Femoral neck system as a safe alternative to cannulated compression screw and dynamic hip screw in femoral neck fractures: an early comparative study.

INTRODUCTION: The femoral neck system (FNS) is a safe alternative to cannulated compression screw (CCS) and dynamic hip screw (DHS) in femoral neck fractures. METHODS: A dual-centre retrospective cohort study was performed on femoral neck fractures (AO type 31-B) treated with closed reduction and internal fixation using FNS, DHS or CCS between April 2016 and April 2020. Exclusion criteria were as follows: patients aged below 16 years; chronic fractures beyond 7 days; pathological fractures; fracture extension to the intertrochanteric region or ipsilateral neck and shaft fractures; and open fractures. A total of 85 patients were identified: FNS (n = 28), DHS (n = 29) and CCS (n = 28). RESULTS: The FNS and CCS groups had a lower Garden and Pauwels classification compared to the DHS group (both P < 0.001). Both FNS and CCS groups were comparable in postoperative orthopaedic complications (10.7% [n = 3] vs. 3.6% [n = 1], adjusted P = 0.321). The DHS group had more postoperative orthopaedic complications than the FNS group, but this was not statistically significant (27.6% [n = 8] vs. 10.7% [n = 3], adjusted P = 0.321). There were no significant differences in median time to radiological union or median femoral neck shortening at union (both P > 0.05) among the three groups. CONCLUSION: The new DePuy Synthes FNS is a safe alternative to CCS with comparable complication rates for femoral neck fractures that are less displaced and more stable. The FNS also appears to be a safe alternative to DHS in the fixation of femoral neck fractures for the few cases of high-energy femoral neck fractures.

Aberrant follicular regulatory T cells associate with immunoglobulin hyperproduction in nasal polyps with ectopic lymphoid tissues.

BACKGROUND: Ectopic lymphoid tissues (eLTs) and associated follicular helper T (TFH) cells contribute to local immunoglobulin hyperproduction in nasal polyps (NPs). Follicular regulatory T (TFR) cells in secondary lymphoid organs counteract TFH cells and suppress immunoglobulin production; however, the presence and function of TFR cells in eLTs in peripheral diseased tissues remain poorly understood. OBJECTIVE: We sought to investigate the presence, phenotype, and function of TFR cells in NPs. METHODS: The presence, abundance, and phenotype of TFR cells in NPs were examined using single-cell RNA sequencing, immunofluorescence staining, and flow cytometry. Sorted polyp and circulating T-cell subsets were cocultured with autologous circulating naïve B cells, and cytokine and immunoglobulin production were measured by ELISA. RESULTS: TFR cells were primarily localized within eLTs in NPs. TFR cell frequency and TFR cell/TFH cell ratio were decreased in NPs with eLTs compared with NPs without eLTs and control inferior turbinate tissues. TFR cells displayed an overlapping phenotype with TFH cells and FOXP3+ regulatory T cells in NPs. Polyp TFR cells had reduced CTLA-4 expression and decreased capacity to inhibit TFH cell-induced immunoglobulin production compared with their counterpart in blood and tonsils. Blocking CTLA-4 abolished the suppressive effect of TFR cells. Lower vitamin D receptor expression was observed on polyp TFR cells compared with TFR cells in blood and tonsils. Vitamin D treatment upregulated CTLA-4 expression on polyp TFR cells and restored their suppressive function in vitro. CONCLUSIONS: Polyp TFR cells in eLTs have decreased CLTA-4 and vitamin D receptor expression and impaired capacity to suppress TFH cell-induced immunoglobulin production, which can be reversed by vitamin D treatment in vitro.

A postoperative in-hospital mortality risk model for elderly patients undergoing cardiac valvular surgery based on LASSO-logistic regression / 中国胸心血管外科临床杂志

