Targeting 5-Hydroxytryptamine Receptor 1A in the Portal Vein to Decrease Portal Hypertension.

BACKGROUND & AIMS: Portal hypertension (PH) is one of the most frequent complications of chronic liver disease. The peripheral 5-hydroxytryptamine (5-HT) level was increased in cirrhotic patients. We aimed to elucidate the function and mechanism of 5-HT receptor 1A (HTR1A) in the portal vein (PV) on PH. METHODS: PH models were induced by thioacetamide injection, bile duct ligation, or partial PV ligation. HTR1A expression was detected using real-time polymerase chain reaction, in situ hybridization, and immunofluorescence staining. In situ intraportal infusion was used to assess the effects of 5-HT, the HTR1A agonist 8-OH-DPAT, and the HTR1A antagonist WAY-100635 on portal pressure (PP). Htr1a-knockout (Htr1a-/-) rats and vascular smooth muscle cell (VSMC)-specific Htr1a-knockout (Htr1aΔVSMC) mice were used to confirm the regulatory role of HTR1A on PP. RESULTS: HTR1A expression was significantly increased in the hypertensive PV of PH model rats and cirrhotic patients. Additionally, 8-OH-DPAT increased, but WAY-100635 decreased, the PP in rats without affecting liver fibrosis and systemic hemodynamics. Furthermore, 5-HT or 8-OH-DPAT directly induced the contraction of isolated PVs. Genetic deletion of Htr1a in rats and VSMC-specific Htr1a knockout in mice prevented the development of PH. Moreover, 5-HT triggered adenosine 3',5'-cyclic monophosphate pathway-mediated PV smooth muscle cell contraction via HTR1A in the PV. We also confirmed alverine as an HTR1A antagonist and demonstrated its capacity to decrease PP in rats with thioacetamide-, bile duct ligation-, and partial PV ligation-induced PH. CONCLUSIONS: Our findings reveal that 5-HT promotes PH by inducing the contraction of the PV and identify HTR1A as a promising therapeutic target for attenuating PH. As an HTR1A antagonist, alverine is expected to become a candidate for clinical PH treatment.

Approaches for posaconazole therapeutic drug monitoring and their clinical benefits.

OBJECTIVE: This review examines the progress of research on posaconazole therapeutic drug monitoring (TDM) that has focused on differences in the TDM of posaconazole after clinical application in different formulations and in different populations, the factors that affect posaconazole concentrations, the advantages of posaconazole TDM in terms of clinical efficacy and cost savings, and measurement methods. METHODS: A literature search (2006 to 2024) was performed in PubMed and Embase with the following search terms: noxafil, posaconazole hydrate, posaconazole, drug monitoring, therapeutic drug monitoring, and TDM. Abstracts of review articles, prospective studies, and retrospective studies were reviewed. RESULTS: TDM should be implemented earlier for posaconazole tablets and injections than for oral posaconazole suspensions. Posaconazole TDM is beneficial for improving clinical efficacy, and the incidence of breakthrough invasive fungal infections (IFIs) can be significantly reduced by gradually adjusting the posaconazole dose in response to TDM in patients with inadequate trough concentrations. Early TDM allows more patients to achieve target therapeutic posaconazole concentrations. TDM can also facilitate dose adjustments, which reduce the cost of this expensive drug. Different assay techniques, including chromatography, microbiological detection, chemofluorimetry, paper spray mass spectrometry, and capillary electrophoresis, can be used for posaconazole TDM. CONCLUSIONS: Posaconazole TDM has potential clinical utility and cost-saving benefits and could improve the outcomes of IFI treatment.

Independent effect of the triglyceride-glucose index on all-cause mortality in critically ill patients with chronic obstructive pulmonary disease and asthma: A retrospective cohort study.

