Prediction of clinical risk assessment and survival in chronic obstructive pulmonary disease with pulmonary hypertension.

BACKGROUND: Patients with pulmonary hypertension (PH) and chronic obstructive pulmonary disease (COPD) have an increased risk of disease exacerbation and decreased survival. We aimed to develop and validate a non-invasive nomogram for predicting COPD associated with severe PH and a prognostic nomogram for patients with COPD and concurrent PH (COPD-PH). METHODS: This study included 535 patients with COPD-PH from six hospitals. A multivariate logistic regression analysis was used to analyse the risk factors for severe PH in patients with COPD and a multivariate Cox regression was used for the prognostic factors of COPD-PH. Performance was assessed using calibration, the area under the receiver operating characteristic curve and decision analysis curves. Kaplan-Meier curves were used for a survival analysis. The nomograms were developed as online network software. RESULTS: Tricuspid regurgitation velocity, right ventricular diameter, N-terminal pro-brain natriuretic peptide (NT-proBNP), the red blood cell count, New York Heart Association functional class and sex were non-invasive independent variables of severe PH in patients with COPD. These variables were used to construct a risk assessment nomogram with good discrimination. NT-proBNP, mean pulmonary arterial pressure, partial pressure of arterial oxygen, the platelet count and albumin were independent prognostic factors for COPD-PH and were used to create a predictive nomogram of overall survival rates. CONCLUSIONS: The proposed nomograms based on a large sample size of patients with COPD-PH could be used as non-invasive clinical tools to enhance the risk assessment of severe PH in patients with COPD and for the prognosis of COPD-PH. Additionally, the online network has the potential to provide artificial intelligence-assisted diagnosis and treatment. HIGHLIGHTS: A multicentre study with a large sample of chronic obstructive pulmonary disease (COPD) patients diagnosed with PH through right heart catheterisation. A non-invasive online clinical tool for assessing severe pulmonary hypertension (PH) in COPD. The first risk assessment tool was established for Chinese patients with COPD-PH.

Asymmetric Magnon Frequency Comb.

We theoretically show the asymmetric spin wave transmission in a coupled waveguide-skyrmion structure, where the skyrmion acts as an effective nanocavity allowing the whispering gallery modes for magnons. The asymmetry originates from the chiral spin wave mode localized in the circular skyrmion wall. By inputting two-tone excitations and mixing them in the skyrmion wall, we observe a unidirectional output magnon frequency comb propagating in the waveguide with a record number of teeth (>50). This coupled waveguide-cavity structure turns out to be a universal paradigm for generating asymmetric magnon frequency combs, where the cavity can be generalized to other magnetic structures that support the whispering gallery mode of magnons. Our results advance the understanding of the nonlinear interaction between magnons and magnetic textures and open a new pathway to exploring the asymmetric spin wave transmission and to steering the magnon frequency comb.

Exploring Appropriate Reference Intervals and Clinical Decision Limits for Glucose-6-Phosphate Dehydrogenase Activity in Individuals From Guangzhou, China.

Background: Quantitative detection of glucose-6-phosphate dehydrogenase (G6PD) is commonly done to screen for G6PD deficiency. However, current reference intervals (RIs) of G6PD are unsuitable for evaluating G6PD-activity levels with local populations or associating G6PD variants with hemolysis risk to aid clinical decision-making. We explored appropriate RIs and clinical decision limits (CDLs) for G6PD activity in individuals from Guangzhou, China. Methods: We enrolled 5,852 unrelated individuals between 2020 and 2022 and screened their samples in quantitative assays for G6PD activity. We conducted further investigations, including G6PD genotyping, thalassemia genotyping, follow-up analysis, and statistical analysis, for different groups. Results: In Guangzhou, the RIs for the G6PD activities were 11.20-20.04 U/g Hb in male and 12.29-23.16 U/g Hb in female. The adjusted male median and normal male median (NMM) values were 15.47 U/g Hb and 15.51 U/g Hb, respectively. A threshold of 45% of the NMM could be used as a CDL to estimate the probability of G6PD variants. Our results revealed high hemolysis-risk CDLs (male: <10% of the NMM, female: <30% of the NMM), medium hemolysis-risk CDLs (male: 10%-45% of the NMM, female: 30%-79% of the NMM), and low hemolysis-risk CDLs (male: ≥ 45% of the NMM, female: ≥ 79% of the NMM). Conclusions: Collectively, our findings contribute to a more accurate evaluation of G6PD-activity levels within the local population and provide valuable insights for clinical decision-making. Specifically, identifying threshold values for G6PD variants and hemolysis risk enables improved prediction and management of G6PD deficiency, ultimately enhancing patient care and treatment outcomes.

