Pulmonary Vasculature Research Articles

Placental transmogrification of the lung: CT findings with pathologic correlation in six patients.

Placental transmogrification of the lung is a very rare benign lung disease with a characteristic finding being alveoli resembling chorionic villi of the placenta. The purpose of this study was to assess the computed tomography (CT) findings of placental transmogrification of the lung in six patients and their relation to the histopathologic findings. Six patients with histopathologically proven placental transmogrification of the lung from 2004 to 2021 were included. Their CT findings were analyzed and their imaging features were compared with pathology specimens. In four of six cases, CT showed variable sized cystic lesions confined to a unilateral lung. One case presented nodule and cystic lesion together. The other case showed solitary pulmonary nodule without cystic lesion. Moreover, nodular interlobular septal thickening and clustered interstitial nodules were observed in all six cases. In four of the six cases, these nodules merged into dense nodular consolidation. Three cases showed dilated pulmonary vasculatures of the involved lung. On CT, placental transmogrification of the lung typically presents as cystic lesion confined to a unilateral lung. Pulmonary nodule with or without associated cystic lesion can also be seen. Nodular interlobular septal thickening and clustered interstitial nodules were observed in all cases. This might be attributable to the proliferation of chorionic villi-like structures in interstitium which are found in histopathologic specimens.

Identification of Zip8-correlated hub genes in pulmonary hypertension by informatic analysis.

Pulmonary hypertension (PH) is a syndrome characterized by marked remodeling of the pulmonary vasculature and increased pulmonary vascular resistance, ultimately leading to right heart failure and even death. The localization of Zrt/Irt-like Protein 8 (ZIP8, a metal ion transporter, encoded by SLC39A8) was abundantly in microvasculature endothelium and its pivotal role in the lung has been demonstrated. However, the role of Zip8 in PH remains unclear. Bioinformatics analysis was employed to identify SLC39A8 expression patterns and differentially expressed genes (DEGs) between PH patients and normal controls (NC), based on four datasets (GSE24988, GSE113439, GSE117261, and GSE15197) from the Biotechnology Gene Expression Omnibus (NCBI GEO) database. Gene set enrichment analysis (GSEA) was performed to analyze signaling pathways enriched for DEGs. Hub genes were identified by cytoHubba analysis in Cytoscape. Reverse transcriptase-polymerase chain reaction was used to validate SLC39A8 and its correlated metabolic DEGs expression in PH (SU5416/Hypoxia) mice. SLC39A8 expression was downregulated in PH patients, and this expression pattern was validated in PH (SU5416/Hypoxia) mouse lung tissue. SLC39A8-correlated genes were mainly enriched in the metabolic pathways. Within these SLC39A8-correlated genes, 202 SLC39A8-correlated metabolic genes were screened out, and seven genes were identified as SLC39A8-correlated metabolic hub genes. The expression patterns of hub genes were analyzed between PH patients and controls and further validated in PH mice. Finally, four genes (Fasn, Nsdhl, Acat2, and Acly) were downregulated in PH mice. However, there were no significant differences in the expression of the other three hub genes between PH mice and controls. Of the four genes, Fasn and Acly are key enzymes in fatty acids synthesis, Nsdhl is involved in cholesterol synthesis, and Acat2 is implicated in cholesterol metabolic transformation. Taken together, these results provide novel insight into the role of Zip8 in PH.

Impact of cancer on the prevalence, management, and outcome of patients with chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) results from unresolved thrombotic obstruction of the pulmonary vasculature. Cancer is a known risk factor for CTEPH. This study aimed to determine the impact of cancer on the prevalence, management, and outcomes of patients with CTEPH. In this retrospective study involving 99 patients sequentially diagnosed with CTEPH in our hospital, the prevalence of 10 comorbid conditions including a past history of cancer at the time of CTEPH diagnosis were calculated. Among the 99 patients, 17 (17%) had a history of cancer. Breast cancer (n = 6) was the most common cancer type, followed by gastrointestinal cancer (n = 3), uterine cancer (n = 2), and malignant lymphoma (n = 2). Between patients with and without cancer, there were no differences in the demographics, severity of CTEPH, and management; however, the 5-year survival rate was lower for patients with cancer (65%) than for those without (89%). In addition, patients with cancer had significantly worse survival than those without (p = 0.03 by log-rank test). During follow-up, nine patients developed cancer after the diagnosis of CTEPH. Among the 99 patients, 13 died during follow-up, 6 (46%) of whom died of cancer. 17% of our patients with CETPH were diagnosed with cancer, with breast and gastrointestinal tract cancers being the most common. Cancer comorbidity was associated with a poor prognosis and contributed to death in 46% of deceased patients. The impact of cancer on CTEPH should be further evaluated in the future.

