The Effect of Sodium Glucose Cotransporter-2 Inhibitors on Hemoglobin A1c Variability and Acute Kidney Injury: A Causal Mediation Analysis.

PURPOSE: The role of lower hemoglobin A1c (HbA1c) variability in the effect of sodium glucose cotransporter-2 inhibitors (SGLT2i) on acute kidney injury (AKI) remains unclear. We compared AKI risk between SGLT2i and dipeptidyl peptidase 4 inhibitors (DPP4i) initiators. Additionally, we aimed to explore the extent to which SGLT2i's influence on AKI risk is mediated by reducing long-term HbA1c variability. METHODS: Using 2018-2022 year data in Yinzhou Regional Health Care Database, we included adult, type 2 diabetes patients who were new users of SGLT2i or DPP4i. The effect of SGLT2i versus DPP4i on AKI, HbA1c variability, and AKI through HbA1c variability was compared using inverse probability of treatment weighted Cox proportional hazards models, median regression models, and causal mediation analysis. RESULTS: With a median follow-up of 1.76 years, 19 717 adults (for SGLT2i, n = 6008; for DPP4i, n = 13 709) with type 2 diabetes were included. The adjusted hazard ratio for SGLT2i versus DPP4i was 0.79 (95% confidence interval [CI] 0.64-0.98) for AKI. The adjusted differences in median HbA1c variability score (HVS) and HbA1c reduction were -16.67% (95% CI: -27.71% to -5.62%) and -1.98% (95% CI: -14.34% to 10.38%), respectively. Furthermore, lower AKI risk associated with SGLT2i was moderately mediated (22.77%) through HVS. The results remained consistent across various subgroups and sensitivity analyses. CONCLUSIONS: Compared to DPP4i, lower AKI risk associated with SGLT2i is moderately mediated through HbA1c variability. These findings enhance our understanding of the effect of SGLT2i on AKI and underscore the importance of considering HbA1c variability in diabetes treatment and management.

Glucagon-like Peptide 1 Receptor Agonists and Asthma Exacerbations: Which Patients Benefit Most?

RATIONALE: While recent evidence suggested glucagon-like peptide 1 receptor agonists (GLP1RA) may reduce the risk of asthma exacerbations, it remains unclear which subpopulations might derive the most benefit from GLP1RA treatment. OBJECTIVE: To identify characteristics of patients with asthma that predict who might benefit the most from GLP1RA treatment using real-world data. METHODS: We implemented an active-comparator, new-user design analysis using commercially insured patients ages 18-65 from Marketscan data 2007-2019 and identified two cohorts: GLP1RA vs thiazolidinediones and GLP1RA vs sulfonylureas. The outcome was acute exacerbation of asthma (hospital admission or emergency department (ED) visit for asthma) within 180 days after initiation. We applied iterative causal forest (iCF), a novel causal machine learning subgrouping algorithm, to assess HTE. In identified subgroups, we predicted propensity score, conducted propensity score trimming, and then estimated adjusted risk differences (aRD) for the effect of GLP1RA relative to comparators on asthma exacerbation using inverse probability treatment weighting in propensity score trimmed subpopulation. RESULTS: Among 10,989 patients initiating GLP1RA or thiazolidinediones and 17,088 patients initiating GLP1RA vs sulfonylurea, GLP1RA initiators had fewer exacerbations with an aRD of -0.5% (95% CI -1.1% to 0.1%) and -1.6% (95% CI -2.2% to -1.1%), respectively. In the GLP1RAvsSUcohort where we observed beneficial effect, our iCF analysis identified 5 subgroups with different treatment effects, defined by number of ED visits, number of prescriptions of short-acting beta2-agonsit (SABA), number of prescriptions of inhaled steroid (ICS) and long-acting beta-agonists (LABA) (either combination therapy or concurrent use), and aged 50+. Among these, patients with 2+ ED visits during 12-month baseline period had the largest absolute exacerbation risk reduction, with a decrease of 2.8% for GLP1RA (95% CI: -4.8% to -0.9%). CONCLUSIONS: GLP1RA demonstrated beneficial effect on reducing asthma exacerbation relative to sulfonylureas. Asthma patients with 2+ ED visits (a proxy for disease severity) benefit most from GLP1RA. ED visit frequency, and number of maintenance and reliever inhalers, and age may help individualize prediction of the short-term benefit from GLP1RA on asthma exacerbation.