@#Objective     To evaluate the risk factors for postoperative in-hospital mortality in elderly patients receiving cardiac valvular surgery, and develop a new prediction models using the least absolute shrinkage and selection operator (LASSO)-logistic regression. Methods     The patients≥65 years who underwent cardiac valvular surgery from 2016 to 2018 were collected from the Chinese Cardiac Surgery Registry (CCSR). The patients who received the surgery from January 2016 to June 2018 were allocated to a training set, and the patients who received the surgery from July to December 2018 were allocated to a testing set. The risk factors for postoperative mortality were analyzed and a LASSO-logistic regression prediction model was developed and compared with the EuroSCOREⅡ. Results     A total of 7 163 patients were collected in this study, including 3 939 males and 3 224 females, with a mean age of 69.8±4.5 years. There were 5 774 patients in the training set and 1 389 patients in the testing set. Overall, the in-hospital mortality was 4.0% (290/7 163). The final LASSO-logistic regression model included 7 risk factors: age, preoperative left ventricular ejection fraction, combined coronary artery bypass grafting, creatinine clearance rate, cardiopulmonary bypass time, New York Heart Association cardiac classification. LASSO-logistic regression had a satisfying discrimination and calibration in both training [area under the curve (AUC)=0.785, 0.627] and testing cohorts (AUC=0.739, 0.642), which was superior to EuroSCOREⅡ. Conclusion     The mortality rate for elderly patients undergoing cardiac valvular surgery is relatively high. LASSO-logistic regression model can predict the risk of in-hospital mortality in elderly patients receiving cardiac valvular surgery.

Research progress on cardiovascular hemodynamic assessment based on computational fluid dynamics / 中国胸心血管外科临床杂志

@#Hemodynamics plays a vital role in the development and progression of cardiovascular diseases, and is closely associated with changes in morphology and function. Reliable detection of hemodynamic changes is essential to improve treatment strategies and enhance patient prognosis. The combination of computational fluid dynamics with cardiovascular imaging technology has extended the accessibility of hemodynamics. This review provides a comprehensive summary of recent developments in the application of computational fluid dynamics for cardiovascular hemodynamic assessment and a succinct discussion for potential future development.

Clinical application and strategy of total-arterial coronary artery bypass grafting / 中国胸心血管外科临床杂志

@#Since the advent of coronary artery bypass grafting (CABG), the selection of bypass conduits has always been one of the most controversial topics in this field. Arterial conduits have received extensive attention due to their excellent biological features and high patency. In recent years, the application of arterial grafting and total arterial grafting in China keeps increasing in recent years, but there is still a gap compared to the Europe and America. Previous clinical studies have indicated the benefits of the total arterial grafting in terms of patency and long-term outcomes, but the advantage of multiple arterial grafting over other procedures is still in need to be confirmed with high-quality randomized controlled trials. This article reviews the clinical application and strategy of total-arterial CABG, aiming to provide objective reference for future clinical research and application.

Lipidomics Profiling Reveals Serum Phospholipids Associated with Albuminuria in Early Type 2 Diabetic Kidney Disease.

Early screening and administration of DKD are beneficial for renal outcomes of type 2 diabetic patients. However, the current early diagnosis using the albuminuria/creatine ratio (ACR) contains limitations. This study aimed to compare serum lipidome variation between type 2 diabetes and early DKD patients with increased albuminuria through an untargeted lipidomics method to explore the potential lipid biomarkers for DKD identification. 92 type 2 diabetic patients were enrolled and divided into two groups: DM group (ACR < 3 mg/mmol, n = 49) and early DKD group (3 mg/mmol ≤ ACR < 30 mg/mmol, n = 43). Fasting serum was analyzed through an ultraperformance liquid mass spectrometry tandem chromatography system (LC-MS). Orthogonal partial least-squares discriminant analysis (OPLS-DA) and univariate and multivariate analysis were performed to filter differentially depressed lipids. Receiver operating characteristic (ROC) curves were used to estimate the diagnostic capability of potential lipid biomarkers. We found that serum phospholipids including phosphatidylserine (PS), sphingomyelin (SM), and phosphatidylcholine (PC) were significantly upregulated in the DKD group and were highly correlated with the ACR. In addition, a panel of two phospholipids including PS(27:0)-H and PS(30:2e)-H showed good performance to help clinical lipids in early DKD identification, which increased the area under the curve (AUC) from 0.568 to 0.954. The study exhibited the serum lipidome variation in early DKD patients, and the increased phospholipids might participate in the development of albuminuria. The panel of PS(27:0)-H and PS(30:2e)-H could be a potential biomarker for DKD diagnosis.

Promoting Access to Innovative Anticancer Medicines: A Review of Drug Price and National Reimbursement Negotiation in China.

