Cost-effectiveness of ivosidenib versus chemotherapy for previously treated IDH1-mutant advanced intrahepatic cholangiocarcinoma in Taiwan.

BACKGROUND: International guidelines recommend ivosidenib followed by modified FOLFOX (mFOLFOX) for advanced intrahepatic cholangiocarcinoma (ICC) with isocitrate dehydrogenase 1 (IDH1) mutations. Taiwan National Health Insurance covers only fluorouracil/leucovorin (5-FU/LV) chemotherapy for this ICC group, and there has been no prior economic evaluation of ivosidenib. Therefore, we aimed to assess ivosidenib's cost-effectiveness in previously treated, advanced ICC-presenting IDH1 mutations compared with mFOLFOX or 5-FU/LV. METHODS: A 3-state partitioned survival model was employed to assess ivosidenib's cost-effectiveness over a 10-year horizon with a 3% discount rate, setting the willingness-to-pay threshold at 3 times the 2022 GDP per capita. Efficacy data for Ivosidenib, mFOLFOX, and 5-FU/LV were sourced from the ClarIDHy, ABC06, and NIFTY trials, respectively. Ivosidenib's cost was assumed to be NT$10,402/500 mg. Primary outcomes included incremental cost-effectiveness ratios (ICERs) and net monetary benefit. Deterministic sensitivity analyses (DSA) and probabilistic sensitivity analyses (PSA) were employed to evaluate uncertainty and explore price reduction scenarios. RESULTS: Ivosidenib exhibited ICERs of NT$6,268,528 and NT$5,670,555 compared with mFOLFOX and 5-FU/LV, respectively, both exceeding the established threshold. PSA revealed that ivosidenib was unlikely to be cost-effective, except when it was reduced to NT$4,161 and NT$5,201/500 mg when compared with mFOLFOX and 5-FU/LV, respectively. DSA underscored the significant influence of ivosidenib's cost and utility values on estimate uncertainty. CONCLUSIONS: At NT$10,402/500 mg, ivosidenib was not cost-effective for IDH1-mutant ICC patients compared with mFOLFOX or 5-FU/LV, indicating that a 50-60% price reduction is necessary for ivosidenib to be cost-effective in this patient group.

Defining three ferroptosis-based molecular subtypes and developing a prognostic risk model for high-grade serous ovarian cancer.

BACKGROUND: As a newly defined regulated cell death, ferroptosis is a potential biomarker in ovarian cancer (OV). However, its underlying mechanism in tumor microenvironment (TME) and clinical prediction significance in OV remained to be elucidated. METHODS: The transcriptome data of high-grade serous OV from The Cancer Genome Atlas (TCGA) database were downloaded. Molecular subtypes were classified based on ferroptosis-correlated genes from the FerrDb database by performing consensus clustering analysis. The associations between the subtypes and clinicopathologic characteristics, mutation, regulatory pathways and immune landscape were assessed. A ferroptosis-related prognostic model was constructed and verified using International Cancer Genome Consortium (ICGC) cohort and GSE70769. RESULTS: Three molecular subtypes of OV were defined. Patients in subtype C3 tended to have the most favorable prognosis, while subtype C1 showing more mesenchymal cells, increased immune infiltration of Macrophages_M2, lower tumor purity, and epithelial-to-mesenchymal transition (EMT) features had the poorest prognosis. A ferroptosis-related risk model was constructed using 8 genes (PDP1, FCGBP, EPHA4, GAS1, SLC7A11, BLOC1S1, SPOCK2, and CXCL9) and manifested a strong prediction performance. High-risk patients had enriched EMT pathways, more Macrophages_M2, less plasma cells and CD8 cell infiltration, greater tendency of immune escape and worse prognosis. The risk score has negatively correlated relation with LAG3, TIGIT, CTLA4, IDO1, CD27, ICOS, and IL2RB but positively correlated with PVR, CD276, and CD28. Moreover, low-risk patients were more sensitive to Cisplatin and Gefitinib, Gemcitabine. CONCLUSIONS: Our results could improve the understanding of ferroptosis in OV, providing promising insights for the clinical targeted therapy for the cancer.

(±)-hypermonanones A-G, seven pairs of monoterpenoid polyprenylated acylphloroglucinol enantiomers from Hypericum monanthemum.

