Dynamic changes in serum (1-3)-ß-D-glucan caused by intravenous immunoglobulin infusion: A prospective study.

PURPOSE: The purpose of this study was to investigate the dynamic changes in serum (1-3)-ß-D-glucan (BDG) caused by intravenous immunoglobulins (IVIG) infusion in adults. METHODS: This study included patients who received IVIG infusion from October 2021 to October 2022 during hospitalization. We randomly examined two IVIG samples for every patient. Serum samples were collected at nine time points: before (Tpre), immediately (T1-0), 6h (T1-1) and 12h (T1-2) later on the first day; immediately (T2-0) and six hours later (T2-1) on the second day during IVIG infusion, and within three days after IVIG infusion (Ta1, Ta2, and Ta3, respectively). The Friedman test was used for statistical analysis. RESULTS: A total of 159 serum BDG from 19 patients were included in the analysis. The BDG content of IVIG ranged from 249 pg/ml to 4812 pg/ml. Patients had significantly elevated serum BDG on T1-0 (176 (113, 291) pg/ml, p = 0.002) and Ta1 (310 (199, 470) pg/ml, p < 0.001), compared with Tpre (41 (38, 65) pg/ml). The increments of serum BDG (ΔBDG) were associated with BDG concentration of IVIG (Spearman r = 0.59, p = 0.02). Individuals with abnormal renal function indexes showed higher serum ΔBDG values at Ta1 (403 (207, 484) pg/ml) than patients with normal renal function (172 (85, 316) pg/ml, p = 0.036). CONCLUSION: Patients who received IVIG had significantly higher serum BDG values. Elevated BDG levels correlate with BDG content of IVIG and abnormal renal function indexes.

Positive fluid balance and poor outcomes after initial intensive care unit admission in sepsis resuscitation: a retrospective study.

Introduction: Fluid resuscitation of patients with sepsis is crucial. This study explored the role of fluid balance in the early resuscitation of sepsis patients in the intensive care unit (ICU). Material and methods: A retrospective study of patients with sepsis using the Peking Union Medical College Hospital Intensive Care Medical Information System and Database from January 2014 to June 2020 was performed. Based on the survival status on day 28, the training cohort was divided into an alive group (n = 1,803) and a deceased group (n = 429). Univariate and multivariate analyses were used to identify risk factors, and the integrated learning XGBoost algorithm was used to construct a model for predicting outcomes. ROC and Kaplan-Meier survival curves were used to evaluate the effectiveness of the model. A verification cohort (n = 433) was used to verify the model. Results: Univariate analysis showed that fluid balance is an important covariate. Based on the scatterplot distribution, a significant difference in mortality was determined between groups stratified with a balance of 1000 ml. There were associations in the multivariate analysis between poor outcomes and sex, PO2/FiO2, serum creatinine, FiO2, platelets, respiratory rate, SPO2, temperature, and total fluid volume (1000 ml). Among these variables, total fluid balance (1000 ml) had an OR of 1.98 (CI: 1.41-2.77, p < 0.001). Therefore, the model was built with these nine factors using XGBoost. Cross validation was used to verify generalizability. This model performed better than the SOFA and APACHE II models. The result was well verified in the verification cohort. A causal forest model suggested that patients with hypoxemia may suffer from positive fluid balance. Conclusions: Sepsis fluid resuscitation in the ICU should be a targeted and goal-oriented treatment. A new prognostic prediction model was constructed and indicated that a 6-hour positive fluid balance after ICU initial admission is a risk factor for poor outcomes in sepsis patients. A 6-hour fluid balance above 1000 ml should be performed with caution.

The association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio with type 2 diabetes mellitus: recent findings from NHANES 2007-2018.

