Specification and guideline for technical aspects and scanning parameter settings of neonatal lung ultrasound examination.

Lung ultrasound (LUS) is now widely used in the diagnosis and monitor of neonatal lung diseases. Nevertheless, in the published literatures, the LUS images may display a significant variation in technical execution, while scanning parameters may influence diagnostic accuracy. The inter- and intra-observer reliabilities of ultrasound exam have been extensively studied in general and in LUS. As expected, the reliability declines in the hands of novices when they perform the point-of-care ultrasound (POC US). Consequently, having appropriate guidelines regarding to technical aspects of neonatal LUS exam is very important especially because diagnosis is mainly based on interpretation of artifacts produced by the pleural line and the lungs. The present work aimed to create an instrument operation specification and parameter setting guidelines for neonatal LUS. Technical aspects and scanning parameter settings that allow for standardization in obtaining LUS images include (1) select a high-end equipment with high-frequency linear array transducer (12-14 MHz). (2) Choose preset suitable for lung examination or small organs. (3) Keep the probe perpendicular to the ribs or parallel to the intercostal space. (4) Set the scanning depth at 4-5 cm. (5) Set 1-2 focal zones and adjust them close to the pleural line. (6) Use fundamental frequency with speckle reduction 2-3 or similar techniques. (7) Turn off spatial compounding imaging. (8) Adjust the time-gain compensation to get uniform image from the near-to far-field.

Application of modified closed biopsy in rabbit model of VX2-transplanted bone tumor.

BACKGROUND: This study was aimed to explore the application value of modified closed biopsy technique in puncture biopsy of rabbit VX2 transplanted bone tumor model. METHODS: VX2 tumor was transplanted into the bilateral tibia of 30 rabbits through the tibial plateau to make the model of VX2 transplanted bone tumor. Seven days after modeling, the proximal tibia biopsy was performed under the guidance of X-ray, and the biopsy specimen was examined pathologically. The left leg was biopsied with modified closed biopsy technique (experimental group), and the right leg was biopsied with hollow needle (control group). After 14 days of modeling, all rabbits were killed after X-ray examination around the puncture hole, and the soft tissue around the puncture hole was taken for pathological examination, and the expression levels of PCNA and CD34 in the tissue extract were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: By the end of the experiment, a total of 3 rabbits died, and finally, 27 rabbits were included in the study. Tumor cells were detected in all the intramedullary specimens obtained by puncture biopsy. On the 14th day after modeling, X-ray showed that the occurrence rate of periosteal reaction and extraosseous high-density shadow around the puncture hole was 14.81% (4/27) in the experimental group and 40.74% (11/27) in the control group. The difference was statistically significant (P<0.05). The pathological results of soft tissue around the puncture hole showed that the tumor cell metastasis rate was 29.63% (8/27) in the experimental group and 100% (27/27) in the control group, and the difference was statistically significant (P<0.05). The expression levels of PCNA and CD34 in the experimental group were lower than those in the control group (P < 0.05). CONCLUSION: Both the modified closed biopsy technique and needle aspiration biopsy can provide sufficient biopsy tissue for the diagnosis of VX2-transplanted bone tumor in rabbits. At the same time, the improved closed biopsy technique has a certain application value in preventing local metastasis of tumor cells along the puncture channel.

International Expert Consensus and Recommendations for Neonatal Pneumothorax Ultrasound Diagnosis and Ultrasound-guided Thoracentesis Procedure.

Pneumothorax (PTX) represents accumulation of the air in the pleural space. A large or tension pneumothorax can collapse the lung and cause hemodynamic compromise, a life-threatening disorder. Traditionally, neonatal pneumothorax diagnosis has been based on clinical images, auscultation, transillumination, and chest X-ray findings. This approach may potentially lead to a delay in both diagnosis and treatment. The use of lung US in diagnosis of PTX together with US-guided thoracentesis results in earlier and more precise management. The recommendations presented in this publication are aimed at improving the application of lung US in guiding neonatal PTX diagnosis and management.

Protocol and Guidelines for Point-of-Care Lung Ultrasound in Diagnosing Neonatal Pulmonary Diseases Based on International Expert Consensus.

