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Abstract Background Serum (1,3)-β-D-glucan (BDG) detection for diagnosis of Pneumocystis jirovecii pneumonia (PJP) in non-human immunodeficiency virus (HIV) immunocompromised patients lacks intensive care unit (ICU)-specific data. We aimed to assess its performance and determine the optimal cutoff for PJP in ICU population. Methods This retrospective study included critically ill non-HIV immunocompromised patients admitted to a medical ICU with suspected pneumonia, undergoing simultaneous microbiological testing for P. jirovecii on lower respiratory tract specimens and serum BDG. Confounders affecting BDG positivity were explored by multivariable logistic regression. Optimal cut-offs were derived from Youden’s index for the entire cohort and subgroups stratified by confounders. Diagnostic performance of serum BDG was estimated at different cutoffs. Results Of 400 patients included, 42% were diagnosed with PJP and 58.3% had positive serum BDG. Serum BDG’s area under the receiver operating characteristic curve was 0.90 (0.87–0.93). At manufacturer’s 150 pg/ml cut-off, serum BDG had high sensitivity and negative predictive value (94%), but low specificity and positive predictive value (67%). Confounders associated with a positive serum BDG in PJP diagnosis included IVIG infusion within 3 days (odds ratio [OR] 9.24; 95% confidence interval [CI] 4.09–20.88, p

Abstract Backgrounds Increased respiratory drive has been demonstrated to correlate with weaning failure, which could be quantified by electrical activity of the diaphragm (EAdi). We described the physiological process of EAdi-based parameters during the spontaneous breathing trial (SBT) and evaluated the change of EAdi-based parameters as potential predictors of weaning failure. Methods We conducted a prospective study in 35 mechanically ventilated patients who underwent a 2-hour SBT. EAdi and ventilatory parameters were continuously measured during the SBT. Diaphragm ultrasound was performed before the SBT and at the 30 min of the SBT. Three EAdi-based parameters were calculated: neuro-ventilatory efficiency, neuro-excursion efficiency and neuro-discharge per min. Results Of the thirty 35 patients studied, 25 patients were defined as SBT success, including 22 patients weaning successfully and 3 patients reintubated. Before the SBT, neuro-excursion efficiency differed significantly between two groups and had the highest predictive value for SBT failure (AUROC 0.875, p

Abstract Atrial fibrillation (AF) is the most common arrhythmia and its incidence increases with sepsis. However, data on new-onset AF during sepsis hospitalization remain limited in China. We aimed to evaluate the incidence, risk factors, and associated mortality of new-onset AF in sepsis patients in China. We conducted a retrospective study using the National Data Center for Medical Service system, from 1923 tertiary and 2363 secondary hospitals from 31 provinces in China from 2017 to 2019.In total we included 1,425,055 sepsis patients ≥ 18 years without prior AF. The incidence of new-onset AF was 1.49%. Older age, male sex, hypertension, heart failure, coronary disease, valvular disease, and mechanical ventilation were independent risk factor. New-onset AF was associated with a slight increased risk of mortality (adjusted RR 1.03, 95% CI 1.01–1.06). Population attributable fraction suggested AF accounted for 0.2% of sepsis deaths. In this large nationwide cohort, new-onset AF occurred in 1.49% of sepsis admissions and was associated with a small mortality increase. Further research should examine whether optimized AF management can improve sepsis outcomes in China.

Abstract Introduction The impact of immunosuppression on prognosis of carbapenem-resistant organism (CRO) bloodstream infection (BSI) remains unclear. The aim of this study was to clarify the relationship between immunosuppression and mortality of CRO-BSI and to identify the risk factors associated with mortality in immunosuppressed patients. Methods This retrospective study included 279 patients with CRO-BSI from January 2018 to March 2023. Clinical characteristics and outcomes were compared between the immunosuppressed and immunocompetent patients. The relationship between immunosuppression and 30-day mortality after BSI onset was assessed through logistic-regression analysis, propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). Factors associated with mortality in immunosuppressed patients were analyzed using multivariable logistic regression analysis. Results A total of 88 immunocompetent and 191 immunosuppressed patients were included, with 30-day all-cause mortality of 58.8%. Although the 30-day mortality in immunosuppressed patients was significantly higher than in immunocompetent patients (46.6% vs. 64.4%, P = 0.007), immunosuppression was not an independent risk factor for mortality in multivariate logistic regression analysis (odds ratio [OR] 3.53, 95% confidence interval [CI] 0.74–18.89; P = 0.123), PSM (OR 1.38, 95% CI 0.60–3.18; P = 0.449,) or IPTW (OR 1.40, 95% CI 0.58–3.36; P = 0.447). For patients with CRO-BSI, regardless of immune status, appropriate antibiotic therapy was associated with decreased 30-day mortality, while Charlson comorbidity index (CCI), intensive care unit (ICU)-acquired infection and thrombocytopenia at CRO-BSI onset were associated with increased mortality. Conclusion Despite the high mortality rate of CRO-BSI, immunosuppression did not affect the mortality. Appropriate antibiotic therapy is crucial for improving the prognosis of CRO-BSI, regardless of the immune status.