Study of the Acute Hemodynamic Effects of Inhaled Milrinone versus Inhaled Nitroglycerin on Mechanically Ventilated Patients with Pulmonary Hypertension after Mitral Valve Replacement Surgeries

Abstract Background Pulmonary hypertension is a usual complication of long-standing mitral valve disease. Perioperative pulmonary hypertension is a risk factor for right ventricular failure and is an important cause of morbidity and mortality in patients with pulmonary hypertension undergoing mitral valve surgery. Aim of the Work To compare inhaled milrinone and inhaled nitroglycerin hemodynamic effects on mechanically ventilated patients with pulmonary hypertension after mitral valve replacement surgery by measuring invasive blood pressure, heart rate, central venous pressure and bedside transthoracic echocardiography to assess pulmonary artery pressure. Patients and Methods The study was conducted in National Heart Institute, Giza, Egypt during the six months between October, 2020 and March, 2021. This study was conducted on 40 patients. Patients were randomized on the basis of computer-generated random numbers into two equal groups (20 patients each) Using PASS11 program for sample size calculation. In group A, patients received inhaled nitroglycerin (50 µ/kg) and in group B, patients received inhaled milrinone (50 µ/kg) through jet nebulizer. Results Both inhaled milrinone and inhaled nitroglycerin proved to be selective pulmonary vasodilators, since they induced significant reductions in mPAP, SPAP, and DPAP. The favorable effects of both agents on the pulmonary vasculature was confirmed by both hemodynamic and echocardiographic measurements. At the same time, both agents were devoid of systemic side effects, since mean arterial pressure, systolic arterial pressure and diastolic arterial pressure were not affected. Conclusion There was no significance between two groups, so inhaled nitroglycerin appears to be an effective, easy to administer, inexpensive, available and save alternative for treatment of PH in mechanically ventilated patients after mitral valve replacement surgeries as there was no significance between two groups.

Pulmonary Hypertension in Left Ventricular Valvular Diseases: A Comprehensive Review on Pathophysiology and Prognostic Value.

Left ventricular (LV) valvular diseases, make up one of the most common etiologies for pulmonary hypertension (PH), and it is not well understood how and at which degree it affects prognosis. The aim of the present study was a comprehensive review of the pathophysiologic mechanism of PH in patients with LV valvular diseases and the prognostic value of baseline and post-intervention PH in patients undergoing interventional treatment. The pathophysiology of PH in patients with LV valvular diseases involves gradual elevation of left ventricular filling pressure and left atrial pressure, which are passively transmitted to the pulmonary circulation and raise pulmonary artery systolic pressure (PASP). A long-lasting exposure to elevated PASP progressively leads to initially functional and thereafter irreversible structural changes in the pulmonary vasculature, leading up to high pulmonary vascular resistance. Surgical treatment of severe LV valvular diseases is highly effective in patients without resting PH or those with exercise-induced PH (EIPH) before intervention. In the case of pre-operative PH, successful interventional therapy decreases PASP, but the post-operative cardiac and all-cause mortality remain higher compared to patients without pre-operative PH. Hence, it is of paramount importance to detect patients with severe LV valvulopathies before the development of PH, since they will get greater benefits from early intervention.

Systematic Evaluation of the Impact of Lung Segmentation Methods on 4-Dimensional Computed Tomography Ventilation Imaging Using a Large Patient Database

