Alteration Trend and Overlap Analysis of Positive Features in Different-Sized Benign and Malignant Thyroid Nodules: Based on Chinese Thyroid Imaging Reporting and Data System.

Purpose: This study aimed to investigate the alteration trends and overlaps of positive features in benign and malignant thyroid nodules of different sizes based on the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS). Patients and Methods: 1337 patients with 1558 thyroid nodules were retrospectively recruited from November 2021 to December 2023. These nodules were divided into three groups according to maximum diameter: A (≤10 mm), B (10-20 mm), and C (≥20 mm). C-TIRADS positive features were compared between benign and malignant thyroid nodules of different sizes. In addition, the trends of positive features with changes in nodule size among malignant thyroid nodules were analyzed. Results: The incidence of positive features in malignant thyroid nodules was higher than that in benign. As benign nodules grow, the incidence of all positive features showed a linear decreasing trend (Z values were 72.103, 101.081, 17.344, 33.909, and 129.304, P values < 0.001). With the size of malignant thyroid nodules increased, vertical orientation, solid, marked hypoechogenicity, and ill-defined/irregular margins/extrathyroidal extension showed a linear decreasing trend (Z = 148.854, 135.378, 8.590, and 69.239, respectively; P values < 0.05), while suspicious microcalcifications showed a linear increasing trend (Z = 34.699, P<0.001). In terms of overlapping characteristics, group A had a significantly higher overlapping rate than the other two groups, and the overlapping rate of solid indicators remained the highest among all three groups (P < 0.05). Conclusion: Differences in positive features were observed between thyroid nodules of different sizes. Except for suspicious microcalcifications, the incidence of other four positive features decreased with increasing nodule size. In addition, a negative correlation was observed between the overlap rate and nodule size. These results may provide a basis for sonographers to upgrade or downgrade thyroid nodules based on their own experience.

Prevalence and risk factors of diabetes mellitus among elderly patients in the Lugu community.

BACKGROUND: Age is a significant risk factor of diabetes mellitus (DM). With the develop of population aging, the incidence of DM remains increasing. Understanding the epidemiology of DM among elderly individuals in a certain area contributes to the DM interventions for the local elderly individuals with high risk of DM. AIM: To explore the prevalence of DM among elderly individuals in the Lugu community and analyze the related risk factors to provide a valid scientific basis for the health management of elderly individuals. METHODS: A total of 4816 elderly people who came to the community for physical examination were retrospectively analyzed. The prevalence of DM among the elderly was calculated. The individuals were divided into a DM group and a non-DM group according to the diagnosis of DM to compare the differences in diastolic blood pressure (DBP) and systolic blood pressure (SBP), fasting blood glucose, body mass index (BMI), waist-to-hip ratio (WHR) and incidence of hypertension (HT), coronary heart disease (CHD), and chronic kidney disease (CKD). RESULTS: DM was diagnosed in 32.70% of the 4816 elderly people. The BMI of the DM group (25.16 ± 3.35) was greater than that of the non-DM group (24.61 ± 3.78). The WHR was 0.90 ± 0.04 in the non-DM group and 0.90 ± 0.03 in the DM group, with no significant difference. The left SBP and SBP in the DM group were 137.9 mmHg ± 11.92 mmHg and 69.95 mmHg ± 7.75 mmHg, respectively, while they were 126.6 mmHg ± 12.44 mmHg and 71.15 mmHg ± 12.55 mmHg, respectively, in the non-DM group. These findings indicate higher SBP and lower DBP in DM patients than in those without DM. In the DM group, 1274 patients were diagnosed with HT, accounting for 80.89%. Among the 3241 non-DM patients, 1743 (53.78%) were hypertensive and 1498 (46.22%) were nonhypertensive. The DM group had more cases of HT than did the non-DM group. There were more patients with CHD or CKD in the DM group than in the non-DM group. There were more patients who drank alcohol more frequently (≥ 3 times) in the DM group than in the non-DM group. CONCLUSION: Older adults in the Lugu community are at a greater risk of DM. In elderly individuals, DM is closely related to high BMI and HT, CHD, and CKD. Physical examinations should be actively carried out for elderly people to determine their BMI, SBP, DBP, and other signs, and sufficient attention should be given to abnormalities in the above signs before further diagnosis.

Acute ischemic stroke in tuberculous meningitis.

