Optical Fiber Probe with Integrated Micro-Optical Filter for Raman and Surface-Enhanced Raman Scattering Sensing.

Optical fiber Raman and surface-enhanced Raman scattering (SERS) probes hold great promise for in vivo biosensing and in situ monitoring of hostile environments. However, the silica Raman scattering background generated within the optical fiber increases in proportion to the length of the fiber, and it can swamp the signal from the target analyte. While filtering can be applied at the distal end of the fiber, the use of bulk optical elements has limited probe miniaturization to a diameter of 600 µm, which in turn limits the potential applications. To overcome this limitation, femtosecond laser micromachining was used to fabricate a prototype micro-optical filter, which was directly integrated on the tip of a 125 µm diameter double-clad fiber (DCF) probe. The outer surface of the microfilter was further modified with a nanostructured, SERS-active, plasmonic film that was used to demonstrate proof-of-concept performance with thiophenol as a test analyte. With further optimization of the associated spectroscopic system, this ultra-compact microprobe shows great promise for Raman and SERS optical fiber sensing.

Low-Cycle Fatigue Properties of Bimetallic Steel Bar with Buckling: Energy-Based Numerical and Experimental Investigations.

A bimetallic steel bar (BSB) consisting of stainless-steel cladding and carbon steel substrate exhibits excellent corrosion resistance and good mechanical properties. The bimetallic structure of BSBs may affect their low-cycle fatigue performance, and current investigations on the above issue are limited. In this study, the low-cycle fatigue properties of bimetallic steel bars (BSBs) with inelastic buckling were investigated. Experiments and numerical studies were conducted to investigate the low-cycle fatigue capacity for BSBs, considering buckling. The buckling mode of BSBs is discussed. The hysteretic loops and energy properties of BSBs with various slenderness ratios (L/D) and fatigue strain amplitudes (εa) are investigated. With increases in the L/D and εa, the original symmetry for hysteresis loops disappears gradually, which is caused by the buckling. A predictive equation revealing the relation between the εa and fatigue life is suggested, which considers the effects of the L/D. A numerical modelling method is suggested to predict the hysteretic curves of BSBs. The effect of buckling on the stress and energy properties of BSBs is discussed through the numerical analysis of 44 models including the effects of the L/D, εa, and cladding ratios. The numerical analysis results illustrate that the hysteresis loops of BSBs with various εa values exhibit similar shapes. The increase in the cladding ratio reduces the peak stress and the dissipated energy properties of BSBs. The hysteresis loop energy density decreases by about 3% with an increase of 0.1 in the cladding ratio. It is recommended that the proportion of stainless steel inBSBs should be minimized once the corrosion resistance requirements are met.

Tensile Properties of Cryorolled Cu/Al Clad Sheet with an SUS304 Interlayer after Annealing at Various Temperatures.

This paper investigates the tensile properties and microstructures of Cu/Al clad sheets with an SUS304 interlayer after cryorolling and subsequent annealing and compares them with hot-rolled samples. The experimental results show that the inhibition of dynamic recovery by cryorolling enables the Cu/Al clad sheets to achieve a tensile strength of 302 MPa. After annealing, the tensile strength sharply drops to 159 MPa, while the elongation recovers to 29.0%. Compared with hot-rolled samples, the tensile strength of cryorolled samples is increased by 13.1% due to the effect of fine-grain strengthening. During the annealing process, the cryorolled samples exhibit improved elongation under a comparable strength with the hot-rolled samples, profiting from the higher degree of recrystallization and a higher proportion of annealing twins. The tensile properties of Cu/Al clad sheet with an SUS304 interlayer are strengthened by cryorolling and subsequent annealing, providing a new method for the fabrication of high-performance Cu/Al clad sheets.

Scalable Fabrication of Large-Scale, 3D, and Stretchable Circuits.