Abstract Background The scarcity of sepsis epidemiologic data from most low- and middle-income countries (LMICs) hampered estimation of regional and global burden of the disease, and provided limited guidance for policy makers. We aimed to characterize and analyze the temporal trends of sepsis-related mortality in China, by population groups, underlying causes of death, geographic regions, and sociodemographic index (SDI) levels. Methods Sepsis-related deaths were identified from the National Mortality Surveillance System (NMSS) of China from 2006 to 2020. Trends of sepsis-related mortality and years of life lost (YLLs), stratified by age, sex, underlying diseases, and regions were analyzed using the Jointpoint regression analysis. We investigated the association of SDI with trends of sepsis-related mortality. Results In 2020, sepsis was estimated to be responsible for 986,929 deaths and 17.1 million YLLs in China. Age-standardized sepsis-related mortality significantly declined from 130.2 (95%CI, 129.4–131) per 100,000 population in 2006 to 76.6 (76.3–76.9) in 2020. Age-standardized YLLs decreased from 2172.7 (2169.4–2176) per 100,000 population in 2006 to 1271 (1269.8–1272.2) in 2020. Substantial variations of sepsis-related mortality and YLLs were observed between population groups and regions, with higher burden in males, the elderly, and western China. An inverse relation was noted between SDI and sepsis-related mortality or YLLs. Conclusions Despite declining trends of age-standardized mortality and YLLs of sepsis in China, significant disparities between population groups and regions highlight a need for targeted policies and measures to close the gaps and improve the outcome of sepsis.

Abstract Background Tissue oxygen saturation (StO2) decrease could appear earlier than lactate alteration. However, the correlation between StO2 and lactate clearance was unknown. Methods This was a prospective observational study. All consecutive patients with circulatory shock and lactate over 3 mmol/L were included. Based on the rule of nines, a BSA (body surface area) weighted StO2 was calculated from four sites of StO2 (masseter, deltoid, thenar and knee). The formulation was as follows: masseter StO2 × 9% + (deltoid StO2 + thenar StO2) × (18% + 27%)/ 2 + knee StO2 × 46%. Vital signs, blood lactate, arterial and central venous blood gas were measured simultaneously within 48 h of ICU admission. The predictive value of BSA-weighted StO2 on 6-hour lactate clearance > 10% since StO2 initially monitored was assessed. Results A total of 34 patients were included, of whom 19 (55.9%) had a lactate clearance higher than 10%. The mean SOFA score was lower in cLac ≥ 10% group compared with cLac

Abstract Background Sepsis is a leading cause of preventable death around the world. Population-based estimation of sepsis incidence is lacking in China. In this study, we aimed to estimate the population-based incidence and geographic variation of hospitalized sepsis in China. Methods We retrospectively identified hospitalized sepsis from the nationwide National Data Center for Medical Service (NDCMS) and the National Mortality Surveillance System (NMSS) by ICD-10 codes for the period from 2017 to 2019. In-hospital sepsis case fatality and mortality rate were calculated to extrapolate the national incidence of hospitalized sepsis. The geographic distribution of hospitalized sepsis incidence was examined using Global Moran's Index. Results We identified 9,455,279 patients with 10,682,625 implicit-coded sepsis admissions in NDCMS and 806,728 sepsis-related deaths in NMSS. We estimated that the annual standardized incidence of hospitalized sepsis was 328.25 (95% CI 315.41–341.09), 359.26 (95% CI 345.4–373.12) and 421.85 (95% CI 406.65–437.05) cases per 100,000 in 2017, 2018 and 2019, respectively. We observed 8.7% of the incidences occurred among neonates less than 1 year old, 11.7% among children aged 1–9 years, and 57.5% among elderly older than 65 years. Significant spatial autocorrelation for incidence of hospitalized sepsis was observed across China (Moran's Index 0.42, p = 0.001; 0.45, p = 0.001; 0.26, p = 0.011 for 2017, 2018, 2019, respectively). Higher number of hospital bed supply and higher disposable income per capita were significantly associated with a higher incidence of hospitalized sepsis. Conclusion Our study showed a greater burden of sepsis hospitalizations than previous estimated. The geographical disparities suggested more efforts were needed in prevention of sepsis.

