Lung transplantation is a life-saving treatment for patients with end-stage lung disease; however, it is infrequently considered for patients with acute respiratory distress syndrome (ARDS) ...attributable to infectious causes. We aimed to describe the course of disease and early post-transplantation outcomes in critically ill patients with COVID-19 who failed to show lung recovery despite optimal medical management and were deemed to be at imminent risk of dying due to pulmonary complications.
We established a multi-institutional case series that included the first consecutive transplants for severe COVID-19-associated ARDS known to us in the USA, Italy, Austria, and India. De-identified data from participating centres-including information relating to patient demographics and pre-COVID-19 characteristics, pretransplantation disease course, perioperative challenges, pathology of explanted lungs, and post-transplantation outcomes-were collected by Northwestern University (Chicago, IL, USA) and analysed.
Between May 1 and Sept 30, 2020, 12 patients with COVID-19-associated ARDS underwent bilateral lung transplantation at six high-volume transplant centres in the USA (eight recipients at three centres), Italy (two recipients at one centre), Austria (one recipient), and India (one recipient). The median age of recipients was 48 years (IQR 41-51); three of the 12 patients were female. Chest imaging before transplantation showed severe lung damage that did not improve despite prolonged mechanical ventilation and extracorporeal membrane oxygenation. The lung transplant procedure was technically challenging, with severe pleural adhesions, hilar lymphadenopathy, and increased intraoperative transfusion requirements. Pathology of the explanted lungs showed extensive, ongoing acute lung injury with features of lung fibrosis. There was no recurrence of SARS-CoV-2 in the allografts. All patients with COVID-19 could be weaned off extracorporeal support and showed short-term survival similar to that of transplant recipients without COVID-19.
The findings from our report show that lung transplantation is the only option for survival in some patients with severe, unresolving COVID-19-associated ARDS, and that the procedure can be done successfully, with good early post-transplantation outcomes, in carefully selected patients.
National Institutes of Health. VIDEO ABSTRACT.
Display omitted
•Inhalation of microplastics may lead to their inclusion in lung epithelium during repair phase.•Human airway organoids are a suitable model for testing effects of airborne ...pollutants.•Tumble drying of polyester fabrics released 0.44 g of dry microplastic fibers kg−1 dry fabric.
Three-dimensional (3D) structured organoids are the most advanced in vitro models for studying human health effects, but their application to evaluate the biological effects associated with microplastic exposure was neglected until now. Fibers from synthetic clothes and fabrics are a major source of airborne microplastics, and their release from dryer machines is poorly understood. We quantified and characterized the microplastic fibers (MPFs) released in the exhaust filter of a household dryer and tested their effects on airway organoids (1, 10, and 50 µg mL−1) by optical microscopy, scanning electron microscopy (SEM), confocal microscopy and quantitative reverse transcription–polymerase chain reaction (qRT-PCR). While the presence of MPFs did not inhibit organoid growth, we observed a significant reduction of SCGB1A1 gene expression related to club cell functionality and a polarized cell growth along the fibers. The MPFs did not cause relevant inflammation or oxidative stress but were coated with a cellular layer, resulting in the inclusion of fibers in the organoid. This effect could have long-term implications regarding lung epithelial cells undergoing repair. This exposure study using human airway organoids proved suitability of the model for studying the effects of airborne microplastic contamination on humans and could form the basis for further research regarding the toxicological assessment of emerging contaminants such as micro- or nanoplastics.
We study the dynamics of a one-dimensional Bose gas in presence of strong two-body losses.
In this dissipative quantum Zeno regime, the gas fermionises and its dynamics can be described with a simple ...set of rate equations.
Employing the local density approximation and a Boltzmann-like dynamical equation, the description is extended to take into account an external potential.
We show that in the absence of confinement the population is depleted in an anomalous way and that the gas behaves as a low-temperature classical gas.
The harmonic confinement accelerates the depopulation of the gas and introduces a novel decay regime, which we thoroughly characterise.
Human multipotent mesenchymal stromal cells (MSC) are isolated from a plethora of tissue sources for cell therapy purposes. In 2006, the International Society for Cellular Therapy (ISCT) published ...minimal guidelines to define MSC identity. Nevertheless, many independent studies demonstrated that cells meeting the ISCT criteria possessed heterogeneous phenotypes and functionalities, heavily influenced by culture conditions. In this study, human MSC derived from many adult (bone marrow and adipose tissue) or fetal (cord blood, Wharton's jelly, umbilical cord perivascular compartment and amniotic fluid) tissues were investigated. Their immunophenotype was analyzed to define consistent source-specific markers by extensive flow cytometry analysis and real-time qRT-PCR. CD271
subpopulations were detected in adult MSC, whereas NG2 was significantly more expressed in fetal MSC but failed validation on independent samples coming from an external laboratory. The highest number of CD271
adult MSC were detected soon after isolation in serum-based culture conditions. Furthermore, heterogeneous percentages of CD271 expression were found in platelet lysate-based or serum-free culture conditions. Finally, CD271
adult MSC showed high clonogenic and osteogenic properties as compared to CD271
cells. To conclude, in this phenotype-function correlation study CD271
subpopulation confers heterogeneity on adult MSC, confirming the need of more specific markers to address MSC properties.