A novel form of lung functional imaging applied for functional avoidance radiation therapy has been developed that uses 4-dimensional computed tomography (4DCT) data and image processing techniques to calculate lung ventilation (4DCT-ventilation). Lung segmentation is a common step to define a region of interest for 4DCT-ventilation generation. The purpose of this study was to quantitatively evaluate the sensitivity of 4DCT-ventilation imaging using different lung segmentation methods. The 4DCT data of 350 patients from 2 institutions were used. Lung contours were generated using 3 methods: (1) reference segmentations that removed airways and pulmonary vasculature manually (Lung-Manual), (2) standard lung contours used for planning (Lung-RadOnc), and (3) artificial intelligence (AI)-based contours that removed the airways and pulmonary vasculature (Lung-AI). The AI model was based on a residual 3-dimensional U-Net and was trained using the Lung-Manual contours of 279 patients. We compared the Lung-RadOnc or Lung-AI with Lung-Manual contours for the entire 4DCT-ventilation functional avoidance process including lung segmentation (surface Dice similarity coefficient [Surface DSC]), 4DCT-ventilation generation (correlation), and subanalysis of 10 patients on a dosimetric endpoint (percentage of high functional volume of lung receiving ≥20 Gy [fV20{%}]). Surface DSC comparing Lung-Manual/Lung-RadOnc and Lung-Manual/Lung-AI contours was 0.40 ± 0.06 and 0.86 ± 0.04, respectively. The correlation between 4DCT-ventilation images generated with Lung-Manual/Lung-RadOnc and Lung-Manual/Lung-AI were 0.48 ± 0.14 and 0.85 ± 0.14, respectively. The difference in fV20[%] between 4DCT-ventilation generated with Lung-Manual/Lung-RadOnc and Lung-Manual/Lung-AI was 2.5% ± 4.1% and 0.3% ± 0.5%, respectively. Our work showed that using standard planning lung contours can result in significantly variable 4DCT-ventilation images. The study demonstrated that AI-based segmentations generate lung contours and 4DCT-ventilation images that are similar to those generated using manual methods. The significance of the study is that it characterizes the lung segmentation sensitivity of the 4DCT-ventilation process and develops methods that can facilitate the integration of this novel imaging in busy clinics.

The vascular perspective on acute and chronic lung disease.

The pulmonary vasculature has been frequently overlooked in acute and chronic lung diseases, such as acute respiratory distress syndrome (ARDS), pulmonary fibrosis (PF), and chronic obstructive pulmonary disease (COPD). The primary emphasis in the management of these parenchymal disorders has largely revolved around the injury and aberrant repair of epithelial cells. However, there is increasing evidence that the vascular endothelium plays an active role in the development of acute and chronic lung diseases. The endothelial cell network in the capillary bed and the arterial and venous vessels provides a metabolically highly active barrier that controls the migration of immune cells, regulates vascular tone and permeability, and participates in the remodeling processes. Phenotypically and functionally altered endothelial cells, and remodeled vessels, can be found in acute and chronic lung diseases, although to different degrees, likely because of disease-specific mechanisms. Since vascular remodeling is associated with pulmonary hypertension, which worsens patient outcomes and survival, it is crucial to understand the underlying vascular alterations. In this Review, we describe the current knowledge regarding the role of the pulmonary vasculature in the development and progression of ARDS, PF, and COPD; we also outline future research directions with the hope of facilitating the development of mechanism-based therapies.

A topological data analysis study on murine pulmonary arterial trees with pulmonary hypertension

Pulmonary hypertension (PH), defined by a mean pulmonary arterial blood pressure above 20 mmHg in the main pulmonary artery, is a cardiovascular disease impacting the pulmonary vasculature. PH is accompanied by chronic vascular remodeling, wherein vessels become stiffer, large vessels dilate, and smaller vessels constrict. Some types of PH, including hypoxia-induced PH (HPH), also lead to microvascular rarefaction. This study analyzes the change in pulmonary arterial morphometry in the presence of HPH using novel methods from topological data analysis (TDA). We employ persistent homology to quantify arterial morphometry for control and HPH mice characterizing normalized arterial trees extracted from micro-computed tomography (micro-CT) images. We normalize generated trees using three pruning algorithms before comparing the topology of control and HPH trees.This proof-of-concept study shows that the pruning method affects the spatial tree statistics and complexity. We find that HPH trees are stiffer than control trees but have more branches and a higher depth. Relative directional complexities are lower in HPH animals in the right, ventral, and posterior directions. For the radius pruned trees, this difference is more significant at lower perfusion pressures enabling analysis of remodeling of larger vessels. At higher pressures, the arterial networks include more distal vessels. Results show that the right, ventral, and posterior relative directional complexities increase in HPH trees, indicating the remodeling of distal vessels in these directions. Strahler order pruning enables us to generate trees of comparable size, and results, at all pressure, show that HPH trees have lower complexity than the control trees.Our analysis is based on data from 6 animals (3 control and 3 HPH mice), and even though our analysis is performed in a small dataset, this study provides a framework and proof-of-concept for analyzing properties of biological trees using tools from Topological Data Analysis (TDA). Findings derived from this study bring us a step closer to extracting relevant information for quantifying remodeling in HPH.

