Mitigation of thallium threat in paddy soil and rice plant by application of functional biochar.

Thallium (Tl) is a highly toxic metal, and its contamination in soils entails high risks to human health via food chain. It remains largely unknown of the effects of applying biochar on Tl uptake in paddy systems despite that few studies have shown that biochar exhibits great potential for decreasing Tl bioavailability in soils. Herein, we examined the mitigating effects of the application of biochar (5 and 20 g/kg pristine biochar; 5 and 20 g/kg Fe/Mn-modified biochar) on Tl uptake in paddy soil and rice plant after an entire rice growth period. The results suggested that the application of Fe/Mn-modified biochar (FMBC) considerably mitigated the accumulation of Tl in different tissues of rice plants. Specifically, total Tl content in rice plants treated with FMBC-20 decreased by over 75% compared with control experiment. In addition, the amendment of FMBC in Tl-rich paddy soils can enhance the communities of microorganisms (Actinobacteria and Proteobacteria). Further analysis of the soil microbial symbiosis network revealed that FMBC promotes the living microorganisms to play modular synergistic interactions, which is crucial for FMBC-induced Tl stabilization in soils. All these findings indicated that FMBC is an efficient and environmentally friendly Tl-immobilization alternative material and can be potentially used in the remediation of Tl-contaminated paddy soils and/or cropland.

Effects of nusinersen on motor function in children with spinal muscular atrophy: a retrospective study.

Background: Spinal muscular atrophy (SMA) is a genetic progressive neuromuscular disease. Nusinersen is the first disease modifying drug approved to treat patients with SMA. Our study aimed to evaluate the efficacy of nusinersen treatment on motor function in children with SMA. Methods: A retrospective analysis was conducted on the data of 52 genetically confirmed SMA patients from November 2020 to September 2023. Motor function was assessed based on standardized scales from baseline to 14 months of follow-up. Results: Of patients in this study, the majority had SMA type 2 (40/52, 76.9%), 5 (9.6%) and 7 (13.5%) patients had SMA types 1 and 3, respectively. The median disease duration was 11 months (range 0-52), and the median age at initiation of treatment was 44.5 months (range 5-192). Motor function of all the patients with SMA improved from baseline to 14 months of follow-up. Mean increases of 4.6-point (p = 0.173), 4.7-point (p = 0.021) and 2.7-point (p = 0.013) were observed from baseline to 14 months of follow-up for the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders scores, the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM), respectively. Increased disease duration and age of treatment initiation were negatively correlated with the changes in HFMSE scores (r = -0.567, p = 0.043; r = -0.771 and p = 0.002, respectively). Similar results were observed for the RULM scores (r = -0.714, p = 0.014; r = -0.638 and p = 0.035, respectively). Conclusion: Our study suggested that 14 months of treatment with nusinersen was effective and improved the motor function of children with SMA types 1, 2, or 3. In addition, disease duration and age at treatment initiation were negatively correlated with treatment outcome in the patients.

Distribution and correlates of plasma folate, vitamin B12, and homocysteine in a sample of low-income minority children aged 6 months to 9 years in the U.S.