Background: The underlying mechanism for stroke in patients with tuberculous meningitis (TBM) remains unclear. This study aimed to investigate the predictors of acute ischemic stroke (AIS) in TBM and whether AIS mediates the relationship between inflammation markers and functional disability. Methods: TBM patients admitted to five hospitals between January 2011 and December 2021 were consecutively observed. Generalized linear mixed model and subgroup analyses were performed to investigate predictors of AIS in patients with and without vascular risk factors (VAFs). Mediation analyses were performed to explore the potential causal chain in which AIS may mediate the relationship between neuroimaging markers of inflammation and 90-day functional outcomes. Results: A total of 1,353 patients with TBM were included. The percentage rate of AIS within 30 days after admission was 20.4 (95% CI, 18.2-22.6). A multivariate analysis suggested that age ≥35 years (OR = 1.49; 95% CI, 1.06-2.09; P = 0.019), hypertension (OR = 3.56; 95% CI, 2.42-5.24; P < 0.001), diabetes (OR = 1.78; 95% CI, 1.11-2.86; P = 0.016), smoking (OR = 2.88; 95% CI, 1.68-4.95; P < 0.001), definite TBM (OR = 0.19; 95% CI, 0.06-0.42; P < 0.001), disease severity (OR = 2.11; 95% CI, 1.50-2.90; P = 0.056), meningeal enhancement (OR = 1.66; 95% CI, 1.19-2.31; P = 0.002), and hydrocephalus (OR = 2.98; 95% CI, 1.98-4.49; P < 0.001) were associated with AIS. Subgroup analyses indicated that disease severity (P for interaction = 0.003), tuberculoma (P for interaction = 0.008), and meningeal enhancement (P for interaction < 0.001) were significantly different in patients with and without VAFs. Mediation analyses revealed that the proportion of the association between neuroimaging markers of inflammation and functional disability mediated by AIS was 16.98% (95% CI, 7.82-35.12) for meningeal enhancement and 3.39% (95% CI, 1.22-6.91) for hydrocephalus. Conclusion: Neuroimaging markers of inflammation were predictors of AIS in TBM patients. AIS mediates < 20% of the association between inflammation and the functional outcome at 90 days. More attention should be paid to clinical therapies targeting inflammation and hydrocephalus to directly improve functional outcomes.

Endoscopic treatment of extreme esophageal stenosis complicated with esophagotracheal fistula: A case report.

BACKGROUND: At present, there is no unified and effective treatment for extreme corrosive esophageal stenosis (CES) with esophagotracheal fistula (ETF). This case had extreme and severe esophageal stenosis (ES) and ETF after ingesting an enzyme-based chemical detergent, resulting in a serious pulmonary infection and severe malnutrition. Upper gastrointestinal imaging showed that he had an ETF, and endoscopy showed that he had extreme and severe esophageal stricture. This case was complex and difficult to treat. According to the domestic and foreign literature, there is no universal treatment that is low-risk. CASE SUMMARY: A patient came to our hospital with extreme ES, an ETF, and severe malnutrition complicated with pulmonary tuberculosis 1 mo after the consumption of an enzyme-based detergent. The ES was serious, and the endoscope was unable to pass through the esophagus. We treated him by endoscopic incision method (EIM), esophageal stent placement (ESP), and endoscopic balloon dilation (EBD) by using the bronchoscope and gastroscope. This treatment not only closed the ETF, but also expanded the esophagus, with minimal trauma, greatly reducing the pain of the patient. According to the literature, there are no similar reported cases. CONCLUSION: We report, for the first time, a patient with extreme CES complicated with ETF, where the endoscope could not be passed through his esophagus but he could be examined by bronchoscopy and treated by EIM, ESP, and EBD.

Clinical Subtypes of Neutrophilic Asthma: A Cluster Analysis From Australasian Severe Asthma Network.