Abstract P3002: Role Of Vascular Fibroblast Growth Factor Signaling In Group 3 Hypoxia-induced Pulmonary Hypertension

Pulmonary hypertension (PH) is a debilitating disease characterized by pathologic changes in the pulmonary vasculature that increases pulmonary vascular resistance and leads to right heart failure. Group 3 PH is caused by lung disease and/or hypoxia, including bronchopulmonary dysplasia (BPD) and chronic obstructive lung disease (COPD), and is the second largest cause of mortality in PH patients. PH further increases the morbidity and mortality in both COPD and BPD patients. Fibroblast Growth Factor 2 (FGF2) and FGF Receptor 1 (FGFR1) expression is elevated in lung tissue of PH patients. To study the role of FGF signaling in the pathogenesis of group 3 PH, we developed a physiologically relevant mouse model in which mice are challenged with 10% hypoxia for 2 weeks. Following hypoxia exposure, cardiac catheterization is used to measure right ventricular (RV) pressure that mimics Group 3 PH. Lung tissue is then analyzed for histological and molecular changes. Our initial work showed that inactivation of FGFRs in endothelial cells (EC) worsened hypoxia-induced PH while expression of a constitutively active FGFR1 (caFGFR1) in ECs protected against hypoxia-induced PH. Here we hypothesize that FGF signaling may also affect the pathogenic response to hypoxia of vascular smooth muscle (VSMC), potentially by limiting vascular muscularization in response to hypoxia. We show that in vitro inhibition of FGF2 signaling in human pulmonary artery VSMCs reduced hypoxia-induced proliferation while promoting a contractile phenotype, and in vivo inactivation of FGFRs 1 and 2 worsened hypoxia-induced vascular remodeling. These data suggest the potential for a dual beneficial effect of activation of FGF signaling, both in regulating EC-VSMC interactions and directly preventing VSMC remodeling.

Ginsenoside Rg3 attenuates pulmonary fibrosis by inhibiting endothelial to mesenchymal transition

ABSTRACT Pulmonary fibrosis (PF) is a progressive and chronic lung disease characterized by excessive extracellular matrix (ECM) deposition and fibroblast proliferation. Endothelial-to-mesenchymal transition (EndMT) serves as a source of fibroblasts and contributes to PF progression. Ginsenoside Rg3 (Rg3), a steroidal saponin extracted from ginseng, is known to have pharmacological effects on vascular diseases. We have previously demonstrated that Rg3 inhibits EndMT and prevents endothelial dysfunction. Thus, we hypothesized that Rg3 may be a potential therapeutic agent for PF-targeting EndMT. EndMT occurs in the lung tissue of a bleomycin-induced PF mouse model, which was confirmed by co-staining of endothelial and mesenchymal markers in the pulmonary vasculature and changes in the expression of these markers. Rg3 administration decreased EndMT and suppressed PF development. We also examined the effect of Rg3 in an in vitro EndMT model induced by co-treatment with TGF-β2 and IL-1β. Rg3 treatment alleviated the characteristics of EndMT such as spindle-shaped morphological changes, EndMT marker expression changes, Dil-Ac-LDL uptake and migratory properties. In addition, we demonstrated the mechanism by which Rg3 inhibits EndMT by regulating the Smad2/3 signaling pathway. Collectively, Rg3 can be a potential therapeutic agent for PF using the EndMT inhibition strategy, furthermore, it can be considered Rg3 as a therapeutic candidate for various EndMT-associated vascular diseases.

Prenatal assessment of pulmonary vasculature development in fetuses with congenital diaphragmatic hernia: A literature review.

Pathophysiological studies have shown that pulmonary vascular development is impaired in fetuses with a congenital diaphragmatic hernia (CDH), leading to a simplified vascular tree and increased vascular resistance. Multiple studies have described prenatal ultrasound parameters for the assessment of the pulmonary vasculature, but none of these parameters are used in daily clinical practice. We provide a comprehensive review of the literature published between January 1990 and February 2022 describing these parameters, and aim to explain the clinical relevance of these parameters from what is known from pathophysiological studies. Prenatal detection of a smaller diameter of the contralateral (i.e. contralateral to the diaphragmatic defect) first branch of the pulmonary artery (PA), higher pulsatility indices (PI), higher peak early diastolic reverse flow values, and a lower vascularization index seem of added value for the prediction of survival and, to a lesser extent, morbidity. Integration within the routine evaluation is complicated by the lack of uniformity of the methods used. To address the main components of the pathophysiological changes, we recommend future prenatal studies in CDH with a focus on PI values, PA diameters and pulmonary vascular branching.