OBJECTIVE: This study aims to assess the relationship between NHHR (non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio) and Type 2 diabetes mellitus (T2DM) in US adults, using National Health and Nutrition Examination Survey (NHANES) data from 2007 to 2018. METHODS: This study explored the connection between NHHR and T2DM by analyzing a sample reflecting the adult population of the United States (n = 10,420; NHANES 2007-2018). NHHR was characterized as the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol. T2DM was defined based on clinical guidelines. This research used multivariable logistic models to examine the connection between NHHR and T2DM. Additionally, it included subgroup and interaction analyses to assess variations among different groups. Generalized additive models, smooth curve fitting, and threshold effect analysis were also employed to analyze the data further. RESULTS: The study included 10,420 subjects, with 2160 diagnosed with T2DM and 8260 without. The weighted multivariate logistic regression model indicated an 8% higher probability of T2DM for each unit increase in NHHR (OR: 1.08, 95% CI: 1.01-1.15) after accounting for all covariates. Subgroup analysis outcomes were uniform across various categories, demonstrating a significant positive relationship between NHHR and T2DM. Interaction tests showed that the positive link between NHHR and T2DM remained consistent regardless of age, body mass index, smoking status, moderate recreational activities, hypertension, or stroke history, with all interaction P-values exceeding 0.05. However, participants' sex appeared to affect the magnitude of the connection between NHHR and T2DM (interaction P-value < 0.05). Also, a nonlinear association between NHHR and T2DM was discovered, featuring an inflection point at 1.50. CONCLUSIONS: Our study suggests that an increase in NHHR may be correlated with a heightened likelihood of developing T2DM. Consequently, NHHR could potentially serve as a marker for estimating the probability of T2DM development.

Central venous oxygen saturation changes as a reliable predictor of the change of CI in septic shock: To explore potential influencing factors.

PURPOSE: Assessing fluid responsiveness relying on central venous oxygen saturation (ScvO2) yields varied outcomes across several studies. This study aimed to determine the ability of the change in ScvO2 (ΔScvO2) to detect fluid responsiveness in ventilated septic shock patients and potential influencing factors. METHODS: In this prospective, single-center study, all patients conducted from February 2023 to January 2024 received fluid challenge. Oxygen consumption was measured by indirect calorimetry, and fluid responsiveness was defined as an increase of cardiac index (CI) ≥ 10% measured by transthoracic echocardiography. Multivariate linear regression analysis was conducted to evaluate the impact of oxygen consumption, arterial oxygen saturation, CI, and hemoglobin on ScvO2 and its change before and after fluid challenge. RESULTS: Among 49 patients (31 men, aged (59 ± 18) years), 27 were responders. The patients had an acute physiology and chronic health evaluation II score of 24 ± 8, a sequential organ failure assessment score of 11 ± 4, and a blood lactate level of (3.2 ± 3.1) mmol/L at enrollment. After the fluid challenge, the ΔScvO2 (mmHg) in the responders was greater than that in the non-responders (4 ± 6 vs. 1 ± 3, p = 0.019). Multivariate linear regression analysis suggested that CI was the only independent influencing factor of ScvO2, with R2 = 0.063, p = 0.008. After the fluid challenge, the change in CI became the only contributing factor to ΔScvO2 (R2 = 0.245, p < 0.001). ΔScvO2 had a good discriminatory ability for the responders and non-responders with a threshold of 4.4% (area under the curve = 0.732, p = 0.006). CONCLUSION: ΔScvO2 served as a reliable surrogate marker for ΔCI and could be utilized to assess fluid responsiveness, given that the change of CI was the sole contributing factor to the ΔScvO2. In stable hemoglobin conditions, the absolute value of ScvO2 could serve as a monitoring indicator for adequate oxygen delivery independent of oxygen consumption.

[Difference of effective component content and key enzyme gene expression of biosynthesis in Atractylodes chinensis with different leaf shapes].