Providing universal access to high-cost medications like anticancer drugs is not an easy feat. Although basic medical insurance has covered over 95% of China's population since 2012, reimbursement for high-priced medicines is limited. In 2015, the Chinese government proposed establishing an open and transparent price negotiation mechanism for some patented and expensive drugs, where oncology was among the prioritized areas. In 2016, three drugs (gefitinib, icotinib, and tenofovir disoprox) underwent negotiation with the government, eventually reducing their prices by over 50% so that they could be prioritized during reimbursement processes. Focusing on anticancer medicines, this study comprehensively summarizes the progress in drug price and national reimbursement negotiation in China. Furthermore, we investigated the changes and development regarding negotiated anticancer medicines from quantity negotiated, classification, indication coverage, utilization, and procurement spending. Our findings could provide a reference for follow-up negotiations and reimbursement policies for high-value anticancer medications in other countries. From 2016 to 2021, 82 anticancer medicines were newly incorporated into the national reimbursement drug list (NRDL) via 6 rounds of negotiation. The majority of these were innovative pharmaceutics (ie, protein kinase inhibitors (28) and monoclonal antibodies (13)). Drug pricing and national reimbursement negotiation led to a marked decrease in prices and a sharp increase in the utilization of negotiated anticancer medicines. Following negotiations, the defined daily doses (DDDs) of innovative anticancer medicines experienced remarkable growth. Their proportion in total anticancer drugs DDDs also increased from 3.4% in 2014 to 20.9% in 2019. However, although drug prices decreased substantially after the negotiations, insurance spending still showed an upward trend owing to the significant increase in utilization. This calls for the government to carefully monitor the rational use of these expensive medicines and explore innovative payment models.

MEX3B inhibits collagen production in eosinophilic nasal polyps by downregulating epithelial cell TGFBR3 mRNA stability.

Although the expression of Mex3 RNA-binding family member B (MEX3B) is upregulated in human nasal epithelial cells (HNECs) predominately in the eosinophilic chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) subtype, its functions as an RNA binding protein in airway epithelial cells remain unknown. Here, we revealed the role of MEX3B based on different subtypes of CRS and demonstrated that MEX3B decreased the TGF-ß receptor III (TGFBR3) mRNA level by binding to its 3' UTR and reducing its stability in HNECs. TGF-ßR3 was found to be a TGF-ß2-specific coreceptor in HNECs. Knocking down or overexpressing MEX3B promoted or inhibited TGF-ß2-induced phosphorylation of SMAD2 in HNECs, respectively. TGF-ßR3 and phosphorylated SMAD2 levels were downregulated in CRSwNP compared with controls and CRS without nasal polyps with a more prominent downregulation in the eosinophilic CRSwNP. TGF-ß2 promoted collagen production in HNECs. Collagen abundance decreased and edema scores increased in CRSwNP compared with control, again more prominently in the eosinophilic type. Collagen expression in eosinophilic CRSwNP was negatively correlated with MEX3B but positively correlated with TGF-ßR3. These results suggest that MEX3B inhibits tissue fibrosis in eosinophilic CRSwNP by downregulating epithelial cell TGFBR3 expression; consequently, MEX3B might be a valuable therapeutic target against eosinophilic CRSwNP.

Application of extracorporeal membrane oxygenation in early allograft dysfunction after heart transplantation / 器官移植

Objective To evaluate the effect of extracorporeal membrane oxygenation (ECMO) on early allograft dysfunction (EAD) after heart transplantation. Methods Clinical data of 614 heart transplant recipients were retrospectively analyzed. All recipients were divided into the ECMO group (n=43) and non-ECMO group (n=571) according to postoperative application of ECMO. In the ECMO group, the conditions of recipients undergoing ECMO after heart transplantation were summarized. Perioperative status and long-term prognosis of recipients were compared between two groups. Results Among 43 recipients undergoing ECMO, 17 cases underwent thoracotomy due to bleeding, 10 cases of infection, 4 cases of venous thrombosis of the lower limbs, and 1 case of stroke, respectively. Twenty-six recipients were recovered and discharged after successful weaning from ECMO, six died during ECMO support, six died after weaning from ECMO, five received retransplantation due to unsuccessful weaning from ECMO, and only one survived after retransplantation. Compared with the non-ECMO group, intraoperative cardiopulmonary bypass duration was significantly longer, the proportion of recipients requiring postoperative intra-aortic balloon pump (IABP), dialysis due to renal insufficiency, reoperation for hemostasis, infection, mechanical ventilation time≥96 h and tracheotomy was significantly higher, and the length of postoperative intensive care unit (ICU) stay was significantly longer in the ECMO group (all P < 0.05). The survival rate after discharge and 90-d survival rate in the ECMO group were 63% and 96%, significantly lower than 97% and 100% in the non-ECMO group (both P < 0.05). Survival analysis showed that the long-term survival rate in the ECMO group was significantly lower than that in the non-ECMO group (P < 0.05). After excluding the recipients who died within 90 d after heart transplantation, no significant difference was observed in the long-term survival rate (P > 0.05). Conclusions ECMO is an effective treatment of EAD after heart transplantation. The short-term survival rate of recipients using ECMO after heart transplantation is lower than that of those who do not use ECMO, and there is no significant difference in long-term survival of recipients surviving 90 d after heart transplantation.