Cu(I)-Glutathione Assembly Supported on ZIF-8 as Robust and Efficient Catalyst for Mild CO2 Conversions.

The Cu-glutathione (GSH) redox system, essential in biology, is designed here as a supramacromolecular assembly in which the tetrahedral 18e Cu(I) center loses a thiol ligand upon adsorption onto ZIF-8, as shown by EXAFS and DFT calculation, to generate a very robust 16e planar trigonal single-atom Cu(I) catalyst. Synergy between Cu(I) and ZIF-8, revealed by catalytic experiments and DFT calculation, affords CO2 conversion into high-value-added chemicals with a wide scope of substrates by reaction with terminal alkynes or propargyl amines in excellent yields under mild conditions and reuse at least 10 times without significant decrease in catalytic efficiency.

Bridge-layered decompression technique for vertebral artery-involved hemifacial spasm: technical note.

BACKGROUND: Hemifacial spasm (HFS) is most effectively treated with microvascular decompression (MVD). However, there are certain challenges in performing MVD for HFS when the vertebral artery (VA) is involved in compressing the facial nerve (VA-involved). This study aimed to introduce a "bridge-layered" decompression technique for treating patients with VA-involved HFS and to evaluate its efficacy and safety to treat patients with HFS. METHODS: A single-center retrospective analysis was conducted on the clinical data of 62 patients with VA-involved HFS. The tortuous trunk of VA was lifted by a multi-point "bridge" decompression technique to avoid excessive traction of the cerebellum and reduce the risk of damage to the facial-acoustic nerve complex. To fully decompress all the responsible vessels, the branch vessels of VA were then isolated using the "layered" decompression technique. RESULTS: Among the 62 patients, 59 patients were cured immediately after the surgery, two patients were delayed cured after two months, and one had occasional facial muscle twitching after the surgery. Patients were followed up for an average of 19.5 months. The long-term follow-up results showed that all patients had no recurrence of HFS during the follow-up period, and no patients developed hearing loss, facial paralysis, or other permanent neurological damage complications. Only two patients developed tinnitus after the surgery. CONCLUSION: The "bridge-layered" decompression technique could effectively treat VA-involved HFS with satisfactory safety and a low risk of hearing loss. The technique could be used as a reference for decompression surgery for VA-involved HFS.

A fast-charging/discharging and long-term stable artificial electrode enabled by space charge storage mechanism.

Lithium-ion batteries with fast-charging/discharging properties are urgently needed for the mass adoption of electric vehicles. Here, we show that fast charging/discharging, long-term stable and high energy charge-storage properties can be realized in an artificial electrode made from a mixed electronic/ionic conductor material (Fe/LixM, where M = O, F, S, N) enabled by a space charge principle. Particularly, the Fe/Li2O electrode is able to be charged/discharged to 126 mAh g-1 in 6 s at a high current density of up to 50 A g-1, and it also shows stable cycling performance for 30,000 cycles at a current density of 10 A g-1, with a mass-loading of ~2.5 mg cm-2 of the electrode materials. This study demonstrates the critical role of the space charge storage mechanism in advancing electrochemical energy storage and provides an unconventional perspective for designing high-performance anode materials for lithium-ion batteries.