Background: Precision nutrition emphasizes tailoring dietary requirements across populations and life stages. Optimal folate and vitamin B12 levels are important for normal growth and development, but data are lacking for low-income minority U.S. children during early life periods. This study aimed to describe folate, vitamin B12, homocysteine (Hcy) levels, and influencing factors to address the gaps. Methods: Blood samples from children aged 6 months to 9 years and mothers 48-72 hours postpartum in the Boston Birth Cohort (BBC) were tested for folate, vitamin B12, and Hcy. Maternal and child characteristics, sociodemographic factors, and feeding status were obtained from a standard maternal questionnaire interview at the enrollment and follow-up, and medical records. The distribution of children's folate, vitamin B12, and Hcy were described and factors influencing these biomarkers were analyzed. Results: A wide distribution of folate, vitamin B12, and Hcy levels was observed in this sample, with longitudinal trends consistent with National Health and Nutrition Examination Survey (NHANES) data. Multivariate analysis showed that very preterm birth correlated with higher folate levels (adjusted ß 4.236; 95% CI: 1.218, 7.253; p=0.006). Children aged 1-2 years and 3-8 years had lower folate levels compared to those <1 year (adjusted ß -10.191 and -7.499 respectively; p<0.001). Vitamin B12 levels were higher in Black children (adjusted fold change 1.139; 95% CI: 1.052, 1.233; p=0.001) and those children whose mothers' B12 levels were at the highest quartile (Q4) (adjusted fold change 1.229; 95% CI: 1.094, 1.380; p=0.001). Delayed solid food introduction (> 6 months) correlated with lower children's B12 levels (adjusted fold change 0.888; 95% CI: 0.809, 0.975; p=0.013). Hcy levels were lower in Black children (adjusted fold change 0.962; 95% CI: 0.932, 0.993; p=0.018), higher in children with maternal Hcy levels in Q4 (adjusted fold change 1.081; 95% CI: 1.03, 1.135; p=0.002) and in children aged 3-8 years (adjusted fold change 1.084; 95% CI: 1.040, 1.131; p< 0.001). Conclusions: This study revealed wide variations in plasma folate, vitamin B12, and Hcy levels among low-income minority U.S. children and identified race, maternal levels, child's age, prematurity, and timing of solid food introduction as significant correlates.

Association of point-of-care testing for sST2 with clinical outcomes in patients hospitalized with heart failure.

AIMS: This study aimed to investigate the association of soluble suppression of tumorigenicity-2 (sST2) measured by point-of-care testing assay with clinical outcomes in patients hospitalized with heart failure after adjusting for other predictors including N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT). METHODS: A total of 1726 consecutive patients hospitalized with heart failure from July 2015 to December 2021 were enrolled. Baseline serum sST2 concentrations were measured by immunofluorescence assay. Primary endpoint event was the composite of all-cause death, heart transplantation, or left ventricular assist device. RESULTS: During the median follow-up duration of 682 days, 434 patients (25.1%) suffered from primary endpoint events. Baseline sST2 remained an independent predictor of the primary endpoint event in patients hospitalized with heart failure after adjusting for other predictors including NT-proBNP and hs-cTnT [per log (unit) increase, adjusted hazard ratio (HR) (95% confidence interval) (CI): 1.20 (1.09, 1.32), P < 0.001]. And baseline sST2 had a better prognostic value for patients with chronic decompensated heart failure [per log (unit) increase, adjusted HR (95% CI): 1.19 (1.07, 1.31)] than for those with acute new onset heart failure [per log (unit) increase, adjusted HR (95% CI): 1.28 (0.94, 1.75), P value for interaction <0.001], as well as a better prognostic value for patients with New York Heart Association (NYHA) functional class I-II [per log (unit) increase, adjusted HR (95% CI): 1.67 (1.11, 2.52)] than for those with NYHA functional class III-IV [per log (unit) increase, adjusted HR (95% CI): 1.18 (1.07, 1.31), P value for interaction <0.001]. Baseline sST2 was also a good predictor of the primary endpoint event in patients hospitalized with heart failure at 1 month, 3 months, 1 year and 2 years (area under the curve: 0.789, 0.775, 0.736 and 0.733, respectively), and the best cut-off values were 27.2 ng/ml, 27.1 ng/ml, 27.1 ng/ml and 25.1 ng/ml, respectively. Furthermore, baseline sST2 could provide additional prognostic value when added to baseline NT-proBNP and hs-cTnT (all P values <0.05). According to the category of elevated biomarkers (including NT-proBNP, hs-cTnT, and sST2), patients with three elevated biomarkers had a higher risk of the primary endpoint event compared with those with one or two elevated biomarkers (all P values <0.05). CONCLUSIONS: Baseline sST2 remained an independent predictor of adverse events after adjusting for other predictors including NT-proBNP and hs-cTnT, particularly in patients with chronic decompensated heart failure and NYHA functional class I-II. And in the basis of baseline NT-proBNP and hs-cTnT, adding baseline sST2 could provide additional prognostic value for patients hospitalized with heart failure.

A sustained decrease in the systolic/diastolic ratio may be a sign of severe adverse events in the umbilical cord: a report of eight cases.