BACKGROUND: The triglyceride-glucose (TyG) index serves as a reliable proxy for insulin resistance (IR). IR has been linked to heightened incidence, prevalence, or severity of chronic obstructive pulmonary disease (COPD) and asthma. Prior research indicates that critically ill patients are prone to developing IR. Nevertheless, few studies have delved into the correlation between IR and all-cause mortality in critically ill patients with COPD and asthma. Therefore, the aim of this study is to explore the association between the TyG index and all-cause mortality in patients with COPD and asthma, with the goal of assessing the impact of IR on the prognosis of this patient population. METHODS: This is a retrospective study, and all data are from the Medical Information Mart for Intensive Care IV (MIMIC-IV) critical care database. This study included 684 ICU patients with COPD and asthma and divided them into quartiles based on TyG index levels. The primary outcomes of this study were all-cause mortality during follow-up, encompassing mortality at 30 days, 90 days, and 180 days. The Kaplan-Meier analysis was used to compare all-cause mortality among the above four groups. Cox proportional hazards analyses were performed to examine the association between TyG index and all-cause mortality in critically ill patients with COPD and asthma. Restricted cubic spline analysis was used to assess potential nonlinear association between the TyG index and the primary outcome. RESULTS: A total of 684 patients (53.9% female) were included. The 90-days all-cause mortality rate and 180-days all-cause mortality were 11.7% and 12.3%, respectively. Kaplan-Meier analysis revealed a significant association between the TyG index and both 90-days all-cause mortality (log-rank p = .039) and 180-days all-cause mortality (log-rank p = .017). Cox proportional hazards analysis revealed a significant association between the TyG index and 90-days all-cause mortality in both the unadjusted model (HR, 1.30 [95% CI 1.08-1.57] p = .005) and the model adjusted for age, gender, and diabetes (HR, 1.38 [95% CI 1.15-1.67] p < .001). Similarly, the TyG index was associated with 180-days all-cause mortality in the unadjusted model (HR, 1.30 [95% CI 1.09-1.56] p = .004) and the model adjusted for age, sex, and diabetes (HR, 1.38 [95% CI 1.15-1.66] p < .001). The restricted cubic splines (RCS) regression model indicated a significant nonlinear association between the TyG index and both 90-days and 180-days all-cause mortality. Specifically, TyG index >4.8 was associated with an increased risk of mortality at both 90 days and 180 days. CONCLUSIONS: In summary, our results extend the utility of the TyG index to critically ill patients with COPD and asthma. Our study shows that the TyG index is a potential predictor of all-cause mortality in critically ill patients with COPD and asthma. In addition, in patients with a TyG index exceeding 4.8, there was a heightened risk of mortality. Measuring the TyG index may help with risk stratification and prognosis prediction in critically ill patients with COPD and asthma. Further prospective studies are needed to confirm our findings.

Heavy metals in paired samples of hair and nails in China: occurrence, sources and health risk assessment.

The occurrence of heavy metals including chromium (Cr), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), cadmium (Cd) and lead (Pb) was investigated in paired samples of hair and nails collected from 121 volunteers in 16 cities, China. Results showed that the mean concentrations of Zn, Cu, As, Pb, Cr, Ni and Cd were 205, 18.0, 7.79, 6.18, 3.54, 2.02, 0.533 µg g-1 in hair and 103, 8.09, 0.760, 7.27, 6.07, 8.81, 0.485 µg g-1 in nails, respectively. The concentrations of Zn, Ni, Cr, Cd and Pb were positively correlated in paired samples of hair and nails, whereas a negative correlation was found for Cu and As between hair and nails. Higher concentrations of heavy metals were found in northern China than southern China. The multivariate analysis of variance revealed that dwelling environment was the dominant factor influencing the levels of Cd in hair (p < 0.05), while age was the dominant factor influencing the levels of Cr in nails (p < 0.05). Moreover, industrial pollution and smoking were also the important factors leading to the accumulation of heavy metals in human body. Principal component analysis (PCA) showed that industrial pollution and decoration material immersion were the main factors for the high concentrations of Cr and Ni in hair, accounting for 62.9% of the total variation; As in hair was dominantly related to groundwater pollution. The concentrations of heavy metals were within the recommended ranges in nails from this study. However, the mean levels of Cr, Ni and As in hair exceeded their recommended reference values, indicating potential health risks from heavy metals for residents in China.

A nationwide survey of polycyclic aromatic hydrocarbons (PAHs) in household dust in China: spatial distribution, sources, and health risk assessment.

As a carrier of toxic substances, household dust has a great impact on human health. Here we collected 73 household dust samples from 27 provinces and 1 municipality in China to investigate the levels, spatial distribution, sources, and carcinogenic risk of 16 polycyclic aromatic hydrocarbons (PAHs). The total concentrations of 14 detected PAHs (∑14 PAHs) ranged from 3.72 to 60,885 ng g-1. High ∑14 PAHs were found in Northeast and Southwest China. High molecular weights (HMW) PAHs (4-6 rings) were predominant PAHs in most dust samples, accounting for 93.6% of ∑14 PAHs. Household fuel, cooking frequency, air conditioning, and smoking were the main factors influencing PAH concentrations in household dust. Principal component analysis model indicated that fossil combustion (81.5%) and biomass combustion and vehicle exhaust (8.1%) are the primary sources of PAHs. Positive matrix factorization model suggested that household cooking and heating contributed about 70% of ∑14 PAHs, and smoking contributed another 30%. The values of benzo[a]pyrene equivalent in rural dust were found to be higher than those in urban dust. The sum of toxic equivalents (TEQs) of 14 PAHs were in range of 0.372-7241 ng g-1, in which 7 HMW PAHs accounted for 98.0 ± 1.98% of the total TEQs. Monte Carlo Simulation showed a low to moderate potential carcinogenic risk of PAHs in household dusts. This study documents comprehensive information on human exposure to PAHs in household dust at a national-scale.