CD109 identified in circulating proteomics mitigates postoperative recurrence in chronic rhinosinusitis with nasal polyps by suppressing TGF-ß1-induced epithelial-mesenchymal transition.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disorder with a high rate of recurrence. This study aimed to explore biomarkers for identifying patients with recurrent CRSwNP (rCRSwNP). METHODS: We recruited two independent cohorts. In the discovery cohort, rCRSwNP patients and non-recurrent CRSwNP (non-rCRSwNP) patients were recruited, and the serum proteomic profile was characterized. The top 5 upregulated and downregulated proteins were confirmed in the validation cohort by ELISA, WB, and qRT-PCR, and their predictive values for postoperative recurrence were assessed. In vitro, human nasal epithelial cells (HNEpCs) were employed to assess the ability of candidate proteins to induce epithelial-mesenchymal transition (EMT). RESULTS: Serum proteomics identified 53 different proteins, including 30 increased and 23 decreased, between the rCRSwNP and non-rCRSwNP groups. ELISA results revealed that serum levels of CD163 and TGF-ß1 were elevated, CD109 and PRDX2 were decreased in the rCRSwNP group compared to the non-rCRSwNP group, and serum CD163, TGF-ß1, and CD109 levels were proved to be associated with the risk of postoperative recurrence. In addition, qRT-PCR and WB revealed that tissue CD163, TGF-ß1, and CD109 expressions in rCRSwNP patients were enhanced compared to those non-rCRSwNP patients. Kaplan-Meier analysis showed that increased CD163 and TGF-ß1 expression and decreased CD109 expression are associated with the risk of recurrence in CRSwNP patients. Receiver operating characteristic curves showed that TGF-ß1 and CD109 had superior diagnostic performances for rCRSwNP. In vitro experiments showed that TGF-ß1 promoted EMT in HNEpCs, and overexpression of CD109 reversed this effect. Functional recovery experiments confirmed that CD109 could attenuate EMT in HNEpCs by inhibiting the TGF-ß1/Smad signaling pathway, attenuating EMT in epithelial cells. CONCLUSION: Our data suggested that TGF-ß1 and CD109 might serve as promising predictors of rCRSwNP. The TGF-ß1/Smad pathway was implicated in fostering EMT in epithelial cells, particularly those exhibiting low expression of CD109. Consequently, the absence of CD109 expression in epithelial cells could be a potential mechanism underlying rCRSwNP.

Serum Proteomic Analysis Revealed Biomarkers for Eosinophilic Chronic Rhinosinusitis with Nasal Polyps Pathophysiology.

Background: Individuals with eosinophilic chronic rhinosinusitis with nasal polyps(eCRSwNP) exhibited worse outcomes and higher postoperative recurrence rates. This study aimed to identify biomarkers that can aid in the early differentiation of eCRSwNP and enhance our comprehension of its pathophysiology. Methods: We recruited two independent cohorts. In the discovery cohort, CRSwNP was categorized into eCRSwNP and non-eosinophilic CRSwNP(neCRSwNP), and serum proteomics was performed to identify differentially expressed proteins between the two groups. These candidate proteins were chosen and confirmed in the validation cohort using an enzyme-linked immunosorbent assay (ELISA), Western blot (WB), quantitative real time-polymerase chain reaction (qRT-PCR), immunofluorescence (IF), and their predictive values and associations with tissue eosinophilic pathophysiology were evaluated. Results: We identified a total of 39 differential proteins between the two groups, including 20 proteins upregulated and 19 downregulated in the eCRSwNP group. Further validation was conducted on the top 5 proteins that were up or down-regulated. Results from the ELISA showed that levels of serum MRC1, CDH13, and MMP2 were significantly higher, TRIM28 was lower in the eCRSwNP group compared to the neCRSwNP group (all P<0.05), and serum MRC1 (AUC=0.742, P<0.001) and MMP2 (AUC=0.766, P<0.001) levels exhibited promising predicting values for eCRSwNP. Moreover, qRT-PCR and WB analysis found that MMP2 and MRC1 expressions were enhanced in the eCRSwNP group compared to the neCRSwNP group (all P<0.01), and their levels were positively correlated with the number and percentages of tissue eosinophils (all P<0.01). The IF suggested that MMP2 and MRC1 were overexpressed in the nasal polyps tissues of eCRSwNP patients, and MMP2 was mainly located on eosinophils. Conclusion: Circulating proteins identified by proteomics could serve as potential preoperative biomarkers for distinguishing eCRSwNP. Among them, MMP2 was enhanced in eCRSwNP and correlated with tissue eosinophilia, which provided valuable insights into the pathophysiology of eCRSwNP.

Validation of an international classification of disease, tenth revision, clinical modification (ICD-10-CM) algorithm in identifying severe hypoglycaemia events for real-world studies.