We generalize the theory of flow equations to open quantum systems focusing on Lindblad master equations.
We introduce and discuss three different generators of the flow that transform a linear ...non-Hermitian operator into a diagonal one.
We first test our dissipative flow equations on a generic matrix and on a physical problem with a driven-dissipative single fermionic mode. We then move to problems with many fermionic modes and discuss the interplay between coherent (disordered) dynamics and localized losses.
Our method can also be applied to non-Hermitian Hamiltonians.
Despite the promising results achieved so far in long-term survival after lung transplantation (LuTx), airway complications (ACs) still arise in the post-operative period. Early diagnosis and prompt ...treatment of ACs play a critical role in preventing their onset. Specifically, large bronchi ischemia has been recognized as a triggering factor for ACs. Autofluorescence bronchoscopy, which was first introduced for early cancer diagnosis, displays ischemic mucosae as red spots, while normal vascularized mucosae appear in green. The aim of this study is to investigate whether a significant correlation exists between ACs and the red/green (RG) ratio detected on scheduled autofluorescence bronchoscopy up to 1 year after LuTx. This prospective, observational, single-center cohort study initially considered patients who underwent LuTx between July 2014 and February 2016. All patients underwent concomitant white-light and autofluorescence bronchoscopy at baseline (immediately after LuTx), on POD7, POD14, POD21, POD28, POD45, 3 months, 6 months, and 1 year after LuTx. An autofluorescence image of the first bronchial carina distal to the anastomosis was captured and analyzed using histograms for red and green pixels; the R/G ratio was then recorded. Potential ACs were classified according according to the presence of a white-light following the MDS (macroscopic aspect, diameter and suture) criteria. The authors assessed the association between the R/G ratio and the ACs occurrence using a generalized estimating equations model. Thirty-one patients met the inclusion criteria and were therefore selected. Out of a total of 53 bronchial anastomoses, 8 developed complications (late bronchial stenosis), with an average onset time of 201 days after LuTx. ACs showed a similar baseline covariate value when compared to anastomoses that involved no complication. Generalized estimating equations regression indicated a clear association over time between the R/G ratio and the rise of complications (p = 0.023). The authors observed a significant correlation between post-anastomotic stenosis and the delayed decrease of the R/G ratio. Preliminary outcomes suggest that autofluorescence bronchoscopy may be an effective and manageable diagnostic tool, proving complementary to other instruments for early diagnosis of ACs after LuTx. Further research is needed to confirm and detail preliminary findings.
Unilateral proximal interruption of the pulmonary artery (UPIPA) is a rare congenital disease, and its optimal management remains undefined in the existing literature. The occasional necessity for ...pneumonectomy is still supported by limited evidence.
A systematic review of the literature was conducted using the PubMed search engine, focusing on UPIPA cases that received pneumonectomy. Thirty-one pertinent articles were selected and included in the analysis. A case reported from our institution was included in the analysis.
We found 25 adults and seven children affected by UPIPA who received an indication for pneumonectomy, plus an additional case that was reported by our institution. Among adult patients, the predominant indication was hemoptysis (57%), followed by suspected or confirmed lung cancer (23%). Approximately 46% of surgical procedures were classified as urgent or emergent. Postoperative complications were observed in 36% of cases, with no recorded mortality. In pediatric cases, pneumonectomy was primarily a life-saving intervention, performed urgently or emergently in 75% of instances. A possible late complication in pediatric patients involves a mediastinal shift leading to respiratory distress, which may be mitigated using an inflatable prosthesis.
Pneumonectomy achieves complete resolution of UPIPA symptoms. In the adult population, its primary indication is hemoptysis, with procedures conducted in both elective and urgent/emergent settings. Despite a mortality rate of zero, a notable proportion of patients may experience postoperative complications. In pediatric cases, the clinical presentation varies more extensively, and pneumonectomy is typically reserved for life-threatening situations, emphasizing the need for careful patient selection.