Stretchable electronics have demonstrated excellent potential in wearable healthcare and conformal integration. Achieving the scalable fabrication of stretchable devices with high functional density is the cornerstone to enable the practical applications of stretchable electronics. Here, a comprehensive methodology for realizing large-scale, 3D, and stretchable circuits (3D-LSC) is reported. The soft copper-clad laminate (S-CCL) based on the "cast and cure" process facilitates patterning the planar interconnects with the scale beyond 1 m. With the ability to form through, buried and blind VIAs in the multilayer stack of S-CCLs, high functional density can be achieved by further creating vertical interconnects in stacked S-CCLs. The application of temporary bonding substrate effectively minimizes the misalignments caused by residual strain and thermal strain. 3D-LSC enables the batch production of stretchable skin patches based on five-layer stretchable circuits, which can serve as a miniaturized system for physiological signals monitoring with wireless power delivery. The fabrications of conformal antenna and stretchable light-emitting diode display further illustrate the potential of 3D-LSC in realizing large-scale stretchable devices.

Pseudomonas aeruginosa infection correlates with high MFI donor-specific antibody development following lung transplantation with consequential graft loss and shortened CLAD-free survival.

BACKGROUND: Donor-specific antibodies (DSAs) are common following lung transplantation (LuTx), yet their role in graft damage is inconclusive. Mean fluorescent intensity (MFI) is the main read-out of DSA diagnostics; however its value is often disregarded when analyzing unwanted post-transplant outcomes such as graft loss or chronic lung allograft dysfunction (CLAD). Here we aim to evaluate an MFI stratification method in these outcomes. METHODS: A cohort of 87 LuTx recipients has been analyzed, in which a cutoff of 8000 MFI has been determined for high MFI based on clinically relevant data. Accordingly, recipients were divided into DSA-negative, DSA-low and DSA-high subgroups. Both graft survival and CLAD-free survival were evaluated. Among factors that may contribute to DSA development we analyzed Pseudomonas aeruginosa (P. aeruginosa) infection in bronchoalveolar lavage (BAL) specimens. RESULTS: High MFI DSAs contributed to clinical antibody-mediated rejection (AMR) and were associated with significantly worse graft (HR: 5.77, p < 0.0001) and CLAD-free survival (HR: 6.47, p = 0.019) compared to low or negative MFI DSA levels. Analysis of BAL specimens revealed a strong correlation between DSA status, P. aeruginosa infection and BAL neutrophilia. DSA-high status and clinical AMR were both independent prognosticators for decreased graft and CLAD-free survival in our multivariate Cox-regression models, whereas BAL neutrophilia was associated with worse graft survival. CONCLUSIONS: P. aeruginosa infection rates are elevated in recipients with a strong DSA response. Our results indicate that the simultaneous interpretation of MFI values and BAL neutrophilia is a feasible approach for risk evaluation and may help clinicians when to initiate DSA desensitization therapy, as early intervention could improve prognosis.

Investigation of the Properties of Anti-Friction Coatings Deposited with Different Casting Methods.

This article presents the research results of depositing anti-friction coatings (Babbitt) using three different casting methods: static casting, flame soldering, and clad welding. Babbitt alloy coatings deposited with different casting methods are discussed and explained in terms of changes in the coating properties, such as the microstructure, hardness, strength, and chemical composition. The results showed significant differences in the aforementioned properties, depending on the chosen coating deposition method. The results of the tests confirmed the importance of using shielding gas during deposition to ensure the chemical composition of the coating. The analysis revealed that decreases in the amounts of antimony and copper in the Babbitt coating compared with the initial concentrations were influenced by selective evaporation, oxidation, and the coating process parameters associated with different coating methods. To maintain the desired balance of mechanical properties in Babbitt coatings, it is important to control the antimony and copper contents. Clad welding deposition using a non-consumable tungsten electrode and argon shielding gas achieved a chemically stable coating quite close to the initial chemical composition of the Babbitt alloy.

Results from randomized trial of pirfenidone in patients with chronic rejection (STOP-CLAD study).