AIM: The transition to the ICD-10-CM coding system has reduced the utility of hypoglycaemia algorithms based on ICD-9-CM diagnosis codes in real-world studies of antidiabetic drugs. We mapped a validated ICD-9-CM hypoglycaemia algorithm to ICD-10-CM codes to create an ICD-10-CM hypoglycaemia algorithm and assessed its performance in identifying severe hypoglycaemia. MATERIALS AND METHODS: We assembled a cohort of Medicare patients with DM and linked electronic health record (EHR) data to the University of North Carolina Health System and identified candidate severe hypoglycaemia events from their Medicare claims using the ICD-10-CM hypoglycaemia algorithm. We confirmed severe hypoglycaemia by EHR review and computed a positive predictive value (PPV) of the algorithm to assess its performance. We refined the algorithm by removing poor performing codes (PPV ≤0.5) and computed a Cohen's κ statistic to evaluate the agreement of the EHR reviews. RESULTS: The algorithm identified 642 candidate severe hypoglycaemia events, and we confirmed 455 as true severe hypoglycaemia events, PPV of 0.709 (95% confidence interval: 0.672, 0.744). When we refined the algorithm, the PPV increased to 0.893 (0.862, 0.918) and missed <2.42% (<11) true severe hypoglycaemia events. Agreement between reviewers was high, κ = 0.93 (0.89, 0.97). CONCLUSIONS: We translated an ICD-9-CM hypoglycaemia algorithm to an ICD-10-CM version and found its performance was modest. The performance of the algorithm improved by removing poor performing codes at the trade-off of missing very few severe hypoglycaemia events. The algorithm has the potential to be used to identify severe hypoglycaemia in real-world studies of antidiabetic drugs.

Effects of Metabolic Syndrome and its components on the postoperative recurrence in Chronic Rhinosinusitis with Nasal Polyps' patients.

OBJECTIVES: Metabolic Syndrome (MetS) has been established as a significant factor in the pathogenesis of numerous chronic inflammatory conditions. However, its role in Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is unknown. This study aims to investigate the association between MetS, its components, and the risk of postoperative recurrence in Chinese patients with CRSwNP. METHODS: A retrospective cohort study was conducted on CRSwNP patients who underwent endoscopic sinus surgery in our hospital. Patients were divided into MetS and non-MetS groups, and the clinical characteristics and recurrence rates were compared. All CRSwNP patients were followed up for more than 2-years and further categorized into non-recurrent and recurrent groups. Binary logistic regression analyses were performed to examine the effects of MetS and its components on the risk of postoperative recurrence. RESULTS: A total of 555 CRSwNP patients were enrolled in the present study, 157 patients were included in the MetS group and 398 patients were categorized into the non-MetS group. The recurrence rate in the MetS group was significantly higher compared to the non-MetS group (p < 0.05). The rate of MetS, overweight or obesity, hyperglycemia and dyslipidemia were higher in the recurrent group in comparison with the non-recurrent group (p < 0.05). Multivariate logistic regression analysis suggested that MetS, overweight or obesity, hyperglycemia, dyslipidemia, and accompanying allergic rhinitis were associated with the risk of postoperative recurrence of CRSwNP (p < 0.05). Moreover, adjusted and unadjusted regression models showed that MetS was an independent risk factor for postoperative recurrence of CRSwNP, and the risk increased with more components of MetS included (p < 0.05). CONCLUSION: Our findings revealed that MetS independently increased the risk of postoperative recurrence in patients with CRSwNP, with the risk escalating as the number of MetS components increased. Moreover, accompanying allergic rhinitis was also demonstrated to be a potential risk factor for CRSwNP recurrence. LEVEL OF EVIDENCE: Level 4.

Revealing the Dominance of the Dissolution-Deposition Mechanism in Aqueous Zn-MnO2 Batteries.

