Elabela mitigates the early stage of inflammation in sepsis by inhibiting pyroptosis.

OBJECTIVES: This study aims to investigate the potential therapeutic role of Elabela (ELA) in mitigating the sepsis-induced inflammatory storm, a phenomenon commonly associated with multiple organ dysfunction syndrome (MODS) and increased mortality. Our findings show the pathogenesis of sepsis, identifying ELA as a promising therapeutic target. METHODS: We conducted a comprehensive analysis of electronic medical records and blood samples from septic patients to assess the incidence of severe organ complication and characterize the inflammatory response. Subsequently, we measured the expression levels of ELA and various inflammatory factors in serum, and performed correlation analysis to explore the relationship between them, aiming to identify the cells and inflammatory pathways targeted by ELA. Furthermore, animal and cellular experiments were conducted to investigate the molecular mechanism underlying the therapeutic effect of ELA. RESULTS: Our findings revealed a higher prevalence of severe organ complications among septic patients, contributing to adverse prognoses and increased mortality. Notably, these patients exhibited significantly elevated levels of inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) in their sera, indicating a robust inflammatory response. Correlation analysis revealed a negative correlation between ELA and IL-1ß in septic patients. Through animal and cellular experiments, we demonstrated that ELA inhibits the cleavage of caspase-1 and gasdermin D (GSDMD), thereby attenuating pyroptosis and the inflammatory response. CONCLUSIONS: ELA is a promising therapeutic agent for mitigating the deleterious effects of sepsis. Its ability to inhibit macrophage pyroptosis and suppress the inflammatory response offers a novel approach.

An insight into the causal relationship between sarcopenia-related traits and venous thromboembolism: A mendelian randomization study.

BACKGROUND: As a geriatric syndrome, sarcopenia has a high prevalence in the old population and represents an impaired state of health with adverse health outcomes. A strong clinical interest in its relationship with venous thromboembolism (VTE), which is a complex trait disease with a heterogeneous annual incidence rate in different countries, has emerged. The relationship between sarcopenia and venous thromboembolism has been reported in observational studies but the causality from sarcopenia to VTE remained unclarified. We aimed to assess the causal effect of sarcopenia on the risk of VTE with the two-sample Mendelian randomization (MR) method. METHODS: Two sets of single-nucleotide polymorphisms (SNPs), derived from two published genome-wide association study (GWAS) meta-analyses and genetically indexing muscle weakness and lean muscle mass separately, were pooled into inverse variance weighted (IVW), weighted median and MR-Egger analyses. RESULTS: No evidence was found for the causal effect of genetically predicted muscle weakness (IVW: OR = 0.90, 95% CI = 0.76-1.06, p = 0.217), whole body lean mass (IVW: OR = 1.01, 95% CI = 0.87-1.17, p = 0.881) and appendicular lean mass (IVW: OR = 1.13, 95% CI = 0.82-1.57, p = 0.445) on the risk of VTE. However, both genetically predicted whole-body lean mass and appendicular lean mass can causally influence diabetes mellitus (IVW of whole-body lean mass: OR = 0.87, 95% CI = 0.78-0.96, p = 0.008; IVW of appendicular lean mass: OR = 0.71, 95% CI = 0.54-0.94, p = 0.014) and hypertension (IVW of whole-body lean mass: OR = 0.92, 95% CI = 0.87-0.98, p = 0.007; IVW of appendicular lean mass: OR = 0.84, 95% CI = 0.73-0.96, p = 0.013). CONCLUSIONS: Genetically predicted sarcopenia does not causally influence VTE directly, but it might still have an indirect effect on VTE incidence via diabetes mellitus and hypertension.

[Efficacy and Safety of Medical Thoracoscopic Bulla Volume Reduction in the Treatment of Chronic Obstructive Pulmonary Disease Combined With Giant Emphysematous Bullae]. / ç»å† ç§‘èƒ¸è ”é•œè‚ºå¤§ç–±å‡å®¹æœ¯æ²»ç–—æ ¢æ€§é˜»å¡žæ€§è‚ºç–¾ç— åˆå¹¶å·¨åž‹è‚ºå¤§ç–±çš„ç–—æ•ˆå’Œå®‰å ¨æ€§ç ”ç©¶.