In this study, four Atractylodes chinensis(A. chinensis) with different leaf shapes, such as the split leaf, long and narrow leaf, oval leaf, and large round leaf, were used as experimental materials to establish a method for simultaneously determining atractylodin, atractylenolide Ⅰ, ß-eudesmol, and atractylon in the rhizome of A. chinensis. The expression of key enzyme genes for biosynthesis of acetyl-CoA carboxylase(ACC), 3-hydroxy-3-methylglutaryl-CoA reductase(HMGR), and farnesyl pyrophosphate synthase(FPPS) was detected by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR). High performance liquid chromatography(HPLC) was used to compare the difference in the content of four active components in A. chinensis with different leaf shapes, and the correlation between the content of active components and the expression of key enzyme genes in biosynthesis was discussed. The results show that there was good linearity among atractylodin, atractylenolide Ⅰ, ß-eudesmol, and atractylon in the range of 3.30-33.00 µg·mL~(-1)(r =0.999 7), 12.04-120.40 µg·mL~(-1)(r =0.999 5), 29.16-291.60 µg·mL~(-1)(r =0.999 5), and 14.20-142.00 µg·mL~(-1)(r =0.999 5), respectively. The average recoveries were 99.77%(RSD=2.1%), 98.56%(RSD=1.2%), 103.0%(RSD=1.2%), and 100.6%(RSD=1.5%), respectively. The method was accurate and had good reproducibility, which could be used to simultaneously detect atractylodin, atractylenolide Ⅰ, ß-eudesmol, and atractylon. The results showed that there were significant differences in the content of four active components in A. chinensis with different leaf shapes. The content of atractylodin, atractylenolide Ⅰ, and ß-eudesmol in A. chinensis with split leaves was the highest, which were 1.341 9, 5.237 2, and 12.084 3 mg·g~(-1), respectively. The content of atractylon in A. chinensis with long and narrow leaves was the highest(5.470 1 mg·g~(-1)). The content of atractylodin, atractylenolide Ⅰ, ß-eudesmol, and atractylon in A. chinensis with oval leaves was the lowest. The total content of the four effective components in descending order was A. chinensis with split leaves > A. chinensis with long and narrow leaves > A. chinensis with large round leaves > A. chinensis with oval leaves. The gene expression levels of key enzymes ACC, HMGR, and FPPS in A. chinensis with split leaves were the highest(P < 0.05), and the gene expression levels of key enzymes ACC and HMGR in A. chinensis with oval leaves were the lowest(P < 0.05). The gene expression level of key enzyme FPPS in A. chinensis with large round leaves was the lowest. In A. chinensis with different leaf shapes, the key enzyme gene ACC was significantly positively correlated with the polyacetylene component, namely atractylodin(P < 0.01), and the key enzyme genes HMGR and FPPS were positively correlated with the sesquiterpene components, namely atractylenolide Ⅰ, ß-eudesmol, and atractylon. In summary, the quality of A. chinensis with split leaves is the best, and the biosynthesis of atractylodin is significantly correlated with the gene expression of key enzyme ACC, which provides a theoretical basis for screening and optimizing the germplasm resources of A. chinensis and improving the quality of medicinal materials.

A nationwide study on new onset atrial fibrillation risk factors and its association with hospital mortality in sepsis patients.

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.

The diaphragmatic electrical activity during spontaneous breathing trial in patients with mechanical ventilation: physiological description and potential clinical utility.

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 < 0.01). Early increases in EAdi were observed in SBT, which are more prominent in SBT failure group. One minute, changes in EAdi and neuro-discharge per min also predicted weaning outcome (AUROCs 0.944 and 0.918, respectively). CONCLUSIONS: EAdi-based parameters, especially neuro-excursion efficiency and changes in neuro-discharge per min, may detect impending weaning failure earlier than conventional indices. EAdi monitoring provides physiological insights and a more tailored approach to facilitate successful weaning. Further research should validate these findings and explore the utility of combined EAdi and diaphragm ultrasound assessment in weaning ICU patients from mechanical ventilation. TRIAL REGISTRATION: Registered at ClinicalTrials.gov on 20 September 2022 (Identifier: NCT05632822).

Extracorporeal vs. conventional CPR for out-of-hospital cardiac arrest: A systematic review and meta-analysis.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) remains a significant cause of mortality and morbidity worldwide. Extracorporeal cardiopulmonary resuscitation (ECPR) is a potential intervention for OHCA, but its effectiveness compared to conventional cardiopulmonary resuscitation (CCPR) needs further evaluation. METHOD: We systematically searched PubMed, Embase, the Cochrane Library, Web of Science, and ClinicalTrials.gov for relevant studies from January 2010 to March 2023. Pooled meta-analysis was performed to investigate any potential association between ECPR and improved survival and neurological outcomes. RESULTS: This systematic review and meta-analysis included two randomized controlled trials enrolling 162 participants and 10 observational cohort studies enrolling 4507 participants. The pooled meta-analysis demonstrated that compared to CCRP, ECPR did not improve survival and neurological outcomes at 180 days following OHCA (RR: 3.39, 95% CI: 0.79 to 14.64; RR: 2.35, 95% CI: 0.97 to 5.67). While a beneficial effect of ECPR was obtained regarding 30-day survival and neurological outcomes. Furthermore, ECPR was associated with a higher risk of bleeding complications. Subgroup analysis showed that ECPR was prominently beneficial when exclusively initiated in the emergency department. Additional post-resuscitation treatments did not significantly impact the efficacy of ECPR on 180-day survival with favorable neurological outcomes. CONCLUSIONS: There is no high-quality evidence supporting the superiority of ECPR over CCPR in terms of survival and neurological outcomes in OHCA patients. However, due to the potential for bias, heterogeneity among studies, and inconsistency in practice, the non-significant results do not preclude the potential benefits of ECPR. Further high-quality research is warranted to optimize ECPR practice and provide more generalizable evidence. Clinical trial registration PROSPERO, https://www.crd.york.ac.uk/prospero/, registry number: CRD42023402211.

