Chronic lung allograft dysfunction phenotype and prognosis by machine learning CT analysis

BackgroundChronic lung allograft dysfunction (CLAD) is the principal cause of graft failure in lung transplant recipients and prognosis depends on CLAD phenotype. We used machine learning computed tomography (CT) lung texture analysis tool at CLAD diagnosis for phenotyping and prognostication compared to radiologists’ scoring.MethodsThis retrospective study included all adult first double-lung transplant patients (01/2010–12/2015) with CLAD (censored 12/2019) and inspiratory CT near CLAD diagnosis. The machine learning tool quantified ground-glass opacity, reticulation, hyperlucent lung, and pulmonary vessel volume (PVV). Two radiologists scored for ground-glass opacity, reticulation, consolidation, pleural effusion, air trapping and bronchiectasis. Receiver operating characteristic curve analysis was used to evaluate the diagnostic performance of machine learning and radiologist for CLAD phenotype. Multivariable Cox proportional-hazards regression analysis for allograft survival controlled for age, sex, native lung disease, cytomegalovirus serostatus, and CLAD phenotype (bronchiolitis obliterans syndrome [BOS] and restrictive allograft syndrome [RAS]/mixed).Results88 patients were included (57 BOS, 20 RAS/mixed, and 11 unclassified/undefined) with CT a median 9.5 days from CLAD onset. Radiologist and machine learning parameters phenotyped RAS/mixed with PVV as the strongest indicator (AUC 0.85). Machine learning hyperlucent lung phenotyped BOS using only inspiratory CT (AUC=0.76). Radiologist and machine learning parameters predicted graft failure in the multivariable analysis, best with PVV (HR=1.23, 95%CI 1.05–1.44, p=0.01).ConclusionsMachine learning discriminated between CLAD phenotypes on CT. Both radiologist and machine learning scoring were associated with graft failure, independent of CLAD phenotype. PVV, unique to machine learning, was the strongest in phenotyping and prognostication.

Antenatal Mesenchymal Stromal Cell Extracellular Vesicle Treatment Preserves Lung Development in a Model of Bronchopulmonary Dysplasia Due to Chorioamnionitis

Background: Antenatal stressors such as chorioamnionitis (CA) increase the risk for bronchopulmonary dysplasia (BPD). Studies have shown that experimental BPD can be ameliorated by postnatal treatment with mesenchymal stromal cell-derived extracellular vesicles (MEx). However, the antenatal efficacy of MEx to prevent BPD is unknown. Objective: To determine whether antenatal MEx therapy attenuates intrauterine inflammation and preserves lung growth in a rat model of CA-induced BPD. Methods: At embryonic day (E)20, rat litters were treated with intra-amniotic injections of saline, endotoxin (ETX) to model chorioamnionitis, MEx, or ETX plus MEx followed by cesarean section delivery with placental harvest at E22. Placental and lung evaluations were conducted at day 0 and day 14, respectively. To assess the effects of ETX and MEx on lung growth in vitro, E15 lung explants were imaged for distal branching. Results: Placental tissues from ETX-exposed pregnancies showed increased expression of inflammatory markers NLRP-3 and IL-1ß and altered spiral artery morphology. Additionally, infant rats exposed to intrauterine ETX had reduced alveolarization and pulmonary vessel density (PVD), increased right ventricular hypertrophy (RVH), and decreased lung mechanics. Intrauterine MEx therapy of ETX-exposed pups reduced inflammatory cytokines, normalized spiral artery architecture, and preserved distal lung growth and mechanics. In vitro studies showed that MEx treatment enhanced distal lung branching and increased VEGF and SPC gene expression. Conclusions: Antenatal MEx treatment preserved distal lung growth and reduced intrauterine inflammation in a model of CA-induced BPD. We speculate that MEx may provide a novel therapeutic strategy to prevent BPD due to antenatal inflammation.

Role of Store-Operated Ca2+ Entry in the Pulmonary Vascular Remodeling Occurring in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a severe and multifactorial disease. PAH pathogenesis mostly involves pulmonary arterial endothelial and pulmonary arterial smooth muscle cell (PASMC) dysfunction, leading to alterations in pulmonary arterial tone and distal pulmonary vessel obstruction and remodeling. Unfortunately, current PAH therapies are not curative, and therapeutic approaches mostly target endothelial dysfunction, while PASMC dysfunction is under investigation. In PAH, modifications in intracellular Ca2+ homoeostasis could partly explain PASMC dysfunction. One of the most crucial actors regulating Ca2+ homeostasis is store-operated Ca2+ channels, which mediate store-operated Ca2+ entry (SOCE). This review focuses on the main actors of SOCE in human and experimental PASMC, their contribution to PAH pathogenesis, and their therapeutic potential in PAH.