Clinical research progress and mechanism on myocardial injury in hearts from donors with stroke / 器官移植

At present, the heart of donor from donation after brain death are the primary organ sources for heart transplantation. After brain death, severe hemodynamic changes and a series of organ functional changes will occur, thereby leading to the functional damage or even loss of tissues and organs, especially the heart. Intimate relationship and interaction have been found in the physiology and pathophysiology between nervous and cardiovascular systems. After stroke, autonomic nervous disorder, neuroendocrine disorder and intense and persistent inflammatory reaction could be caused by the brain-heart axis reaction, leading to stroke-induced cardiac injuries, such as sympathetic storm, catecholamine storm, inflammatory storm, etc. In this article, research progresses on the mechanism of myocardial injury in heart from donors with stroke and the effect on clinical efficacy and prognosis after heart transplantation were reviewed, aiming to provide reference for clinical practice and subsequent research.

Interpretation of methodological standards for the design, implementation, and analysis of randomized trials in cardiac surgery: A scientific statement from the American Heart Association in 2022 / 中国胸心血管外科临床杂志

@#Cardiac surgery presents specific challenges in conducting randomized controlled trials (RCTs). The American Heart Association made a scientific statement of methodological standards, with the purpose to review key concepts and standards in design, implementation, and analysis of cardiac surgery RCTs, and to provide recommendations. Recommendations include an evaluation of the suitability of the research question, clinical equipoise, feasibility of enrolling a representative patient cohort, impact of practice variations on the effect of the study intervention, likelihood and impact of crossover, and duration of follow-up. Trial interventions and study end points should be predefined, and adequate deliverability of the trial interventions should be ensured. Every effort must be made to keep a high completeness of follow-up. Trial design and analytic techniques must be tailored to the specific research question and trial setting. In this paper, the authors made an interpretation of this scientific statement based on their practical experience.

Progress in clinical studies in cardiovascular surgery 2022 / 中国胸心血管外科临床杂志

@#In 2022, many excellent clinical studies emerged in the field of cardiovascular surgery. Selecting papers published in The New England Journal of Medicine and other top medicine and cardiology journals, this review focused on the research progress on 7 topics in the field of cardiovascular surgery: coronary artery surgery, vascular surgery, valvular surgery, structural heart disease, congenital heart disease, heart transplantation, perioperative management, and special population.

Morbidity and risk factors of de novo malignancy after heart transplantation / 中华器官移植杂志

Objective:To explore the morbidity and risk factors of de novo malignancy after heart transplantation (HT).Methods:From June 2004 to August 2021, 995 patients undergoing HT were selected and followed up.The epidemiological characteristics, the morbidity of de novo malignancy (DNM) and its risk factors were examined.Kaplan-Meier survival analysis was performed for calculating the cumulative incidence and mortality of DNM.Log rank test was utilized for comparing the survival rate of each subgroup.Cox regression model was employed for examining the relationship between the included factors and the endpoint of DNM.Results:The median follow-up period was 6.36(3.64, 10.18) years.Thirty-six patients (3.6%) developed DNM during follow-up.Lung cancer accounted for 22.2%(8/36) of DNM while digestive system tumors accounted for 38.9% (including gastric cancer 6/36, 16.7%; liver cancer 3/36, 8.3%; colon cancer 2/36, 5.6%). The cumulative morbidity of DNM at Year 1/5/10/15 post-HT was 0.1%, 2.3%, 4.9% and 7.6% respectively.The median survival time of DNM recipients was 83.32 months.The mean survival time was significantly lower than those without DNM[(115.32±13.12) vs.(194.22±2.58), P<0.001]. The mortality of DNM recipients was around 6.57 folds higher ( HR=6.57, 95% CI: 4.06-10.64, P<0.01). Age was an independent risk factor for an occurrence of DNM.Hypertension and diabetes were also correlated with DNM. Conclusions:DNM after HT is associated with shorter survival time.And age is an independent risk factor for DNM after HT.