Impact of Immunosuppressed Status on Prognosis of Carbapenem-Resistant Organisms Bloodstream Infections.

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.

Association between Cholecystectomy and the Incidence of Pancreaticobiliary Cancer after Endoscopic Choledocholithiasis Management.

(1) Background: Previous studies have raised concerns about a potential increase in pancreaticobiliary cancer risk after cholecystectomy, but few studies have focused on patients who undergo cholecystectomy after receiving endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis. This study aims to clarify cancer risks in these patients, who usually require cholecystectomy, to reduce recurrent biliary events. (2) Methods: We conducted a nationwide cohort study linked to the National Health Insurance Research Database, the Cancer Registry Database, and the Death Registry Records to evaluate the risk of pancreaticobiliary cancers. All patients who underwent first-time therapeutic ERCP for choledocholithiasis from 2011 to 2017 in Taiwan were included. We collected the data of 13,413 patients who received cholecystectomy after endoscopic retrograde cholangiopancreatography and used propensity score matching to obtain the data of 13,330 patients in both the cholecystectomy and non-cholecystectomy groups with similar age, gender, and known pancreaticobiliary cancer risk factors. Pancreaticobiliary cancer incidences were further compared. (3) Results: In the cholecystectomy group, 60 patients had cholangiocarcinoma, 61 patients had pancreatic cancer, and 15 patients had ampullary cancer. In the non-cholecystectomy group, 168 cases had cholangiocarcinoma, 101 patients had pancreatic cancer, and 49 patients had ampullary cancer. The incidence rates of cholangiocarcinoma, pancreatic cancer, and ampullary cancer were 1.19, 1.21, and 0.3 per 1000 person-years in the cholecystectomy group, all significantly lower than 3.52 (p < 0.0001), 2.11 (p = 0.0007), and 1.02 (p < 0.0001) per 1000 person-years, respectively, in the non-cholecystectomy group. (4) Conclusions: In patients receiving ERCP for choledocholithiasis, cholecystectomy is associated with a significantly lower risk of developing pancreaticobiliary cancer.

Reduced-Reference Learning for Target Localization in Deep Brain Stimulation.

This work proposes a supervised machine learning method for target localization in deep brain stimulation (DBS). DBS is a recognized treatment for essential tremor. The effects of DBS significantly depend on the precise implantation of electrodes. Recent research on diffusion tensor imaging shows that the optimal target for essential tremor is related to the dentato-rubro-thalamic tract (DRTT), thus DRTT targeting has become a promising direction. The tractography-based targeting is more accurate than conventional ones, but still too complicated for clinical scenarios, where only structural magnetic resonance imaging (sMRI) data is available. In order to improve efficiency and utility, we consider target localization as a non-linear regression problem in a reduced-reference learning framework, and solve it with convolutional neural networks (CNNs). The proposed method is an efficient two-step framework, and consists of two image-based networks: one for classification and the other for localization. We model the basic workflow as an image retrieval process and define relevant performance metrics. Using DRTT as pseudo groundtruths, we show that individualized tractography-based optimal targets can be inferred from sMRI data with high accuracy. For two datasets of 280x220/272x227 (0.7/0.8 mm slice thickness) sMRI input, our model achieves an average posterior localization error of 2.3/1.2 mm, and a median of 1.7/1.02 mm. The proposed framework is a novel application of reduced-reference learning, and a first attempt to localize DRTT from sMRI. It significantly outperforms existing methods using 3D-CNN, anatomical and DRTT atlas, and may serve as a new baseline for general target localization problems.

Surplus fatty acid synthesis increases oxidative stress in adipocytes and lnduces lipodystrophy.

Adipocytes are the primary sites for fatty acid storage, but the synthesis rate of fatty acids is very low. The physiological significance of this phenomenon remains unclear. Here, we show that surplus fatty acid synthesis in adipocytes induces necroptosis and lipodystrophy. Transcriptional activation of FASN elevates fatty acid synthesis, but decreases NADPH level and increases ROS production, which ultimately leads to adipocyte necroptosis. We identify MED20, a subunit of the Mediator complex, as a negative regulator of FASN transcription. Adipocyte-specific male Med20 knockout mice progressively develop lipodystrophy, which is reversed by scavenging ROS. Further, in a murine model of HIV-associated lipodystrophy and a human patient with acquired lipodystrophy, ROS neutralization significantly improves metabolic disorders, indicating a causal role of ROS in disease onset. Our study well explains the low fatty acid synthesis rate in adipocytes, and sheds light on the management of acquired lipodystrophy.

