Evaluation of the Relationship Between Pulmonary Perfusion Via Chest Digital Dynamic Radiography System and Diffusing Capacity Test.

Non-invasive, visual, and quantitative in vivo evaluation of pulmonary blood flow is helpful in assessing gas exchange at the alveolar level. A chest digital dynamic radiography system (CDDR) has the potential to visually and quantitatively express pulmonary haemodynamics using temporal changes in radiographic transparency synchronised with the heartbeat. The lung-diffusing capacity (DLCO) test involves membranous factors comprising the alveolar membrane, interstitium, and vascular walls. Additionally, DLCO includes pulmonary blood flow factors defined by pulmonary capillary blood flow and haemoglobin levels. In individuals lacking an alveolar septum, interstitial abnormalities or anaemia leading to changes in DLCO may reflect changes in the pulmonary blood flow. Here, we investigated the usefulness of CDDR in evaluating pulmonary blood flow by comparing it with DLCO.For pulmonary blood flow, we extracted and visualised signal changes in the lung field synchronised with heart rate during CDDR imaging and created a maximum intensity projection (MIP). The DLCO was measured using the single-breath method. Among the patients who underwent CDDR, 10 with FEV/FVC (FEV1.0%) > 70% and 16 with COPD (FEV1.0% < 70%) without noticeable interstitial changes were included, with a cutoff = 70%/predicted value. MIP was compared as a pulmonary blood flow evaluation method in the DLCO≥70% group (control group: n = 15) and the DLCO<70% group (decreased DLCO group: n = 11). The mean and median values of MIP in the reduced group were lower than those in the control group (p < 0.05).Pulmonary blood flow evaluated using CDDR may be able to assess pulmonary circulatory disturbances visually and quantitatively, as indicated by decreased pulmonary diffusion capacity in patients with negligible pulmonary interstitial changes and anaemia.

Effect of sevoflurane preconditioning on sleep reintegration after alteration by lipopolysaccharide.

Despite extensive evidence on the organ protective effects of sevoflurane, its effect on disturbed sleep remains unclear. We hypothesised that sevoflurane preconditioning positively impacts disturbed sleep caused by systemic inflammation. A prospective, randomised laboratory investigation was conducted in C57BL/6J mice. A mouse model of lipopolysaccharide (LPS)-induced systemic inflammation was employed to investigate the effects of sevoflurane on sleep recovery. Symptom recovery was evaluated through electroencephalography/electromyography (EEG/EMG) and histological studies. The mice were exposed to 2% sevoflurane before and after peritoneal injection of LPS. The EEG and EMG were recorded for 24 h after the procedure. Brain tissue was harvested after the sevoflurane/LPS procedure and was immunostained using individual antibodies against choline acetyltransferase (ChAT) and Fos. The ChAT-positive and ChAT/Fos double-positive cells were analysed quantitatively in the pedunculopontine tegmental nucleus and laterodorsal tegmental nucleus (PPTg/LDTg). Compared with control mice, mice preconditioned with sevoflurane but not post-conditioned showed a significant increase in rapid eye movement (REM) sleep during EEG recording following the LPS challenge. They also demonstrated a shorter REM latency, indicating an early recovery from LPS-altered sleep. The bouts of REM episodes were retained with sevoflurane preconditioning. More ChAT/Fos double-positive cells were observed in the PPTg/LDTg in the sevoflurane preconditioning plus LPS group than in the LPS-only group. Sevoflurane preconditioning promotes recovery from altered sleep induced by systemic inflammation. Activation of PPTg/LDTg is considered a mechanism underlying sleep reintegration. The recovery phenomenon shows potential for clinical application in cases of sleep disturbances induced by systemic inflammation.

Pulmonary perfusion by chest digital dynamic radiography: Comparison between breath-holding and deep-breathing acquisition.