Association between preoperative on-site CCU visits and postoperative delirium in patients undergoing cardiac surgery: A retrospective cohort study.

BACKGROUND: Postoperative delirium (POD) is a common complication after cardiac surgery (CS), with symptoms like attention disorders and even delays patients' recovery. AIMS: To evaluate the impact of preoperative on-site visits in the cardiac care unit (CCU) on POD after CS. STUDY DESIGN: Patients admitted to the CCU with extracorporeal CS were included in the visiting or non-visiting group according to whether they were on visiting week. The visiting group received a preoperative visit from a nurse-led multidisciplinary visiting team (including CCU nurses and physicians) 1 week before surgery in addition to standard care. The non-visiting group received standard care like unstructured information from the CS team and anesthesiologists and so on. The Confusion Assessment Method for the ICU (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) were used to evaluate the POD severity. The incidence, occurrence and duration of POD, as well as the CCU length of stay, postoperative mechanical ventilation duration and length of hospital stay were compared between the two groups. RESULTS: A total of 735 participants (369 in the visited group and 366 in the unvisited group) were included in this study. Preoperative on-site visits were associated with a decreased POD incidence (odds ratio [OR]: 0.524, 95% CI: 0.336-0.817), an improved POD severity (OR: 0.578, 95% CI: 0.359-0.932) and a shortening POD duration (OR: 0.972, 95% CI: 0.951-0.994). There was a significant difference between the visiting and non-visiting groups in the mechanical ventilation duration (OR: 0.987, 95% CI: 0.978-0.996). CONCLUSIONS: Preoperative on-site visits are associated with a reduction in the incidence, duration, and severity of POD, as well as the mechanical ventilation duration of patients. RELEVANCE TO CLINICAL PRACTICE: This study found that preoperative on-site visits were associated with the onset, duration, severity and duration of mechanical ventilation of POD. Although many factors influence the occurrence of POD, a multidisciplinary visiting team led by a nurse (including CCU nurses and physicians) can provide early nursing interventions through preoperative visits, better obtain postoperative cooperation from patients, establish a good nurse-patient relationship and provide better health services to patients. In a realistic CCU setting, nurses and physicians can act as educators, assessing patients before surgery, enhancing preoperative education, improving patient familiarity with the CCU environment and teaching sign language communication skills when patients are mechanically ventilated. These findings can therefore provide the basis for effective clinical care to prevent postoperative POD.

[Relationship between dietary fiber intake and glucose metabolism in the elderly of China in 2015].

OBJECTIVE: To investigate the dietary fiber intake status and analyze the relationship between dietary fiber and glucose metabolic disorder of the elderly in China. METHODS: Data were collected from the participants of Chinese adult chronic diseases and nutrition surveillance in 2015. General information were collected by standardized questionnaires, anthropometric index and blood pressure of respondents were measured according to standard method. Food intake was collected by three consecutive day 24 h dietary recalls, dietary fiber was calculated through China food composition. Fasting venous blood were collected to measure glucose, HbA1C, and other related biochemical index. Subjects were divided into three groups: normal glucose(NG, normal glucose), pre-diabetes(Pre-DM, pre-diabetes mellitus) and diabetes(T2DM, type 2 diabetes mellitus). Multiple logistic regression model was used to analyze the relationship between dietary fiber intake and Pre-DM as well as T2DM. RESULTS: A total of 20 996 elderly people aged 60 years and above were included. There 10 773 cases were males(51.3%) and 10 223 cases were females(48.7%), the age of both gender were(68.21±6.26) years and(67.67±6.26) years. A total of 6526 cases of pre-diabetes were detected in 20 996 elderly participants with detection rate of 31.1%. There 3274 cases were male and 3252 cases were female, the detection rates of both genders were 30.4% and 31.8%, respectively. While 1572 participants were detected as T2DM(784 of males and 788 of females), the detection rate of T2DM was 7.5%, 7.3% for males and 7.7% for females. There were significant differences in mean age, BMI, waist circumference, systolic blood pressure, diastolic blood pressure, TC, TG, HDL-C, LDL-C, HbA1c level among different dietary intake groups(P<0.005). With the increase of dietary fiber intake, the proportion of overweight and obesity, central obesity and dyslipidemia showed an increasing trend(P<0.05), and the proportion of hypertension showed a decreasing trend(P<0.000 1). After adjusting for potential confounding factors, compared to participants with lowest fiber intake, participants in subgroups of lower, minor lower, and higher fiber intake were associated with decreased risk of pre-diabetes, the OR and 95%CI were(OR=0.911, 95%CI 0.835-0.993), (OR= 0.861, 95%CI 0.790-0.938) and(OR= 0.913, 95%CI 0.838-0.994), respectively. However, there was only a statistically significant negative association between the higher intake of dietary fiber and T2DM(OR = 0.848, 95%CI 0.726-0.991). CONCLUSION: Dietary fiber intake was negatively related with diabetes and pre-diabetes mellitus. The risk of glucose metabolic disorder was decreased with the increase of dietary fiber intake.