A high systolic/diastolic (S/D) ratio of umbilical cord blood is a manifestation of intrauterine hypoxia. However, the clinical significance of a persistently decreased S/D ratio of umbilical cord blood has not been reported. We report eight cases of a persistently decreased S/D ratio of umbilical cord blood, with two cases of umbilical thrombus, five cases of excessive torsion, and one case of a true cord knot. Fetuses with a persistently decreased S/D ratio of umbilical cord blood may be at risk, and it may be an important indication of umbilical cord lesions.

Selection of Fermentation Supernatant from Probiotic Strains Exhibiting Intestinal Epithelial Barrier Protective Ability and Evaluation of Their Effects on Colitis Mouse and Weaned Piglet Models.

The intestinal epithelial barrier can prevent the invasion of pathogenic microorganisms and food antigens to maintain a consistent intestinal homeostasis. However, an imbalance in this barrier can result in various diseases, such as inflammatory bowel disease, malnutrition, and metabolic disease. Thus, the aim of this study was to select probiotic strains with epithelial barrier-enhancing ability in cell-based model and further investigate them for their improving effects on colitis mouse and weaned piglet models. The results showed that selected specific cell-free fermentation supernatants (CFSs) from Ligilactobacillus salivarius P1, Lactobacillus gasseri P12, and Limosilactobacillus reuteri G7 promoted intestinal epithelial cell growth and proliferation, strengthening the intestinal barrier in an intestinal epithelial cell line Caco-2 model. Further, the administration of CFSs of L. salivarius P1, L. gasseri P12, and L. reuteri G7 were found to ameliorate DSS-induced colitis in mice. Additionally, spray-dried powders of CFS from the three strains were examined in a weaned piglet model, only CFS powder of L. reuteri G7 could ameliorate the feed/gain ratio and serum levels of D-lactate and endotoxin. In conclusion, a new potential probiotic strain, L. reuteri G7, was selected and showed ameliorating effects in both colitis mouse and weaned piglet models.

Synergy of de-walled Ganoderma Lucidum spore powder (GLSP) on targeted therapy in advanced non-squamous non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutant: protocol for a randomized, double-blind, placebo-controlled study.

BACKGROUND: Osimertinib is regarded as a promising third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for advanced non-squamous non-small cell lung cancer (NSCLC) patients who developed T790M. However the adverse effects, primarily fatigue, remain an overwhelming deficiency of Osimertinib, hindering it from achieving adequate clinical efficacy for such NSCLC. Ganoderma lucidum has been used for thousands of years in China to combat fatigue, while Ganoderma Lucidum spores powder (GLSP) is the main active ingredient. The aim of this study is to investigate whether GLSP is sufficiently effective and safe in improving fatigue and synergizing with Osimertinib in non-squamous NSCLC patients with EGFR mutant. METHOD/DESIGN: A total of 140 participants will be randomly assigned to receive either de-walled GSLP or placebo for a duration of 56 days. The primary outcome measure is the fatigue score associated with EGFR-TKI adverse reactions at week 8, evaluated by the Chinese version of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer Patients (QLQ-C30). Secondary outcomes include evaluation of treatment effectiveness, assessment of quality of life (QoL), and exploration of immune indicators and gut microbiota relationships. Following enrollment, visits are scheduled biweekly until week 12. TRIAL REGISTRATION: China Clinical Trial Registry ChiCTR2300072786. Registrated on June 25, 2023.

Renal function modifies the association between hemoconcentration and outcomes in hospitalized heart failure patients.

