with mild adverse events in LTRs. Repeated vaccination might be warranted for LTRs to prevent SARS-CoV-2 infection.

14.
Article in English | MEDLINE | ID: mdl-38972753

ABSTRACT

PURPOSE: This meta-analysis aimed to examine the prognosis of patients with acute exacerbation of interstitial lung disease (AE-ILD) treated with lung transplantation compared to those with stable interstitial lung disease (ILD). METHODS: We conducted a detailed search in PubMed, Embase, Web of Science, and the Cochrane Library, with the primary outcomes being overall survival (OS), acute cellular rejection (ACR), primary graft dysfunction (PGD), and length of stay (LOS). RESULTS: Five cohort studies were included in this meta-analysis, with 183 patients enrolled in the AE-ILD group and 337 patients in the stable-ILD group. The results showed that in regard to perioperative outcomes, the AE-ILD group did not differ from the stable-ILD group in the incidence of ACR (relative risks [RR] = 0.34, p = 0.44) and the incidence of PGD Ⅲ (RR = 0.53, p = 0.43), but had a longer LOS (mean difference = 9.15, p = 0.02). Regarding prognosis, the two also did not differ in 90-day OS (RR = 0.97, p = 0.59), 1-year OS (RR = 1.05, p = 0.66), and 3-year OS (RR = 0.91, p = 0.76). CONCLUSION: Our study concluded that the efficacy of lung transplantation in patients with AE-ILD is not inferior to that of patients with stable ILD. Lung transplantation is one of the potential treatments for patients with AE-ILD.


Subject(s)
Disease Progression , Graft Rejection , Length of Stay , Lung Diseases, Interstitial , Lung Transplantation , Adult , Aged , Female , Humans , Male , Middle Aged , Graft Rejection/mortality , Graft Rejection/diagnosis , Lung Diseases, Interstitial/mortality , Lung Diseases, Interstitial/surgery , Lung Diseases, Interstitial/diagnosis , Lung Diseases, Interstitial/physiopathology , Lung Transplantation/mortality , Lung Transplantation/adverse effects , Primary Graft Dysfunction/mortality , Primary Graft Dysfunction/diagnosis , Primary Graft Dysfunction/etiology , Primary Graft Dysfunction/physiopathology , Risk Factors , Time Factors , Treatment Outcome
15.
Article in English | MEDLINE | ID: mdl-39038563

ABSTRACT

BACKGROUND: By causing inflammation and tissue damage, neutrophil extracellular traps (NETs) constitute an underlying mechanism of aspiration-induced lung injury, a major factor of the low utilization of donor lungs in lung transplantation (LTx). METHOD: To determine whether NET removal during ex vivo lung perfusion (EVLP) can restore lung function and morphology in aspiration-damaged lungs, gastric aspiration lung injury was induced in 12 pigs. After confirmation of acute respiratory distress syndrome, the lungs were explanted and assigned to NET removal connected to EVLP (treated) (n=6) or EVLP only (non-treated) (n=6). Hemodynamic measurements were taken, and blood and tissue samples were collected to assess lung function, morphology, levels of cell-free DNA, extracellular histones, and nucleosomes as markers of NETs as well as cytokine levels. RESULTS: After EVLP and NET removal in porcine lungs, PaO2/FiO2 ratios increased significantly compared to those undergoing EVLP alone (p=0.0411). Treated lungs had lower cell-free DNA (p=0.0260) and lower levels of extracellular histones in EVLP perfusate than non-treated lungs (p=0.0260). According to histopathology, treated lungs showed less immune cell infiltration and less oedema compared with non-treated lungs which was reflected in decreased levels of pro-inflammatory cytokines in EVLP perfusate and BALF. CONCLUSION: To conclude, removing NETs during EVLP improved lung function and morphology in aspiration-damaged donor lungs. The ability to remove NETs during EVLP could represent a new therapeutic approach for LTx and potentially expand the donor pool for transplantation.