Xper computed tomography-guided translumbar inferior vena cava catheterization for long-term hemodialysis: A case report and literature review.

Hemodialysis is the most widely used renal replacement therapy for end-stage renal disease patients. Exhausted vascular access due to repeated indwelling central venous catheters is becoming a challenging clinical problem, which also contributes to reduced survival of the hemodialysis patients. Lack of conventional peripheral and central venous access mandates the use of alternative strategies. We present a case of translumbar dialysis catheter (TLDC) for long-term hemodialysis in a patient with central venous occlusion refractory to conventional endovascular techniques. After a careful literature review, totally 10 cohort studies including 216 cases through TLDC were reported. The incidence of procedure-related complications was very low. The catheter-related infection rate of TLDC was comparable with overall tunneled cuffed catheters (TCCs) reported by clinical practice guidelines for vascular access. Although the patency might be relatively low due to the catheter-related complications, TLDC could be rescued by multiple systemic and topical medications and interventional therapies. Percutaneous translumbar placement of a cuffed tunneled hemodialysis catheter directly into the inferior vena cava (IVC) can provide a relatively safe salvage when traditional central venous sites such as the internal jugular, femoral, subclavian veins are unavailable. Xper computed tomography together with real-time fluoroscopic guidance can reduce the intraoperative risks and complications.

Cost-effectiveness of anticoagulants for preventing stroke in patients with non-valvular atrial fibrillation in mainland China.

WHAT IS KNOWN AND OBJECTIVE: With the high cost, the long-term persistence of new oral anticoagulants (NOACs) was lower than that of warfarin in Chinese patients with non-valvular atrial fibrillation (NVAF) for a long time. The prices of NOACs (apixaban, rivaroxaban and dabigatran) decreased significantly over the past year in mainland China. The objective of this study was to evaluate the cost-effectiveness of NOACs versus warfarin for preventing stroke in patients with NVAF from a Chinese healthcare system perspective. METHODS: A decision tree and Markov model were used to assess the treatment strategies of four NOACs versus warfarin over a lifetime horizon. For each treatment strategy, the total lifetime cost, quality-adjusted life-years (QALY) and incremental cost-effectiveness ratio (ICER) were calculated. The impact of parameter uncertainties on base-case analysis results was evaluated using sensitivity analyses. RESULTS AND DISCUSSION: In the base-case analysis, compared with warfarin, apixaban had a decreased total lifetime cost of USD 389 and rivaroxaban of USD 1482, while low-dose dabigatran had an increased total lifetime cost of USD 925 and high-dose dabigatran of USD 6641, with QALY increasing by 0.53, 1.32, 0.92 and 1.83, respectively. The ICER of low-dose dabigatran versus warfarin was USD 1005 per QALY gain, while those of apixaban (-USD 734 per QALY gain) and rivaroxaban (-USD 1123 per QALY gain) were negative. One-way and probabilistic sensitivity analyses indicated that the base-case results were robust by applying certain varying parameters to the model. WHAT IS NEW AND CONCLUSION: These four NOAC (apixaban, rivaroxaban, low-dose dabigatran and high-dose dabigatran) treatment strategies were cost-effective compared with warfarin and recommended as substitutes for warfarin treatment for preventing stroke in patients with NVAF in the healthcare system of China, which might be driven by large drug price reductions in the past year.