Evidence-based management of decongestion is lacking in hospitalized heart failure (HHF) patients, especially in patients with impaired renal function. Hemoconcentration is an objective measure of decongestion that portends a favorable prognosis and guides management in HHF patients with preserved renal function. We aim to investigate whether it remains a prognosticator in patients with renal impairment, and to refine the identification of subpopulations who will benefit from hemoconcentration-guided therapy. HHF patients admitted to Heart Failure Center of Fuwai Hospital were consecutively included from December 2006 to June 2018. Patient characteristics were depicted. Relationships between in-hospital hemoconcentration, worsening renal function (WRF), and one-year all-cause mortality were investigated in the total population and compared between renal function groups using survival analysis and cubic splines, with a special focus on renal function-based interactions. The association was further validated in sensitivity analyses. Clinically relevant cut-offs and subpopulations were identified by subpopulation treatment effect pattern plots (STEPP) and subgroup analysis. 3661 participants (30.4% with impaired renal function) were included. Hemoconcentration, reflected by an in-hospital increase in hemoglobin, hematocrit, or a relative reduction in estimated plasma volume from baseline to discharge, was predictive of decreased one-year mortality in the total cohort despite its correlation with higher WRF incidence. The prognostic value of hemoconcentration differed in patients with impaired and preserved renal function. Hemoconcentration was related to a favorable prognosis in patients with preserved renal function (HR, 0.69; 95% CI, 0.53-0.90; P = 0.007), especially in young male patients with New York Heart Association functional class III-IV, reduced ejection fraction, and baseline eGFR > 75 mL/min/1.73m2. Contrarily, impaired renal function patients experienced a higher incidence of WRF, and hemoconcentration was no longer related to outcome (HR, 0.90; 95% CI, 0.64-1.26; P = 0.545), with findings consistent in all clinically relevant subgroups. In HHF patients, the prognostic value of hemoconcentration differs by renal function, and the clinical utility of hemoconcentration is contingent on preserved renal function.

Phenotypic and genotypic characterization of NPRL3-related epilepsy: Two case reports and literature review.

Nitrogen permease regulator-like 3 (NPRL3) has been reported to play a role in seizure onset. The principal manifestation of NPRL3-related epilepsy is a range of epilepsy-associated syndromes, such as familial focal epilepsy with variable foci (FFEVF), sleep-related hypermotor epilepsy (SHE), and temporal lobe epilepsy (TLE). The association between phenotype and genotype of NPRL3 mutations remains inadequately described. This study aimed to explore the phenotypic and genotypic spectra of NPRL3-related epilepsy. We reported two novel NPRL3 variants in two unrelated epilepsy cases, including a nonsense (c.1174C > T, p.Gln392*) and a missense variant (c.1322C > T, p.Thr441Met). Following a review of the literature, a total of 116 cases of NPRL3-related epilepsy were assessed, mostly with nonsense and frameshift mutations. Our findings suggest that patients harboring various NPRL3 variants exhibit variable clinical manifestations. In addition, it may be worthwhile to consider the existence of NPRL3 mutations in epilepsy patients with a family history. This study provides useful information for the treatment and prognosis by expanding the phenotypic and genotypic spectrum of NPRL3-related epilepsy. PLAIN LANGUAGE SUMMARY: This study expands the phenotypic and genotypic spectra of NPRL3-related epilepsy by reporting two cases with different novel variants. Following a review of the literature, it was observed that patients harboring various NPRL3 variants exhibited a variability of clinical manifestations. Also, patients carrying nonsense mutations are frequently prone to drug resistance and other severe comorbidities such as developmental delay, but more cases need to be collected to confirm these findings.

Factors associated with urinary retention after vaginal delivery under intraspinal anesthesia: a path analysis model.

INTRODUCTION AND HYPOTHESIS: Women who have intraspinal anesthesia for delivery are more likely to experience postpartum urinary retention (PUR), which, if not recognized and treated promptly, can result in long-term urinary dysfunction. Many factors influencing PUR have been proposed, but no study has been conducted to investigate the relationship between them. This study is aimed at determining the influencing factors of PUR and to explore the relationship between them. METHODS: A prospective, cross-sectional survey using self-made questionnaires was conducted among 372 puerperae in a Grade A hospital in Guangzhou, China, from April to September 2022. SPSS25.0 and AMOS24.0 were used for data analysis, and a path analysis model was established to determine the relationship between the influencing factors. RESULTS: The incidence of PUR was 49.85%. Residence, the level of postpartum pain, and the change of postnatal urination position had a direct effect on PUR. Episiotomy and analgesic duration have both direct and indirect effects on PUR. Forceps delivery, perineal edema and oxytocin had an indirect effect on PUR. Variables could influence the occurrence of PUR by mediating the analgesic duration, episiotomy, postpartum pain level, and postnatal urination position changes. CONCLUSIONS: This study provides an empirical model to illustrate the relationship between PUR and related factors in women who delivered under intraspinal anesthesia. In future management, more attention should be paid to women who live in cities, have higher levels of postpartum pain, longer analgesic duration, higher grade of perineal edema, and received episiotomy, forceps delivery, and oxytocin during labor.