Seven pairs of undescribed monoterpenoid polyprenylated acylphloroglucinol enantiomers [(±)-hypermonanones A-G (1-7)], together with three known analogues, were identified from the whole plant of Hypericum monanthemum Hook. The structures of these compounds were determined by analyses of their UV, HRESIMS, 1D/2D NMR spectroscopic data, and NMR calculations. The absolute configurations of these compounds were assigned by ECD calculations after chiral HPLC separation. Diverse monoterpene moieties were fused at C-3/C-4 of the dearomatized acylphloroglucinol core, which led to 3,4-dihydro-2H-pyran-integrated angular or linear type 6/6/6 tricyclic skeletons in 1-7. Compounds (-)-2 and (+)-2 exhibited significant NO inhibitory activity against LPS induced RAW264.7 cells with the IC50 values of 7.07 ± 1.02 µM and 11.39 ± 0.24 µM, respectively.

A non-invasive nomogram for predicting heart failure with preserved ejection fraction in taiwanese outpatients with unexplained dyspnea and fatigue.

BACKGROUND: While Reddy proposed the H2FPEF diagnostic algorithm to aid in diagnosing heart failure with preserved ejection fraction (HFpEF), certain parameters like age and obesity are not suitable for Asian population, especially given the increasing incidence of HFpEF in younger individuals. Therefore, this study aimed to develop an easy-to-use nomogram with non-invasive indices that can be used in outpatient clinics in Taiwan to quickly estimate the probability of HFpEF and help decide whether further invasive cardiopulmonary exercise test (CPET) is needed. METHODS: Outpatients with unexplained dyspnea and fatigue were recruited divided into HFpEF (n = 64) and non-HFpEF (n = 34) groups based on invasive CPET and echocardiography. Multivariate logistic regression analyses identified independent noninvasive variables for developing an HFpEF nomogram. The nomogram's performance was assessed and validated using the concordance index (C-index), area under the curve (AUC), calibration curves, and decision curve analysis. RESULTS: Multivariate logistic regression analyses identified five independent noninvasive variables for developing an HFpEF nomogram, including dyslipidemia (OR = 5.264, p = 0.010), diabetes (OR = 3.929, p = 0.050), left atrial area (OR = 1.130, p = 0.046), hemoglobin <13 g/dL (OR = 5.372, p = 0.010), and NT-proBNP ≥245 pg/mL (OR = 5.108, p = 0.027). The nomogram showed good discriminatory ability (C-index = 0.842) and calibration performance (p = 0.873) and high net benefit (0.1-0.95). Notably, the HFpEF nomogram showed better diagnostic accuracy than the H2FPEF score model in predicting Taiwanese HFpEF patients (AUC: 0.873 vs. 0.608, p = 0.0006). CONCLUSION: The noninvasive HFpEF nomogram provides a preliminary estimation of the probability of HFpEF in Taiwanese outpatients with unexplained dyspnea and fatigue, which may help the decision-making on further invasive CPET.

Early Diagnosis of Syndromic Congenital Cataracts in a Large Cohort of Congenital Cataracts.

PURPOSE: To explore the factors related to the diagnosis yield of syndromic congenital cataracts and describe the phenotype-genotype correlation in congenital cataract patients. DESIGN: Prospective cohort study. METHODS: Setting: the participants from underwent clinical examinations between 2021 and 2022. Facial and anterior eye segment photographs, pre- and postoperative ocular parameters, and medical and family histories were recorded. Bioinformatics analysis was performed using whole-exome sequencing data. Statistical and correlation analyses were performed using the basic characteristics, deep phenotype, and genotype data. PARTICIPANTS: 115 patients with unrelated congenital cataract. INTERVENTIONS: performing clinical examinations, whole-exome sequencing, and bioinformatics analysis for all participants. MAIN OUTCOMES AND MEASURES: factors related to the genetic diagnosis yield of syndromic congenital cataracts. RESULTS: Bilaterally asymmetrical cataracts were identified to be associated with syndromic congenital cataracts. The overall genetic diagnostic yield in the cohort was 72.2%. In total, 34.8% of the probands were early diagnosed with various syndromes with the help of genetic information. A phenotype-genotype correlation was detected for some genes and deep phenotypes. CONCLUSIONS: We highlight the importance of screening syndromic diseases in the patients with asymmetrical congenital cataracts. Application of whole-exome sequencing helps provide early diagnosis and treatment for the patients with syndromic congenital cataracts. This study also achieved a high genetic diagnostic yield, expanded the genotypic spectrum, and found phenotype-genotype correlations. A comprehensive analysis of cataract symmetricity, family history, and deep phenotypes makes the genotype prediction of some congenital cataract patients possible.