BACKGROUND: Clinical heterogeneity may exist within asthma subtypes defined by inflammatory markers. However, the heterogeneity of neutrophilic asthma (NA) remains largely unexplored. OBJECTIVE: To explore potential clusters and the stability of NA. METHODS: Participants with NA from the Australasian Severe Asthma Network underwent a multidimensional assessment. They were then asked to participate in a 12-month longitudinal cohort study. We explored potential clusters using a hierarchical cluster analysis and validated the differential future risk of asthma exacerbations in the identified clusters. A decision tree analysis was developed to predict cluster assignments. Finally, the stability of prespecified clusters was examined within 1 month. RESULTS: Three clusters were identified in 149 patients with NA. Cluster 1 (n = 99; 66.4%) was characterized by female-predominant nonsmokers with well-controlled NA, cluster 2 (n = 16; 10.7%) by individuals with comorbid anxiety/depressive symptoms with poorly controlled NA, and cluster 3 by older male smokers with late-onset NA. Cluster 2 had a greater proportion of participants with severe exacerbations (P = .005), hospitalization (P = .010), and unscheduled visits (P = .013) and a higher number of emergency room visits (P = .039) than that of the other two clusters. The decision tree assigned 92.6% of participants correctly. Most participants (87.5%; n = 7) in cluster 2 had a stable NA phenotype, whereas participants of clusters 1 and 3 had variable phenotypes. CONCLUSIONS: We identified three clinical clusters of NA, in which cluster 2 represents an uncontrolled and stable NA subtype with an elevated risk of exacerbations. These findings have clinical implications for the management of NA.

Interaction effect of chronic cough and ageing on increased risk of exacerbation in patients with asthma: a prospective cohort study in a real-world setting.

Background: Older adults with asthma have the greatest burden and worst outcomes, and there is increasing evidence that chronic cough (CC) is associated with asthma severity and poor prognosis. However, the clinical characteristics of older adult patients with both asthma and CC remain largely unknown. Methods: Participants with stable asthma underwent two cough assessments within 3 months to define the presence of CC. Patients were divided into four groups based on CC and age (cut-off ≥60 years). Multidimensional assessment was performed at baseline, followed by a 12-month follow-up to investigate asthma exacerbations. Logistic regression models were used to explore the interaction effect of CC and age on asthma control and exacerbations. Results: In total, 310 adult patients were prospectively recruited and divided into four groups: older CC group (n=46), older non-CC group (n=20), younger CC group (n=112) and younger non-CC group (n=132). Compared with the younger non-CC group, the older CC group had worse asthma control and quality of life and increased airflow obstruction. The older CC group showed an increase in moderate-to-severe exacerbations during the 12-month follow-up. There was a significant interaction effect of CC and ageing on the increased moderate-to-severe exacerbations (adjusted risk ratio 2.36, 95% CI 1.47-3.30). Conclusion: Older asthma patients with CC have worse clinical outcomes, including worse asthma control and quality of life, increased airway obstruction and more frequent moderate-to-severe exacerbations, which can be partly explained by the interaction between CC and ageing.

Comparison of Diagnostic Values of ACR TI-RADS versus C-TIRADS Scoring and Classification Systems for the Elderly Thyroid Cancers.

Purpose: To compare the diagnostic value of the Thyroid Imaging Reporting and Data System (TI-RADS) of the American College of Radiology (ACR) versus the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) scoring and classification system for elderly thyroid cancers. Patients and Methods: A total of 512 nodules from 465 patients aged ≥60 with surgical pathology-proven thyroid nodules were enrolled in our study. The ultrasound features of thyroid nodules were independently evaluated by the ACR TI-RADS and C-TIRADS classification systems, and the receiver operating characteristic curve (ROC) was plotted. The optimal cut-off values of the ACR TI-RADS and C-TIRADS scoring and classification systems for diagnosing elderly thyroid nodules were estimated, and the diagnostic efficacy was analyzed. Results: The ACR TI-RADS and C-TIRADS scores and classifications of thyroid cancers were both higher than benign nodules (both P < 0.05). The area under the curve (AUC) of ACR TI-RADS and C-TIRADS scoring and classification systems were 0.861, 0.897, 0.879, and 0.900, respectively, and the AUC of the scoring system was greater than the classification system for both criteria. When the Youden index was the highest, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the ACR TI-RADS scoring and classification systems were consistent, ie, they were 89.66%, 41.70%, 89.93%, and 59.00%, respectively; the sensitivity, specificity, PPV, and NPV of the C-TIRADS scoring and classification systems were also consistent, ie, they were 88.71%, 44.26%, 90.23%, 59.69%, respectively. The diagnostic efficacy between the two systems was not statistically significant. Conclusion: ACR TI-RADS and C-TIRADS systems had relatively high diagnostic efficacy for elderly thyroid cancer. The diagnostic efficiency of the scoring systems of ACR TI-RADS and C-TIRADS were higher than the classification systems. In addition, the two systems had high clinical practical values, while there is still a significant risk of missed diagnosis.