Zn-MnO2 batteries have attracted extensive attention for grid-scale energy storage applications, however, the energy storage chemistry of MnO2 in mild acidic aqueous electrolytes remains elusive and controversial. Using α-MnO2 as a case study, we developed a methodology by coupling conventional coin batteries with customized beaker batteries to pinpoint the operating mechanism of Zn-MnO2 batteries. This approach visually simulates the operating state of batteries in different scenarios and allows for a comprehensive study of the operating mechanism of aqueous Zn-MnO2 batteries under mild acidic conditions. It is validated that the electrochemical performance can be modulated by controlling the addition of Mn2+ to the electrolyte. The method is utilized to systematically eliminate the possibility of Zn2+ and/or H+ intercalation/de-intercalation reactions, thereby confirming the dominance of the MnO2 /Mn2+ dissolution-deposition mechanism. By combining a series of phase and spectroscopic characterizations, the compositional, morphological and structural evolution of electrodes and electrolytes during battery cycling is probed, elucidating the intrinsic battery chemistry of MnO2 in mild acid electrolytes. Such a methodology developed can be extended to other energy storage systems, providing a universal approach to accurately identify the reaction mechanism of aqueous aluminum-ion batteries as well.

Effects of Metabolic Syndrome and its components on the postoperative recurrence in Chronic Rhinosinusitis with Nasal Polyps' patients

Abstract Objectives Metabolic Syndrome (MetS) has been established as a significant factor in the pathogenesis of numerous chronic inflammatory conditions. However, its role in Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is unknown. This study aims to investigate the association between MetS, its components, and the risk of postoperative recurrence in Chinese patients with CRSwNP. Methods A retrospective cohort study was conducted on CRSwNP patients who underwent endoscopic sinus surgery in our hospital. Patients were divided into MetS and non-MetS groups, and the clinical characteristics and recurrence rates were compared. All CRSwNP patients were followed up for more than 2-years and further categorized into non-recurrent and recurrent groups. Binary logistic regression analyses were performed to examine the effects of MetS and its components on the risk of postoperative recurrence. Results A total of 555 CRSwNP patients were enrolled in the present study, 157 patients were included in the MetS group and 398 patients were categorized into the non-MetS group. The recurrence rate in the MetS group was significantly higher compared to the non-MetS group (p< 0.05). The rate of MetS, overweight or obesity, hyperglycemia and dyslipidemia were higher in the recurrent group in comparison with the non-recurrent group (p< 0.05). Multivariate logistic regression analysis suggested that MetS, overweight or obesity, hyperglycemia, dyslipidemia, and accompanying allergic rhinitis were associated with the risk of postoperative recurrence of CRSwNP (p< 0.05). Moreover, adjusted and unadjusted regression models showed that MetS was an independent risk factor for postoperative recurrence of CRSwNP, and the risk increased with more components of MetS included (p< 0.05). Conclusion Our findings revealed that MetS independently increased the risk of postoperative recurrence in patients with CRSwNP, with the risk escalating as the number of MetS components increased. Moreover, accompanying allergic rhinitis was also demonstrated to be a potential risk factor for CRSwNP recurrence. Level of evidence: Level 4.

Iterative Causal Forest: A Novel Algorithm for Subgroup Identification.

Precisely and efficiently identifying subgroups with heterogeneous treatment effects (HTEs) in real-world evidence studies remains a challenge. Based on the causal forest (CF) method, we developed an iterative CF (iCF) algorithm to identify HTEs in subgroups defined by important variables. Our method iteratively grows different depths of the CF with important effect modifiers, performs plurality votes to obtain decision trees (subgroup decisions) for a family of CFs with different depths, then finds the cross-validated subgroup decision that best predicts the treatment effect as a final subgroup decision. We simulated 12 different scenarios and showed that the iCF outperformed other machine learning methods for interaction/subgroup identification in the majority of scenarios assessed. Using a 20% random sample of fee-for-service Medicare beneficiaries initiating sodium-glucose cotransporter-2 inhibitors (SGLT2i) or glucagon-like peptide-1 receptor agonists (GLP1RA), we implemented the iCF to identify subgroups with HTEs for hospitalized heart failure. Consistent with previous studies suggesting patients with heart failure benefit more from SGLT2i, iCF successfully identified such a subpopulation with HTEs and additive interactions. The iCF is a promising method for identifying subgroups with HTEs in real-world data where the potential for unmeasured confounding can be limited by study design.

The Consistency Between the Preoperative 3D-Reconstructed Meckel's Cave and the Intraoperative Balloon Results in Percutaneous Balloon Compression.