Ultrasound is a safe bedside imaging tool that obviates the use of ionizing radiation diagnostic procedures. Due to its convenience, the lung ultrasound has received increasing attention from neonatal physicians. Nevertheless, clear reference standards and guideline limits are needed for accurate application of this diagnostic modality. This document aims to summarize expert opinions and to provide precise guidance to help facilitate the use of the lung ultrasound in the diagnosis of neonatal lung diseases.

A bispecific enediyne-energized fusion protein targeting both epidermal growth factor receptor and insulin-like growth factor 1 receptor showing enhanced antitumor efficacy against non-small cell lung cancer.

Epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF-1R) both overexpressed on non-small cell lung cancer (NSCLC) and are known cooperatively to promote tumor progression and drug resistance. This study was to construct a novel bispecific fusion protein EGF-IGF-LDP-AE consisting of EGFR and IGF-IR specific ligands (EGF and IGF-1) and lidamycin, an enediyne antibiotic with potent antitumor activity, and investigate its antitumor efficacy against NSCLC. Binding and internalization assays showed that EGF-IGF-LDP protein could bind to NSCLC cells with high affinity and then internalized into cells with higher efficiency than that of monospecific proteins. In vitro, the enediyne-energized analogue of bispecific fusion protein (EGF-IGF-LDP-AE) displayed extremely potent cytotoxicity to NSCLC cell lines with IC50<10-11 mol/L. Moreover, the bispecific protein EGF-IGF-LDP-AE was more cytotoxic than monospecific proteins (EGF-LDP-AE and LDP-IGF-AE) and lidamycin. In vivo, EGF-IGF-LDP-AE markedly inhibited the growth of A549 xenografts, and the efficacy was more potent than that of lidamycin and monospecific counterparts. EGF-IGF-LDP-AE caused significant cell cycle arrest and it also induced cell apoptosis in a dosage-dependent manner. Pretreatment with EGF-IGF-LDP-AE inhibited EGF-, IGF-stimulated EGFR and IGF-1R phosphorylation, and blocked two main downstream signaling molecules AKT and ERK activation. These data suggested that EGF-LDP-IGF-AE protein would be a promising targeted agent for NSCLC patients with EGFR and/or IGF-1R overexpression.

A ligand-based and enediyne-energized bispecific fusion protein targeting epidermal growth factor receptor and insulin-like growth factor-1 receptor shows potent antitumor efficacy against esophageal cancer.

Recent studies have revealed that the epidermal growth factor receptor (EGFR) and insulin-like growth factor-1 receptor (IGF-1R) are overexpressed in various types of human tumors and are attractive targets for anticancer drugs. In the present study, the expression of EGFR and IGF-1R in esophageal squamous cell carcinoma (ESCC) and adjacent normal tissues in a tissue microarray was firstly detected by immunohistochemical staining. In addition, their co-overexpression was observed in 48 out of 75 (64%) patients. Based on the findings, the antitumor activity of an EGFR/IGF-1R bispecific and enediyne-energized fusion protein EGF-LDP-IGF-AE, which we constructed recently by fusing two ligands (EGF and IGF-1) with an enediyne antibiotic lidamycin (LDM), on ESCC were evaluated. Binding assay indicated that the EGF-LDP-IGF protein bound to esophageal cancer cells, and then internalized into the cytoplasm. In vitro, the enediyne­energized fusion protein EGF-LDP-IGF-AE exhibited extremely potent cytotoxicity to ESCC cells with IC50 values between 10-10 and 10-15 mol/l. In vivo, EGF-LDP­IGF-AE also markedly suppressed the growth of human KYSE450 xenografts by 75.1% when administered at 0.3 mg/kg in a nude mouse model, and its efficacy was significantly higher than that of LDM (at maximum tolerated dosage) and mono-specific counterparts. In addition, EGF-LDP-IGF-AE arrested cell cycle progression and it concentration-dependently induced cell apoptosis as well as inhibited the activation of EGFR/IGF-1R and two major downstream signaling pathways (PI3K/AKT and RAS/MAPK). These data imply the potential clinical application of EGF-LDP-IGF-AE for ESCC patients with EGFR and/or IGF-1R overexpression.

Lung ultrasonography to diagnose meconium aspiration syndrome of the newborn.