BACKGROUND: Chronic lung allograft dysfunction (CLAD) is the leading long-term cause of poor outcomes after transplant and manifests by fibrotic remodeling of small airways and/or pleuroparenchymal fibroelastosis. This study evaluated the effect of pirfenidone on quantitative radiographic and pulmonary function assessment in patients with CLAD. METHODS: We performed a single-center, 6-month, randomized, placebo-controlled trial of pirfenidone in patients with CLAD. Randomization was stratified by CLAD phenotype. The primary outcome for this study was change in radiographic assessment of small airways disease, quantified as percentage of lung volume using parametric response mapping analysis of computed tomography scans (PRMfSAD); secondary outcomes included change in forced expiratory volume in 1 second (FEV1), change in forced vital capacity (FVC), and change in radiographic quantification of parenchymal disease (PRMPD). Linear mixed models were used to evaluate the treatment effect on outcome measures. RESULTS: The goal enrollment of 60 patients was not met due to the coronavirus disease of 2019 pandemic, with 23 patients included in the analysis. There was no significant difference over the study period between the pirfenidone vs placebo groups with regards to the observed change in PRMfSAD (+4.2% vs -0.4%; p = 0.22), FEV1 (-3.5% vs -3.6%; p = 0.97), FVC (-1.9% vs -4.6%; p = 0.41), or PRMPD (-0.6% vs -2.5%; p = 0.30). The study treatment tolerance and adverse events were generally similar between the pirfenidone and placebo groups. CONCLUSIONS: Pirfenidone had no apparent impact on radiographic evidence of allograft dysfunction or pulmonary function decline in a single-center randomized trial of CLAD patients that did not meet enrollment goals but had an acceptable tolerance and side-effect profile.

Welding-induced corrosion and protective measures for clad rebars in neutral chloride environments.

Corrosion-resistant steel plays a vital role in marine steel structures. This study developed an SS304/HRB400 stainless-steel-clad rebar for application in a cross-sea bridge in Zhejiang Province. CO2 gas shielded welding was employed in the prefabricated steel structure, with SS304 steel as the welding wire. This study investigated the welding on the corrosion resistance of clad rebars and explored corrosion protection measures for welded joints.The results indicated that refined grains appeared in both stainless steel and carbon steel due to distinct dynamic recrystallization (DRX) during welding. The corrosion resistance, as determined by potentiodynamic polarization curve analysis of the material's interaction with the solution ranked as follows: clad rebar (polished) > clad rebar welding (CRW) > painting the clad rebar after welding (PCRW) > clad rebar (unpolished) > carbon-steel welding (CSW) > carbon-steel bar > cold spraying zinc after clad rebar welding (ZCRW). However, an accelerated corrosion test with four samples for 600 s with a corrosion current of 0.8 A revealed minimal corrosion damage on zinc-coated surfaces. Hence, welding joints for clad steel structures are considered feasible and must be subject to cold zinc spraying after polishing to enhance their corrosion resistance.

Statistical Analysis of Morphological Characteristics of Inconel 718 Formed by High Deposition Rate and High Laser Power Laser Cladding.

Laser cladding is one of the emerging additive manufacturing technologies and has been adopted in various industrial fields. In this study, the morphological characteristics of a single clad of Inconel 718 manufactured by coaxial laser cladding with high laser power from 4200 W to 5400 W, powder feeding rate from 25 g/min to 50 g/min, and cladding speed from 20 mm/s to 50 mm/s are studied. The cross-section of the melt pool is analyzed and classified by type into three types: shallow dilution, flat dilution, and fluctuating dilution. Nine parameters are designed to describe the morphological characteristics of the clad, and the corresponding linear regression models are developed to establish a quantitative relationship between the combined process parameters and morphological characteristics. The results indicate that the total area of the cross-section A, the clad area above the substrate Ac, the area of the molten substrate Am, the total height of the cross-section H, the height of the clad above the substrate hc, the penetration depth hm, the clad width W, the dilution ratio D, and the wetting angle θ are determined by complex coupling of energy input and mass accumulation, and they are proportional to PF0.4/V, P0.5F/V, P/F0.2/V0.4, P2F0.6/V, PF0.7/V, P2/F/V0.3, P/V0.8, P/FV0.2, and PF7/V0.8, respectively. The large linear regression coefficients and the analysis residuals indicate the high reliability of the statistical linear regression models. This work aims to provide a comprehensive understanding of the influence of the main processing parameters on the morphological characteristics of the clad, which is of great value in providing a reference and laying a basis for the practical application of laser cladding technology at a high deposition rate.