Objective: To explore the efficacy and safety of medical thoracoscopic bulla volume reduction for the treatment of chronic obstructive pulmonary disease (COPD) combined with giant emphysematous bullae (GEB). Methods: A total of 66 patients with COPD combined with GEB were enrolled in the study. All the subjects received treatment at Zhengzhou Central Hospital affiliated with Zhengzhou University between March 2021 and December 2022. The subjects were divided into two groups, a medical thoracoscope group consisting of 30 cases treated with medical thoracoscopic bulla volume reduction and a surgical thoracoscope group consisting of 36 cases treated by video-assisted thoracoscopic surgery. All patients were followed up before discharge and 3 months and 6 months after discharge. The preoperative and postoperative levels of the pulmonary function, 6-minute walk distance (6MWD), and St. George's Respiratory Questionnaire (SGRQ) scores and differences in postoperative complications were compared between the two groups. The operative duration, postoperative length-of-stay, and surgical costs and hospitalization bills, and the maximum visual analog scale (VAS) pain scores at 24 h after the procedure were assessed. Results: The baseline data of the two groups were comparable, showing no statistically significant difference. The forced expiratory volume in 1 second (FEV1) 6 months after the procedures improved in both the medical thoracoscopy group ([0.78±0.29] L vs. [1.02±0.31] L, P<0.001) and the surgical thoracoscopy group ([0.80±0.21] L vs. [1.03±0.23] L, P<0.001) compared to that before the procedures. Improvements to a certain degree in 6MWT and SGRQ scores were also observed in the two groups at 3 months and 6 months after the procedures (P<0.05). In addition, no statistically significant difference in these indexes was observed during the follow-up period of the patients in the two groups. There was no significant difference in operating time between the two groups. The medical thoracoscopy group had shorter postoperative length-of-stay ([7.3±2.6] d) and 24-hour postoperative VAS pain scores (3.0 [2.0, 3.3]) than the surgical thoracoscopic group did ([10.4±4.3] d and 4.5 [3.0, 5.0], respectively), with the differences being statistically significant (P<0.05). Surgical cost and total hospitalization bills were lower in the medical thoracoscopy group than those in the surgical thoracoscopy group (P<0.05). The complication rate in the medical thoracoscopy group was lower than that in the surgical thoracoscopy group (46.7% vs. 52.8%), but the difference was not statistically significant. Conclusion: Medical thoracoscopic reduction of bulla volume can significantly improve the pulmonary function, quality of life, and exercise tolerance of patients with COPD combined with GEB, and it can reduce postoperative short-term pain and shorten postoperative length-of-stay. The procedure has the advantages of minimal invasiveness, quick recovery, and low costs. Hence extensive clinical application is warranted.

Efficacy and safety of thoracoscopic-guided multiple paravertebral block for video-assisted thoracoscopic lobectomy surgery: a randomized blinded controlled study.

Background: Paravertebral block (PVB) has been increasingly popular for postoperative analgesia. However, few studies estimated the efficacy and safety of multiple PVB using thoracoscope-assisted technique for intraoperative analgesia and postoperative pain management for video-assisted thoracoscopic lobectomy (VATS LOBECTOMY). Methods: A total of 120 patients scheduled to undergo VATS LOBECTOMY were randomly assigned into two groups: a placebo group and a PVB group in a ratio of 1:2. Thoracoscopic-guided multi-point PVB was carried out with 0.5% ropivacaine (PVB group) or 0.9% NaCl (placebo group) at the beginning and the end of surgery. The primary endpoint was consumption of intraoperative opioid. Results: Consumption rate of intraoperative opioids was significantly lower in the PVB group (878.14 ± 98.37 vs. 1,432.20 ± 383.53 for remifentanil; 123.83 ± 17.98 vs. 266.42 ± 41.97 for fentanyl). Postoperatively, significantly longer duration of using patient-controlled intravenous analgesia for the first time, reduced times of analgesic pump pressing, and less rescue analgetic consumption were observed in the PVB group. Visual analog scale scores at rest and during exercising were significantly lower in the PVB group at all time points within the first 48 h after surgery. The PVB group was also associated with significantly higher total QoR-40 scores and lower incidence of analgesia-related adverse events. Conclusions: Thoracoscopic-guided multiple PVB was a simple and effective technique in controlling pain both intra- and postoperatively for VATS LOBECTOMY. It was also associated with the absence of detrimental effects attributed to opioid overuse and benefits of the early resumption of activity and physical function recovery. Therefore, this regional anesthesia technique should be advocated as part of a multimodal analgesia protocol for VATS LOBECTOMY.

Effects of high intensity interval training versus moderate intensity continuous training on exercise capacity and quality of life in patients with heart failure: A systematic review and meta-analysis.