Prediction significance of autophagy-related genes in survival probability and drug resistance in diffuse large B-cell lymphoma.

BACKGROUND/AIMS: Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin lymphoma, has significant prognostic heterogeneity. This study aimed to generate a prognostic prediction model based on autophagy-related genes for DLBCL patients. METHODS: Utilizing bioinformatics techniques, we analyzed the clinical information and transcriptome data of DLBCL patients from the Gene Expression Omnibus (GEO) database. Through unsupervised clustering, we identified new autophagy-related molecular subtypes and pinpointed differentially expressed genes (DEGs) between these subtypes. Based on these DEGs, a prognostic model was constructed using Cox and Lasso regression. The effectiveness, accuracy, and clinical utility of this prognostic model were assessed using numerous independent validation cohorts, survival analyses, receiver operating characteristic (ROC) curves, multivariate Cox regression analysis, nomograms, and calibration curves. Moreover, functional analysis, immune cell infiltration, and drug sensitivity analysis were performed. RESULTS: DLBCL patients with different clinical characterizations (age, molecular subtypes, ECOG scores, and stages) showed different expression features of autophagy-related genes. The prediction model was constructed based on the eight autophagy-related genes (ADD3, IGFBP3, TPM1, LYZ, AFDN, DNAJC10, GLIS3, and CCDC102A). The prognostic nomogram for overall survival of DLBCL patients incorporated risk level, stage, ECOG scores, and molecular subtypes, showing excellent agreement between observed and predicted outcomes. Differences were noted in the proportions of immune cells (native B cells, Treg cells, CD8+ T cell, CD4+ memory activated T cells, gamma delta T cells, macrophages M1, and resting mast cells) between high-risk and low-risk groups. LYZ and ADD3 exhibited correlations with drug resistance to most chemotherapeutic drugs. CONCLUSIONS: This study established a novel prognostic assessment model based on the expression profile of autophagy-related genes and clinical characteristics of DLBCL patients, explored immune infiltration and predicted drug resistance, which may guide precise and individualized immunochemotherapy regimens.

Comparing the impact of three-dimensional digital visualization technology versus traditional microscopy on microsurgeons in microsurgery: a prospective self-controlled study.

BACKGROUND: Emerging three-dimensional digital visualization technology (DVT) provides more advantages than traditional microscopy in microsurgery; however, its impact on microsurgeons' visual and nervous systems and delicate microsurgery is still unclear, which hinders the wider implementation of DVT in digital visualization for microsurgery. METHODS AND MATERIAL: Forty-two microsurgeons from the Zhongshan Ophthalmic Center were enrolled in this prospective self-controlled study. Each microsurgeon consecutively performed 30 min conjunctival sutures using a three-dimensional digital display and a microscope, respectively. Visual function, autonomic nerve activity, and subjective symptoms were evaluated before and immediately after the operation. Visual functions, including accommodative lag, accommodative amplitude, near point of convergence and contrast sensitivity function (CSF), were measured by an expert optometrist. Heart rate variability was recorded by a wearable device for monitoring autonomic nervous activity. Subjective symptoms were evaluated by questionnaires. Microsurgical performance was assessed by the video-based Objective Structured Assessment of Technical Skill (OSATS) tool. RESULTS: Accommodative lag decreased from 0.63 (0.18) diopters (D) to 0.55 (0.16) D ( P =0.014), area under the log contrast sensitivity function increased from 1.49 (0.15) to 1.52 (0.14) ( P =0.037), and heart rate variability decreased from 36.00 (13.54) milliseconds (ms) to 32.26 (12.35) ms ( P =0.004) after using the DVT, but the changes showed no differences compared to traditional microscopy ( P >0.05). No statistical significance was observed for global OSATS scores between the two rounds of operations [mean difference, 0.05 (95% CI: -1.17 to 1.08) points; P =0.95]. Subjective symptoms were quite mild after using both techniques. CONCLUSIONS: The impact of DVT-based procedures on microsurgeons includes enhanced accommodation and sympathetic activity, but the changes and surgical performance are not significantly different from those of microscopy-based microsurgery. Our findings indicate that short-term use of DVT is reliable for microsurgery and the long-term effect of using DVT deserve more consideration.

Lung-PNet: An Automated Deep Learning Model for the Diagnosis of Invasive Adenocarcinoma in Pure Ground-Glass Nodules on Chest CT.