Ultra-sensitive molecular residual disease detection through whole genome sequencing with single-read error correction.

While whole genome sequencing (WGS) of cell-free DNA (cfDNA) holds enormous promise for molecular residual disease (MRD) detection, its performance is limited by WGS error rate. Here we introduce AccuScan, an efficient cfDNA WGS technology that enables genome-wide error correction at single read level, achieving an error rate of 4.2×10 -7 , which is about two orders of magnitude lower than a read-centric de-noising method. When applied to MRD detection, AccuScan demonstrated analytical sensitivity down to 10 -6 circulating tumor allele fraction at 99% sample level specificity. In colorectal cancer, AccuScan showed 90% landmark sensitivity for predicting relapse. It also showed robust MRD performance with esophageal cancer using samples collected as early as 1 week after surgery, and predictive value for immunotherapy monitoring with melanoma patients. Overall, AccuScan provides a highly accurate WGS solution for MRD, empowering circulating tumor DNA detection at parts per million range without high sample input nor personalized reagents. One Sentence Summary: AccuScan showed remarkable ultra-low limit of detection with a short turnaround time, low sample requirement and a simple workflow for MRD detection.

Comparison of different criteria of metagenomic next-generation sequencing for the diagnosis of invasive pulmonary aspergillosis in critically ill patients.

OBJECTIVE: To compare different criteria of Metagenomic Next-Generation Sequencing (mNGS) in bronchoalveolar lavage fluid (BALF) for diagnosing invasive pulmonary aspergillosis (IPA). METHODS: We compared the diagnostic agreement and performances of six BALF mNGS-derived criteria (SDSMRN>1, SDSMRN≥3, SMRN≥10, SMRN≥50, RPM ratio≥10, and relative abundance of genus>30 %) in pneumonia patients. RESULTS: A total of 115 patients were analyzed, with 28 identified with IPA. Diagnostic agreement among the six mNGS-derived criteria was moderate, with a Cohen's kappa of 0.577(P < 0.001). mNGS-derived criteria had low sensitivity ranging from 21.4 % to 57.1 % and high specificity from 88 % to 92 %. The optimal threshold of SDSMRN, SMRN, RPM ratio, and relative abundance of genus for diagnosing IPA were 5, 0.25, 8, and 20 %, respectively. Although using the optimal threshold, the sensitivity of mNGS is lower than 50 %. CONCLUSIONS: All mNGS-derived criteria had low sensitivity for diagnosing IPA. A combination of mNGS and conventional mycological tests may be the best diagnostic strategy.

Sepsis-induced Coagulopathy: The Different Prognosis in Severe Pneumonia and Bacteremia Infection Patients.

Sepsis-induced coagulopathy (SIC) is a critical condition in sepsis patients, with varying outcomes depending on the type of infection. This study aims to analyze the prognosis of different infections in SIC cohort. A retrospective cohort study was conducted on 525 patients diagnosed with SIC in the intensive care unit from December 2013 to December 2022. These patients were divided into four groups: a non-pneumonia or bacteremia group, a severe pneumonia group, a bacteremia group, and a severe pneumonia concomitant with bacteremia group. The 28-day mortality was 18% (49/271) in the other infections group, 31% (33/106) in the lung infections group, 23% (29/126) in the blood infections group and 36% (8/36) in the lung and blood co-infections group, respectively. Pearson correlation analysis showed that procalcitonin (PCT) correlated strongly with all detected hemostatic markers (p < 0.001). The 28-day mortality rate in Lung infections group was significantly higher (p = 0.019), while Blood infections group had a higher incidence of disseminated intravascular coagulation (p = 0.011). By multivariable model analyses, longer duration of ventilation (p = 0.039) and severe pneumonia (p = 0.040) are risk factors associated with mortality. Different infections, including Lung and Blood infections, indicated different conditions in vivo. Longer duration of ventilation is associated with mortality, while Lung infections indicated higher 28-day mortality rate.

Blood gas analysis as a surrogate for microhemodynamic monitoring in sepsis.