Exosomal-miRNas expression and growth factors released by mononuclear cells of CLAD patients in response to extracorporeal photopheresis.

BACKGROUND: CLAD (Chronic Lung Allograft Dysfunction) remains a serious complication following lung transplantation. Some evidence shows that portions of Extracorporeal Photopheresis (ECP)-treated patients improve/stabilize their graft function. In spite of that, data concerning molecular mechanisms are still lacking. Aims of our study were to assess whether ECP effects are mediated by Mononuclear Cells (MNCs) modulation in term of microRNAs (miRNAs) expression and growth factors release. METHODS: Cells from leukapheresis of 16 CLAD patients, at time 0 and 6-months (10 cycles), were cultured for 48h ± PHA (10 ug/ml) or LPS (2 ug/ml). Expression levels of miR-146a-5p, miR-155-5p, miR-31-5p, miR181a-5p, miR-142-3p, miR-16-5p and miR-23b-5p in MNCs-exosomes were evaluated by qRT-PCR, while ELISA assessed different growth factors levels on culture supernatants. RESULTS: Our result showed miR-142-3p down-regulation (p = 0.02) in MNCs of ECP-patients after the 10 cycles and after LPS stimulation (p = 0.005). We also find miR-146a-5p up-regulation in cells after the 10 cycles stimulated with LPS (p = 0.03). Connective tissue growth factor (CTGF) levels significantly decreased in MNCs supernatant (p = 0.04). The effect of ECP is translated into frequency changes of Dendritic Cell (DC) subpopulations and a slight increase in T regulatory cells (Treg) number and a significant decrease in CTGF release. CONCLUSIONS: ECP might affect regulatory T cell functions, since both miR-142 and miR-146a have been shown to be involved in the regulation of suppressor regulatory T cell functions and DCs. On the other side ECP, possibly by regulating macrophage activation, is able to significantly down modulate CTGF release.

Immunological Landscapes in Lung Transplantation: Insights from T Cell Profiling in BAL and PBMC.

Lung transplant recipients frequently encounter immune-related complications, including chronic lung allograft dysfunction (CLAD). Monitoring immune cells within the lung microenvironment is pivotal for optimizing post-transplant outcomes. This study examined the proportion of T cell subsets in paired bronchoalveolar lavage (BAL) and peripheral PBMC comparing healthy (n = 4) and lung transplantation patients (n = 6, no CLAD and n = 14 CLAD) using 14-color flow cytometry. CD4+ T cell proportions were reduced in CD3 cells in both PBMC and BAL, and positive correlations were discerned between T cell populations in peripheral PBMC and BAL, suggesting the prospect of employing less invasive PBMC sampling as a means of monitoring lung T cells. Furthermore, regulatory T cells (Tregs) were enriched in BAL when compared to peripheral PBMC for transplant recipients. A parallel positive correlation emerged between Treg proportions in BAL and peripheral PBMC, underscoring potential avenues for monitoring lung Tregs. Finally, the most promising biomarker was the Teff (CD8+Granzyme B+)-Treg ratio, which was higher in both the PBMC and BAL of transplant recipients compared to healthy individuals, and increased in the patients with CLAD compared to no CLAD and healthy patients. Conclusions: Distinct T cell profiles in BAL and peripheral PBMC underscore the significance of localized immune monitoring in lung transplantation. The Teff (CD8+granzyme B+)-Treg ratio, particularly within the context of CLAD, emerges as a promising blood and BAL biomarker reflective of inflammation and transplant-related complications. These findings emphasize the imperative need for personalized immune monitoring strategies that tailored to address the unique immunological milieu in post-transplant lungs.

Unique Changes in the Lung Microbiome following the Development of Chronic Lung Allograft Dysfunction.

