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Lung transplant (LUTX) candidates have subclinical right ventricular (RV) dysfunction, which has not yet been assessed by speckle-tracking echocardiography (STE)-derived RV free-wall longitudinal strain (RVFWLS). To evaluate the prevalence of RV dysfunction by RVFWLS and its relationship with conventional RV echocardiographic indexes in LUTX candidates. In a single-center prospective observational cohort study, from January 2021 to March 2023 consecutive LUTX candidates underwent cardiac catheterization, radionuclide ventriculography, standard and STE. The diagnostic accuracy of RV ejection fraction by ventriculography (RVEF), tricuspid annular plane excursion (TAPSE), fractional area change (FAC), tricuspid peak annulus systolic velocity (S') versus RVFWS were computed. Thirty-four patients (female, 41%) with a mean age of 48 [36-59] years old enlisted for pulmonary fibrosis (35%) and cystic fibrosis (30%) were included. At cardiac catheterization, only 7 (23%) had pulmonary hypertension. Around 15-25% presented right heart enlargement. Tricuspid regurgitation was present in 20 (60%) of the patients. Median RVFWLS was -20.1% [-22.5%--17%], being impaired (> -20%) in 16 (47%) of the patients. RVFWLS identified the highest percentage (47%) of RV dysfunction, compared to TAPSE (32%), S' (27%), FAC (26%), and ventriculography (15%), which had very low sensitivity for detecting RV dysfunction compared to RVFWLS. In patients enlisted for LUTX, RV dysfunction assessed by STE-derived RVFWLS is highly prevalent. STE can detect RV dysfunction better than standard two-dimensional echocardiography and ventriculography. Further studies are urgently needed to define the clinical implications and the prognostic value of RV dysfunction measured with RVFWLS.

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.

Lung transplantation offers a lifesaving option for patients with end-stage lung disease, but it is marred by a high risk of post-transplant infections, particularly involving multidrug-resistant bacteria, Cytomegalovirus, and fungal pathogens. This elevated infection rate, the highest among solid organ transplants, poses a significant challenge for clinicians, particularly within the first year post-transplantation, where infections are the leading cause of mortality. The direct exposure of lung allografts to the external environment exacerbates this vulnerability leading to constant immune stimulation and consequently to an elevated risk of triggering alloimmune responses to the lung allograft. The necessity of prolonged immunosuppression to prevent allograft rejection further complicates patient management by increasing susceptibility to infections and neoplasms, and complicating the differentiation between rejection and infection, which require diametrically opposed management strategies. This review explores the intricate balance between preventing allograft rejection and managing the heightened infection risk in lung transplant recipients.

Background Localized lung insult, such as pneumonia, can increase respiratory drive and effort. The interplay between the initial injury, the inflammatory reaction and increased drive and effort could damage other areas and progress to bilateral lung injury. Methods Localized pulmonary inflammation was induced through instillation of 0.5 mg/kg lipopolysaccharide (LPS) in the left lower lobe of 18 pigs, while 5 animals served as sham controls. After 24 hours of spontaneous breathing, the severity of right lung injury was assessed by the validated histological score and correlated with potential physiological and biological determinants. Results Animals challenged with lobar inflammation developed bilateral lung injury, associated with increased respiratory drive and effort. Histological score of the right lung was characterized by wide inter-individual variability (median 11 [8-14], range 3-25). Right lung injury score was correlated with respiratory drive and effort; with respiratory rate and minute ventilation, but not with tidal volume; with peak inspiratory and driving transpulmonary pressures, and with EIT-derived lung strain; with lower sub-atmospheric alveolar pressure and with more negative end-expiratory transpulmonary pressure. Right lung injury score was also correlated with inflammatory plasma cytokines: higher SDF-1α and lower IL-1Ra, IL-5 and GM-CSF. Conclusions An experimental model of localized lung inflammation allowed us to investigate the role of specific pathophysiological mechanisms for the development of injury in previously healthy lung regions.

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.