BACKGROUND: Emergency patients with sepsis or septic shock are at high risk of death. Despite increasing attention to microhemodynamics, the clinical use of advanced microcirculatory assessment is limited due to its shortcomings. Since blood gas analysis is a widely used technique reflecting global oxygen supply and consumption, it may serve as a surrogate for microcirculation monitoring in septic treatment. METHODS: We performed a search using PubMed, Web of Science, and Google scholar. The studies and reviews that were most relevant to septic microcirculatory dysfunctions and blood gas parameters were identified and included. RESULTS: Based on the pathophysiology of oxygen metabolism, the included articles provided a general overview of employing blood gas analysis and its derived set of indicators for microhemodynamic monitoring in septic care. Notwithstanding flaws, several parameters are linked to changes in the microcirculation. A comprehensive interpretation of blood gas parameters can be used in order to achieve hemodynamic optimization in septic patients. CONCLUSION: Blood gas analysis in combination with clinical performance is a reliable alternative for microcirculatory assessments. A deep understanding of oxygen metabolism in septic settings may help emergency physicians to better use blood gas analysis in the evaluation and treatment of sepsis and septic shock.

HOXD9/miR-451a/PSMB8 axis is implicated in the regulation of cell proliferation and metastasis via PI3K/AKT signaling pathway in human anaplastic thyroid carcinoma.

Anaplastic thyroid carcinoma (ATC) is a deadly disease with a poor prognosis. Thus, there is a pressing need to determine the mechanism of ATC progression. The homeobox D9 (HOXD9) transcription factor has been associated with numerous malignancies but its role in ATC is unclear. In the present study, the carcinogenic potential of HOXD9 in ATC was investigated. We assessed the differential expression of HOXD9 on cell proliferation, migration, invasion, apoptosis, and epithelial-mesenchymal transition (EMT) in ATC and explored the interactions between HOXD9, microRNA-451a (miR-451a), and proteasome 20S subunit beta 8 (PSMB8). In addition, subcutaneous tumorigenesis and lung metastasis in mouse models were established to investigate the role of HOXD9 in ATC progression and metastasis in vivo. HOXD9 expression was enhanced in ATC tissues and cells. Knockdown of HOXD9 inhibited cell proliferation, migration, invasion, and EMT but increased apoptosis in ATC cells. The UCSC Genome Browser and JASPAR database identified HOXD9 as an upstream regulator of miR-451a. The direct binding of miR-451a to the untranslated region (3'-UTR) of PSMB8 was established using a luciferase experiment. Blocking or activation of PI3K by LY294002 or 740Y-P could attenuate the effect of HOXD9 interference or overexpression on ATC progression. The PI3K/AKT signaling pathway was involved in HOXD9-stimulated ATC cell proliferation and EMT. Consistent with in vitro findings, the downregulation of HOXD9 in ATC cells impeded tumor growth and lung metastasis in vivo. Our research suggests that through PI3K/AKT signaling, the HOXD9/miR-451a/PSMB8 axis may have significance in the control of cell proliferation and metastasis in ATC. Thus, HOXD9 could serve as a potential target for the diagnosis of ATC.

Validation of an ICD-Based Algorithm to Identify Sepsis: A Retrospective Study.

Background: Sepsis surveillance was important for resources allocation, prevention, and development of health policy. Objective: The aim of the study was to validate a modified International Classification of Diseases (ICD)-10 based algorithm for identifying hospitalized patients with sepsis. Methods: We retrospectively analyzed a prospective, single-center cohort of adult patients who were consecutively admitted to one medical ICU ward and ten non-ICU wards with suspected or confirmed infections during a 6-month period. A modified ICD-10 based algorithm was validated against a reference standard of Sequential Organ Failure Assessment (SOFA) score based on Sepsis-3. Sensitivity (SE), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), and areas under the receiver operating characteristic curves (AUROCs) were calculated for modified ICD-10 criteria, eSOFA criteria, Martin's criteria, and Angus's criteria. Results: Of the 547 patients in the cohort, 332 (61%) patients met Sepsis-3 criteria and 274 (50%) met modified ICD-10 criteria. In the ICU setting, modified ICD-10 criteria had SE (84.47%), SP (88.57%), PPV (95.60), and NPV (65.96). In non-ICU settings, modified ICD-10 had SE (64.19%), SP (80.00%), PPV (80.33), and NPV (63.72). In the whole cohort, the AUROCs of modified ICD-10 criteria, eSOFA, Angus's criteria, and Martin's criteria were 0.76, 0.75, 0.62, and 0.62, respectively. Conclusion: This study demonstrated that modified ICD-10 criteria had higher validity compared with Angus's criteria and Martin's criteria. Validity of the modified ICD-10 criteria was similar to eSOFA criteria. Modified ICD-10 algorithm can be used to provide an accurate estimate of population-based sepsis burden of China.