Objective To investigate the diagnostic value of lung ultrasonography for neonatal meconium aspiration syndrome (MAS). Methods This prospective observational study enrolled patients diagnosed with MAS based on medical history, clinical manifestations and chest X-ray and control newborns without MAS. During ultrasonography, each lung was divided into three regions (front, lateral, and back), using anterior and posterior axillary lines as the boundary. While scanning each region of the lungs, the hand piece was perpendicular or parallel to the ribs. Results This study enrolled 117 newborns with MAS and 100 controls. The main lung ultrasonographic findings in patients with MAS were: (i) pulmonary consolidation with air bronchogram was found in all patients; (ii) pleural line anomalies and the disappearance of the A-line was found in all patients; (iii) atelectasis was found in 19 (16.2%) severe cases, who demonstrated severe massive atelectasis and visible lung pulse; (iv) pleural effusion was found in 16 patients (13.7%); and (v) alveolar-interstitial syndrome or B-line in the non-consolidation area was found in all patients with MAS. Conclusion Ultrasonography can be used routinely to diagnose MAS in an accurate, reliable, convenient, and non-invasive manner.

The significance and the necessity of routinely performing lung ultrasound in the neonatal intensive care units.

Various lung diseases are the most common conditions and the leading cause of hospital admission and death in newborns. Historically, the diagnosis and differential diagnosis of lung diseases primarily relied on conventional chest X-ray and computed tomography (CT) scans, however, chest X-ray and CT scans suffer from obvious limitations, while lung ultrasound has many kinds of advantages for the diagnosis and differential diagnosis of lung diseases. The significance and the necessity of lung ultrasound in the diagnosis of neonatal lung diseases will be introduced in this paper.

The Role of Lung Ultrasound in Diagnosis of Respiratory Distress Syndrome in Newborn Infants.

BACKGROUND: Respiratory distress syndrome (RDS) is one of the most common causes of neonatal respiratory failure and mortality. The risk of developing RDS decreases with both increasing gestational age and birth weight. OBJECTIVES: The aim of this study was to evaluate the value of lung ultrasound in the diagnosis of respiratory distress syndrome (RDS) in newborn infants. MATERIALS AND METHODS: From March 2012 to May 2013, 100 newborn infants were divided into two groups: RDS group (50 cases) and control group (50 cases). According to the findings of chest x-ray, there were 10 cases of grade II RDS, 15 grade III cases, and 25 grade IV cases in RDS group. Lung ultrasound was performed at bedside by a single expert. The ultrasound indexes observed in this study included pleural line, A-line, B-line, lung consolidation, air bronchograms, bilateral white lung, interstitial syndrome, lung sliding, lung pulse etc. RESULTS: In all of the infants with RDS, lung ultrasound consistently showed generalized consolidation with air bronchograms, bilateral white lung or alveolar-interstitial syndrome, pleural line abnormalities, A-line disappearance, pleural effusion, lung pulse, etc. The simultaneous demonstration of lung consolidation, pleural line abnormalities and bilateral white lung, or lung consolidation, pleural line abnormalities and A-line disappearance co-exists with a sensitivity and specificity of 100%. Besides, the sensitivity was 80% and specificity 100% of lung pulse for the diagnosis of neonatal RDS. CONCLUSIONS: This study indicates that using an ultrasound to diagnose neonatal RDS is accurate and reliable too. A lung ultrasound has many advantages over other techniques. Ultrasound is non-ionizing, low-cost, easy to operate, and can be performed at bedside, making this technique ideal for use in NICU.

The role of lung ultrasound in diagnosis of respiratory distress syndrome in newborn infants.