Objective: To predict the volume and shape of the balloon before PBC by reconstructing the Meckel's cave (MC) and establishing a volumetric measurement model, supporting preoperative preparation and intraoperative decisions. Methods: The clinical data of 31 patients with good therapeutic effects who underwent PBC are retrospectively collected, including preoperative MRI, the volume of contrast agent injected into the balloon, and intraoperative lateral X-ray images. The MC on the affected side of the 31 patients is reconstructed based on MRI using 3D Slicer, while the volume of the MC is calculated to compare with the volume of contrast agent. The width (W) and length (L) of the model of the MC in lateral view are measured and used to classify the shape of the MC based on W/L. The consistency between the W/L of the model of the MC and the W/L of the intraoperative balloon is evaluated. Results: For volume, the mean value of the models of the MC (V1) in 31 patients is 399.77±155.13 mm³, while the mean value of the contrast agent injected during PBC (V2) is 539.03±111.93 mm³. The formula obtained by linear regression is V2= 392.1 + 0.3676×V1. Based on the value of W/L, the shape of the MC is classified into thin "pear" in 5 patients (16.13%), standard "pear" in 22 patients (70.97%), and square "pear" in 4 patients (12.90%). There is no significant difference in W/L between the models of the MC and the intraoperative balloons in 31 patients (P=0.221). Conclusion: In 31 patients with good efficacy, it is verified that the prediction of the MC before PBC by 3D Slicer is consistent with the actual situation of the intraoperative balloon. This method can provide certain basis for preoperative preparation and intraoperative judgment.

Initiation of Antihypertensive Medication from Midlife on Incident Dementia: The Health and Retirement Study.

BACKGROUND: Hypertension has been identified as a risk factor of dementia, but most randomized trials did not show efficacy in reducing the risk of dementia. Midlife hypertension may be a target for intervention, but it is infeasible to conduct a trial initiating antihypertensive medication from midlife till dementia occurs late life. OBJECTIVE: We aimed to emulate a target trial to estimate the effectiveness of initiating antihypertensive medication from midlife on reducing incident dementia using observational data. METHODS: The Health and Retirement Study from 1996 to 2018 was used to emulate a target trial among non-institutional dementia-free subjects aged 45 to 65 years. Dementia status was determined using algorithm based on cognitive tests. Individuals were assigned to initiating antihypertensive medication or not, based on the self-reported use of antihypertensive medication at baseline in 1996. Observational analog of intention-to-treat and per-protocol effects were conducted. Pooled logistic regression models with inverse-probability of treatment and censoring weighting using logistic regression models were applied, and risk ratios (RRs) were calculated, with 200 bootstrapping conducted for the 95% confidence intervals (CIs). RESULTS: A total of 2,375 subjects were included in the analysis. After 22 years of follow-up, initiating antihypertensive medication reduced incident dementia by 22% (RR = 0.78, 95% CI: 0.63, 0.99). No significant reduction of incident dementia was observed with sustained use of antihypertensive medication. CONCLUSION: Initiating antihypertensive medication from midlife may be beneficial for reducing incident dementia in late life. Future studies are warranted to estimate the effectiveness using large samples with improved clinical measurements.

Overexpression of AXL on macrophages associates with disease severity and recurrence in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by high tissue heterogeneity and risk of postoperative recurrence, but the underlying mechanisms are poorly elucidated. This study aims to explore the expressions of AXL on macrophages and their roles in the pathogenesis of CRSwNP, and evaluate their associations with disease severity and recurrence. METHODS: Healthy controls (HCs), chronic rhinosinusitis without nasal polyps (CRSsNP) and CRSwNP patients were recruited in this study. Protein and mRNA levels of AXL and macrophage markers were detected in tissue samples, and their relationships with clinical variables and risk of postoperative recurrence were assessed. Immunofluorescence staining was conducted to confirm the location of AXL and its co-expression with macrophages. Regulated AXL in THP-1 and peripheral blood mononuclear cells (PBMC)-derived macrophages, and evaluated their polarization and cytokine secretion. RESULTS: We found that AXL was enhanced in the mucosa and serum samples of CRSwNP patients, especially in recurrent cases. Tissue AXL levels were positively correlated with peripheral eosinophil count and percentage, Lund-Mackay score, Lund-Kennedy score, and macrophage M2 markers levels. Immunofluorescence staining results demonstrated that AXL was augmented and predominantly expressed on M2 macrophages in the tissues of CRSwNP, particularly in recurrent cases. In vitro experiment, overexpression of AXL promoted the M2 polarization of THP-1 and PBMC-derived macrophages, and facilitated the production of TGF-ß1 and CCL-24. CONCLUSIONS: AXL driving the M2 macrophage polarization exacerbated the disease severity and contributed to the postoperative recurrence in CRSwNP patients. Our findings supported AXL-targeted prevention and treatment of recurrent CRSwNP.