Comparing Diagnostic Efficacy of C-TIRADS Positive Features on Different Sizes of Thyroid Nodules.

Purpose: To explore the diagnostic value of positive features in the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) for thyroid nodules of different sizes. Patients and Methods: A total of 1864 patients with 2347 thyroid nodules were selected from January 2021 to December 2022 and assessed according to C-TIRADS. According to the maximum diameter, nodules were divided into the A1 group (≤10 mm), A2 group (>10 mm,<20 mm), and A3 group (≥20 mm). With surgical pathology as the golden standard, the receiver operating characteristic curves (ROC) were constructed, and each group's area under the curve (AUC) was calculated. The diagnostic value of positive features in C-TIRADS for different sizes of thyroid nodules was analyzed. Results: In all groups, malignant thyroid nodules had a higher incidence of positive features than benign nodules (P < 0.05). In A1 group, the diagnostic efficiency of C-TIRADS positive features for thyroid nodules was vertical orientation> ill-defined/irregular margin or extrathyroidal extension> solid composition> markedly hypoechoic> microcalcifications. The AUCs were 0.718, 0.675, 0.609, 0.558, and 0.581, respectively. In A2 group, the diagnostic efficacy of each positive features for thyroid nodules was ill-defined/irregular margins or extra-thyroid invasion> solid composition> microcalcifications> markedly hypoechoic> vertical orientation. The AUCs were 0.854, 0.730, 0.719, 0.670, and 0.609, respectively. In A3 group, the diagnostic efficacy of each positive features for thyroid nodules was ill-defined/irregular margin or extrathyroidal extension> microcalcifications> solid composition> vertical orientation> markedly hypoechoic. The AUCs were 0.847, 0.778, 0.767, 0.584, and 0.560, respectively. Conclusion: C-TIRADS positive features exhibited different diagnostic efficacy for thyroid nodules of various sizes, especially for thyroid nodules ≤10 mm, for which all positive features had low diagnostic efficacy.

Glucocorticoids ameliorate cardiorenal syndrome through the NPR1/SGK1 pathway in natriuretic peptide receptor A­heterozygous mice.

Natriuretic peptides, which are produced by the heart, bind to natriuretic peptide receptor A (NPR1 encoded by natriuretic peptide receptor 1 gene) and cause vasodilation and natriuresis. Thus, they serve an important role in regulating blood pressure. In the present study, microinjection of CRISPR associated protein 9/single guide RNA into fertilized C57BL/6N mouse eggs was performed to generate filial generation zero (F0) Npr1 knockout homozygous mice (Npr1-/-). F0 mice mated with wild-type (WT) mice to obtain F1 Npr1 knockout heterozygous mice with stable heredity (Npr1+/-). F1 self-hybridization was used to expand the population of heterozygous mice (Npr1+/-). The present study performed echocardiography to investigate the impact of NPR1 gene knockdown on cardiac function. Compared with those in the WT group (C57BL/6N male mice), the left ventricular ejection fraction, myocardial contractility and renal sodium and potassium excretion and creatinine-clearance rates were decreased, indicating that Npr1 knockdown induced cardiac and renal dysfunction. In addition, expression of serum glucocorticoid-regulated kinase 1 (SGK1) increased significantly compared with that in WT mice. However, glucocorticoids (dexamethasone) upregulated NPR1 and inhibited SGK1 and alleviated cardiac and renal dysfunction caused by Npr1 gene heterozygosity. SGK1 inhibitor GSK650394 ameliorate cardiorenal syndrome by suppressing SGK1. Briefly, glucocorticoids inhibited SGK1 by upregulating NPR1, thereby ameliorating cardiorenal impairment caused by Npr1 gene heterozygosity. The present findings provided novel insight into the understanding of cardiorenal syndrome and suggested that glucocorticoids targeting the NPR1/SGK1 pathway may be a potential therapeutic target to treat cardiorenal syndrome.

Dyslipidemia Is Associated With Worse Asthma Clinical Outcomes: A Prospective Cohort Study.