A new integrative approach combining right heart catheterization and echocardiography to stage aortic stenosis-related cardiac damage.

Although staging of the extent of aortic stenosis (AS)-related cardiac damages is usually performed via echocardiography, this technique has considerable limitations in assessing pulmonary artery and right chamber pressures. The present hypothesis-generating study sought to explore the efficacy of a staging system of cardiac damage based on echocardiographic and invasive [right heart catheterization (RHC)] hemodynamic parameters in patients undergoing transcatheter aortic valve implantation (TAVI). We studied 90 symptomatic patients with severe AS in whom echocardiographic and invasive evaluation by RHC was obtained prior to TAVI. Cardiac damage stages were defined as follows: no cardiac damage (stage 0), left ventricular (LV) damage (stage 1), left atrial or mitral valve damage (stage 2), pulmonary vasculature or tricuspid valve damage (stage 3), and right ventricular (RV) dysfunction or low-flow state (stage 4). With the integrative approach using RHC, pulmonary hypertension (PH) was defined as an mPAP ≥25 mmHg and the low-flow state corresponded to a cardiac index of <1.8 L/min/m2 and a right atrial pressure of >10 mmHg. During follow-up (median: 2.9 years), 43 patients (47.8%) died. The integrative cardiac damage staging was associated with a significant increase in all-cause and cardiovascular mortality per each increase of cardiac damage stage, whereas the outcome was similar according to the echocardiographic staging. A staging system of cardiac lesion based on echocardiographic and invasive hemodynamic parameters in patients with severe AS undergoing TAVI predicts mortality. Patients with pre-existing PH, ≥ moderate tricuspid regurgitation and/or RV dysfunction, and a low-flow state had a markedly increased risk of death. Further larger studies are needed to validate our findings.

Console and bedside surgeon fused robot-assisted thoracic surgery.

In the last decade, even thoracic surgery has seen an increase in the use of robotic surgical systems, and robot-assisted thoracic surgery (RATS) is considered one of the main issues. While RATS is associated with solo manipulative freedom and high-definition optical systems, several disadvantages, such as the lack of tactile sensation and difficult learning curves for the whole team, have been raised. Therefore, to overcome these issues, we developed a 'fusion surgery' approach combining a robotic procedure with manual maneuvers, where the table surgeon retracts the lung and staples the pulmonary vasculature and bronchus. Herein, we introduce our 'fusion surgery' procedure and elaborate on its advantage from technical and educational perspectives.

Pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a rare and progressive disease characterised by remodelling of the pulmonary arteries and progressive narrowing of the pulmonary vasculature. This leads to a progressive increase in pulmonary vascular resistance and pulmonary arterial pressure and, if left untreated, to right ventricular failure and death. A correct diagnosis requires a complete work-up including right heart catheterisation performed in a specialised centre.Although our knowledge of the epidemiology, pathology and pathophysiology of the disease, as well as the development of innovative therapies, has progressed in recent decades, PAH remains a serious clinical condition. Current treatments for the disease target the three specific pathways of endothelial dysfunction that characterise PAH: the endothelin, nitric oxide and prostacyclin pathways.The current treatment algorithm is based on the assessment of severity using a multiparametric risk stratification approach at the time of diagnosis (baseline) and at regular follow-up visits. It recommends the initiation of combination therapy in PAH patients without cardiopulmonary comorbidities. The choice of therapy (dual or triple) depends on the initial severity of the condition. The main treatment goal is to achieve low-risk status. Further escalation of treatment is required if low-risk status is not achieved at subsequent follow-up assessments. In the most severe patients, who are already on maximal medical therapy, lung transplantation may be indicated.Recent advances in understanding the pathophysiology of the disease have led to the development of promising emerging therapies targeting dysfunctional pathways beyond endothelial dysfunction, including the TGF-β and PDGF pathways.

The Stereotypic Response of the Pulmonary Vasculature to Respiratory Viral Infections: Findings in Mouse Models of SARS-CoV-2, Influenza A and Gammaherpesvirus Infections.