INTRODUCTION AND AIMS: High intensity interval training (HIIT) is considered as an alternative exercise modality to moderate intensity continuous training (MICT) for heart failure (HF) patients. Yet a growing number of trials demonstrated inconsistent findings about the effectiveness of HIIT versus MICT until SMARTEX study and OptimEx-Clin study have made a consistent negative conclusion that HIIT was not superior to MICT. The aim of this study was to conduct a meta-analysis involving a subgroup analysis of total exercise time (TET) and disease categories of HF to investigate if TET could affect the superiority of HIIT when compared with MICT. METHODS AND RESULTS: An electronic literature search of Pubmed, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov was performed for this review. 16 studies of 661 patients were finally pooled into quantitative synthesis. The weighted mean difference (WMD) and standard mean difference (SMD) with 95% confidence interval (CI) were calculated for quantitative synthesis of outcomes. HIIT was superior to MICT in improving peak oxygen consumption (Peak VO2) (WMD: 1.68 ml · kg-1 · min-1 95% CI: 0.81 to 2.55 n = 661). The subgroup analysis of TET showed that HIIT was superior to MICT in improving Peak VO2 in "short time" subgroup (WMD: 1.61 ml · kg-1 · min-1 95% CI: 0.45 to 2.77 n = 166) and in "medium time" subgroup (WMD: 1.74 ml · kg-1 · min-1 95% CI: 0.53 to 2.95 n = 420), and that there was no significant difference between HIIT and MICT in improving Peak VO2 in "long time" subgroup (WMD: 0.62 ml · kg-1 · min-1 95% CI: -1.34 to 2.58 n = 75). CONCLUSIONS: The superiority of HIIT to MICT in improving Peak VO2 arose in a short to medium length of TET whereas it was effaced by an increment of TET. This "paradox" of TET on HIIT versus MICT might be due to the increasing poor adherence to target exercise intensity over time. TRIAL REGISTRATION: PROSPERO registration number: CRD42022375076.

Application of a new tracheal inducer to therapeutic flexible bronchoscopy for airway management: a case report.

The ventilation methods during therapeutic flexible bronchoscopy vary among anesthesiologists and institutions, but each method has its own pitfalls. Therefore, improvement of the airway equipment is important. Here, we present a case in which a new tracheal inducer (Safe Easy Endotracheal Kit-flexible, SEEKflex) was applied in bronchoscopic balloon dilation under general anesthesia for airway management. This technology utilizes a flexible bronchoscope to reveal the glottis for tracheal placement of the SEEKflex to allow subglottic jet ventilation, illustrating the prominent function of performing SEEKflex-guided tracheal intubation in case of rapid sequence intubation. The SEEKflex can be easily inserted into the trachea transnasally without the aid of other devices, without significant kink and displacement during the jet ventilation. The SEEKflex could provide good airway control by facilitating sufficient ventilation, optimizing surgical access and guiding tracheal intubation when necessary.

C-Reactive Protein-to-Albumin Ratio Predicts Sepsis and Prognosis in Patients with Severe Burn Injury.

BACKGROUND: Sepsis is a leading cause of mortality among severe burns. This study was conducted to investigate the predictive role of C-reactive protein-to-albumin ratio (CAR) for sepsis and prognosis in severe burns. METHODS: Patients with severe burn injuries from 2013 to 2017 were enrolled and divided into septic and nonseptic groups based on the presence of sepsis within 30 days postburn. Independent risk factors for sepsis were performed by the univariate and multivariate logistic regression analyses. The association between CAR level at admission and postburn 30-day mortality was designed via the Kaplan-Meier method. RESULTS: Of all the 196 enrolled patients, 83 patients developed sepsis within 30 days postburn injury, with an incidence of 42.3%. TBSA percentage (OR: 1.65, 95% CI: 1.17-2.32, P = 0.014) and CAR at admission (OR: 2.25, 95% CI: 1.33-3.56, P = 0.009) were the two independent risk factors for sepsis in severe burns by the multivariate logistic regression analysis. A higher CAR level (≥1.66) at admission was associated with a lower postburn 30-day survival rate (P = 0.005). CONCLUSIONS: The CAR level at admission was an independent risk factor for sepsis and prognosis in severe burns.

Obstructive sleep apnea is associated with fatty liver index, the index of nonalcoholic fatty liver disease.