The importance of lung microbiome changes in developing chronic lung allograft dysfunction (CLAD) after lung transplantation is poorly understood. The lung microbiome-immune interaction may be critical in developing CLAD. In this context, examining alterations in the microbiome and immune cells of the lungs following CLAD, in comparison to the lung condition immediately after transplantation, can offer valuable insights. Four adult patients who underwent lung retransplantation between January 2019 and June 2020 were included in this study. Lung tissues were collected from the same four individuals at two different time points: at the time of the first transplant and at the time of the explantation of CLAD lungs at retransplantation due to CLAD. We analyzed whole-genome sequencing using the Kraken2 algorithm and quantified the cell fractionation from the bulk tissue gene expression profile for each lung tissue. Finally, we compared the differences in lung microbiome and immune cells between the lung tissues of these two time points. The median age of the recipients was 57 years, and most (75%) had undergone lung transplants for idiopathic pulmonary fibrosis. All patients were administered basiliximab for induction therapy and were maintained on three immunosuppressants. The median CLAD-free survival term was 693.5 days, and the median time to redo the lung transplant was 843.5 days. Bacterial diversity was significantly lower in the CLAD lungs than at transplantation. Bacterial diversity tended to decrease according to the severity of the CLAD. Aerococcus, Caldiericum, Croceibacter, Leptolyngbya, and Pulveribacter genera were uniquely identified in CLAD, whereas no taxa were identified in lungs at transplantation. In particular, six taxa, including Croceibacter atlanticus, Caldiserium exile, Dolichospermum compactum, Stappia sp. ES.058, Kinetoplastibacterium sorsogonicusi, and Pulveribacter suum were uniquely detected in CLAD. Among immune cells, CD8+ T cells were significantly increased, while neutrophils were decreased in the CLAD lung. In conclusion, unique changes in lung microbiome and immune cell composition were confirmed in lung tissue after CLAD compared to at transplantation.

Flame-Retardant GF-PSB/DOPO-POSS Composite with Low Dk/Df and High Thermal Stability for High-Frequency Copper Clad Applications.

In the field of high-frequency communications devices, there is an urgent need to develop high-performance copper clad laminates (CCLs) with low dielectric loss (Df) plus good flame retardancy and thermal stability. The hydrocarbon resin styrene-butadiene block copolymer (PSB) was modified with the flame-retardant 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide/polyhedral oligomeric silsesquioxanes (DOPO-POSS) to meet the demands of high-frequency and high-speed applications. The resulting DOPO-POSS-modified PSB was used as the resin matrix along with other additives to fabricate PSB/DOPO-POSS laminates. At a high-frequency of 10 GHz, the laminates containing 20 wt.% of DOPO-POSS and with a thickness of 0.09 mm exhibited a Df of 0.00328, which is much lower compared with the commercial PSB/PX-200 composite (Df: 0.00498) and the PSB without flame retardancy (Df: 0.00453). Afterwards, glass fiber cloth (GF) was used as a reinforcing material to manufacture GF-PSB/DOPO-POSS composite laminates with a thickness of 0.25 mm. The flame retardancy of GF-PSB/DOPO-POSS composite laminate reached vertical burning (UL-94) V-1 grade, and GF-PSB/DOPO-POSS exhibited higher thermal and dynamic mechanical properties than GF-PSB/PX-200. The results of a limited oxygen index (LOI) and self-extinguishing time tests also demonstrated the superior flame-retardant performance of DOPO-POSS compared with PX-200. The investigation indicates that GF-PSB/DOPO-POSS composite laminates have significant potential for use in fabricating a printed circuit board (PCB) for high-frequency and high-speed applications.