Exploring Eye Movement Biometrics in Real-World Activities: A Case Study of Wayfinding.

Eye movement biometrics can enable continuous verification for highly secure environments such as financial transactions and defense establishments, as well as a more personalized and tailored experience in gaze-based human-computer interactions. However, there are numerous challenges to recognizing people in real environments using eye movements, such as implicity and stimulus independence. In the instance of wayfinding, this research intends to investigate implicit and stimulus-independent eye movement biometrics in real-world situations. We collected 39 subjects' eye movement data from real-world wayfinding experiments and derived five sets of eye movement features (the basic statistical, pupillary response, fixation density, fixation semantic and saccade encoding features). We adopted a random forest and performed biometric recognition for both identification and verification scenarios. The best accuracy we obtained in the identification scenario was 78% (equal error rate, EER = 6.3%) with the 10-fold classification and 64% (EER = 12.1%) with the leave-one-route-out classification. The best accuracy we achieved in the verification scenario was 89% (EER = 9.1%). Additionally, we tested performance across the 5 feature sets and 20 time window sizes. The results showed that the verification accuracy was insensitive to the increase in the time window size. These findings are the first indication of the viability of performing implicit and stimulus-independent biometric recognition in real-world settings using wearable eye tracking.

Polycyclic Aromatic Hydrocarbons (PAHs) in Indoor Dust Across China: Occurrence, Sources and Cancer Risk Assessment.

In this study, the occurrence of 16 polycyclic aromatic hydrocarbons (PAHs) was investigated in 31 household dusts that were sampled from 27 areas located in 10 provinces, China. The total concentrations of PAHs (∑ PAHs) were in the range of 613-10,111 ng·g-1 with a median of 2565 ng·g-1. The predominant PAHs were 2 to 3 ringed compounds, accounting for 85.3% of ∑ PAHs. The geographical location had little impact on the contents of PAHs. Higher concentrations of ∑ PAHs and individual homologues of PAHs except for naphthalene (NAP) were observed in rural areas, which is related to the higher usage of coal or biomass for cooking. Cooking method played a major role in contributing to the concentrations of PAHs. Both household cooking and petrogenic sources from outdoors were the primary sources of PAHs in household dust. Cancer risk assessment indicated that dermal contact and ingestion are the main exposure pathways to indoor residents. Furthermore, the average values of sum of incremental lifetime cancer risks (ILCRs) were 2.22 × 10-7 for adults and 2.51 × 10-7 for children, suggesting that there is a low health risk posed by PAHs in indoor dust. The contribution percentage of 4 to 6 rings PAHs to ILCRs was up to 96.3%, indicating that higher molecular weight PAHs in indoor dust, especially benzo[a]pyrene (BaP) and dibenzo[a,h]anthracene (DahA), are major factors contributing to cancer risk.

Perfluorinated Compounds (PFCs) in Soil of the Pearl River Delta, China: Spatial Distribution, Sources, and Ecological Risk Assessment.

This study investigated the levels, spatial distribution, sources, and ecological risks of 16 perfluorinated compounds (PFCs) in 68 surface soil samples (0-20 cm) from 7 cities in the Pearl River Delta (PRD), China. Sixteen target PFCs, including perfluoroalkyl carboxylic acids (PFCAs, C5-C14, C16, and C18) and perfluoroalkyl sulfonic acids (PFSAs, C4, C6, C8, and C10), were analyzed by high-performance liquid chromatography-negative electrospray ionization-tandem mass spectrometry (HPLC/ESI-MS/MS). Concentrations of total PFCs (∑PFCs) ranged from 2.19 to 98.5 µg kg-1 (dry weight, dw), with an average of 5.97 µg kg-1 dw. Perfluorooctane sulfonate (PFOS) was the dominant PFC, accounting for 23.9% of ∑PFCs. The highest ∑PFCs was found in the soil sample collected from Dongguan with a large number of manufacturing industries. There were no significant differences of ∑PFCs among unban, industrial, and agricultural soils, indicating similar pollution sources in soil of the PRD. More than 70% of ∑PFCs in soil of the PRD could be attributed to the four principal components, represented by PFOS and perfluorooctanoic acid (PFOA), perfluoropentanoic acid (PFPeA) and perfluorohexanoic acid (PFHxA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUdA). Ecological risk assessment indicated that PFOA had low risk to soil plants and animals. However, the risk of PFOS to soil plants was relatively high in some studied regions.