Ten-Year Cardiovascular Disease Risk Score and Cognitive Function Among Older Adults: The National Health and Nutrition Examination Survey 2011 to 2014.

Background The Framingham 10-year cardiovascular disease risk score, which is based on age, sex, smoking, total cholesterol, high-density lipoprotein-cholesterol, blood pressure, and diabetes, has been found to be associated with cognitive health, but these findings have not been validated in a representative sample in the United States. We aimed to examine the associations of Framingham risk score with cognitive function among older adults in a nationally representative sample, as well as by race or ethnicity, education, and family income. Methods and Results A total of 2254 older adults ≥60 years (57% female, 79% non-Hispanic White) in the National Health and Nutrition Examination Survey 2011 to 2014 were included in the final sample for analysis. All components of the Framingham risk score were obtained with questionnaire or measured in the laboratory. Cognitive function was examined using the Consortium to Establish a Registry for Alzheimer's Disease Word List Memory Task (immediate and delayed memory), Digit Symbol Substitution Test, and Animal Fluency Test. Multivariable linear regression models were used to assess the associations between Framingham risk score and test-specific and global cognition Z scores. Each incremental 5% in Framingham 10-year cardiovascular disease risk was associated with lower Z scores for Digit Symbol Substitution Test (ß=-0.06 [95% CI, -0.09 to -0.03]), delayed memory (ß=-0.05 [95% CI, -0.08 to -0.01]), immediate memory (ß=-0.07 [95% CI, -0.10 to -0.03]), and global cognition (ß=-0.05 [95% CI, -0.09 to -0.02]). Socioeconomic status, particularly race or ethnicity and monthly income levels, were strong effect measure modifiers of the associations. Conclusions Lower cardiovascular risk factors are associated with better cognitive function.

Chinese Expert Consensus on the Use of Biologics in Patients with Chronic Rhinosinusitis (2022, Zhuhai).

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

Correlation between expression of Lin28B and C-myc in patients with laryngeal squamous cell carcinoma and clinicopathological features and prognosis. / Lin28B和C-mycè›‹ç™½åœ¨å–‰é³žç™Œä¸­çš„è¡¨è¾¾åŠå ¶ä¸Žä¸´åºŠç— ç†ç‰¹å¾å’Œé¢„åŽçš„ç›¸å ³æ€§.

OBJECTIVES: Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor of head and neck. Screening of target genes for malignant tumor therapy is one of the focuses of cancer research, with proto-oncogene and tumor suppressor gene as the breakthrough. It has become an urgent need to find the target gene related to the treatment and prognosis of LSCC.This study aims to explore the role of Lin28B and C-myc in LSCC by detecting the expressions of these two proteins and analyze the correlation between the expression of Lin28B and C-myc and clinicopathological features and prognosis of LSCC. METHODS: We detected the expression of Lin28B and C-myc proteins in 102 specimens of LSCC and 90 specimens of adjacent tissues by immunochemistry, and analyzed the correlation between Lin28B and C-myc protein expressions in LSCC as well as the correlation between the expressions of the two proteins and the clinicopathological features of LSCC. At the same time, the Kaplan-Meier method was used to analyze the relation between Lin28B and C-myc protein levels with the postoperative survival rate of LSCC patients. RESULTS: The protein levels of Lin28B and C-myc in the LSCC tissnes were significantly higher than those in the adjacent tissues (both P<0.05),and there was a positive correlation between the expression of Lin28B and C-myc in LSCC (r＝0.476, P<0.05). The expression of Lin28B protein was closely related to age, lymph node metastasis, clinical stage, tumor size, and pathological differentiation of LSCC patients (all P<0.05). while the expression of C-myc protein was closely related to lymph node metastasis, clinical stage, tumor size, and pathological differentiation of LSCC patients (all P<0.05). A relevant survival analysis showed that in patients with higher level of Lin28B (P＝0.001) or C-myc protein (P<0.001), the postoperative survival rate was relatively low. CONCLUSIONS: Lin28B and C-myc proteins are highly expressed in LSCC with a positive correlation. Furthermore, they are closely related to lymph node metastasis, clinical stage, tumor size, pathological differentiation and prognosis, suggesting that both Lin28B and C-myc might be involved in the occurrence and development of LSCC.