PURPOSE: Pulmonary perfusion is an important factor for gas exchange. Chest digital dynamic radiography (DDR) by the deep-breathing protocol can evaluate pulmonary perfusion in healthy subjects. However, respiratory artifacts may affect DDR in patients with respiratory diseases. We examined the feasibility of a breath-holding protocol and compared it with the deep-breathing protocol to reduce respiratory artifacts. MATERIALS AND METHODS: A total of 42 consecutive patients with respiratory diseases (32 males; age, 68.6 ± 12.3 yr), including 21 patients with chronic obstructive pulmonary disease, underwent chest DDR through the breath-holding protocol and the deep-breathing protocol. Imaging success rate and exposure to radiation were compared. The correlation rate of temporal changes in each pixel value between the lung fields and left cardiac ventricles was analyzed. RESULTS: Imaging success rate was higher with the breath-holding protocol vs the deep-breathing protocol (97% vs 69%, respectively; P < 0.0001). The entrance surface dose was lower with the breath-holding protocol (1.09 ± 0.20 vs 1.81 ± 0.08 mGy, respectively; P < 0.0001). The correlation rate was higher with the breath-holding protocol (right lung field, 41.7 ± 9.3%; left lung field, 44.2 ± 8.9% vs right lung field, 33.4 ± 6.6%; left lung field, 36.0 ± 7.1%, respectively; both lung fields, P < 0.0001). In the lower lung fields, the correlation rate was markedly different (right, 15.3% difference; left, 14.1% difference; both lung fields, P < 0.0001). CONCLUSION: The breath-holding protocol resulted in high imaging success rate among patients with respiratory diseases, yielding vivid images of pulmonary perfusion.

Analysis of key clinical features for achieving complete remission in stage III and IV non-small cell lung cancer patients.

BACKGROUND: Although development of immune checkpoint inhibitors and various molecular target agents has extended overall survival time (OS) in advanced non-small cell lung cancer (NSCLC), a complete cure remains rare. We aimed to identify features and treatment modalities of complete remission (CR) cases in stages III and IV NSCLC by analyzing long-term survivors whose OS exceeded 3 years. METHODS: From our hospital database, 1,699 patients, registered as lung cancer between 1st Mar 2004 and 30th Apr 2011, were retrospectively examined. Stage III or IV histologically or cytologically confirmed NSCLC patients with chemotherapy initiated during this period were enrolled. A Cox proportion hazards regression model was used. Data collection was closed on 13th Feb 2017. RESULTS: There were 164 stage III and 279 stage IV patients, including 37 (22.6%) and 51 (18.3%) long-term survivors and 12 (7.3%) and 5 (1.8%) CR patients, respectively. The long-term survivors were divided into three groups: 3 ≤ OS < 5 years, 5 years ≤ OS with tumor, and 5 years ≤ OS without tumor (CR). The median OS of these groups were 1,405, 2,238, and 2,876 days in stage III and 1,368, 2,503, and 2,643 days in stage IV, respectively. The mean chemotherapy cycle numbers were 16, 20, and 10 in stage III and 24, 25, and 5 in stage IV, respectively. In the stage III CR group, all patients received chemoradiation, all oligometastases were controlled by radiation, and none had brain metastases. Compared with non-CR patients, the stage IV CR patients had smaller primary tumors and fewer metastases, which were independent prognostic factors for OS among long-term survivors. The 80% stage IV CR patients received radiation or surgery for controlling primary tumors, and the surgery rate for oligometastases was high. Pathological findings in the stage IV CR patients revealed that numerous inflammatory cells existed around and inside resected lung and brain tumors, indicating strong immune response. CONCLUSIONS: Multiple line chemotherapies with primary and oligometastatic controls by surgery and/or radiation might achieve cure in certain advanced NSCLC. Cure strategies must be changed according to stage III or IV. This study was retrospectively registered on 16th Jun 2019 in UMIN Clinical Trials Registry (number UMIN000037078).

Retracted: Chest digital dynamic radiography to detect changes in human pulmonary perfusion in response to alveolar hypoxia.