BACKGROUND AND OBJECTIVES: The relationship between obstructive sleep apnea (OSA) and nonalcoholic fatty liver disease (NAFLD) is gaining increased attention. The aim of the present study was to examine the relationship of OSA with NAFLD defined by an elevated fatty liver index (FLI). MATERIALS AND METHODS: A total of 319 consecutive patients who underwent standard polysomnography were enrolled. Fasting blood samples were obtained from all patients for biological profile measurements, and demographic data were collected. Values of FLI were determined and assessed as predictors of the presence of NAFLD, as measured by ultrasound. The discriminative ability of FLI was estimated on the basis of the area under the receiver operator characteristic curve. RESULTS: An FLI of 60 achieved the highest diagnostic accuracy and yielded an area under the receiver operator characteristic curve of 0.822 (95% confidence interval: 0.729-0.916) in the detection of NAFLD. Patients with an FLI of 60 or higher had a significantly lower lowest O2 saturation (73 vs. 83%, P<0.001), a lower mean nocturnal oxygen saturation (93 vs. 95%, P<0.001), a higher apnea-hypopnea index (39.7 vs. 18.4, P<0.001), a higher oxygen desaturation index (39 vs. 10.6, P<0.001), and a higher percentage of sleep time spent with SpO2 less than 90% (4.63 vs. 0.92%, P<0.001) compared with those with FLI less than 60. In multivariate analysis, the presence of OSA was independently associated with elevated FLI after adjusting for confounding factors (odds ratio: 5.141, 95% confidence interval: 1.414-18.696, P=0.013). CONCLUSION: Our results suggest a positive association between the severity of OSA and NAFLD defined by an elevated FLI, which may serve as a good biomarker for detecting NAFLD in OSA patients.

The relationship between excessive daytime sleepiness and metabolic syndrome in severe obstructive sleep apnea syndrome.

BACKGROUND: Excessive daytime sleepiness (EDS), which is commonly considered a cardinal sign of obstructive sleep apnea (OSA), may lead to an increased rate of metabolic syndrome (MetS), and be an independent risk factor for cardiovascular morbidity and mortality. The aim of this cross-sectional study was to examine the role of EDS in MetS and its components by researching severe OSA patients. METHODS: The records of 175 consecutive patients who underwent standard polysomnography and diagnosed severe OSA were included. Subjective daytime sleepiness was assessed using the Epworth sleepiness scale (ESS). Fasting glucose, lipids, insulin and polysomnography parameters were measured. A metabolic score was counted as the total number of the positive diagnostic criteria of MetS for each subject, which indicated the level of metabolic disorder. RESULTS: The prevalence of central obesity, hypertriglyceridemia, low high density lipoprotein-cholesterol and MetS (78.2% vs 28.6%) was significantly higher among EDS group compared with control group. Compared with non-EDS patients, patients with EDS showed significantly higher metabolic score (3.22 ± 0.94 vs 1.96 ± 1.06). After adjustment for confounders, ESS score, log insulin and age significantly predicted the metabolic score (ß = 0.567, P = 0.000; ß = 0.197, P = 0.001 and ß = 0.118, P = 0.048, respectively). CONCLUSION: EDS was independently correlated with the sum of metabolic components in severe OSA patients. Our study suggested that EDS might be a potentially useful clinical marker to identify patients with severe OSA at risk of MetS.

Obstructive sleep apnea syndrome is associated with metabolic syndrome and inflammation.

Obstructive sleep apnea (OSA) is an independent risk factor for cardiovascular morbidity and mortality. However, the underlying mechanism is unclear. In this cross-sectional study, we investigated the influence of OSA on metabolic syndrome (MetS) and inflammation, which were considered as cardiovascular risks. A total of 144 consecutive male patients who underwent standard polysomnography were enrolled. Fasting blood samples were obtained from all patients for glucose, high-sensitivity C-reactive protein (hs-CRP) and lipids measurement. A metabolic score was established as the total number of the positive diagnostic criteria of metabolic syndrome for each patient. Systolic blood pressure, diastolic blood pressure, fasting glucose, hs-CRP and metabolic score significantly increased with the aggravation of OSA severity. Metabolic score increased from 1.74 ± 1.20 to 2.89 ± 0.99 with OSA severity (p = 0.000). hs-CRP increased from 0.68 (0.43-1.10) to 1.44 (0.62-4.02) mg/L with OSA severity (p = 0.002). After adjustment for confounders, apnea-hypopnea index and body mass index (BMI) were the major contributing factors for metabolic score (ß = 0.257, p = 0.003 and ß = 0.344, p = 0.000, respectively), lowest O2 saturation and BMI were the independent predictors of hs-CRP (ß = -0.255, p = 0.003 and ß = 0.295, p = 0.001, respectively). OSA is independently associated with sum of metabolic components and hs-CRP.