Comparison of clopidogrel and ticagrelor in treating acute coronary syndrome undergoing PCI: A systematic review and meta-analysis.

Objective: The study aims to evaluate and compare the efficacy and safety between ticagrelor and clopidogrel in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). Methods: We searched MEDLINE (via PubMed), Cochrane, Embase, and the Cochrane library databases for eligible citations (the last search was up to December 2021). Subgroup analyses were performed based on region, study design, dose, and single-center/multicenter. Meta regressions were conducted to explore the source of heterogeneity. A sensitivity analysis was conducted to assess the robustness of the results. Funnel plots and Egger's test were preformed to test publication bias of the meta-analysis. Results: A total of 29 studies were included, totaling 165,981 patients. Ticagrelor reduced the overall incidence rate of major adverse cardiovascular events (MACEs) (HR 0.74; 95% CI, 0.62, 0.89; P = 0.001; I2 = 88.3%, P < 0.001) and all-cause mortality (HR 0.85; 95% CI, 0.75, 0.97; P = 0.019; I2 = 39.7%, P = 0.052) compared with clopidogrel. However, there was a higher risk of major bleeding (HR 1.21; 95% CI, 1.02,1.44; P = 0.026, I2 = 59.3%, P = 0.012) and all bleeding (HR 1.42; 95% CI, 1.24, 1.62; P < 0.001, I2 = 76.4%, P < 0.001) with ticagrelor compared to clopidogrel. The stability of the results was demonstrated by sensitivity analysis. Furthermore, subgroup analyses and meta-regression revealed that the heterogeneity in the study may stem from factors such as whether it was conducted in a single-center or multicenter setting, as well as the geographical region. Conclusion: Ticagrelor has demonstrated superior efficacy compared to clopidogrel in ACS patients undergoing PCI, particularly in Asia and Europe. Nevertheless, it is crucial to acknowledge that the utilization of ticagrelor is linked to a heightened risk of bleeding. To provide guidance for clinical decision-making regarding the use of ticagrelor, future multicenter randomized trials that are relevant and encompass longer follow-up periods are necessary. The category of the manuscript a meta-analysis: PROSPERO registration number CRD42021274198.

A rare sequelae of esophageal perforation: Fibrosing mediastinitis.

Fibrosing mediastinitis (FM) is a rare disease caused by different causes. If left untreated, the prognosis is poor. The common causes of FM are Tuberculosis and Histoplasma capsulatum infection. Esophageal perforation is also a rare condition that is often easily under- and mis-diagnosed due to the lack of specificity of symptoms. Here we report a case of FM caused by esophageal perforation.

Nonlinear Topological Magnon Spin Hall Effect.

When a magnon passes through two-dimensional magnetic textures, it will experience a fictitious magnetic field originating from the 3×3 skew-symmetric gauge fields. To date, only one of the three independent components of the gauge fields has been found to play a role in generating the fictitious magnetic field, while the other two are perfectly hidden. In this Letter, we show that they are concealed in the nonlinear magnon transport in magnetic textures. Without loss of generality, we theoretically study the nonlinear magnon-skyrmion interaction in antiferromagnets. By analyzing the scattering features of three-magnon processes between the circularly polarized incident magnon and breathing skyrmion, we predict a giant Hall angle of both the confluence and splitting modes. Furthermore, we find that the Hall angle reverses its sign when one switches the handedness of the incident magnons. We dub this the nonlinear topological magnon spin Hall effect. Our findings are deeply rooted in the bosonic nature of magnons that the particle number is not conserved, which has no counterpart in low-energy fermionic systems and may open the door for probing gauge fields by nonlinear means.

Targeting the cochlin/SFRP1/CaMKII axis in the ocular posterior pole prevents the progression of nonpathologic myopia.