Analysis of risk factors for kidney dysfunction after heart transplantation and its impact onprognosis / 中华器官移植杂志

Objective:To summarize the incidence and long-term outcomes of postoperative renal dysfunction(RD) and explore the clinical predictors of postoperative RD to provide reference for preoperative evaluation and perioperative management of heart transplantation(HT).Methods:The relevant clinical data are retrospectively reviewed for 1 095 HT recipients.They are grouped into two groups of RD(352 cases)and non-RD(normal, 743 cases)according to whether or not RD occurred after HT.Two groups are compared to explore the clinical predictors associated with postoperative RD.For further examining the prognostic impact of perioperative renal dysfunction, the recipients are assigned into four groups based upon perioperative renal function.The long-term outcomes of four groups are compared.Results:The median follow-up period is 5.6 years.Among 352 RD patients (32.1%), there are new-onset(276 cases, 25.2%), occurring during postoperative hospitalization (99, 28.1%)and post-discharge until Year 1(111 cases, 31.5%).Compared with normal group, RD group have advanced age, greater body mass index(BMI), higher preoperative serum creatinine, longer cardiopulmonary bypass time, a higher ratio of male, diabetic history, preoperative RD, transplantation for previous graft failure, preoperative extracorporeal membrane oxygenerator(ECMO)and intra-aortic balloon pump(IABP); donors in this group had advanced age and higher ratio of male (all P<0.05).In terms of postoperative data, RD group had higher ratios of ECMO/IABP implantation, tracheostomy, infection, longer postoperative mechanical ventilation time, intensive care unit(ICU)stay and in-hospital stay than normal group( P<0.05).Long-term survival of patients with postoperative RD is significantly lower than that with postoperative normal kidney function( P<0.01).Long-term survival rate of patients with preoperative RD is significantly lower than that of those without preoperative RD, regardless of whether or not kidney function normalized postoperatively; long-term survival rate of patients with postoperative new-onset RD is significantly lower than that in those with normal kidney function( P<0.01).Advanced recipient age, higher BMI, existence of preoperative RD, postoperative cyclosporine dosing(versus tacrolimus)and cold ischemic time≥6 h are independent risk factors of RD post-HT. Conclusions:RD occurs predominantly within the first year post-HT.Advanced recipient age, higher BMI, existence of preoperative RD and cold ischemic time≥6 h are independent predictors of RD post-HT.The incidence of RD post-HT significantly affects perioperative and long-term survivals.

Analysis of effect of preoperative renal insufficiency on clinical prognosis of heart transplant recipients / 器官移植

Objective To evaluate the effect of renal insufficiency before heart transplantation on perioperative death, complications and long-term survival, and to compare the differences between preoperative serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) in preoperative risk assessment. Methods Clinical data of 1 095 heart transplant recipients were retrospectively analyzed. According to preoperative Scr level, all recipients were divided into the Scr < 133 μmol/L(n=980), Scr 133-176 μmol/L (n=83) and Scr≥177 μmol/L groups (n=32). According to preoperative eGFR, all recipients were divided into eGFR≥90 mL/(min·1.73m2) (n=436), eGFR 60-89 mL/(min·1.73m2) (n=418) and eGFR < 60 mL/(min·1.73m2) groups (n=241). Clinical prognosis of postoperative renal function, perioperative and long-term outcomes of recipients were compared among different groups. The effect of eGFR and Scr level on renal function injury and long-term survival after heart transplantation was assessed. Results With the increase of preoperative Scr level, the proportion of recipients undergoing postoperative continuous renal replacement therapy (CRRT) was increased, the proportion of recipients receiving postoperative mechanical circulatory support was elevated, the incidence of postoperative complications was increased, the duration of mechanical ventilation and intensive care unit(ICU) stay was prolonged, and the in-hospital fatality was increased. The differences among three groups were statistically significant (all P < 0.05). With the decrease of preoperative eGFR, the proportion of recipients receiving postoperative CRRT was increased, the proportion of recipients using postoperative intra-aortic balloon pump (IABP) was elevated, the duration of mechanical ventilation and ICU stay was prolonged, and the in-hospital fatality was increased. The differences among three groups were statistically significant (all P < 0.05). Scr≥177 μmol/L was an independent risk factor for postoperative death [adjusted hazard ratio (HR) 3.64, 95% confidence interval (CI) 1.89-6.99, P < 0.01]. Among different groups classified by Scr and eGFR, the cumulative incidence rate of postoperative renal function injury and long-term survival rate were statistically significant among three groups (all P < 0.05). In patients with preoperative Scr < 133 μmol/L, the cumulative incidence rate of postoperative long-term renal function injury was significantly increased with the decrease of preoperative eGFR (P < 0.01). There was no significant difference in postoperative long-term survival rate among patients stratified by different eGFR (P > 0.05). Conclusions Renal insufficiency before heart transplantation is associated with poor perioperative and long-term prognosis. Preoperative Scr and eGFR are the independent risk factors for postoperative renal function injury. Scr yields low sensitivity in the assessment of preoperative renal function, whereas it has high accuracy in predicting perioperative death risk. And eGFR is a more sensitive parameter to evaluate preoperative renal function, which may identify early-stage renal functional abnormality and take effective measures during early stage to reduce adverse effect on prognosis.