17.
Transpl Int ; 37: 12897, 2024.
Article in English | MEDLINE | ID: mdl-38979122

ABSTRACT

Mutual interactions between the diaphragm and lung transplantation (LTx) are known to exist. Before LTx, many factors can exert notable impact on the diaphragmatic function, such as the underlying respiratory disease, the comorbidities, and the chronic treatments of the patient. In the post-LTx setting, even the surgical procedure itself can cause a stressful trauma to the diaphragm, potentially leading to morphological and functional alterations. Conversely, the diaphragm can significantly influence various aspects of the LTx process, ranging from graft-to-chest cavity size matching to the long-term postoperative respiratory performance of the recipient. Despite this, there are still no standard criteria for evaluating, defining, and managing diaphragmatic dysfunction in the context of LTx to date. This deficiency hampers the accurate assessment of those factors which affect the diaphragm and its reciprocal influence on LTx outcomes. The objective of this narrative review is to delve into the complex role the diaphragm plays in the different stages of LTx and into the modifications of this muscle following surgery.


Subject(s)
Diaphragm , Lung Transplantation , Humans , Postoperative Complications/etiology
18.
Iran J Med Sci ; 49(6): 394-398, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38952636

ABSTRACT

Despite its rarity, pulmonary capillary hemangiomatosis (PCH) presents a significant diagnostic challenge. Due to its similarity to other pulmonary vascular diseases, such as pulmonary veno-occlusive disease, it is characterized by abnormal pulmonary capillary proliferation, which is a rare cause of primary pulmonary hypertension. This case was the first reported instance of PCH in Shahid Rajaee Heart Hospital in Tehran, Iran, in 2023, which was confirmed by genetic testing. It highlighted the importance of considering PCH among the differential diagnoses for pulmonary hypertension, even in adolescent patients. The 13-year-old patient's main complaints were progressive exertional dyspnea and chest pain. He had no previous medical history and had not taken any pharmaceutical or herbal medications. Critical clinical findings included a heart murmur, an electrocardiogram revealing right ventricular hypertrophy, and echocardiogram evidence of pulmonary hypertension. The main diagnosis was PCH, as shown by CT findings of pulmonary artery dilatation and diffuse nodular ground glass opacities. Genetic tests indicated pathogenic EIF2AK4 mutations and suspicion of PCH. Therapeutic intervention included vasodilator therapy, which exacerbated the patient's condition. This case emphasized the importance of maintaining a high index of suspicion for rare causes of pulmonary hypertension, such as PCH. The outcome was to prepare the patient for lung transplantation. To differentiate PCH from other pulmonary vascular diseases, a combination of clinical presentation, radiologic studies, genetic analysis, and response to treatment is required to determine appropriate management, particularly lung transplantation.


Subject(s)
Hemangioma, Capillary , Humans , Adolescent , Male , Hemangioma, Capillary/complications , Hemangioma, Capillary/physiopathology , Hemangioma, Capillary/diagnosis , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/physiopathology , Hypertension, Pulmonary/complications , Lung Neoplasms/complications , Lung Neoplasms/diagnosis , Protein Serine-Threonine Kinases
19.
Clin Transplant ; 38(7): e15374, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38979724