Myopia is a major public health issue. However, interventional modalities for nonpathologic myopia are limited due to its complicated pathogenesis and the lack of precise targets. Here, we show that in guinea pig form-deprived myopia (FDM) and lens-induced myopia (LIM) models, the early initiation, phenotypic correlation, and stable maintenance of cochlin protein upregulation at the interface between retinal photoreceptors and retinal pigment epithelium (RPE) is identified by a proteomic analysis of ocular posterior pole tissues. Then, a microarray analysis reveals that cochlin upregulates the expression of the secreted frizzled-related protein 1 (SFRP1) gene in human RPE cells. Moreover, SFRP-1 elevates the intracellular Ca2+ concentration and activates Ca2+/calmodulin-dependent protein kinase II (CaMKII) signaling in a simian choroidal vascular endothelial cell line, and elicits vascular endothelial cell dysfunction. Furthermore, genetic knockdown of the cochlin gene and pharmacological blockade of SFRP1 abrogates the reduced choroidal blood perfusion and prevents myopia progression in the FDM model. Collectively, this study identifies a novel signaling axis that may involve cochlin in the retina, SFRP1 in the RPE, and CaMKII in choroidal vascular endothelial cells and contribute to the pathogenesis of nonpathologic myopia, implicating the potential of cochlin and SFRP1 as myopia interventional targets.

Genotypic and phenotypic characterization of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Guangzhou, China.

BACKGROUND: G6PD deficiency is a common inherited disorder worldwide and has a higher incidence rate in southern China. Many variants of G6PD result from point mutations in the G6PD gene, leading to decreased enzyme activity. This study aimed to analyse the genotypic and phenotypic characteristics of G6PD deficiency in Guangzhou, China. METHODS: In this study, a total of 20,208 unrelated participants were screened from 2020 to 2022. G6PD deficiency was further analysed by quantitative enzymatic assay and G6PD mutation analysis. The unidentified genotype of the participants was further ascertained by direct DNA sequencing. RESULTS: A total of 12 G6PD mutations were identified. Canton (c.1376G>T) and Kaiping (c.1388G>A) were the most common variants, and different mutations led to varying levels of G6PD enzyme activity. Comparing the enzyme activities of the 6 missense mutations between the sexes, we found significant differences (P < 0.05) in the enzyme activities of both male hemizygotes and female heterozygotes. Two previously unreported mutations (c.1438A>T and c.946G>A) were identified. CONCLUSIONS: This study provided detailed genotypes of G6PD deficiency in Guangzhou, which could be valuable for diagnosing and researching G6PD deficiency in this area.

Machine Learning Based on Computed Tomography Pulmonary Angiography in Evaluating Pulmonary Artery Pressure in Patients with Pulmonary Hypertension.

BACKGROUND: Right heart catheterization is the gold standard for evaluating hemodynamic parameters of pulmonary circulation, especially pulmonary artery pressure (PAP) for diagnosis of pulmonary hypertension (PH). However, the invasive and costly nature of RHC limits its widespread application in daily practice. PURPOSE: To develop a fully automatic framework for PAP assessment via machine learning based on computed tomography pulmonary angiography (CTPA). MATERIALS AND METHODS: A machine learning model was developed to automatically extract morphological features of pulmonary artery and the heart on CTPA cases collected between June 2017 and July 2021 based on a single center experience. Patients with PH received CTPA and RHC examinations within 1 week. The eight substructures of pulmonary artery and heart were automatically segmented through our proposed segmentation framework. Eighty percent of patients were used for the training data set and twenty percent for the independent testing data set. PAP parameters, including mPAP, sPAP, dPAP, and TPR, were defined as ground-truth. A regression model was built to predict PAP parameters and a classification model to separate patients through mPAP and sPAP with cut-off values of 40 mm Hg and 55 mm Hg in PH patients, respectively. The performances of the regression model and the classification model were evaluated by analyzing the intraclass correlation coefficient (ICC) and the area under the receiver operating characteristic curve (AUC). RESULTS: Study participants included 55 patients with PH (men 13; age 47.75 ± 14.87 years). The average dice score for segmentation increased from 87.3% ± 2.9 to 88.2% ± 2.9 through proposed segmentation framework. After features extraction, some of the AI automatic extractions (AAd, RVd, LAd, and RPAd) achieved good consistency with the manual measurements. The differences between them were not statistically significant (t = 1.222, p = 0.227; t = -0.347, p = 0.730; t = 0.484, p = 0.630; t = -0.320, p = 0.750, respectively). The Spearman test was used to find key features which are highly correlated with PAP parameters. Correlations between pulmonary artery pressure and CTPA features show a high correlation between mPAP and LAd, LVd, LAa (r = 0.333, p = 0.012; r = -0.400, p = 0.002; r = -0.208, p = 0.123; r = -0.470, p = 0.000; respectively). The ICC between the output of the regression model and the ground-truth from RHC of mPAP, sPAP, and dPAP were 0.934, 0.903, and 0.981, respectively. The AUC of the receiver operating characteristic curve of the classification model of mPAP and sPAP were 0.911 and 0.833. CONCLUSIONS: The proposed machine learning framework on CTPA enables accurate segmentation of pulmonary artery and heart and automatic assessment of the PAP parameters and has the ability to accurately distinguish different PH patients with mPAP and sPAP. Results of this study may provide additional risk stratification indicators in the future with non-invasive CTPA data.

