Quantitative analyzes of the variability in airways via four-dimensional dynamic ventilation CT in patients with chronic obstructive pulmonary disease: correlation with spirometry data and severity of airflow limitation.

Background: In chronic obstructive pulmonary disease (COPD) patients, the diagnosis and assessment of disease severity are mainly based on spirometry, which may lead to misjudgments due to poor patient compliance. Thoracic four-dimensional dynamic ventilation computed tomography (4D-CT) provides more airway data approximating true physiological function than conventional CT. We aimed to determine dynamic changes in airways to elucidate the pathological mechanism underlying COPD and predict the severity of airflow limitation in patients. Methods: Forty-two COPD patients underwent 4D-CT and spirometry. The minimum lumen diameter changed with the breathing cycle in 4th-generation airways and was continuously measured in the apical (RB1), lateral (RB4) and posterior basal segments (RB10) of the right lung. The minimum lumen diameter in the peak inspiration and peak expiration as well as the peak expiratory/peak inspiratory ratio (E/I ratio), and dynamic coefficient of variance (CV) were calculated. Results: Correlations of FEV1% with the CV of minimum lumen diameter in RB1 (ρ=-0.473, P=0.002) and in RB10 (ρ=-0.480, P=0.005) were observed, suggesting that the dynamic variability in 4th-generation airways was associated with airflow limitation in COPD patients. The CV of the minimum lumen diameter in RB1 significantly differed between the GOLD I + II and GOLD III + IV groups {8.59 [interquartile range (IQR), 6.63-14.86] vs. 14.64 (10.65-25.88), respectively; P=0.016}, suggesting that the dynamic CV in RB1 increased significantly in the GOLD III + IV group, which had worse pulmonary ventilation function. Based on the receiver operating characteristic (ROC) curve analysis, CV-RB1 predicted FEV1% <50% with an optimal cut-off of 9.43% [sensitivity 85.7%, specificity 57.1%, area under the curve (AUC) 0.717]. Conclusions: 4D-CT might be an available method to help diagnose and evaluate the severity of COPD.

Eosinophil and IFN-γ associated with immune-related adverse events as prognostic markers in patients with non-small cell lung cancer treated with immunotherapy.

Objectives: Immune checkpoint inhibitors (ICIs) alone or combined with other antitumor agents are largely used in lung cancer patients, which show both positive effects and side effects in particular subjects. Our study aims to identify biomarkers that can predict response to immunotherapy or risk of side effects, which may help us play a positive role and minimize the risk of adverse effects in clinical practice. Methods: We retrospectively collected data from patients with advanced non-small cell lung cancer (NSCLC) treated with ICIs at our center. Patients who received initial ICI therapy for >1 year without progression of disease were classified as long-term treatment (LT) group, while others were classified as the non-long-term treatment (NLT) group. Multivariate logistic analysis was performed to identify independent risk factors of progression-free survival (PFS) and immune-related adverse events (irAEs). Results: A total of 83 patients (55.7%) had irAEs. The median PFS for patients in grades 1-2 of irAEs vs. grades 3-4 vs non-irAEs groups was (undefined vs. 12 vs. 8 months; p = 0.0025). The 1-year PFS rate for multisystem vs. single vs. non-irAE groups was 63%, 56%, and 31%, respectively. Signal transduction of inflammatory cytokines improves clinical prognosis through immunomodulatory function, but the benefit is also limited by the resulting organ damage, making it a complex immune balance. Serum biomarkers including EOS% of ≥ 1.15 (HR: 8.30 (95% CI, 2.06 to 33.42); p = 0.003) and IFN-γ of ≥ 3.75 (HR: 5.10 (95% CI, 1.29 to 20.15), p = 0.02) were found to be predictive for irAEs. Conclusion: EOS% of ≥1.15% and IFN-γ of ≥3.75 ng/L were considered peripheral-blood markers for irAEs and associated with improved clinical outcomes for immunotherapy in patients with advanced NSCLC.

A new handheld fundus camera combined with visual artificial intelligence facilitates diabetic retinopathy screening.