Evaluation of chest computed tomography features in COVID-19: a single-center retrospective study

Background: Even though Real-Time Polymerase Chain Reaction (RT-PCR) is a gold standard for confirming COVID-19, it continues to be plagued by a lack of RT-PCR kits and the potential of false-negative results. Hence, during the second wave of COVID-19 in India, Computed Tomography (CT) scan is an emerging diagnostic tool in evaluating the severity of illness in COVID-19 pneumonia. The present study endeavored to assess chest CT features of COVID-19 pneumonia in Indian population. Methods: This was a single-center, retrospective, observational study conducted in 300 consecutive adults RT-PCR confirmed COVID-19 patients from 1, Jan 2021 to 31, March 2021 at a private radio diagnostic center. Data regarding baseline demographics, clinical and laboratory characteristics, extent, pattern, and type of abnormal CT findings were noted. Results: The study population (204 males and 108 females) had mean age of 43.18 ± 8.27 years. Our study's most common clinical presentation was cough (48.1%) and fever (47.1%), respectively. Lung parenchymal abnormalities were found in 294 (94.2%) patients. Abnormal CT findings revealed the involvement of bilateral (45.6%) and multilobar (42.9%) with a predominant peripheral (92.3%) and posterior (80.8%) distribution. According to the type of opacity, Ground Glass Opacity (GGO) was the dominant abnormality found in 270 (91.8%) patients, in which pure GGO (36.7%), GGO with crazy paving pattern (39.8%), and GGO mixed with consolidation (52.0 %) were noted. Peri-lesional or intralesional segmental or subsegmental pulmonary vessel enlargement was found in 192 (65.3 %) patients. Conclusion: During the second wave of COVID-19, a chest CT scan is a modality of choice in diagnosing COVID-19 pneumonia and related lung parenchymal changes.

Integrative Studies of Human Cord Blood Derived Mononuclear Cells and Umbilical Cord Derived Mesenchyme Stem Cells in Ameliorating Bronchopulmonary Dysplasia

Bronchopulmonary dysplasia (BPD) is a common pulmonary complication observed in preterm infants that is composed of multifactorial pathogenesis. Current strategies, albeit successful in moderately reducing morbidity and mortality of BPD, failed to draw overall satisfactory conclusion. Here, using a typical mouse model mimicking hallmarks of BPD, we revealed that both cord blood-derived mononuclear cells (CB-MNCs) and umbilical cord-derived mesenchymal stem cells (UC-MSCs) are efficient in alleviating BPD. Notably, infusion of CB-MNCs has more prominent effects in preventing alveolar simplification and pulmonary vessel loss, restoring pulmonary respiratory functions and balancing inflammatory responses. To further elucidate the underlying mechanisms within the divergent therapeutic effects of UC-MSC and CB-MNC, we systematically investigated the long noncoding RNA (lncRNA)–microRNA (miRNA)–messenger RNA (mRNA) and circular RNA (circRNA)–miRNA–mRNA networks by whole-transcriptome sequencing. Importantly, pathway analysis integrating Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG)/gene set enrichment analysis (GSEA) method indicates that the competing endogenous RNA (ceRNA) network is mainly related to the regulation of GTPase activity (GO: 0043087), extracellular signal-regulated kinase 1 (ERK1) and ERK2 signal cascade (GO: 0070371), chromosome regulation (GO: 0007059), and cell cycle control (GO: 0044770). Through rigorous selection of the lncRNA/circRNA-based ceRNA network, we demonstrated that the hub genes reside in UC-MSC- and CB-MNC-infused networks directed to the function of cell adhesion, motor transportation (Cdk13, Lrrn2), immune homeostasis balance, and autophagy (Homer3, Prkcd) relatively. Our studies illustrate the first comprehensive mRNA–miRNA–lncRNA and mRNA–miRNA–circRNA networks in stem cell-infused BPD model, which will be valuable in identifying reliable biomarkers or therapeutic targets for BPD pathogenesis and shed new light in the priming and conditioning of UC-MSCs or CB-MNCs in the treatment of neonatal lung injury.