BACKGROUND. Pure ground-glass nodules (pGGNs) on chest CT representing invasive adenocarcinoma (IAC) warrant lobectomy with lymph node resection. For pGGNs representing other entities, close follow-up or sublobar resection without node dissection may be appropriate. OBJECTIVE. The purpose of this study was to develop and validate an automated deep learning model for differentiation of pGGNs on chest CT representing IAC from those representing atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), and minimally invasive adenocarcinoma (MIA). METHODS. This retrospective study included 402 patients (283 women, 119 men; mean age, 53.2 years) with a total of 448 pGGNs on noncontrast chest CT that were resected from January 2019 to June 2022 and were histologically diagnosed as AAH (n = 29), AIS (n = 83), MIA (n = 235), or IAC (n = 101). Lung-PNet, a 3D deep learning model, was developed for automatic segmentation and classification (probability of IAC vs other entities) of pGGNs on CT. Nodules resected from January 2019 to December 2021 were randomly allocated to training (n = 327) and internal test (n = 82) sets. Nodules resected from January 2022 to June 2022 formed a holdout test set (n = 39). Segmentation performance was assessed with Dice coefficients with radiologists' manual segmentations as reference. Classification performance was assessed by ROC AUC and precision-recall AUC (PR AUC) and compared with that of four readers (three radiologists, one surgeon). The code used is publicly available (https://github.com/XiaodongZhang-PKUFH/Lung-PNet.git). RESULTS. In the holdout test set, Dice coefficients for segmentation of IACs and of other lesions were 0.860 and 0.838, and ROC AUC and PR AUC for classification as IAC were 0.911 and 0.842. At threshold probability of 50.0% or greater for prediction of IAC, Lung-PNet had sensitivity, specificity, accuracy, and F1 score of 50.0%, 92.0%, 76.9%, and 60.9% in the holdout test set. In the holdout test set, accuracy and F1 score (p values vs Lung-PNet) for individual readers were as follows: reader 1, 51.3% (p = .02) and 48.6% (p = .008); reader 2, 79.5% (p = .75) and 75.0% (p = .10); reader 3, 66.7% (p = .35) and 68.3% (p < .001); reader 4, 71.8% (p = .48) and 42.1% (p = .18). CONCLUSION. Lung-PNet had robust performance for segmenting and classifying (IAC vs other entities) pGGNs on chest CT. CLINICAL IMPACT. This automated deep learning tool may help guide selection of surgical strategies for pGGN management.

Cuproptosis-related lncRNAs ovarian cancer: Multi-omics analysis of molecular mechanisms and potential therapeutic targets.

Ovarian cancer (OV) is an aggressive malignancy that poses a significant threat to the health and lives of women. Cuproptosis is a newly discovered form of programmed cell death that offers a promising therapeutic target, although its significance in cancer progression remains uncertain. In this study, we established a prognostic model of OV with six cuproptosis-related long non-coding RNAs (lncRNAs), including CTC.246B18.8, LINC00337, RP11.568N6.1, RP11.158I9.8, RP11.678G14.3 and CYP4F26P, based on the data of The Cancer Genome Atlas (TCGA). Lower risk scores were associated with favorable prognosis. In addition, a negative outcome was associated with high expression of CTC.246B18.8. According to the ESTIMATE algorithm, CTC.246B18.8 was negatively correlated with the ImmuneScore, and positively with immune checkpoints, immune cell infiltration, and tumor mutation burden (TMB). Moreover, gene set enrichment analysis (GSEA) revealed that pathways related to immunosuppression are likely activated in response to CTC-246B18.8 overexpression. Furthermore, CTC-246B18.8 expression was also associated with the sensitivity to various chemotherapy drugs. The expression patterns of the above lncRNAs were verified in ovarian tumor cell lines (SK-OV-3, COC1, and A2780) and normal ovarian epithelial cells (IOSE - 80). Six cuproptosis-related genes (CRGs), including ATP7B, MTF1, SLC31A1, DLD, ATP7A and DLAT, were differentially expressed between CTC-246B18.8high and CTC-246B18.8low patient groups, and exhibited organ-specific expression patterns pan-cancer. Small molecule drugs that target these CRGs were predicted, and potential candidates included DIAMIDE, bathocuproine disulfonate, D-penicillamine, etc. To summarize, our findings provide molecular insights into the role of cuproptosis in OV, and the signature lncRNAs and CRGs should be investigated further as immunotherapy biomarkers of OV.

Symptom-limited exercise capacity is associated with long-term survival.