This study assessed humoral and T cell-mediated immune responses to the BNT162b2 vaccine in orthotopic liver transplant (OLT) and lung transplant (LUT) recipients who received three doses of the ...vaccine from March 2021 at our institution. Serum samples were collected 60 days post-second and third dose to quantify antibodies against the spike region of SARS-CoV-2 while whole blood samples were collected to analyze the SARS-CoV-2-specific T-cell response using an IFN-γ ELISpot assay. We enrolled 244 OLT and 120 LUT recipients. The third dose increased antibody titres in OLT recipients (from a median value of 131 after the second dose to 5523 IU/mL, p < 0.001) and LUT recipients (from 14.8 to 1729 IU/mL, p < 0.001). T-cell response also increased in OLT recipients (from 8.5 to 23 IFN-γ SFU per 250,000 PBMC, p < 0.001) and LUT recipients (from 8 to 15 IFN-γ SFU per 250,000 PBMC, p < 0.001). A total of 128 breakthrough infections were observed: two (0.8%) OLT recipients were hospitalized due to COVID-19 and one died (0.4%); among LUT recipients, seven were hospitalized (5.8%) and two patients died (1.7%). In conclusion, the three-dose schedule of the BNT162b2 vaccine elicited both humoral and T cell-mediated responses in solid organ transplant recipients. The risk of severe COVID-19 post-vaccination was low in this population.
(liver kinase B1) is a master regulator of several processes such as metabolism, proliferation, cell polarity and immunity. About one third of non-small cell lung cancers (NSCLCs) present
...alterations, which almost invariably lead to protein loss, resulting in the absence of a potential druggable target. In addition, LKB1-null tumors are very aggressive and resistant to chemotherapy, targeted therapies and immune checkpoint inhibitors (ICIs). In this review, we report and comment strategies that exploit peculiar co-vulnerabilities to effectively treat this subgroup of NSCLCs. LKB1 loss leads to an enhanced metabolic avidity, and treatments inducing metabolic stress were successful in inhibiting tumor growth in several preclinical models. Biguanides, by compromising mitochondria and reducing systemic glucose availability, and the glutaminase inhibitor telaglenastat (CB-839), inhibiting glutamate production and reducing carbon intermediates essential for TCA cycle progression, have provided the most interesting results and entered different clinical trials enrolling also LKB1-null NSCLC patients. Nutrient deprivation has been investigated as an alternative therapeutic intervention, giving rise to interesting results exploitable to design specific dietetic regimens able to counteract cancer progression. Other strategies aimed at targeting LKB1-null NSCLCs exploit its pivotal role in modulating cell proliferation and cell invasion. Several inhibitors of LKB1 downstream proteins, such as mTOR, MEK, ERK and SRK/FAK, resulted specifically active on
-mutated preclinical models and, being molecules already in clinical experimentation, could be soon proposed as a specific therapy for these patients. In particular, the rational use in combination of these inhibitors represents a very promising strategy to prevent the activation of collateral pathways and possibly avoid the potential emergence of resistance to these drugs. LKB1-null phenotype has been correlated to ICIs resistance but several studies have already proposed the mechanisms involved and potential interventions. Interestingly, emerging data highlighted that
alterations represent positive determinants to the new KRAS specific inhibitors response in
co-mutated NSCLCs. In conclusion, the absence of the target did not block the development of treatments able to hit
-mutated NSCLCs acting on several fronts. This will give patients a concrete chance to finally benefit from an effective therapy.
Early detection of lung cancer is the key to improving treatment and prognosis of this disease, and the advent of advances in computed tomography (CT) imaging and national screening programs have ...improved the detection rate of very small pulmonary lesions. As such, the management of this sub-centimetric and often sub-solid lesions has become quite challenging for clinicians, especially for choosing the most suitable diagnostic method. In clinical practice, to fulfill this diagnostic yield, transthoracic needle biopsy (TTNB) is often the first choice especially for peripheral nodules. For lesions for which TTNB could present technical difficulties or failed, other diagnostic strategies are needed. In this case, video-assisted thoracic surgery (VATS) is the gold standard to reach the diagnosis of lung nodules suspect of being malignant. Nonetheless it's often not easy the identification of such lesions during VATS because of their little dimensions, non-firm consistency, deep localization. In literature various marking techniques have been described, in order to improve intraoperative nodules detection and to reduce conversion rate to thoracotomy: CT-guided hookwire positioning, methylene blue staining, intra-operative ultrasound and electromagnetic navigation bronchoscopy are the most used. The scientific evidence on this matter is weak because there are no randomized clinical trials but only case series on single techniques with no comparison on efficacy, so there are no guidelines to refer. From this standing, in this article we conducted a narrative review of the existing literature on the subject, with the aim of outlining a framework as complete as possible. We analyzed strengths and weaknesses of the main techniques reported, so as to allow the clinician to orient himself with greater ease.
PDF