Ventilatory capacity in CLAD is driven by dysfunctional airway structure.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) encompasses three main phenotypes: bronchiolitis obliterans syndrome (BOS), restrictive allograft syndrome (RAS) and a Mixed phenotype combining both pathologies. How the airway structure in its entirety is affected in these phenotypes is still poorly understood. METHODS: A detailed analysis of airway morphometry was applied to gain insights on the effects of airway remodelling on the distribution of alveolar ventilation in end-stage CLAD. Ex vivo whole lung µCT and tissue-core µCT scanning of six control, six BOS, three RAS and three Mixed explant lung grafts (9 male, 9 female, 2014-2021, Leuven, Belgium) were used for digital airway reconstruction and calculation of airway dimensions in relation to luminal obstructions. FINDINGS: BOS and Mixed explants demonstrated airway obstructions of proximal bronchioles (starting at generation five), while RAS explants particularly had airway obstructions in the most distal bronchioles (generation >12). In BOS and Mixed explants 76% and 84% of bronchioles were obstructed, respectively, while this was 22% in RAS. Bronchiolar obstructions were mainly caused by lymphocytic inflammation of the airway wall or fibrotic remodelling, i.e. constrictive bronchiolitis. Proximal bronchiolectasis and imbalance in distal lung ventilation were present in all CLAD phenotypes and explain poor lung function and deterioration of specific lung function parameters. INTERPRETATION: Alterations in the structure of conducting bronchioles revealed CLAD to affect alveolar ventilatory distribution in a regional fashion. The significance of various obstructions, particularly those associated with mucus, is highlighted. FUNDING: This research was funded with the National research fund Flanders (G060322N), received by R.V.

The Immunopathology of Pulmonary Rejection after Murine Lung Transplantation.

To improve outcomes following lung transplantation, it is essential to understand the immunological mechanisms that result in chronic graft failure. The associated clinical syndrome is termed chronic lung allograft dysfunction (CLAD), which is known to be induced by alloimmune-dependent (i.e., rejection) and alloimmune-independent factors (e.g., infections, reflux and environmental factors). We aimed to explore the alloimmune-related mechanism, i.e., pulmonary rejection. In this study, we use a murine orthotopic left lung transplant model using isografts and allografts (C57BL/6 or BALB/c as donors to C57BL/6 recipients), with daily immunosuppression (10 mg/kg cyclosporin A and 1.6 mg/kg methylprednisolone). Serial sacrifice was performed at days 1, 7 and 35 post-transplantation (n = 6 at each time point for each group). Left transplanted lungs were harvested, a single-cell suspension was made and absolute numbers of immune cells were quantified using multicolor flow cytometry. The rejection process followed the principles of a classic immune response, including innate but mainly adaptive immune cells. At day 7 following transplantation, the numbers of interstitial macrophages, monocytes, dendritic cells, NK cells, NKT cells, CD4+ T cells and CD8+ T and B cells were increased in allografts compared with isografts. Only dendritic cells and CD4+ T cells remained elevated at day 35 in allografts. Our study provides insights into the immunological mechanisms of true pulmonary rejection after murine lung transplantation. These results might be important in further research on diagnostic evaluation and treatment for CLAD.

Late-Onset Exudative Pleural Effusions Without Concomitant Airway Obstruction or Lung Parenchymal Abnormalities: A Novel Presentation of Chronic Lung Allograft Dysfunction.

Restrictive allograft syndrome (RAS) is an aggressive variant of CLAD characterized by progressive restrictive ventilatory decline and persistent pleuro-parenchymal changes that can be seen on chest CT. We identified four lung transplant recipients with a progressive restrictive ventilatory defect due to lymphocyte-predominant exudative pleural effusions, but no pleuro-parenchymal abnormalities typical of RAS. Using molecular analysis, we also found increased levels of previously described immune markers of RAS, including NFkB, 20S proteasome, lipocalin, TNFα, and TGFß, within the circulating small extracellular vesicles of the remaining living lung transplant recipient. Despite the absence of lung parenchymal changes, these patients had a poor prognosis with rapid deterioration in allograft function and no response to pleural-based interventions such as thoracentesis, decortication, and pleurodesis. We hypothesize that these cases represent a distinct CLAD phenotype characterized by progressive restriction due to pleural inflammation, lymphocyte-predominant pleural effusion, resultant compressive atelectasis, and eventual respiratory failure in the absence of lung parenchymal involvement.