The prognostic value of exercise capacity has been demonstrated in subjects with established cardiovascular diseases. We aim to evaluate the independence of exercise capacity measured by treadmill exercise test (TET) in predicting long-term outcomes among various comorbidities. This study was conducted from January 2003 to December 2012 in a tertiary medical center in Taiwan. Subjects referred for symptom-limited TET were recruited. Peak achieved metabolic equivalents (METs) were determined by treadmill grade and speed at peak exercise. The main outcomes were cardiovascular and all-cause mortality by linking to the National Death Registry. A total of 18,954 participants (57.8 ± 12.8 years, 62% men) achieved a mean peak METs of 9.2. Subjects in the lowest tertile of peak METs were older, had poorer renal function, lower hemoglobin, and more comorbidities. During a median follow-up of 4.3 years, there were 642 mortalities and 132 cardiovascular deaths. Peak METs significantly predicted cardiovascular death and all-cause mortality in the multivariable Cox regression models [hazard ratio (95% confidence intervals): 0.788 (0.660-0.940) and 0.835 (0.772-0.903), respectively]. The prognostic influence of peak METs consistently appeared in the subgroups, regardless of age, gender, body weight, comorbidities, use of beta-blockers, or the presence of exercise-induced ischemia. The fitness was more predictive of long-term outcomes in young or those with ischemic changes during TET (P for interaction: 0.035 and 0.018, respectively). The benefit of fitness was nonlinearly associated with long-term survival. The prognostic impacts of exercise capacity were universally observed in subjects with or without various comorbidities.

Surgery for severe mitral regurgitation: The etiology matters.

BACKGROUND: While surgery has been the standard treatment for patients with severe primary mitral regurgitation (PMR), the role of surgery for severe secondary mitral regurgitation (SMR) remained debated. We therefore investigated the prognostic differences of surgery for patients with either severe PMR or SMR. METHODS: Subjects hospitalized for heart failure were enrolled from 2002 to 2012. The severity of MR was assessed by continuity equation, and an effective regurgitant orifice area of ≥40 mm 2 was defined as severe. Long-term survival was then identified by the National Death Registry. RESULTS: A total of 1143 subjects (66.4 ± 16.6 years, 65% men, and 59.7% PMR) with severe MR were analyzed. Compared with PMR, patients with SMR were older, had more comorbidities, greater left atrial and ventricular diameter, and less left ventricular ejection fraction (all p < 0.05). While 47.8% of PMR patients received mitral valve surgery, only 6.9% of SMR patients did. Surgical intervention crudely was associated with 54% reduction of all-cause mortality in PMR (hazard ratio, 0.46; 95% confident interval, 0.32-0.67), and 48% in the subpopulation with SMR (0.52, 0.30-0.91). Propensity score matching analysis demonstrated the survival benefits of mitral valve surgery was observed in patients with PMR (log rank p = 0.024), but not with SMR. Among the unoperated subjects, age, renal function, and right ventricular systolic pressure were common risk factors of mortality, regardless of MR etiology. CONCLUSION: Mitral valve surgery for patients with heart failure and severe MR was associated with better survival in patients with PMR, but not in those with SMR.

Safety and feasibility of preferential manual bronchoplasty in 2-3 cm single-port video-assisted thoracoscopic lobectomy.

BACKGROUND: This retrospective study aimed to compare preferential manual bronchoplasty (PMB) and mechanical stapler closure (MSC) of the bronchial stump after 2-3 cm single-port (SP) video-assisted thoracoscopic surgery (VATS) lobectomy in patients with pathological T1 (pT1) stage lung cancer. METHODS: Between January 2019 and March 2022, patients with pulmonary neoplasms who underwent 2-3 cm SP VATS lobectomy were retrospectively screened. After propensity-matched analysis, we compared perioperative outcomes and analyzed the safety and feasibility of PMB and MSC of the bronchial stump while performing VATS lobectomy. RESULTS: In this study, 280 and 832 patients were enrolled in the PMB and MSC groups, respectively. Propensity score matching produced 280 pairs. The operation time was shorter in the PMB group, whereas the average number of lymph nodes dissected was higher in the PMB group. The conversion rate was significantly lower in the PMB group. The following were similar between the PMB and MSC groups, respectively: average blood loss volume, postoperative hospital stay, and chest tube removal time. Postoperatively, the incidence of atelectasis was significantly higher in the MSC group. As per subgroup analyses, PMB was associated with a shorter operation time in left and right upper lobectomies. Particularly in left upper lobectomy, PMB had more lymph node dissections and less conversion to open and postoperative atelectasis. CONCLUSIONS: In comparison with MSC of the bronchial stump, PMB showed better safety and feasibility in 2-3 cm SP VATS left and right superior lobectomies in patients with pT1 stage lung cancer.