AIM: To explore the performance in diabetic retinopathy (DR) screening of artificial intelligence (AI) system by evaluating the image quality of a handheld Optomed Aurora fundus camera in comparison to traditional tabletop fundus cameras and the diagnostic accuracy of DR of the two modalities. METHODS: Overall, 630 eyes were included from three centers and screened by a handheld camera (Aurora, Optomed, Oulu, Finland) and a table-top camera. Image quality was graded by three masked and experienced ophthalmologists. The diagnostic accuracy of the handheld camera and AI system was evaluated in assessing DR lesions and referable DR. RESULTS: Under nonmydriasis status, the handheld fundus camera had better image quality in centration, clarity, and visible range (1.47, 1.48, and 1.40) than conventional tabletop cameras (1.30, 1.28, and 1.18; P<0.001). Detection of retinal hemorrhage, hard exudation, and macular edema were comparable between the two modalities, in principle, with the area under the curve of the handheld fundus camera slightly lower. The sensitivity and specificity for the detection of referable DR with the handheld camera were 82.1% (95%CI: 72.1%-92.2%) and 97.4% (95%CI: 95.4%-99.5%), respectively. The performance of AI detection of DR using the Phoebus Algorithm was satisfactory; however, Phoebus showed a high sensitivity (88.2%, 95%CI: 79.4%-97.1%) and low specificity (40.7%, 95%CI: 34.1%-47.2%) when detecting referable DR. CONCLUSION: The handheld Aurora fundus camera combined with autonomous AI system is well-suited in DR screening without mydriasis because of its high sensitivity of DR detection as well as its image quality, but its specificity needs to be improved with better modeling of the data. Use of this new system is safe and effective in the detection of referable DR in real world practice.

Chiral Bis(oxazoline)-Copper Complex Catalyzed Asymmetric Alkenylation of Isatin Imines and 3-Vinylindoles for Construction of Optically Active 3-Alkenyl-3-aminooxindoles.

The first catalytic asymmetric alkenylation of isatin imines is described. The reaction, which is promoted by a chiral bis(oxazoline)-copper complex, gives structurally diverse 3-alkenyl-3-aminooxindole derivatives in excellent yields, and with excellent diastereoselectivities and high-to-excellent enantioselectivities. The products can be readily converted to polycyclic indole derivatives without loss of enantioselectivity. A plausible chirality-induced mechanism is proposed to explain the observed stereoselective control.

Evaluation of visual functional and morphology change in young patients with idiopathic choroidal neovascularization.

BACKGROUND: Idiopathic choroidal neovascularization (ICNV) is an uncommon disorder affecting primarily individuals younger than the age of 50 years. In CNV patients, no apparent cause can be determined. This study aimed to evaluate the functional and morphological change of the retina with ICNV in young adults. METHODS: In this retrospective study, 32 eyes of 32 patients with subfoveal or juxta/extra foveal ICNV had been admitted into the Shanghai First People's Hospital from January 2009 to July 2010. The functional changes were evaluated using the best corrected visual acuity (BCVA) and the microperimetry in the macular area. The morphology changes were evaluated using optical coherence tomography (OCT), the color fundus photography and the fluorescein angiography. RESULTS: Seventeen patients with juxta/extra foveal and 15 subfoveal CNV were investigated. The mean logarithm of the minimum angle of resolution (LogMAR) BCVA was 0.39, the mean central retinal thickness (CRT) was 334 µm, and the mean sensitivity (MS) was 11.8 decibels (dB). In the subfoveal group, there was a strong correlation between CRT and BCVA (r = -0.675, F = 2.167, P < 0.01); as well as that between CRT and MS (r = -0.681, F = 22.91, P < 0.01). While in the juxta/extra foveal CNV group, the correlation of CRT and BCVA was not significant (r = -0.071, F = 1.018, P > 0.05); neither was the correlation of CRT and MS (r = -0.142, F = 36.54, P > 0.05). The microperimetry (MP-1) test revealed 17 (53%) patients with stable fixation, 9 (28%) with relatively unstable and 6 (19%) with unstable fixation. Fixation stability correlated positively with sensitivity in the central 2° diameter area (r = 0.380, F = 3.213, P < 0.05) and the duration of symptoms (r = 0.401, F = 7.933, P < 0.05). CONCLUSIONS: ICNV was associated with reduced total MS, unstable fixation and eccentric fixation. These findings emphasized functional change in ICNV is beyond the BCVA and regular morphology change, which provided additional information of functional evaluation in clinical practice.