Risk scores for predicting dysphagia in critically ill patients after cardiac surgery.

BACKGROUND: This study aimed at developing and validating a scoring model to stratify critically ill patients after cardiac surgery based on risk for dysphagia, a common but often neglected complication. METHODS: Data were prospectively collected and analyzed from January 2016 to June 2017 from 395 consecutive post cardiac surgery patients at the cardiac care unit (CCU) at a single center; 103 (26.1%) developed dysphagia. Univariate and multivariate logistic analyses were used to identify independent predictors for dysphagia. The survival nomogram was developed on the basis of a multivariable Cox model, which allowed us to obtain survival probability estimations. The predictive performance of the nomogram was verified for discrimination and calibration. Areas under receiver operating characteristic curve analysis were used to illustrate and evaluate the diagnostic performance of the novel model. RESULTS: The final novel scoring model, named SSG-OD, consists of three independent factors: gastric intubation (OR = 1.024, 95% CI 1.015-1.033), sedative drug use duration (OR = 1.031, 95% CI 1.001-1.063) and stroke or not (OR = 6.182, 95% CI 3.028-12.617). SSG-OD identified patients at risk for dysphagia with sensitivity of 68.5% and specificity of 89.0% (OR = 0.833, 95% CI: 0.782-0.884). The positive and negative likelihood ratios were 6.22 and 0.35. CONCLUSIONS: The novel SSG-OD scoring system to risk stratify CCU patients for dysphagia is an easy-to-use bedside prognostication aid with good predictive performance and the potential to reduce aspiration incidence and accelerate recovery.

Spatial Distribution of Perfluorinated Compounds in Atmosphere of the Pearl River Delta, China.

Perfluorinated compounds (PFCs) are of special concern due to their environmental persistence and biotoxicity. In the present study, spatial distribution of PFCs in atmosphere of the Pearl River Delta (PRD) of Southern China was investigated from November 2013 to January 2014. Forty-two air samples were collected using passive air samplers to determine the 13 target analytes, including perfluoroalkyl carboxylic acids (PFCAs, C5-14) and perfluoroalkyl sulfonic acids (PFSAs, C4, C6, and C8). Results showed that the total concentrations of PFCs (ΣPFCs) ranged from 53.7 to 225 pg m-3 with an average level of 122 ± 41.5 pg m-3, indicating a wide variation on ΣPFCs in atmosphere of the PRD. Perfluorooctane sulfonate (PFOS) was the most abundant PFCs, followed by perfluorooctanoic acid (PFOA), perfluoropentanoic acid (PFPeA), and perfluoroheptanoic acid (PFHpA). PFOS, PFOA, PFPeA, and PFHpA accounted for 26%, 22%, 21%, and 19% of ΣPFCs, respectively. A general decline in ΣPFCs was observed in the atmosphere from south PRD to north PRD. It was likely related to the industrial distribution, population density, and wind direction. In addition, the same order of magnitude of PFOS and lower level of PFOA were observed in this study compared with those in atmosphere sampled in other regions. The lifetime risk indexes on the PFOS and PFOA concentrations were much less than unity, suggesting a lower nononcogenic risk to residents in the PRD.

Occurrence and Partition of Perfluorinated Compounds (PFCs) in Water and Sediment from the Songhua River, China.

This study provided the first evidence that perfluorinated compounds (PFCs) were widely detected in the Songhua River, China. Seventeen surface water and sediment samples were collected and analyzed for the determination of 14 PFCs. The total concentrations of PFCs (Σ PFCs) ranged from 0.143 to 1.41 ng L-1 in water samples. Perfluorooctanoic acid (PFOA) was detected with the highest detection frequency (%) ranging from below LOQ to 0.678 ng L-1. Σ PFCs were relatively low in sediments, and only four individual homologues were detected. Perfluorooctane sulfonate (PFOS) and PFOA were detected with the lowest levels in this study compared with other PFCs detected in all the rivers of China in previous studies. The concentrations of PFCs were highly influenced by distribution of wastewater treatment plants (WWTPs). The effluents from WWTPs, which are discharged into the Songhua River, are regarded as the main contamination sources of PFCs in this study. Even though low risk for the concentrations of PFOS and PFOA to aquatic ecosystem of the Songhua River was found in the analysis of potential adverse effect, further experimental studies on occurrence of PFCs and their potential adverse effects to wildlife and humans should be conducted continuously in the Songhua River basin because of the increasing discharge. The mean partition coefficients (log K oc) of PFOS between sediment and water was 4.49 cm3 g-1, which was probably influenced by the sediment characteristics and hydrodynamic parameters. PFCs tend to accumulate in water compared with other persistent organic pollutants.