INTRODUCTION: Hypoxic pulmonary vasoconstriction optimises oxygenation in the lung by matching the local-blood perfusion to local-ventilation ratio upon exposure to alveolar hypoxia. It plays an important role in various pulmonary diseases, but few imaging evaluations of this phenomenon in humans. This study aimed to determine whether chest digital dynamic radiography could detect hypoxic pulmonary vasoconstriction as changes in pulmonary blood flow in healthy individuals. METHODS: Five Asian men underwent chest digital dynamic radiography before and after 60 sec breath-holding at the maximal inspiratory level in upright and supine positions. Alveolar partial pressure of oxygen and atmospheric pressure were calculated using the blood gas test and digital dynamic radiography imaging, respectively. To evaluate the blood flow, the correlation rate of temporal change in each pixel value between the lung fields and left cardiac ventricles was analysed. RESULTS: Sixty seconds of breath-holding caused a mean reduction of 26.7 ± 6.4 mmHg in alveolar partial pressure of oxygen. The mean correlation rate of blood flow in the whole lung was significantly lower after than before breath-holding (before, upright 51.5%, supine 52.2%; after, upright 45.5%, supine 46.1%; both P < 0.05). The correlation rate significantly differed before and after breath-holding in the lower lung fields (upright, 11.8% difference; supine, 10.7% difference; both P < 0.05). The mean radiation exposure of each scan was 0.98 ± 0.09 mGy. No complications occurred. CONCLUSIONS: Chest digital dynamic radiography could detect the rapid decrease in pulmonary perfusion in response to alveolar hypoxia. It may suggest hypoxic pulmonary vasoconstriction in healthy individuals.

Trans-arterial Embolization in a Patient with Unilateral Absence of Pulmonary Artery: Treatment Success and the Four-year Prognosis.

Unilateral absence of the pulmonary artery (UAPA) with or without other anomalies in the heart is a rare congenital malformation. A 55-year-old Filipino woman without a remarkable medical history was admitted to our hospital for hemoptysis. Contrast-enhanced chest computed tomography revealed the absence of the left pulmonary artery. Echocardiography and right heart catheterization showed no cardiac malformations or pulmonary hypertension. We diagnosed her with isolated left-sided UAPA and performed transarterial embolization of the left inferior phrenic artery. This resolved the hemoptysis, and there was no recurrence during the four-year follow-up period.

Efficacy of Prophylactic Antibiotic Use in Preventing Post-bronchoscopy Pneumonia in Lung Cancer Patients.

OBJECTIVE: Post-bronchoscopy pneumonia can affect the prognosis of lung cancer patients. This prospective study examined the efficacy of prophylactic antibiotics for lung cancer patients at high-risk of post-bronchoscopy pneumonia, determined by our prediction score, using three risk factors: age 70 years or older, current smoking, and central tumors visualized on CT. METHODS: Patients with lung cancer who underwent diagnostic bronchoscopy between June 2018 and March 2020 with a score of 2 points or higher were enrolled. Sulbactam/ampicillin was administered intravenously within one hour prior to bronchoscopy, followed by oral clavulanate/amoxicillin for three days. We used the data of lung cancer patients who underwent diagnostic bronchoscopy between April 2012 and July 2014 and exhibited a score of 2 or higher as the historical control. RESULTS: Post-bronchoscopy pneumonia occurred in none of the 24 patients in the prophylaxis group and in 17 of 144 patients in the control group, with no significant difference in the incidence of pneumonia between the two groups. CONCLUSIONS: Antibiotic prophylaxis can be effective and safe for the patients high-risk of post-bronchoscopy pneumonia. A multicenter prospective study to examine the effects of prophylactic antibiotics in high-risk patients is feasible with a modest number of participants.

OX2R-selective orexin agonism is sufficient to ameliorate cataplexy and sleep/wake fragmentation without inducing drug-seeking behavior in mouse model of narcolepsy.