Remdesivir for COVID-19 and acute kidney injury: disproportionality analysis of data from the U.S. Food and Drug Administration Adverse Event Reporting System.

BACKGROUND: Evidence about remdesivir-associated acute kidney injury (AKI) among patients with novel coronavirus disease 2019 (COVID-19) was controversial. AIM: To investigate the signal of disproportionate reporting of remdesivir-related AKI in COVID-19 patients over time with data from US Food and Drug Administration Adverse Event Reporting System. METHOD: Adverse events in COVID-19 patients reported between April 2020 and September 2022 were included. Reporting odds ratios (RORs) of AKI and renal disorders (a more sensitive definition for AKI) were estimated to compare remdesivir with other medications prescribed in comparable situations of COVID-19. RESULTS: During the entire study period, significant signals were identified for remdesivir-related AKI (ROR 2.00, 95% CI: 1.83-2.18) and renal disorder (ROR 2.35, 95% CI: 2.17-2.54) when compared to all comparable drugs. However, in the third quarter of 2022 (the most recent quarter) signals disappeared as the ROR of AKI was 1.50 (95% CI 0.91-2.45) and ROR of renal disorder was 1.69 (95% CI 1.06-2.70). Number of signals in sensitivity analyses and the proportion of AKI in remdesivir-associated events decreased over time. CONCLUSION: In COVID-19 patients, we observed diminishing signals of remdesivir-associated AKI over time and no significant signal in the most recent quarter, suggesting remdesivir might not be nephrotoxic.

Study on the relationship between obesity and complications of Pediatric Epilepsy surgery.

OBJECTIVE: Studies have shown that obesity has a significant impact on poor surgical outcomes. However, the relationship between obesity and pediatric epilepsy surgery has not been reported. This study aimed to explore the relationship between obesity and complications of pediatric epilepsy surgery and the effect of obesity on the outcome of pediatric epilepsy surgery, and to provide a reference for weight management of children with epilepsy. METHODS: A single-center retrospective analysis of complications in children undergoing epilepsy surgery was conducted. Body mass index (BMI) percentiles were adjusted by age and used as a criterion for assessing obesity in children. According to the adjusted BMI value, the children were divided into the obese group (n = 16) and nonobese group (n = 20). The intraoperative blood loss, operation time, and postoperative fever were compared between the two groups. RESULTS: A total of 36 children were included in the study, including 20 girls and 16 boys. The mean age of the children was 8.0 years old, ranging from 0.8 to 16.9 years old. The mean BMI was 18.1 kg/m2, ranging from 12.4 kg/m2 to 28.3 kg/m2. Sixteen of them were overweight or obese (44.4%). Obesity was associated with higher intraoperative blood loss in children with epilepsy (p = 0.04), and there was no correlation between obesity and operation time (p = 0.21). Obese children had a greater risk of postoperative fever (56.3%) than nonobese children (55.0%), but this was statistically nonsignificant (p = 0.61). The long-term follow-up outcomes showed that 23 patients (63.9%) were seizure-free (Engel grade I), 6 patients (16.7%) had Engel grade II, and 7 patients (19.4%) had Engel grade III. There was no difference in long-term seizure control outcomes between obese and nonobese groups (p = 0.682). There were no permanent neurological complications after surgery. CONCLUSION: Compared with nonobese children with epilepsy, obese children with epilepsy had a higher intraoperative blood loss. It is necessary to conduct early weight management of children with epilepsy as long as possible.