BACKGROUND: Dyslipidemia has been widely documented to be associated with cardiovascular disease, and recent studies have found an association with asthma prevalence. However, longitudinal studies investigating the relationships between dyslipidemia, asthma phenotypes, and future asthma exacerbations (AEs) are lacking. OBJECTIVE: To investigate the relationships between dyslipidemia, asthma phenotypes, and AEs. METHODS: This study used an observational cohort study design with a 12-month follow-up. All subjects underwent serum lipid measurement, and they were then classified into 2 groups: the normal-lipidemia group and the dyslipidemia group. Demographic and clinical information and details regarding pulmonary function and asthma phenotypes at baseline were collected. All patients were followed up regularly to assess AEs. Associations of dyslipidemia with airway obstruction and asthma phenotypes were assessed at baseline, whereas dyslipidemia and AEs were assessed longitudinally. RESULTS: A total of 477 patients with asthma were consecutively enrolled in this study. At baseline, the dyslipidemia group (n = 218) had a higher proportion of uncontrolled asthma, defined by the 6-item Asthma Control Questionnaire score (≥1.5). Furthermore, dyslipidemia was associated with severe asthma, nonallergic asthma, asthma with fixed airflow limitation, and older adult asthma phenotypes at baseline. In addition, dyslipidemia was associated with increased frequencies of severe AEs and moderate to severe AEs during the 12-month follow-up. In sensitivity analyses, after excluding the patients who were receiving statins, results did not differ significantly from those of the main analysis. CONCLUSIONS: We identified the clinical relevance of dyslipidemia, which is associated with specific asthma phenotypes and increased AEs, independent of other components of metabolic syndrome. These findings highlight the importance of considering dyslipidemia as an "extrapulmonary trait" in asthma management.

Self-Reported Insufficient Sleep Is Associated With Clinical and Inflammatory Features of Asthma: A Prospective Cohort Study.

BACKGROUND: A few studies have explored the association between short sleep duration and worse asthma outcomes in patients with self-reported asthma; however, all of them were cross-sectional. OBJECTIVES: To investigate the association between self-reported sleep duration and asthma-related clinical and inflammatory characteristics and whether sleep duration is associated with asthma exacerbations (AEs) in the following year. METHODS: A prospective cohort study consecutively recruited participants with asthma, who were classified into short (n = 58), normal (n = 380), and long (n = 84) sleep duration groups. We investigated the clinical and inflammatory characteristics and exacerbations within a 1-year follow-up. RESULTS: Patients with short sleep duration were older and had significantly lower total IgE and FeNO levels and higher airway inflammation, characterized by increased levels of IL-6 and TNF-α in sputum than those of patients with normal sleep duration. Furthermore, they had a significantly increased risk for poorly controlled asthma (adjusted odds ratio = 2.741; 95% CI, 1.379-5.447; P = .004) and moderate to severe AEs (adjusted incidence rate ratio = 1.798; 95% CI, 1.098-2.942; P = .020). CONCLUSIONS: Short sleep duration was associated with non-type 2 inflammation and is an independent risk factor for future AEs. Therefore, as a potentially treatable trait, sleep duration may have clinical implications for asthma management.

Age-Related Clinical Characteristics, Inflammatory Features, Phenotypes, and Treatment Response in Asthma.

BACKGROUND: Emerging evidence suggests that aging affects asthma outcomes, but the mechanism remains largely unexplored. OBJECTIVE: To explore age-related clinical characteristics, inflammatory features, phenotypes, and treatment response in asthma. METHODS: This was a prospective cohort study of asthmatic patients with a 12-month follow-up in a real-world setting. Clinical inflammatory and phenotypic characteristics, future risk for exacerbations, and treatment response were assessed across different age groups (young was defined as age 18 to 39 years; middle-aged, 40 to 64 years; and elderly, 65 years or older). RESULTS: Compared with young (n = 106) and middle-aged (n = 179) asthmatic patients, elderly patients (n = 55) had worse airway obstruction, more comorbidities including chronic obstructive pulmonary disease and diabetes, less atopy, and lower levels of IgE and FeNO, and were more likely to have late-onset and fixed airflow obstruction asthma and a reduced risk for having type 2 profile asthma. Levels of IFN-gamma, IL-17A, and IL-8 in induced sputum were significantly increased in elderly asthmatic patients (all P < .05). Path analysis indicated that age directly and significantly led to future exacerbations in asthma, partially mediated by an upregulation of airway IFN-gamma. Moreover, elderly patients with asthma had a reduced treatment response (improvement in FEV1 of 12% or greater, or 200 mL, and a reduction in Borg scores of 1 or greater) (adjusted odds ratio = 0.11; 95% CI, 0.02-0.52; and adjusted odds ratio = 0.12; 95% CI, 0.03-0.49, respectively). CONCLUSIONS: This study confirms that asthma in the elderly population represents a specific phenotype and indicates that aging can influence asthma in terms of clinical characteristics, inflammatory features, exacerbations, and treatment response.