OBJECTIVE: The aim of this study was to evaluate the value of lung ultrasound in the diagnosis of respiratory distress syndrome (RDS) in newborn infants. METHODS: From March 2012 to May 2013, 100 newborn infants were divided into two groups: RDS group (50 cases) and control group (50 cases). According to the findings of chest x-ray, there were 10 cases of grade II RDS, 15 grade III cases, and 25 grade IV cases in RDS group. Lung ultrasound was performed at bedside by a single expert. The ultrasound indexes observed in this study included pleural line, A-line, B-line, lung consolidation, air bronchograms, bilateral white lung, interstitial syndrome, lung sliding, lung pulse etc. FINDINGS: In all of the infants with RDS, lung ultrasound consistently showed generalized consolidation with air bronchograms, bilateral white lung or interstitial syndrome, pleural line abnormalities, A-line disappearance, pleural effusion, lung pulse, etc. The simultaneous demonstration of lung consolidation, pleural line abnormalities and bilateral white lung, or lung consolidation, pleural line abnormalities and A-line disappearance co-exists with a sensitivity and specificity of 100% for the diagnosis of neonatal RDS. CONCLUSION: This study indicates that using an ultrasound to diagnose neonatal RDS is accurate and reliable tool. A lung ultrasound has many advantages over other techniques. Ultrasound is non-ionizing, low-cost, easy to operate, and can be performed at bedside, making this technique ideal for use in NICU.

[Lung ultrasonography for the diagnosis of neonatal respiratory distress syndrome: a pilot study].

OBJECTIVE: The diagnosis of respiratory distress syndrome (RDS) is usually based on clinical manifestations, arterial blood gas analysis and chest x-ray. Lung ultrasounds are typically not included in the diagnostic work-up of neonatal RDS. Recently, ultrasounds have been used extensively and successfully in the diagnosis of many kinds of lung diseases, but few studies have addressed neonatal RDS. This study aimed to evaluate the value of lung ultrasound in the diagnosis of neonatal RDS. METHOD: From May, 2012 to September, 2012, 45 newborn infants with RDS and 30 neonates without lung disease were enrolled into this study. Lung ultrasound was performed at bedside by a single expert physician in the first 24 h of life before exogenous pulmonary surfactant administration. The transthoracic approach was performed with longitudinal scans of the anterior, lateral and posterior chest walls. A conventional antero-posterior chest X rag was performed at bedside in the patients immediately when lung ultrasound was finished. RESULT: The ultrasound signs of lung consolidation, pleural line abnormalities, bilateral "white lung" and A-line disappearance were seen in 100% of RDS patients while they were not found in any of the controls (P < 0.001). Lung pulse was 80% in RDS patients and in 0% of controls, respectively (P = 0.001). The pleural effusion were 13.3% in RDS patients and 0% in controls, respectively (P < 0.001). B-lines existed in 4.4% of RDS patients and in 26.7% of controls (P = 0.012). Both the sensitivity and specificity were 100% when ultrasonic signs of lung consolidation, pleural line abnormalities and bilateral "white lung" coexisted or when lung consolidation, pleural line abnormalities and A-line disappearance coexisted. The presence of lung pulse demonstrated a sensitivity of 80% and a specificity of 100% in diagnosis of RDS. CONCLUSION: The main ultrasound imaging features of neonatal RDS include lung consolidation with air bronchograms, pleural line abnormalities, lung pulse and bilateral "white lung" or alveolar-interstitial syndrome. It is accurate and reliable that using ultrasound to diagnose neonatal RDS, which also has many other advantages including non-ionizing, can be performed at bedside, easy-operatinng, can be repeated several times in a day without hazards to the operators and the patients. Therefore, it deserves to be carried out in the neonatal ward.

The pattern and early diagnostic value of Doppler ultrasound for neonatal hypoxic-ischemic encephalopathy.

This article investigates the value of early diagnosis and prognostic evaluation of Doppler ultrasound for neonatal hypoxic-ischemic encephalopathy (HIE). Study population included 40 term neonates with HIE and 30 healthy controls. Color Doppler ultrasound was performed at the bedside within 24 h after birth. The transducer was placed on the temporal fontanelle to detect the hemodynamic parameters of bilateral middle cerebral arteries. The results showed that infants with HIE had significant cerebral hemodynamic disturbance. The cerebral blood flow velocity decreased or increased markedly as resistive index (RI) decreased or increased markedly, which usually suggested the diagnosis of HIE, RI < 0.50 or RI > 0.90 usually occurred in severe patients, while RI > 1.0 would be associated with later brain death. So we believe that using Pulsed Doppler ultrasound to monitor the changes of cerebral hemodynamics can be used for the early diagnosis of HIE and help us to distinguish the grades of HIE.