Choosing Optimal Antifungal Agents To Prevent Fungal Infections in Nonneutropenic Critically Ill Patients: Trial Sequential Analysis, Network Meta-analysis, and Pharmacoeconomic Analysis.

The use of antifungal interventions in critically ill patients prior to invasive fungal infection (IFI) being microbiologically confirmed and the preferred drug are still controversial. A systematic literature search was performed to identify randomized controlled trials (RCTs) that compared untargeted antifungal treatments applied to nonneutropenic critically ill patients. The primary outcomes were all-cause mortality and proven IFI rates. A random-effects model was used with trial sequential analyses (TSA), a network meta-analysis (NMA) was conducted to obtain indirect evidence, and a cost-effectiveness analysis using a decision-analytic model was completed from the patient perspective over a lifetime horizon. In total, 19 RCTs involving 2,556 patients (7 interventions) were included. Untargeted antifungal treatment did not significantly decrease the incidence of all-cause mortality (odds ratio [OR] = 0.89, 95% confidence interval [95%CI] = 0.70 to 1.14), but it did reduce the incidence of proven IFI (OR = 0.45, 95%CI = 0.29 to 0.71) relative to placebo/no intervention. The TSA showed that there was sufficient evidence supporting these findings. In the NMA, the only significant difference found for both primary outcomes was between fluconazole and placebo/no intervention in preventing proven IFI (OR = 0.35, 95%CI = 0.19 to 0.65). Based on drug and hospital costs in China, the incremental cost-effectiveness ratios per life-year saved for fluconazole, caspofungin, and micafungin relative to placebo/no intervention corresponded to US$889, US$9,994, and US$10,351, respectively. Untargeted antifungal treatment significantly reduced proven IFI rates in nonneutropenic critically ill patients but with no mortality benefits relative to placebo/no intervention. Among the well-tolerated antifungals, fluconazole remains the only one that is effective for IFI prevention and significantly cheaper than echinocandins.

Meta-analysis of Comparison of the Newer P2Y12 Inhibitors (Oral Preparation or Intravenous) to Clopidogrel in Patients With Acute Coronary Syndrome.

AIMS: New P2Y12 adenosine diphosphate receptor antagonists have been used in the treatment of acute coronary syndrome (ACS) with different results. This systematic review analyzed and compared the evidence from large, clinical trials regarding the efficacy of clopidogrel relative to that of cangrelor, prasugrel, and ticagrelor in reducing the incidence of cardiovascular events in patients with ACS. METHODS AND RESULTS: This analysis compared newer P2Y12 inhibitors with clopidogrel of 13 clinical trials involved a total of 87,985 patients with ACS. The newer P2Y12 inhibitors include cangrelor, prasugrel, and ticagrelor. Newer P2Y12 inhibitors significantly decreased the risk of myocardial infarction and showed a trend toward reduction of cardiovascular death (odds ratio [OR] = 0.86, 95% confidence interval [CI], 0.77-0.96, and I = 54%, P < 0.05); (OR = 0.85, 95% CI, 0.77-0.93, and I = 42%, P < 0.001). The rates of stroke events and the incidence in patients with ACS did not differ statistically between the clopidogrel group and the group with newer P2Y12 inhibitors (OR = 0.95, 95% CI, 0.79-1.14, and I = 0%, P = 0.57). However, newer P2Y12 inhibitors showed a significant increase in thrombosis in MI major or minor bleeding (OR = 1.21, 95% CI, 1.03-1.42, and I = 56%, P = 0.02) compared with clopidogrel. CONCLUSIONS: Based on this meta-analysis, newer P2Y12 inhibitors were significantly more effective than clopidogrel in the events of myocardial infarction and cardiovascular death in patients with ACS, although the incidence of thrombosis in MI-defined bleeding was higher compared with clopidogrel.

Diagnostic and Prognostic Value of Serum Angiopoietin-Like Protein 2 in Patients with Non-Small Cell Lung Cancer.