Effects of Exercise Training on Cognitive Function in Individuals With Heart Failure: A Meta-Analysis.

OBJECTIVE: Cognitive function is critical for disease self-management; however, it is poorer in individuals with heart failure (HF) than in age-matched people who are healthy. Aging and disease progression collectively threaten the cognitive function of individuals with HF. Exercise has been shown to improve the mobility and mortality risk factors of this population, but the effects of exercise on the cognitive function of individuals with HF are unclear. This meta-analysis aimed to examine these potential effects. METHODS: A systematic literature search was conducted in PubMed, MEDLINE, CINAHL, Cochrane Library, Physiotherapy Evidence Database, and ClinicalKey on literature published until January 2022. Studies examining the effects of exercise training on cognitive function in individuals with HF were included. Characteristics of participants and details of interventions were extracted. Effects of exercise training on global cognitive function, attention, and executive function were analyzed using the Comprehensive Meta-Analysis software. RESULTS: Six studies were included. Individuals with chronic HF were examined in most studies. The average ejection fraction of participants was 23 to 46%. Aerobic exercise was used in most studies. All included studies had exercise frequency of 2 to 3 times per week and a duration of 30 to 60 minutes per session for 12 to 18 weeks. Compared with the control group, exercise training benefited the global cognitive function of individuals with HF and cognitive impairments (standardized mean difference = 0.44; 95% CI = 0.01-0.87). The attention of individuals with HF improved after exercise training compared with that before the intervention. CONCLUSION: Exercise may improve cognitive function in individuals with HF and cognitive impairments. However, due to large heterogeneity in the study design, more studies are needed to support clinical application. IMPACT: These findings should raise clinicians' awareness about the role of exercise on the cognitive function of individuals with HF, in addition to benefits in physical domains.

Association between spirometry pattern, left ventricular diastolic function, and mortality.

BACKGROUND: Spirometric abnormalities have been related to incident heart failure in general population, who generally have preserved left ventricular ejection fraction (LVEF). We aimed to investigate the association between spirometric indices, cardiac functions and clinical outcomes. METHODS: Subjects presenting with exertional dyspnoea and received spirometry and echocardiography were eligible for this study. Forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1)/FVC ratio were measured to define the spirometry patterns: normal (FEV1/FVC ≥ 70%, FVC ≥ 80%), obstructive (FEV1/FVC < 70%, FVC ≥ 80%), restrictive pattern (FEV1/FVC ≥ 70%, FVC < 80%) and mixed (FEV1/FVC < 70%, FVC < 80%). The diastolic dysfunction index (DDi) was the counts of the indicators, including septal e' velocity <7 cm/s, septal E/e' > 15, pulmonary artery systolic pressure > 35 mmHg and left atrial dimension >40 mm. RESULTS: Among a total of 8669 participants (65.8 ± 16.3 years, 56% men), 3739 (43.1%), 829 (9.6%), 3050 (35.2%) and 1051 (12.1%) had normal, obstructive, restrictive and mixed spirometry pattern, respectively. Subjects with restrictive or mixed spirometry pattern had higher DDi and worse long-term survival than those with obstructive or normal ventilation. FVC but not FEV1/FVC was predictive of 5-year mortality, independent of age, sex, renal function, LVEF, DDi, body mass index, and comorbidities (hazard ratio, 95% confidence intervals: .981, .977-.985). Furthermore, there was an inverse nonlinear relationship between FVC and DDi, suggesting the declined FVC may mediate 43% of the prognostic hazard of left ventricular diastolic dysfunction. CONCLUSIONS: The restrictive spirometry pattern or the declined FVC was associated with left ventricular diastolic dysfunction, which aggravated the long-term mortality in the ambulatory dyspnoeic subjects.

Severe Hemoptysis Secondary to Actinomycosis: A Case Report.

Pulmonary actinomycosis (PA) is an uncommon, asymptomatic, and frequently misdiagnosed pulmonary infectious illness. Our patient remained undiagnosed despite extensive regular and invasive testing, significant intermittent hemoptysis, and repeated bronchial artery embolization. Ultimately, a left lower lobectomy was performed via video-assisted thoracoscopic surgery, and a histopathological examination revealed an actinomycete infection.

The joint role of methylation and immune-related lncRNAs in ovarian cancer: Defining molecular subtypes and developing prognostic signature.