The respiratory system is the main target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 19 (COVID-19) where acute respiratory distress syndrome is considered the leading cause of death. Changes in pulmonary blood vessels, among which an endothelialitis/endotheliitis has been particularly emphasized, have been suggested to play a central role in the development of acute lung injury. Similar vascular changes are also observed in animal models of COVID-19. The present study aimed to determine whether the latter are specific for SARS-CoV-2 infection, investigating the vascular response in the lungs of mice infected with SARS-CoV-2 and other respiratory viruses (influenza A and murine gammaherpesvirus) by in situ approaches (histology, immunohistology, morphometry) combined with RNA sequencing and bioinformatic analysis. Non-selective recruitment of monocytes and T and B cells from larger muscular veins and arteries was observed with all viruses, matched by a comparable transcriptional response. There was no evidence of endothelial cell infection in any of the models. Both the morphological investigation and the transcriptomics approach support the interpretation that the lung vasculature in mice mounts a stereotypic response to alveolar and respiratory epithelial damage. This may have implications for the treatment and management of respiratory disease in humans.

Endobronchial Ultrasound for the Screening of Pulmonary Embolism in Patients with Suspected Lung Cancer: A Prospective Cohort Study

Background: Patients with lung cancer exhibit increased risk of pulmonary embolism (PE). While the contrast phase of computed tomography of the chest in the diagnostic work-up of suspected chest malignancy does not allow reliable detection of PE, it may be feasible to screen for present PE during endobronchial ultrasound (EBUS) examination. Objectives: The aim of this study was to establish if screening during EBUS for PE in patients with suspected lung cancer is feasible and if positive findings are predictive of PE. Methods: Patients undergoing EBUS due to suspicion of malignancy of the chest were prospectively enrolled. The pulmonary arteries were assessed during EBUS using a standardized protocol. Patients in whom PE suspicion was raised were referred to confirmatory imaging. Results: From December 2020 to August 2021, 100 patients were included. Median time for vascular assessment during EBUS was 2 min (Q1–Q3: 1–3 min). EBUS identified two suspected PEs (2%), and the number needed to scan was 50. The positive predictive value of EBUS for PE was 100%. Conclusion: EBUS for PE screening seems feasible and with limited time use. The PPV of positive findings for the diagnosis of PE is high, but the utility is somewhat limited by a high number needed to scan even in a high-risk population. Based on our findings, we believe that EBUS assessment of the pulmonary vasculature may have a role as a routine screening tool for PE. The assessment for PE should be implemented in EBUS training programmes, as operators should be able to recognize incidental PEs.

Aging-Related Accumulation of Truncated Oxidized Phospholipids Augments Infectious Lung Injury and Endothelial Dysfunction via Cluster of Differentiation 36-Dependent Mechanism.

Truncated phospholipid oxidation products (Tr-OxPL) increase in blood circulation with aging; however, their role in the severity of vascular dysfunction and bacterial lung injury in aging groups remains poorly understood. We investigated the effects of six Tr-OxPL species: KOdiA-PC, POVPC, PONPC, PGPC, Paz-PC, and Lyso-PC on endothelial dysfunction and lung inflammation caused by heat-killed Staphylococcus aureus (HKSA) in young (aged 2-4 months) and old (aged 12-18 months) mice, organotypic culture of precisely cut lung slices, and endothelial cells (mLEC) isolated from young and old mice. HKSA and Tr-OxPL combination caused a higher degree of vascular leak, the accumulation of inflammatory cells and protein in bronchoalveolar lavage, and inflammatory gene expression in old mice lungs. HKSA caused a greater magnitude of inflammatory gene activation in cell and ex vivo cultures from old mice, which was further augmented by Tr-OxPLs. L37pA peptide targeting CD36 receptor attenuated Tr-OxPL-induced endothelial cell permeability in young and old mLEC and ameliorated KOdiA-PC-induced vascular leak and lung inflammation in vivo. Finally, CD36 knockout mice showed better resistance to KOdiA-PC-induced lung injury in both age groups. These results demonstrate the aging-dependent vulnerability of pulmonary vasculature to elevated Tr-OxPL, which exacerbates bacterial lung injury. CD36 inhibition is a promising therapeutic approach for improving pneumonia outcomes in aging population.