Prevalence and prognostic significance of malnutrition risk in patients with pulmonary tuberculosis: A hospital-based cohort study.

Background: The prevalence and prognostic significance of malnutrition risk remain unclear in Chinese patients with pulmonary tuberculosis. Therefore, we aimed to investigate the malnutrition risk in Chinese patients and explore the relationship between malnutrition risk and follow-up outcomes. Methods: We conducted a hospital-based cohort study from January 2020 to December 2020. Malnutrition risks were evaluated using nutritional scales, including the Nutritional Risk Screening 2002 (NRS-2002), the controlling nutritional status score (CONUT), the geriatric nutritional risk index (GNRI), and the prognostic nutritional index (PNI). The primary outcome was all-cause mortality at a one-year follow-up. Malnutrition risk was calculated, and the relationship between malnutrition and follow-up outcomes was analyzed. We assessed the performance of malnutrition risks to predict clinical outcomes in prognostic models. Results: A total of 1,075 patients were included. According to NRS-2002, CONUT, GNRI, and PNI, 818 (76.09%), 954 (88.74%), 682 (63.44%), and 364 (33.86%) patients were at risk of malnutrition, respectively. Before 1-year follow-up, a total of 99 patients (9.2%) had died. After adjustment for risk factors, the association between severe malnutrition in CONUT (HR = 4.78, 95% CI: 1.14-20.11, P = 0.033), GNRI (HR = 3.53, 95% CI: 1.70-7.34, P = 0.001), or PNI (HR = 2.94, 95% CI: 1.76-4.88, P < 0.001) and death before 1-year follow-up remained significant. The addition of the nutritional scales to prognostic models improved death prediction, as validated by the integrated discrimination index (all P-values of <0.05). Conclusion: Malnutrition in patients with pulmonary tuberculosis was associated with an increased risk of all-cause death in the long-term follow-up. Our findings provided evidence for the use of admission nutrition screening in patients with pulmonary tuberculosis.

Endogenous Adenosine 5'-Monophosphate, But Not Acetylcholine or Histamine, is Associated with Asthma Control, Quality of Life, and Exacerbations.

OBJECTIVE: Endogenous adenosine 5'-monophosphate (AMP), acetylcholine (ACh), and histamine (HA) are known to be important in bronchial contraction, but their clinical relevance to asthma is poorly understood. We aimed to quantify endogenous AMP, ACh, and HA in induced sputum samples and explore their relationships with asthma control and exacerbations. METHODS: 20 healthy subjects and 112 asthmatics underwent clinical assessment, sputum induction, and blood sampling. The level of asthma control was determined by the asthma control test (ACT) questionnaire. Asthma exacerbation was evaluated according to the criteria of the American Thoracic Society/European Respiratory Society. Levels of AMP, ACh, and HA in sputum were measured by liquid chromatography coupled to tandem mass spectrometry. IL-ß, IL-4, IL-5, IL-6, IL-8, IL-13, IL-17A, TNF-α, IFN-γ, and macrophage-derived chemokine (MDC) were also measured. RESULTS: Compared to healthy controls, asthmatics had higher levels of HA, lower levels of ACh, and similar levels of AMP in induced sputum samples. Compared to controlled asthma (n = 54), uncontrolled asthma (n = 58) showed higher AMP levels (P = 0.002), but similar HA and ACh levels. AMP was negatively correlated with ACT scores (r = - 0.348) and asthma quality of life questionnaire scores (r = - 0.188) and positively correlated with blood monocytes percentage (r = 0.195), sputum MDC (r = 0.214), and IL-6 levels (r = 0.196). Furthermore, AMP was associated with an increased risk of exacerbations in the preceding year. CONCLUSION: Endogenous AMP, but not ACh or HA, was associated with asthma control, quality of life, and exacerbations in the previous year, which indicates that AMP could be a clinically useful biomarker of asthma.