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Chronic lung allograft dysfunction (CLAD) is the main cause of poor survival and low quality of life of lung transplanted patients. Several studies have addressed the role of dendritic cells, macrophages, T cells, donor specific as well as anti-HLA antibodies, and interleukins in CLAD, but the expression and function of immune checkpoint molecules has not yet been analyzed, especially in the two CLAD subtypes: BOS (bronchiolitis obliterans syndrome) and RAS (restrictive allograft syndrome). To shed light on this topic, we conducted an observational study on eight consecutive grafts explanted from patients who received lung re-transplantation for CLAD. The expression of a panel of immune molecules (PD1/CD279, PDL1/CD274, CTLA4/CD152, CD4, CD8, hFoxp3, TIGIT, TOX, B-Cell-Specific Activator Protein) was analyzed by immunohistochemistry in these grafts and in six control lungs. Results showed that RAS compared to BOS grafts were characterized by 1) the inversion of the CD4/CD8 ratio; 2) a higher percentage of T lymphocytes expressing the PD-1, PD-L1, and CTLA4 checkpoint molecules; and 3) a significant reduction of exhausted PD-1-expressing T lymphocytes (PD-1 pos /TOX pos ) and of exhausted Treg (PD-1 pos /FOXP3 pos ) T lymphocytes. Results herein, although being based on a limited number of cases, suggest a role for checkpoint molecules in the development of graft rejection and offer a possible immunological explanation for the worst prognosis of RAS. Our data, which will need to be validated in ampler cohorts of patients, raise the possibility that the evaluation of immune checkpoints during follow-up offers a prognostic advantage in monitoring the onset of rejection, and suggest that the use of compounds that modulate the function of checkpoint molecules could be evaluated in the management of chronic rejection in LTx patients.

Water stress is among the most important abiotic constraints affecting forest ecosystem functioning and regeneration, a phenomenon expected to intensify with climate change. It impacts photosynthesis, growth, and seedling survival, therefore threatening biodiversity and accelerating forest degradation. The use of silicon-based biostimulants has emerged as a way of mitigating the effects of water stress by improving water status and stimulating mechanical and biochemical defense. However, its effectiveness on forest tree species remains poorly explored. This study examines how potassium silicate (PS) alleviates the effects of drought on , with the aim of improving our understanding of the resilience mechanisms of tropical forest species. To do this, an experiment with 135 two-year-old saplings has been conducted, testing three irrigation levels in combination with the addition of potassium silicate (PS) at concentrations of 5 and 10 mM, via foliar spraying and soil application. Morphometric and physiological parameters were monitored, followed by the biochemical profiling of the induced responses. Linear mixed models were computed to assess the effects of the different factors on the different growth performance, physiological functioning parameters over time, and ANOVA was used for evaluating the punctual data on the biochemical compounds. Drought had a significant impact on the morphological and physiological behaviour of the seedlings. However, the application of PS modified the drought-induced changes, even at a low concentration of 5 mM. Biochemical defenses were also improved further with PS application. Hormone profiling revealed a predominance of auxins, while abscisic acid was lower in the water stress treatments under drought. Therefore, using PS could support the production of robust seedlings that are more tolerant of, and adaptive to, the challenges of climate change, making restoration more efficient.

Objective. In recent years, pulmonary segmentectomy has emerged as an alternative to lobectomy for the treatment of patients with clinical stage I non-small cell lung cancer. Considering the conflicting results reported in the literature, the oncological effectiveness of segmentectomy remains controversial. To provide new insight into oncological results, we reviewed the literature, including recent randomized trials. Methods. We performed a systematic review for surgical treatment of stage I NSCLC up to 2 cm using MEDLINE and the Cochrane Database from 1990 to December 2022. Primary outcomes for pooled analysis were overall and disease-free survival; secondary outcomes were postoperative complications and 30-day mortality. Results. Eleven studies were considered for the meta-analysis. The pooled analysis included 3074 and 2278 patients who received lobectomy and segmentectomy, respectively. The estimated pooled hazard ratio showed a similar hazard for segmentectomy compared to lobectomy in terms of overall and disease-free survival. The restricted mean survival time difference between the two procedures was statistically and clinically not significant for overall and disease-free survival. Nevertheless, the overall survival hazard ratio was time-dependent: segmentectomy was at a disadvantage starting from 40 months after surgery. Six papers reported 30-day mortality: there were no events on 1766 procedures. The overall relative risk showed that the postoperative complication rate was higher in segmentectomy compared to lobectomy, without statistical significance. Conclusions. Our results suggest that segmentectomy might be a useful alternative to lobectomy for stage I NSCLC up to 2 cm. However, this appears to be time-dependent; in fact, the risk ratio for overall mortality becomes unfavorable for segmentectomy starting at 40 months after surgery. This last observation, together with some still undefined questions (solid/non-solid ratio, depth of the lesion, modest functional savings, etc.), leave room for further investigations on the real oncological effectiveness of segmentectomy.