Acquired loss of hypothalamic orexin (hypocretin)-producing neurons causes the chronic sleep disorder narcolepsy-cataplexy. Orexin replacement therapy using orexin receptor agonists is expected as a mechanistic treatment for narcolepsy. Orexins act on two receptor subtypes, OX1R and OX2R, the latter being more strongly implicated in sleep/wake regulation. However, it has been unclear whether the activation of only OX2R, or both OX1R and OX2R, is required to replace the endogenous orexin functions in the brain. In the present study, we examined whether the selective activation of OX2R is sufficient to rescue the phenotype of cataplexy and sleep/wake fragmentation in orexin knockout mice. Intracerebroventricular [Ala11, D-Leu15]-orexin-B, a peptidic OX2R-selective agonist, selectively activated OX2R-expressing histaminergic neurons in vivo, whereas intracerebroventricular orexin-A, an OX1R/OX2R non-selective agonist, additionally activated OX1R-positive noradrenergic neurons in vivo. Administration of [Ala11, D-Leu15]-orexin-B extended wake time, reduced state transition frequency between wake and NREM sleep, and reduced the number of cataplexy-like episodes, to the same degree as compared with orexin-A. Furthermore, intracerebroventricular orexin-A but not [Ala11, D-Leu15]-orexin-B induced drug-seeking behaviors in a dose-dependent manner in wild-type mice, suggesting that OX2R-selective agonism has a lower propensity for reinforcing/drug-seeking effects. Collectively, these findings provide a proof-of-concept for safer mechanistic treatment of narcolepsy-cataplexy through OX2R-selective agonism.

Novel pulmonary perfusion imaging using chest digital dynamic radiography for pulmonary artery sarcoma.

Chest digital dynamic radiography (DDR) is a novel method for evaluating pulmonary perfusion and ventilation. It could depict ventilation-perfusion mismatch in a pulmonary artery sarcoma with severe stenosis in the right pulmonary artery. This report is the first demonstration of ventilation-perfusion mismatch in a malignant neoplasm using DDR.

Regression of Lung Squamous Cell Carcinoma after the Withdrawal of Cyclosporin A Combined with Pirfenidone Treatment in a Patient with Idiopathic Pulmonary Fibrosis.

A 72-year-old man was treated with prednisolone and cyclosporine A for idiopathic pulmonary fibrosis. A nodule with a diameter of 19 mm was found in the right lung and diagnosed as lung squamous cell carcinoma. Anti-cancer treatments were not performed because of the presence of advanced interstitial pneumonia and chronic respiratory failure. Cyclosporine A was tapered to avoid suppression of anti-tumor immunity, and pirfenidone was initiated. Within 2 months, the tumor had shrunk to 10 mm in diameter and remained regressed for 9 months. This is the first report of a non-hematologic solid organ tumor responding to the discontinuation of immunosuppressants.

Cytokine/Chemokine/Growth Factor Levels in Malignant Pleural Effusion of Non-small Cell Lung Cancer.

OBJECTIVE: Malignant pleural effusions (MPEs) deteriorate the quality of life in patients with advanced stages of cancer. Although vascular endothelial growth factor (VEGF) is known to be a key factor for MPE formation, it is not fully clarified whether there are other components related to its appearance. METHODS: Pleural effusion and serum samples were collected from patients with MPEs of non-small cell lung cancer. Cellular analysis of pleural effusion was performed using fluorescence flow cytometry. The concentrations of 12 cytokines, chemokines, and growth factors in MPEs and serum samples were analyzed using the cytometric bead array method. RESULTS: Fifteen patients (median age: 70 years, 11 males) with non-small cell lung cancer (13 adenocarcinoma, 2 squamous cell carcinoma) were enrolled in this study. Concentrations of VEGF, interleukin (IL)-5, IL-6, IL-8, IL-12/IL-23p40, and C-C motif chemokine ligand (CCL) 2 were significantly higher in MPE than in serum. Pleural IL-5 levels correlated with malignant cell numbers in MPE. There was no factor related to the total amount of drained effusion or period of chest tube insertion. CONCLUSIONS: Production of six molecules were increased in the pleural cavity with MPE of non-small cell lung cancer. Complex interactions among these molecules may regulate MPE formation.