Chest X-ray features facilitate screening for pulmonary hypertension caused by fibrosing mediastinitis.

Background: Misdiagnosis and underdiagnosis of pulmonary hypertension caused by fibrosing mediastinitis (PH-FM) are considerably prevalent due to unspecific symptoms and as well as the lack of awareness of this fatal disease. Objectives: The aim of this study was to evaluate the diagnostic accuracy of the chest X-ray (CXR) for screening the patients with PH-FM from those with pulmonary hypertension (PH). Design: This was a retrospective observational cohort study. Methods: The patients with suspected PH were recruited between October 2014 and October 2020. All the clinical data and CXR findings were collected. The sensitivity, specificity, and likelihood ratio of the CXR features were calculated. Logistic regression was used to identify the factors associated with the CXR characteristics and FM and to generate a prediction model. Finally, the diagnostic efficiency of the prediction model was evaluated using nomogram and internal validation. Results: The patients with PH-FM (n = 36) and PH caused by the diseases other than FM (PH-non-FM, n = 62) were enrolled. The CXR features, including atelectasis, pleural effusion, consolidation, nodules, calcification, interlobular septal thickening, and interstitial reticulation, were more prevalent in patients with PH-FM than in those with PH-non-FM (all p < 0.05). Atelectasis had a specificity of 97%, a sensitivity of 50%, and a greater accuracy for diagnosing of PH-FM [area under the curve (AUC) = 0.720; 95% CI: 0.634-0.806] than the other factors did. The combination of tuberculosis, natural logarithmic NT-proBNP (lnBNP), atelectasis, pleural effusion, and prominent right heart border constituted a prediction model to distinguish the PH-FM from the PH-non-FM, with a sensitivity of 91.7% and a specificity of 83.9%. The model demonstrated good prediction performance by showing an AUC of 0.922 (95% CI: 0.861-0.983) in the internal validation. Conclusion: In this study, atelectasis was the most specific and accurate CXR characteristic for identifying PH-FM in the PH patients. The combination of atelectasis, pleural effusion, prominent right heart border, tuberculosis, and lnBNP constituted a prediction model that distinguished the PH-FM patients from the PH-non-FM ones with good performance.

Pulmonary Hypertension Caused by Fibrosing Mediastinitis.

Pulmonary hypertension (PH) is a progressive and severe disorder in pulmonary hemodynamics. PH can be fatal if not well managed. Fibrosing mediastinitis (FM) is a rare and benign fibroproliferative disease in the mediastinum, which may lead to pulmonary vessel compression and PH. PH caused by FM (PH-FM) is a pathologic condition belonging to group 5 in the World Health Organization PH classification. PH-FM has a poor prognosis because of a lack of effective therapeutic modalities and inappropriate diagnosis. With the development of percutaneous pulmonary vascular interventional therapy, the prognosis of PH-FM has been greatly improved in recent years. This article provides a comprehensive review on the epidemiology, pathophysiologic characteristics, clinical manifestations, diagnostic approaches, and treatment modalities of PH-FM based on data from published reports and our medical center with the goal of facilitating the diagnosis and treatment of this fatal disease.