Sputum Metabolomic Profiling Reveals Metabolic Pathways and Signatures Associated With Inflammatory Phenotypes in Patients With Asthma.

PURPOSE: The molecular links between metabolism and inflammation that drive different inflammatory phenotypes in asthma are poorly understood. We aimed to identify the metabolic signatures and underlying molecular pathways of different inflammatory asthma phenotypes. METHODS: In the discovery set (n = 119), untargeted ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was applied to characterize the induced sputum metabolic profiles of asthmatic patients with different inflammatory phenotypes using orthogonal partial least-squares discriminant analysis (OPLS-DA), and pathway topology enrichment analysis. In the validation set (n = 114), differential metabolites were selected to perform targeted quantification. Correlations between targeted metabolites and clinical indices in asthmatic patients were analyzed. Logistic and negative binomial regression models were established to assess the association between metabolites and severe asthma exacerbations. RESULTS: Seventy-seven differential metabolites were identified in the discovery set. Pathway topology analysis uncovered that histidine metabolism, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism, linoleic acid metabolism as well as phenylalanine, tyrosine and tryptophan biosynthesis were involved in the pathogenesis of different asthma phenotypes. In the validation set, 24 targeted quantification metabolites were significantly expressed between asthma inflammatory phenotypes. Finally, adenosine 5'-monophosphate (adjusted relative risk [adj RR] = 1.000; 95% confidence interval [CI] = 1.000-1.000; P = 0.050), allantoin (adj RR = 1.000; 95% CI = 1.000-1.000; P = 0.043) and nicotinamide (adj RR = 1.001; 95% CI = 1.000-1.002; P = 0.021) were demonstrated to predict severe asthma exacerbation rates. CONCLUSIONS: Different inflammatory asthma phenotypes have specific metabolic profiles in induced sputum. The potential metabolic signatures may identify therapeutic targets in different inflammatory asthma phenotypes.

Laparoscopic-assisted endoscopic full-thickness resection of a large gastric schwannoma: A case report.

BACKGROUND: Schwannomas, also known as neurinomas, are benign tumors derived from Schwann cells. Gastrointestinal schwannomas are rare and are most frequently reported in the stomach. They are usually asymptomatic and are difficult to diagnose preoperatively; however, endoscopy and imaging modalities can provide beneficial preliminary diagnostic data. There are various surgical options for management. Here, we present a case of a large gastric schwannoma (GS) managed by combined laparoscopic and endoscopic surgery. CASE SUMMARY: A 28-year-old woman presented with a 2-mo history of epigastric discomfort and a feeling of abdominal fullness. On upper gastrointestinal endoscopy and endoscopic ultrasonography, a hypoechogenic submucosal mass was detected in the gastric antrum: It emerged from the muscularis propria and projected intraluminally. Computed tomography showed a nodular lesion (4 cm × 3.5 cm), which exhibited uniform enhancement, on the gastric antrum wall. Based on these findings, a preliminary diagnosis of gastrointestinal stromal tumor was established, with schwannoma as a differential. Considering the large tumor size, we planned to perform endoscopic resection and to convert to laparoscopic treatment, if necessary. Eventually, the patient underwent combined laparoscopic and gastroscopic surgery. Immunohistochemically, the resected specimen showed positivity for S-100 and negativity for desmin, DOG-1, α-smooth muscle actin, CD34, CD117, and p53. The Ki-67 index was 3%, and a final diagnosis of GS was established. CONCLUSION: Combined laparoscopic and endoscopic surgery is a minimally invasive and effective treatment option for large GSs.

Reduced bronchodilator reversibility correlates with non-type 2 high asthma and future exacerbations: A prospective cohort study.