ABSTRACT

BACKGROUND: The lack of evidence regarding optimal desensitization strategies for lung transplant candidates with preformed donor specific anti-human leukocyte antigen antibodies (DSAs) has led to varying approaches among centers towards this patient group. Our institution's desensitization protocol for recipients with preformed DSAs and negative flow cytometry crossmatch (FCXM) consists of intravenous immunoglobulin (IVIG) as the sole therapy. The study aimed to determine outcomes using this approach. METHODS: This retrospective study included adults who underwent lung-only transplantation for the first time between January 2015 and March 2022 at a single center. We excluded patients with positive or missing FCXM results. Transplant recipients with any DSA ≥ 1000 MFI on latest testing within three months of transplant were considered DSA-positive, while recipients with DSAs <1000 MFI and those without DSAs were assigned to the low-level/negative group. Graft survival (time to death/retransplantation) and chronic lung allograft dysfunction (CLAD)-free times were compared between groups using Cox proportional hazards models. RESULTS: Thirty-six out of 167 eligible patients (22%) were DSA-positive. At least 50% of preformed DSAs had documented clearance (decrease to <1000 MFI) within the first 6 months of transplant. Multivariable Cox regression analyses did not detect a significantly increased risk of graft failure (aHR 1.04 95%CI 0.55-1.97) or chronic lung allograft dysfunction (aHR 0.71 95%CI 0.34-1.52) in DSA-positive patients compared to patients with low-level/negative DSAs. Incidences of antibody-mediated rejection (p = 1.00) and serious thromboembolic events (p = 0.63) did not differ between study groups. CONCLUSION: We describe a single-center experience of administering IVIG alone to lung transplant recipients with preformed DSAs and negative FCXM. Further studies are required to confirm the efficacy of this strategy against other protocols.


Subject(s)
Desensitization, Immunologic , Flow Cytometry , Graft Rejection , Graft Survival , HLA Antigens , Immunoglobulins, Intravenous , Isoantibodies , Lung Transplantation , Tissue Donors , Humans , Female , Male , Retrospective Studies , Middle Aged , Immunoglobulins, Intravenous/therapeutic use , Immunoglobulins, Intravenous/administration & dosage , Graft Rejection/immunology , Graft Rejection/etiology , Isoantibodies/immunology , Isoantibodies/blood , Graft Survival/immunology , HLA Antigens/immunology , Follow-Up Studies , Prognosis , Desensitization, Immunologic/methods , Histocompatibility Testing , Adult , Transplant Recipients , Risk Factors , Immunologic Factors/therapeutic use
20.
Rehabilitacion (Madr) ; 58(4): 100862, 2024 Jul 09.
Article in Spanish | MEDLINE | ID: mdl-38986344

ABSTRACT

INTRODUCTION: Lung transplant (LT) is the ultimate option for end-stage lung diseases. Malnutrition and sarcopenia, common in LT recipients, can be reversible with adequate exercise and nutrition. This study aims to assess changes in physical performance and aerobic capacity after a 10-week rehabilitation program (RP) in LT recipients, as well as to describe the prevalence of sarcopenia and malnutrition before and after RP and their influence on clinically relevant outcomes. MATERIALS AND METHODS: Quasi-experimental study, before and after a 10-week PR in first-time TP recipients, aged over 18 years, from January 2022 to September 2023. Aerobic exercise capacity was assessed through the 6-minute walking test (6MWT) and peak oxygen consumption (VO2peak); and physical performance was measured using the Short Physical Performance Battery (SPPB). Additionally, the prevalence of sarcopenia was described according to the criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2) and malnutrition according to the criteria of the Global Leadership Initiative on Malnutrition (GLIM). RESULTS: Of the 41 patients, 56% had sarcopenia and 80% had malnutrition. After RP, the distance walked in the 6MWT increased by 66.3m (p=0.004) in men and 61m (p=0.001) in women. VO2peak increased in men by a mean of 3.1ml/min/kg (p=0.024). Physical performance improved significantly in both men and women according to the Short Physical Performance Battery (SPPB), with clinically relevant differences of 1.6 pts (p<0.001) and 1.2 pts (p=0.012), respectively. The prevalence of sarcopenia decreased to 24% and malnutrition to 61%. CONCLUSIONS: RP proved to be an effective and safe intervention for LT recipients. In addition to improvements in skeletal muscle strength and exercise capacity, a reduction in the prevalence of sarcopenia and malnutrition was also observed.

SELECTION OF CITATIONS
SEARCH DETAIL
...