BACKGROUND: Elevated serum angiopoietin-like protein 2 (ANGPTL2) level has been observed in several different types of cancer, but it remains unclear in non-small cell lung cancer (NSCLC). The present study aimed to explore serum ANGPTL2 in sera from NSCLC patients and analyze the association of serum ANGPTL2 with patient diagnosis and prognosis. METHODS: Enzyme Linked Immunosorbent Assay (ELISA) was used to measure serum ANGPTL2 concentration. The associations of serum ANGPTL2 level with clinicopathological characteristics of NSCLC patients were further analyzed. ROC/AUC analysis and Kaplan-Meier analysis were performed to evaluate its diagnostic and prognostic value in NSCLC patients. RESULTS: Serum ANGPTL2 was significantly higher in NSCLC patients (8.38 ± 1.73 vs. 4.87 ± 0.96 ng/mL; p < 0.01). Higher serum ANGPTL2 could be observed in NSCLC patients with late TNM stage, lymph node metastases, distant metastases, and poor differentiation compared to those with early TNM stage, without metastases, and well/moderate differentiation. The ROC/AUC analysis yielded an AUC of 0.86 (0.83 - 0.90) (sensitivity of 0.83, specificity of 0.82) to distinguish NSCLC patients from normal controls, while serum ANGPTL2 was also an efficient indicator to distinguish NSCLC patients with late clinical stage from early stages with an AUC of 0.92 (95% CI 0.89 - 0.95) with sensitivity of 0.91, specificity of 0.86. Prognostic analysis showed that NSCLC patients with high serum ANGPTL2 levels had lower survival rates than those with low levels (p < 0.01 for log-rank test). CONCLUSIONS: Serum ANGPTL2 levels were significantly increased in NSCLC patients, which could serve as a novel potential diagnostic and prognostic biomarker for NSCLC.

Perfluoroalkyl acids (PFAAs) in sediments from rivers of the Pearl River Delta, southern China.

Having been largely used in industrial and household products, perfluoroalkyl acids (PFAAs) appear in environmental and biological systems with prevalence and persistence and have raised great concern in recent years. The present study is aimed at studying concentrations and composition profiles of 16 PFAAs in surface sediments collected from 51 sampling locations in 4 main rivers of the Pearl River Delta, one of the economy-developed areas in China. The total PFAA concentrations (∑ PFAAs) were determined in a wide range of 1.89-15.1 ng g-1 dw (dry weight) with an average concentration to be 3.54 ng g-1 dw. Higher ∑ PFAAs were observed in the downstream of Dongjiang River and the Pearl River, possibly due to the discharge of industrial wastewater. Perfluoropentanoic acid (PFPeA) and perfluorooctane sulfonate (PFOS) were the dominant PFAAs, accounting for 51 to 85% of ∑ PFAAs in 27% of the samples. High PFPeA concentrations in sediments of urban river were scarcely observed in previous studies worldwide. The sources of short-chain perfluoroalkyl carboxylic acids (PFCAs) were significantly different from those of other PFAAs. Preliminary hazard assessment proved negligible for PFOS, perfluorooctanoic acid (PFOA), PFPeA, and perfluorohexanoic acid (PFHxA) concentrations in sediments from rivers of the Pearl River Delta.

Dynamic contrast-enhanced MRI for the assessment of spinal tumor vascularity: correlation with angiography.

PURPOSE: To determine if dynamic contrast-enhanced MRI (DCE-MRI) could correlate well with invasive angiography in the characterization of spinal tumor vascularity. METHODS: Totally 40 patients with untreated spinal tumors underwent MRI before preoperative angiography and embolization. Tumors were assigned to hypervascular, moderate, or hypovascular groups based on angiographic appearance. Tumor vascularity was also evaluated with enhancement degree on standard MR and with DCE-MRI parameters via ROI analysis of enhanced tumor area. The Spearman correlation coefficient was calculated to determine the correlation between the degree of angiographic vascularity and enhancement on MRI and DCE-MRI parameters. ROC analysis was conducted to assess the appropriate cut-off value. RESULTS: There were 12 hypervascular, 12 moderate, and 16 hypovascular tumors, respectively. The Spearman correlation coefficient between DCE-MRI parameter and the degree of angiographic vascularity was 0.899 (RSlopemax), 0.847 (Slopemax), 0.697 (E max), 0.694 (ERmax), and -0.587 (TTP), respectively, which showed excellent-to-moderate relationships. The RSlopemax cut-off value of 1.325 provided the highest specificity of 100 % and sensitivity of 87.5 % in predicting hypovascular tumors and the value of 1.85 provided the highest sensitivity of 100 % and specificity of 96.4 % in characterizing hypervascular ones. CONCLUSIONS: DCE-MRI is an accurate technique for the assessment of spinal tumor vascularity, which may have a potential value in the decision-making of preoperative embolization.