Clinical Decision on Disorders of Consciousness After Acquired Brain Injury: Stepping Forward / 神经科学通报·英文版

Major advances have been made over the past few decades in identifying and managing disorders of consciousness (DOC) in patients with acquired brain injury (ABI), bringing the transformation from a conceptualized definition to a complex clinical scenario worthy of scientific exploration. Given the continuously-evolving framework of precision medicine that integrates valuable behavioral assessment tools, sophisticated neuroimaging, and electrophysiological techniques, a considerably higher diagnostic accuracy rate of DOC may now be reached. During the treatment of patients with DOC, a variety of intervention methods are available, including amantadine and transcranial direct current stimulation, which have both provided class II evidence, zolpidem, which is also of high quality, and non-invasive stimulation, which appears to be more encouraging than pharmacological therapy. However, heterogeneity is profoundly ingrained in study designs, and only rare schemes have been recommended by authoritative institutions. There is still a lack of an effective clinical protocol for managing patients with DOC following ABI. To advance future clinical studies on DOC, we present a comprehensive review of the progress in clinical identification and management as well as some challenges in the pathophysiology of DOC. We propose a preliminary clinical decision protocol, which could serve as an ideal reference tool for many medical institutions.

Year-round RSV Transmission in the Netherlands Following the COVID-19 Pandemic - A Prospective Nationwide Observational and Modeling Study

A nationwide prospective study showed year-round RSV transmission in the Netherlands after an initial 2021 summer outbreak. The pattern was unprecedented and distinct from neighboring countries. Our dynamic simulation model suggests that this transmission pattern could be associated with waning immunity because of low RSV circulation during the COVID-19 pandemic.

Untargeted metabolomic profiling identifies disease-specific and outcome-related signatures in chronic rhinosinusitis.

BACKGROUND: Although metabolomics provides novel insights into disease mechanisms and biomarkers, the metabolic alterations in local tissues affected by chronic rhinosinusitis (CRS) are unknown. OBJECTIVE: This study aimed to determine the metabolomic profiles of sinonasal tissues associated with different types of CRS and their treatment outcomes. METHODS: Untargeted metabolomic profiling was performed on sinonasal tissues obtained from patients with eosinophilic CRS with nasal polyps (CRSwNP), noneosinophilic CRSwNP or CRS without nasal polyps (CRSsNP), and controls. The messenger RNA (mRNA) levels of inflammatory cytokines in nasal tissues were detected by quantitative real-time reverse transcriptase PCR. Nasal polyp tissues were cultured ex vivo and treated with glutathione. RESULTS: Distinct metabolomic profiles were observed for the CRS subtypes. Eosinophilic CRSwNP had profoundly enhanced unsaturated fatty acid oxidization, which correlated with mucosal eosinophil numbers and IL-5 mRNA levels. Noneosinophilic CRSwNP was characterized by uric acid accumulation. Increased uric acid levels were positively correlated with mucosal neutrophil numbers and IFN-γ, IL-17A, IL-1ß, and IL-8 mRNA levels. Disrupted purine metabolism was specifically detected in CRSsNP. Reduced levels of amino acid metabolites were found in eosinophilic CRSwNP and CRSsNP, and were inversely associated with mucosal total inflammatory cell numbers and inflammatory cytokines. Compared to non-difficult-to-treat CRS, difficult-to-treat CRS had higher glutathione disulfide levels, which were positively correlated with IL-8 mRNA levels. Glutathione treatment reduced IL-8 mRNA expression in cultured nasal polyp tissues. CONCLUSIONS: Specific metabolic signatures are associated with different types of CRS, inflammatory patterns, and disease outcomes, which may provide novel insights into pathophysiologic mechanisms, subtype-specific biomarkers, and treatment targets of CRS.