Therapeutic effect of nintedanib on acute exacerbation of interstitial lung diseases.

Although the development of new antifibrotic agents (pirfenidone, nintedanib) has modified the disease progression of idiopathic pulmonary fibrosis (IPF), there is still no effective treatment for acute exacerbation of interstitial lung diseases (ILD) including IPF. We herein report a case of acute exacerbation of ILD (AE-ILD) treated only with nintedanib without any environmental changes and any other medications such as corticosteroid therapy, diuretic and anti-biotics, which resulted in the gradual improvement of the patient's clinical symptoms, high-resolution computed tomography findings, and forced vital capacity. This case might suggest the possibility that nintedanib not only modifies the disease progression of Idiopathic Pulmonary Fibrosis (IPF), but also facilitate the recovery from the acute exacerbation of ILD.

An Autopsy Case of Paradoxical Pulmonary Thromboembolism by Arteriovenous Fistula from Right Common Iliac Artery to Common Iliac Vein: A Rare Cause of Pulmonary Embolism.

BACKGROUND Pulmonary thromboembolism (PTE) sometimes leads to a shock state and sudden death due to acute massive pulmonary arterial thrombosis. The origins of pulmonary arterial thrombi are varied, but most arise from deep vein thrombosis. We herein presented a very rare cause of PTE due to paradoxical embolism caused by arteriovenous fistula from common iliac artery to common iliac vein. CASE REPORT A 74-year-old man was admitted because of increasing dyspnea on exertion. The diagnosis of idiopathic pulmonary fibrosis was made and corticosteroid therapy was started. On the 5th hospital day, the patient suddenly developed cardiopulmonary arrest and died despite cardiopulmonary resuscitation. An autopsy revealed that the left main pulmonary artery was occluded by a massive but organized thrombus that was similar to an arterial thrombus in the right common iliac artery. On histopathological examination, the emboli in the pulmonary artery demonstrated characteristics similar to thrombus in the common iliac artery. This suggested that the emboli had passed through the arteriovenous fistula from the right common iliac artery to the common iliac vein. CONCLUSIONS This is a very rare cause of fatal paradoxical pulmonary thromboembolism. Paradoxical emboli passing through arteriovenous fistula from the right common iliac artery to the common iliac vein are a rare cause of PTE.

Progressive Multifocal Micronodular Pneumocyte Hyperplasia in the Lungs of a Patient with Tuberous Sclerosis Complex: A Case Report.

We report a case of multifocal micronodular pneumocyte hyperplasia (MMPH) in a patient with tuberous sclerosis complex, in whom the lung nodules increased in the number and size over the course of 8 years. We diagnosed MMPH following a lung biopsy performed during video-assisted thoracic surgery. In most of the previously reported cases, the number and size of lung nodules is unchanged during the clinical course. Our case is the first report of progressive disease in pathologically proven MMPH.

Multi-cusp ion source for doping process of flat panel display manufacturing.

We developed a multi-cusp ion source for Nissin ion doping system iG5 which is used in low temperature poly-crystalline silicon processes for flat panel display (FPD) manufacturing. In this ion source, BF3 or PH3 diluted H2 plasmas are produced and large area ribbon ion beams are extracted. In general, ion ratio of B(+) in BF3 plasma is much smaller than BF2 (+) in multi-cusp ion sources. We developed a new method to increase B(+) ratio and obtained mass analyzed B(+) target current of 130 mA. We employed newly improved multi-slot type electrodes for the beam extraction system and obtained stable beams with the uniformity of below 3%. In BF3 plasmas, several undesirable metal fluorides are produced in the plasma chamber and deposited on the electrode system, which cause glitches and poor beam uniformity. We introduce several cleaning methods.