INTRODUCTION: Complex outcome of ovarian cancer (OC) stems from the tumor immune microenvironment (TIME) influenced by genetic and epigenetic factors. This study aimed to comprehensively explored the subclasses of OC through lncRNAs related to both N6-methyladenosine (m6A)/N1-methyladenosine (m1A)/N7-methylguanosine (m7G)/5-methylcytosine (m5C) in terms of epigenetic variability and immune molecules and develop a new set of risk predictive systems. MATERIAL AND METHODS: The lncRNA data of OC were collected from TCGA. Spearman correlation analysis on lncRNA data of OC with immune-related gene expression and with m6A/m5C/m1A/m7G were respectively conducted. The m6A/m5C/m1A/m7G-related m6A/m5C/m1A/m7G related immune lncRNA subtypes were identified on the basis of the prognostic lncRNAs. Heterogeneity among subtypes was evaluated by tumor mutation analysis, tumor microenvironment (TME) component analysis, response to immune checkpoint blocked (ICB) and chemotherapeutic drugs. A risk predictive system was developed based on the results of Cox regression analysis and random survival forest analysis of the differences between each specific cluster and other clusters. RESULTS: Three m6A/m5C/m1A/m7G-related immune lncRNA subtypes of OC showing distinct differences in prognosis, mutation pattern, TIME components, immunotherapy and chemotherapy response were identified. A set of risk predictive system consisting of 10 lncRNA for OC was developed, according to which the risk score of samples in each OC dataset was calculated and risk type was defined. CONCLUSIONS: This study classified three m6A/m5C/m1A/m7G-related immune lncRNA subtypes with distinct heterogeneous mutation patterns, TME components, ICB therapy and immune response, and provided a set of risk predictive system consisted of 10 lncRNA for OC.

Phosphate Adsorption on Cerium/Terephthalic Acid Metal-Organic Frameworks (Ce-MOF) Driven by Effective Electrostatic Attraction and Ligand Exchange in a Wide pH Range.

Eutrophication has posed a threat to aquatic ecosystems, so it's urgent to remove excessive phosphate from water. In this study, we developed an adsorbent material, cerium/terephthalic-acid metal-organic-frameworks (Ce-MOF), to remove phosphate from different water systems. The optimal Ce-MOF presented a maximum phosphate adsorption capacity of 377.2 mg/g, approximately 3.7 times higher than that of the commercial phosphate adsorbent (Phoslock: 101.6 mg/g). Experimental and computational analysis suggested that pH dominated the adsorption process. The main forces driving the adsorption process changed from the synergistic effect of electrostatic attraction and ligand exchange at lower pH to only ligand exchange at the increased pH values. Hence, the Ce-MOF is applicable for phosphate adsorption in a wide pH range. Impressively, the adsorbent remained an excellent phosphate adsorption performance in the real water containing various interfering ions and organic matters, indicating the potential of Ce-MOF for the practical use to solve the water eutrophication issue.

The value on SUV-derived parameters assessed on 18F-FDG PET/CT for predicting mediastinal lymph node metastasis in non-small cell lung cancer.