The Lung Microbiome Predicts Mortality and Response to Azithromycin in Lung Transplant Recipients with Chronic Rejection.

Rationale: Chronic lung allograft dysfunction (CLAD) is the leading cause of death after lung transplant, and azithromycin has variable efficacy in CLAD. The lung microbiome is a risk factor for developing CLAD, but the relationship between lung dysbiosis, pulmonary inflammation, and allograft dysfunction remains poorly understood. Whether lung microbiota predict outcomes or modify treatment response after CLAD is unknown. Objectives: To determine whether lung microbiota predict post-CLAD outcomes and clinical response to azithromycin. Methods: Retrospective cohort study using acellular BAL fluid prospectively collected from recipients of lung transplant within 90 days of CLAD onset. Lung microbiota were characterized using 16S rRNA gene sequencing and droplet digital PCR. In two additional cohorts, causal relationships of dysbiosis and inflammation were evaluated by comparing lung microbiota with CLAD-associated cytokines and measuring ex vivo P. aeruginosa growth in sterilized BAL fluid. Measurements and Main Results: Patients with higher bacterial burden had shorter post-CLAD survival, independent of CLAD phenotype, azithromycin treatment, and relevant covariates. Azithromycin treatment improved survival in patients with high bacterial burden but had negligible impact on patients with low or moderate burden. Lung bacterial burden was positively associated with CLAD-associated cytokines, and ex vivo growth of P. aeruginosa was augmented in BAL fluid from transplant recipients with CLAD. Conclusions: In recipients of lung transplants with chronic rejection, increased lung bacterial burden is an independent risk factor for mortality and predicts clinical response to azithromycin. Lung bacterial dysbiosis is associated with alveolar inflammation and may be promoted by underlying lung allograft dysfunction.

Center variability in the prognostic value of a cumulative acute cellular rejection "A-score" for long-term lung transplant outcomes.

The acute rejection score (A-score) in lung transplant recipients, calculated as the average of acute cellular rejection A-grades across transbronchial biopsies, summarizes the cumulative burden of rejection over time. We assessed the association between A-score and transplant outcomes in 2 geographically distinct cohorts. The primary cohort included 772 double lung transplant recipients. The analysis was repeated in 300 patients from an independent comparison cohort. Time-dependent multivariable Cox models were constructed to evaluate the association between A-score and chronic lung allograft dysfunction or graft failure. Landmark analyses were performed with A-score calculated at 6 and 12 months posttransplant. In the primary cohort, no association was found between A-score and graft outcome. However, in the comparison cohort, time-dependent A-score was associated with chronic lung allograft dysfunction both as a time-dependent variable (hazard ratio, 1.51; P < .01) and when calculated at 6 months posttransplant (hazard ratio, 1.355; P = .031). The A-score can be a useful predictor of lung transplant outcomes in some settings but is not generalizable across all centers; its utility as a prognostication tool is therefore limited.

Lung Re-transplantation after prolonged veno-venous extracorporeal membrane oxygenation (ECMO) in a child with chronic lung allograft dysfunction.

BACKGROUND: Extracorporeal Membrane Oxygenation (ECMO) may be used as a bridge to lung transplantation in selected patients with end-stage respiratory failure. Historically, ECMO use in this setting has been associated with poor outcomes Puri V et.al, J Thorac Cardiovasc Surg, 140:427. More recently, technical advances and the implementation of rehabilitation and ambulation while awaiting transplantation on ECMO have led to improved surgical and post-transplant outcomes Kirkby S et.al, J Thorac Dis, 6:1024. METHODS: We illustrate the case of a 6-year-old child who received prolonged ECMO support as a bridge to lung re-transplantation secondary to Chronic Lung Allograft Dysfunction (CLAD). RESULTS: Early rehabilitation was key in improving the overall pre-transplant conditioning during ECMO. CONCLUSIONS: Despite challenges associated with awake/ambulatory ECMO, the use of this strategy as a bridge to lung transplantation is feasible and has resulted in improved pre-transplant conditioning and post-transplant outcomes.