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.
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.
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.
BackgroundAlthough 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.MethodsFrom 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.ResultsThere 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.ConclusionsMultiple 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).
IntroductionHypoxic 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.MethodsFive 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.ResultsSixty 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.ConclusionsChest 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.
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