PURPOSE: To explore valuable predictors for mediastinal lymph node metastasis in non-small cell lung cancer (NSCLC) patients, we analyzed the potential roles of standardized uptake value (SUV)-derived parameters from preoperative 18F-FDG PET/CT combined with clinical characteristics. METHODS: Data from 224 NSCLC patients who underwent preoperative 18F-FDG PET/CT scans in our hospital were collected. Then, a series of clinical parameters including SUV-derived features [SUVmax of mediastinal lymph node and primary-tumor SUVmax, SUVpeak, SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG)] were evaluated. The best possible cutoff points for all measuring parameters were calculated using receiver operating characteristic curve (ROC) analysis. Predictive analyses were performed using a Logistic regression model to determine the predictive factors for mediastinal lymph node metastasis in NSCLC and lung adenocarcinoma patients. After multivariate model construction, data of another 100 NSCLC patients were recorded. Then, 224 patients and 100 patients were enrolled to validate the predictive model by the area under the receiver operating characteristic curve (AUC). RESULTS: The mediastinal lymph node metastasis rates in 224 patients for model construction and 100 patients for model validation were 24.1% (54/224) and 25% (25/100), respectively. It was found that SUVmax of mediastinal lymph node ≥ 2.49, primary-tumor SUVmax ≥ 4.11, primary-tumor SUVpeak ≥ 2.92, primary-tumor SUVmean ≥ 2.39, primary-tumor MTV ≥ 30.88 cm3, and primary-tumor TLG ≥ 83.53 were more prone to mediastinal lymph node metastasis through univariate logistic regression analyses. The multivariate logistic regression analyses showed that the SUVmax of mediastinal lymph nodes (≥ 2.49: OR 7.215, 95% CI 3.326-15.649), primary-tumor SUVpeak (≥ 2.92: OR 5.717, 95% CI 2.094-15.605), CEA (≥ 3.94 ng/ml: OR 2.467, 95% CI 1.182-5.149), and SCC (< 1.15 ng/ml: OR 4.795, 95% CI 2.019-11.388) were independent predictive factors for lymph node metastasis in the mediastinum. It was found that SUVmax of the mediastinal lymph node (≥ 2.49: OR 8.067, 95% CI 3.193-20.383), primary-tumor SUVpeak (≥ 2.92: OR 9.219, 95% CI 3.096-27.452), and CA19-9 (≥ 16.6 U/ml: OR 3.750, 95% CI 1.485-9.470) were significant predictive factors for mediastinal lymph node metastasis in lung adenocarcinoma patients. The AUCs for the predictive value of the NSCLC multivariate model through internal and external validation were 0.833 (95% CI 0.769- 0.896) and 0.811 (95% CI 0.712-0.911), respectively. CONCLUSION: High SUV-derived parameters (SUVmax of mediastinal lymph node and primary-tumor SUVmax, SUVpeak, SUVmean, MTV and TLG) might provide varying degrees of predictive value for mediastinal lymph node metastasis in NSCLC patients. In particular, the SUVmax of mediastinal lymph nodes and primary-tumor SUVpeak could be independently and significantly associated with mediastinal lymph node metastasis in NSCLC and lung adenocarcinoma patients. Internal and external validation confirmed that the pretherapeutic SUVmax of the mediastinal lymph node and primary-tumor SUVpeak combined with serum CEA and SCC can effectively predict mediastinal lymph node metastasis of NSCLC patients.

HealthNet: A Health Progression Network via Heterogeneous Medical Information Fusion.

Numerous electronic health records (EHRs) offer valuable opportunities for understanding patients' health status at different stages, namely health progression. Extracting the health progression patterns allows researchers to perform accurate predictive analysis of patient outcomes. However, most existing works on this task suffer from the following two limitations: 1) the diverse dependencies among heterogeneous medical entities are overlooked, which leads to the one-sided modeling of patients' status and 2) the extraction granularity of patient's health progression patterns is coarse, limiting the model's ability to accurately infer the patient's future status. To address these challenges, a pretrained Health progression network via heterogeneous medical information fusion, HealthNet, is proposed in this article. Specifically, a global heterogeneous graph in HealthNet is built to integrate heterogeneous medical entities and the dependencies among them. In addition, the proposed health progression network is designed to model hierarchical medical event sequences. By this method, the fine-grained health progression patterns of patients' health can be captured. The experimental results on real disease datasets demonstrate that HealthNet outperforms the state-of-the-art models for both diagnosis prediction task and mortality prediction task.

Left versus right approach for middle and lower esophageal squamous cell carcinoma: A propensity score-matched study.

Background: Despite superior short-term outcomes, there is considerable debate about the oncological efficacy of the left approach esophagectomy for middle and lower squamous esophageal carcinoma (ESCC). A propensity score-matched retrospective study was conducted to evaluate the left approach's short- and long-term effects. Methods: We recorded data from patients with ESCC who underwent curative resection via the left or right approach between January 2010 and December 2015. Propensity score matching (PSM) was performed, and maximally selected rank statistics (MSRS) were utilized to determine the appropriate number of lymph nodes to resect during esophagectomy. Results: One hundred and forty-eight ESCC patients underwent esophagectomy via the right approach, and 108 underwent the left approach esophagectomy. After PSM, the left approach esophagectomy showed statistically significant superiority in operative time and time to oral intake, and there was a trend toward a shorter length of hospital stay. Fewer cervical, upper thoracic, and recurrent laryngeal nerve lymph nodes were harvested via the left approach than the right approach; the total number of lymph nodes harvested via the left and right approaches was similar. Similar long-term survival outcomes were achieved. MSRS suggested that at least 25 lymph nodes are needed to be resected during esophagectomy to improve survival in N0 patients. Conclusions: The left approach esophagectomy might facilitate postoperative recovery in patients with middle and lower ESCC. With adequate lymphadenectomy, the left approach esophagectomy might achieve similar long-term outcomes for middle and lower ESCC patients.