Ultrasound Diagnosis of Congenital Diaphragm Hernia And Successful Outcome After Postnatal Surgery

Background: Congenital diaphragmatic hernia (CDH) is a disorder where abdominal contents protrude into the chest. Congenital diaphragmatic hernias are seen in 1 of every 2000-4000 live births. Mortality is predominantly due to the development of pulmonary hypoplasia which is thought to be due to the mass effect on the developing lung.Case Report:Mrs. Y, a 32-year-old controlled for antenatal care at the fetomaternal polyclinic M Djamil hospital. She had no complaints, the patient was referred from another hospital with a suspected fetal diaphragm hernia. The patient is known to be 38-39 weeks term pregnancy, from ultrasound examination found herniation of abdominal contents into the thoracic cavity and. the liquor was excessive and the doppler study was normal. The ultrasound showed normal growth and corresponded to 38 week Then the patient was planned for caesarean section and a hernia repair surgery. The neonate was admitted to the neonatal intensive care unit (NICU). He was shifted to the pediatric surgeon with ventilator support after 48 h and was undergoing surgery. There was a posterolateral left sided defect (BOCKDALEK type) of around 22–24 mm. The intestines were reduced to the abdomen and the closure was done. Immediately after the surgery, the child was admitted back to the NICU and the further postnatal course was uneventful.Discussion and Conclusion: CDH is a malformation of the diaphragm due to failure of closure of the pleuroperitoneal canal at around 10 weeks leading to herniation of abdominal contents into the thoracic cavity leading to compression of lung tissues at pseudo glandular stage. CDH is often ultrasound diagnosed before birth [120, 121]. The intestine and/or the liver may be in the thorax and the lungs are small. US scan allows detailed assessment of the heart. The survival depends on the contralateral lung volume, Ninety percent of cases are due to posterolateral defect which is also called Bochdalek hernia—80% are left sided, 15% are right sided and 5% are bilateral. Herniated viscera leads to pulmonary hypoplasia and pulmonary hypertension. Prognosis depends on the gestational age at diagnosis (earlier the diagnosis, likely larger the defect), associated anomalies, contralateral lung volume, pulmonary vasculature (Doppler), cardiac function, liver herniation and gestational age at delivery

Perioperative Management in Pulmonary Endarterectomy.

Pulmonary endarterectomy (PEA) is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension (PH), provided lesions are proximal enough in the pulmonary vasculature to be surgically accessible and the patient is well enough to benefit from the operation in the longer term. It is a major cardiothoracic operation, requiring specialized techniques and instruments developed over several decades to access and dissect out the intra-arterial fibrotic material. While in-hospital operative mortality is low (<5%), particularly in high-volume centers, careful perioperative management in the operating theater and intensive care is mandatory to balance ventricular performance, fluid balance, ventilation, and coagulation to avoid or treat complications. Reperfusion pulmonary edema, airway hemorrhage, and right ventricular failure are the most problematic complications, often requiring the use of extracorporeal membrane oxygenation to bridge to recovery. Successful PEA has been shown to improve both morbidity and mortality in large registries, with survival >70% at 10 years. For patients not suitable for PEA or with residual PH after PEA, balloon pulmonary angioplasty and/or PH medical therapy may prove beneficial. Here, we describe the indications for PEA, specific surgical and perioperative strategies, postoperative monitoring and management, and approaches for managing residual PH in the long term.

Portopulmonary Hypertension: An Updated Review.

Portal hypertension may have major consequences on the pulmonary vasculature due to the complex pathophysiological interactions between the liver and lungs. Portopulmonary hypertension (PoPH), a subset of group 1 pulmonary hypertension (PH), is a serious pulmonary vascular disease secondary to portal hypertension, and is the fourth most common subtype of pulmonary arterial hypertension. It is most commonly observed in cirrhotic patients; however, patients with noncirrhotic portal hypertension can also develop it. On suspicion of PoPH, the initial evaluation is by a transthoracic echocardiogram in which, if elevated pulmonary pressures are shown, patients should undergo right heart catheterization to confirm the diagnosis. The prognosis is extremely poor in untreated patients; therefore, management includes pulmonary arterial hypertension therapies with the aim of improving pulmonary hemodynamics and moving patients to orthotopic liver transplantation (OLT). In this article, we review in detail the epidemiology, pathophysiology, process for diagnosis, and most current treatments including OLT and prognosis in patients with PoPH. In addition, we present a diagnostic algorithm that includes the current criteria to properly select patients with PoPH who are candidates for OLT.