Transcatheter Embolization of Systemic-to-pulmonary Artery Fistulas: a Case Report

The systemic artery to pulmonary vessel fistula(SAPVF) is an uncommon vascular abnormal communication between systemic arteries (except bronchial arteries) and the lung parenchyma[1]. It can be divided into congenital and acquired causes. Congenital SAPVF is often accompanied by cardiac or pulmonary artery hypoplasia, and acquired are usually caused by pleural adhesions after pleurisy, empyema, trauma, or surgery[2].We report a case of transcatheter arterial embolization for the treatment of congenital right inferior phrenic artery to pulmonary artery fistula.

Uniportal thoracoscopic lateral and posterior (S9+10) segmentectomy using a modified intersegmental tunneling procedure

The lateral and posterior basal (S9+10) segmentectomy is one of the most challenging operations because it requires exposure and recognition of pulmonary vessel branches and bronchi that are located deep in the lung parenchyma. To perform this difficult operation appropriately, even via a uniportal approach, we adopted a modified version of the intersegmental tunneling procedure. Intersegmental tunneling followed by division of the intersegmental plane between S6 and S9-10 was performed before the division of the A9+10 in the modified version. In addition to the clear recognition of the dominant vessels and bronchi permitted by the tunneling procedure, we were able to divide them smoothly using a stapler in the modified version, although the tip of the inserted stapler stuck to the lung parenchyma in the previous version. This method might be universally preferable, even for less experienced surgeons, when they perform this challenging operation.

Sex-dependent change in the reactivity of isolated pulmonary arteries of gonadectomized rats under the intermittent hypoxia of different degree

Introduction. Pulmonary vasoconstriction is one of factors of hypoxic pulmonary hypertension (HPH). The progression of this disease depends on the degree of hypoxiа and seх. The aim of this study was to investigate the reactivity of isolated pulmonary vessels of male and female rats with HPH to vasoactive factors. Materials and methods. The experiments were on male and female of Wistar rats 190–200 g, which were gonadectomized. All animals were divided into 4 groups. One group of males and female rats was kept in a vivarium (21 % О2 ). To simulate HPH, other rats were exposed to hypobaric hypoxia for 10 hours a day at an oxygen content in the inhaled air equal to 13 % (pP O2 103.7 mmHg) or 10 % (pP O2 78,2 mmHg), or 8 % (pP O2 63,5 mmHg) as compared to its content at 21 % (pP О2 159 mmHg). After that, a third-order pulmonary vessel was perfused at a constant flow rate with vasoconstrictors and vasodilators. The reaction was recorded by the change in perfusion pressure. Results. In females with HРН 10 %O2 , constricting response to serotonin were greater than in males. In normotensive males, the dilatory response to sodium nitroprusside (NP) was less than in female. Exposure to hypoxia induced an increase in NP responses. Conclusion. Increased reactivity of pulmonary vessels to serotonin is a factor of pathogenesis of HPH in females, in contrast to males. Increased reactivity to NO donor in males exposed to hypoxia сan be used for a pharmacological target for HPH.

Vein-first versus artery-first ligation procedure for lung cancer surgery: An updated review

Background The optimal sequence of pulmonary vessel interruption during lung cancer resection remains controversial. This review aimed to elucidate the association of vein-first versus artery-first ligation and survival of the patients. Methods We searched PubMed, Web of Science, Scopus, Embase, Cochrane Library and Google Scholar from their inception to September 2021 for published articles that compared vein-first (the pulmonary vein was interrupted first) and artery-first procedure (the pulmonary artery was ligated first) during lung cancer surgery. Results Finally, a total of 13 full articles were obtained. First, 7 studies with survival information were included for meta-analyses. As compared with the artery-first ligation, vein-first approach did not decrease the risk of local recurrence (risk ratio [RR] 0.92 in favour of vein-first; 95% confidence interval [CI] 0.61–1.39, p = 0.68) or distant metastasis (RR 0.92; 95% CI 0.30–2.85, p = 0.89); but it was associated with better disease-free survival (RR 0.52; 95% CI 0.37–0.73, p < 0.01) as well as 5-year overall survival (RR 0.60; 95% CI 0.41–0.86, p < 0.01). In addition, the operative time, intraoperative blood loss, total complications, and length of postoperative stay were mainly comparable between the two groups. Second, 7 studies provided the data of tumor cells indicated by different biomarkers and detection methods; and 3 of these reports showed that vein-first ligation decreased the extent of intraoperative tumor dissemination. However, a quantitative meta-analysis was not possible due to the significant heterogeneity. Conclusion Vein-first ligation in lung cancer surgery may be associated with improved survival of the patients, which might be ascribed to potentially lower risk of tumor cell dissemination. Well-designed, large-scale trials are warranted to clarify these occasional findings.