Intracranial aneurysm (IA) is a common cerebrovascular disease. Immune system disorders and endothelial dysfunction are essential mechanisms of its pathogenesis. This study aims to explore the therapeutic effect and mechanism of Geniposide (Gen) on IA, which has a protective impact on endothelial cells and cardiovascular and cerebrovascular diseases. IA mouse models were administered intraperitoneal injections of geniposide for 2 weeks following elastase injection into the right basal ganglia of the brain for intervention. The efficacy of Gen in treating IA was evaluated through pathological testing and transcriptome sequencing analysis of Willis ring vascular tissue. The primary mechanism of action was linked to the expression of GSK3β in Th17 cells. The percentage of splenic Th17 cell differentiation in IA mice was significantly inhibited by Gen. GSK3β/STAT3, and other pathway protein expression levels were also significantly inhibited by Gen. Additionally, TNF‐α and IL‐23 cytokine contents were significantly downregulated after Gen treatment. These results indicated that Gen significantly inhibited the percentage of Th17 cell differentiation, an effect that was reversed upon overexpression of the GSK3B gene. Furthermore, Gen‐treated, Th17 differentiation‐inducing cell‐conditioned medium significantly up‐regulated the expression of tight junction proteins ZO‐1, Occludin, and Claudin‐5 in murine aortic endothelial cells. Administering the GSK3β inhibitor Tideglusib to IA mice alleviated the severity of IA disease pathology and up‐regulated aortic tight junction protein expression. In conclusion, Gen inhibits Th17 cell differentiation through GSK3β, which reduces endothelial cell injury and up‐regulates tight junction protein expression. [ABSTRACT FROM AUTHOR]

The superradiant stability of higher dimensional non-extremal Reissner-Nordstrom black hole under charged massive scalar perturbation is analytically studied. We extend our previous studies of four- and five-dimensional non-extremal Reissner-Nordstrom black hole cases to six-dimensional case. By analyzing the derivative of the effective potential with an analytical method, we find that no potential well exists outside the outer horizon of the black hole for the superradiant scalar modes. This means that there is no black hole bomb for the system consisting of six-dimensional Reissner-Nordstrom black hole and charged massive scalar perturbation and the system is superradiantly stable.

Background and purpose: Calmodulin (CaM) levels exhibit significant elevation in the brain tissue of rodent and cell line models infected with prion, as well as in the cerebrospinal fluid (CSF) samples from patients diagnosed with sporadic Creutzfeldt-Jakob disease (sCJD). However, the status of CSF CaM in patients with genetic prion diseases (gPrDs) remains unclear. This study aims to assess the characteristics of CSF CaM in Chinese patients presenting four subtypes of gPrDs. Methods: A total of 103 CSF samples from patients diagnosed with T188KgCJD, E200K-gCJD, D178N-FFI, P102L-GSS were included in this study, along with 40 CSF samples from patients with non-prion diseases (non-PrDs). The presence of CSF CaM and 14-3-3 proteins was assessed using Western blots analysis, while levels of CSF 14-3-3 and total tau were measured using enzymelinked immunosorbent assays (ELISAs). Statistical methods including multivariate logistic regression were employed to evaluate the association between CSF CaM positivity and relevant clinical, laboratory, and genetic factors. Results: The positive rates of CSF CaM were significantly higher in cases of T188K-gCJD (77.1%), E200K-gCJD (86.0%), and P102-GSS (90.9%) compared to non-PrD cases (22.5%). In contrast, CSF CaM positivity was slightly elevated in D178N-FFI (34.3%). CSF CaM positivity was remarkably high in patients who tested positive for CSF 14-3-3 by Western blot and exhibited high levels of total tau (≥1400 pg/ml) as measures by ELISA. Multivariate logistic regression analysis confirmed a significant association between CSF CaM positivity and specific mutations in PRNP, as well as with CSF 14-3-3 positivity. Furthermore, the diagnostic performance of CaM surpassed that of 14-3-3 and tau when analyzing CSF samples from T188K-gCJD and E200K-gCJD patients. Conclusion: Western blot analysis reveals significant variations in the positivity of CSF CaM among the four genotypes of gPrD cases, demonstrating a positive correlation with 14-3-3 positivity and elevated tau levels in CSF. [ABSTRACT FROM AUTHOR]

We obtained TiNiSn-based half-Heusler HfxTi1−xNiSn0.97Sb0.03 bulks with 85%–96% relative densities via 5-min microwave synthesis and 20-min microwave sintering in sealed vacuum. The phase composition and microstructure of samples were characterized by X-ray diffractometer (XRD) and scanning electron microscopy (SEM). Thermoelectric (TE) properties were measured, i.e., Seebeck coefficient (S), electrical resistivity (ρ), and thermal conductivity (κ) through Seebeck coefficient/resistance analysis system (S/RAs) and laser flash thermal analyzer (LFT). The results show that the nearly single phase exists after microwave sintering. The grain sizes and the number of grain boundaries decrease with increase in Hf-doping amount due to an increase in point defects. The matrix grains for Hf0.1Ti0.9NiSn0.97Sb0.03 are ~ 10 μm. The nanoscle pores and precipitates are present as second phases in matrix grain. The real composition for Hf0.1Ti0.9NiSn0.97Sb0.03 matrix grain is Hf3.51Ti28.76Ni34.76Sn31.55Sb1.43. The variation trends of electrical resistivity, Seebeck coefficient, power factor, and thermal conductivity were analyzed in detail. The maximum figure of merit (ZT) of 0.46 is obtained for Hf0.1Ti0.9NiSnSn0.97Sb0.03 at 723 K. The innovation route exhibits advantages for predation of TE bulks when compared to the conventional methods, especially in terms of efficiency while it still maintains TE performance. [ABSTRACT FROM AUTHOR]