Advanced ultrawide-field optical coherence tomography angiography identifies previously undetectable changes in biomechanics-related parameters in nonpathological myopic fundus.

Purpose: To detect previously undetectable changes in vessel density and structural thickness, the two biomechanics-related parameters reflecting hemodynamics and tensile strength, respectively, in the peripheral and central fundi of nonpathological myopic eyes with an advanced ultrawide-field optical coherence tomography angiography (OCTA) system. Methods: A cross-sectional observational clinical study was carried out by recruiting 155 eyes from 79 college students aged 18-28 years. The eyes were stratified into normal, low-myopia, medium-myopia, and high-myopia groups according to diopter. A newly developed OCTA system with scanning dimensions of 24 mm × 20 mm, acquisition speed of 400 kHz, and imaging range of 6 mm was used to examine the vessel densities of superficial vascular complex (SVC), deep vascular complex (DVC), choriocapillary (ChC), and choroidal vessel (ChV) layers, as well as the thicknesses of the inner retina, outer retina, and choroid in the nonpathological myopic eyes. Results: The vessel densities in ChV at the temporal, inferotemporal, inferior, and inferonasal regions in the fundus periphery were significantly reduced in myopic subjects as compared to normal controls (all p < 0.05). The thicknesses of the inner retinal segments in most peripheral regions of the fundus became attenuated along with myopia severity (all p < 0.05). The thicknesses of the outer retinal segments were diminished at the superior and supranasal regions of the peripheral fundi of myopic subjects as compared to normal controls (all p < 0.05). At the central macular region, the decreased vessel densities of SVC and DVC were correlated with the attenuated thicknesses of inner retinal segments, respectively (all p < 0.05). Conclusion: As revealed for the first time by the advanced ultrawide-field OCTA system, the two biomechanics-related parameters that include the densities of the choroidal vessels and thicknesses of the inner retina segments were significantly reduced in the periphery of nonpathological myopic fundi and the reductions were associated with myopia severity. At the central macular region, the newly developed device provides consistent results with the previous findings. Therefore, it is important to use the noninvasive, ultrawide-field OCTA with high resolution for early detection of fundus changes in subjects with nonpathological high myopia. Clinical Trial Registration: clinicaltrials.gov, identifier ChiCTR2100054093.

Twisted Magnon Frequency Comb and Penrose Superradiance.

Quantization effects of the nonlinear magnon-vortex interaction in ferromagnetic nanodisks are studied. We show that the circular geometry twists the spin-wave fields with spiral phase dislocations carrying quantized orbital angular momentum (OAM). Meanwhile, the confluence and splitting scattering of twisted magnons off the gyrating vortex core (VC) generates a frequency comb consisting of discrete and equally spaced spectral lines, dubbed as twisted magnon frequency comb (TMFC). It is found that the mode spacing of the TMFC is equal to the gyration frequency of the VC and the OAM quantum numbers between adjacent spectral lines differ by one. By applying a magnetic field perpendicular to the plane of a thick nanodisk, we observe a magnonic Penrose superradiance inside the cone vortex state, which mimics the amplification of particles scattered from a rotating black hole. It is demonstrated that the higher-order modes of TMFC are significantly amplified while the lower-order ones are trapped within the VC gyrating orbit which manifests as the ergoregion. These results suggest a promising way to generate twisted magnons with large OAM and to drastically improve the flatness of the magnon comb.

Square-root higher-order Weyl semimetals.

The mathematical foundation of quantum mechanics is built on linear algebra, while the application of nonlinear operators can lead to outstanding discoveries under some circumstances, such as the prediction of positron, a direct outcome of the Dirac equation which stems from the square-root of the Klein-Gordon equation. In this article, we propose a model of square-root higher-order Weyl semimetal (SHOWS) by inheriting features from its parent Hamiltonians. It is found that the SHOWS hosts both "Fermi-arc" surface and hinge states that respectively connect the projection of the Weyl points on the side surface and arris. We theoretically construct and experimentally observe the exotic SHOWS state in three-dimensional (3D) stacked electric circuits with honeycomb-kagome hybridizations and double-helix interlayer couplings. Our results open the door for realizing the square-root topology in 3D solid-state platforms.