BACKGROUND: Given that airway obstruction in asthma is not always fully reversible, reduced bronchodilator reversibility (BDR) may be a special asthma phenotype. OBJECTIVE: To explore the characteristics of BDRhigh/low phenotypes (defined using two BDR criteria) and their associations with asthma exacerbations (AEs). METHODS: After baseline assessments, all patients were classified into BDRhigh or BDRlow phenotypes. This study consisted of 2 parts. Part I was a 12-month prospective observational cohort study designed to identify the clinical characteristics and associations with future AEs in BDRhigh/low phenotypes (n = 456). Part II, designed as a post hoc analysis of the data obtained in Part I, was conducted to assess the association between BDRhigh/low phenotypes and treatment responsiveness (n = 360). RESULTS: Subjects with BDRlow phenotypes had better baseline asthma symptom control and was negatively associated with eosinophilic asthma and type 2 (T2) high asthma. During the 12-month follow-up, those with BDRlow phenotypes had a higher risk of severe AEs (SAEs) (guideline-based criterion: RRadj = 2.24, 95% CI = [1.25, 3.68]; Ward's criterion: RRadj = 2.46, 95% CI = [1.40, 4.00]) and moderate-to-severe AEs (MSAEs) (guideline-based criterion: RRadj = 1.83, 95% CI = [1.22, 2.56]; Ward's criterion: RRadj = 1.94, 95% CI = [1.32, 2.68]) in the following year according to logistic regression models. Similar findings were obtained with negative binominal regression models. BDRlow phenotype was a risk factor for an insensitive response to anti-asthma treatment (guideline-based criterion: ORadj = 1.96, 95% CI = [1.05, 3.65]; Ward's criterion: ORadj = 2.01, 95% CI = [1.12, 3.58]). CONCLUSION: We identified that BDRlow phenotype was associated with non-T2 high asthma and future AEs. These findings have clinically relevant implications for asthma management.

Chronic cough in asthma is associated with increased airway inflammation, more comorbidities, and worse clinical outcomes.

Background: Cough is often the most prominent and intractable symptom reported by patients with asthma, but few studies have explored the characteristics of patients with asthma and with chronic cough (CC) in a real-world setting. Methods: In a prospective cohort study, patients ages ≥ 18 years with stable asthma were consecutively recruited at the West China Hospital, Sichuan University. The patients were classified as having asthma with CC (the CC group) or asthma with non-CC (the non-CC group) after 3 months of optimized asthma therapy according to standard guidelines. Multidimensional assessment was performed at baseline, followed by a 12-month follow-up to assess asthma exacerbations. Results: Of 323 patients with asthma, 127 patients were assigned to the CC group and 196 patients were assigned to the non-CC group. The participants with CC were older and had more airflow obstruction; worse asthma control and quality of life; increased airway inflammation; upper respiratory tract infection as a trigger; and more comorbidities, such as psychological dysfunction, rhinitis, chronic obstructive pulmonary disease, and bronchiectasis. They reported greater work productivity loss and daily activity impairment, and increased moderate-to-severe exacerbations. Conclusion: The participants with asthma and with CC had a significant disease burden, with increased exacerbations, health-care utilization, and impaired work productivity and daily activity. These observations indicated potential clinical implications in patients with asthma and with CC, and call for more attention to this aspect of asthma.

An orally available Mpro inhibitor is effective against wild-type SARS-CoV-2 and variants including Omicron.

Emerging SARS-CoV-2 variants continue to cause waves of new infections globally. Developing effective antivirals against SARS-CoV-2 and its variants is an urgent task. The main protease (Mpro) of SARS-CoV-2 is an attractive drug target because of its central role in viral replication and its conservation among variants. We herein report a series of potent α-ketoamide-containing Mpro inhibitors obtained using the Ugi four-component reaction. The prioritized compound, Y180, showed an IC50 of 8.1 nM against SARS-CoV-2 Mpro and had oral bioavailability of 92.9%, 31.9% and 85.7% in mice, rats and dogs, respectively. Y180 protected against wild-type SARS-CoV-2, B.1.1.7 (Alpha), B.1.617.1 (Kappa) and P.3 (Theta), with EC50 of 11.4, 20.3, 34.4 and 23.7 nM, respectively. Oral treatment with Y180 displayed a remarkable antiviral potency and substantially ameliorated the virus-induced tissue damage in both nasal turbinate and lung of B.1.1.7-infected K18-human ACE2 (K18-hACE2) transgenic mice. Therapeutic treatment with Y180 improved the survival of mice from 0 to 44.4% (P = 0.0086) upon B.1.617.1 infection in the lethal infection model. Importantly, Y180 was also highly effective against the B.1.1.529 (Omicron) variant both in vitro and in vivo. Overall, our study provides a promising lead compound for oral drug development against SARS-CoV-2.