Research on the Moisture Stability of Asphalt Mixtures with Three Solid Waste Fillers.

Widespread interest has been drawn to the use of solid waste fillers as a partial replacement for natural fillers in high-performance asphalt mixtures in recent years. However, variations in the material properties of solid waste fillers remain a problem for the recycling method. To address this issue, the limestone powder in asphalt mixtures was replaced with three solid waste fillers, including steel slag powder, tailings powder and calcium carbide slag powder in this study. The chemical composition of the fillers was first characterized to assess the homogeneity of the material. Then, a dense-graded asphalt mixture (AC) and a stone matrix asphalt (SMA) mixture were designed, produced and characterized for wet stability. The results show that the asphalt mixtures with solid waste fillers were superior to limestone powder (LP) asphalt mixtures in terms of resistance to water damage, and the steel slag powder showed the best improvement in moisture stability of the asphalt mixtures. The optimum substitution of solid waste filler for limestone filler was 25%. With the addition of anti-stripping agents, the moisture stability of the asphalt mixture with limestone filler was also greatly enhanced. On the contrary, a marginal enhancement was observed in the moisture stability of asphalt mixtures using solid waste fillers. Solid waste fillers can be used in asphalt mixtures and have a similar function as that of anti-stripping agents. In summary, the use of solid waste fillers to replace mineral fillers in asphalt mixtures is a reliable, value-added recycling option.

sST2 and Big ET-1 as Alternatives of Multi-Biomarkers Strategies for Prognosis Evaluation in Patients Hospitalized with Heart Failure.

Objective: To identify biomarkers with independent prognostic value and investigate the prognostic value of multiple biomarkers in combination in patients hospitalized with heart failure. Methods: A total of 884 consecutive patients hospitalized with heart failure from 2015 to 2017 were enrolled. Twelve biomarkers were measured on admission, and the relationships between biomarkers and outcomes were assessed. Results: During the median follow-up of 913 days, 291 patients (32.9%) suffered from primary endpoint events. Soluble suppression of tumorigenicity-2 (sST2) (per log [unit] increase, adjusted HR [95% CI]: 1.39 [1.13,1.72], P = 0.002) and big endothelin-1 (big ET-1) (per log [unit] increase, adjusted HR [95% CI]: 1.56 [1.23,1.97], P < 0.001) remained independent predictors of primary endpoint event after adjusting for other predictors including N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT). Both sST2 (C-statistic: 0.810 vs 0.801, P = 0.005, and 0.832 vs 0.826, P = 0.024, respectively) and big ET-1 (C-statistic: 0.829 vs 0.801, P = 0.001, and 0.843 vs 0.826, P < 0.001, respectively) significantly improved the predictive value for primary endpoint event at 1 year and 3 years. However, only big ET-1 (C-statistic: 0.852 vs 0.846, P = 0.014) significantly improved the predictive value at 3 months when added to clinical predictors and known biomarkers. According to the number of elevated biomarkers (including NT-proBNP, hs-cTnT, sST2, and big ET-1), patients with three or more elevated biomarkers had a higher risk of primary endpoint event compared to those with two elevated biomarkers (P = 0.001), as well as in patients with two elevated biomarkers compared to those with one elevated biomarker (P = 0.004). However, the risk of primary endpoint event was comparable between patients with one elevated biomarker and those with no elevated biomarker (P = 0.582). Conclusion: Multiple biomarkers in combination could provide a better prognostic value than a single biomarker. sST2 and big ET-1 could act as alternatives of multi-biomarkers strategies for prognosis evaluation beyond NT-proBNP and hs-cTnT in patients hospitalized with heart failure.

Clinical characteristics and outcomes of patients hospitalized with heart failure with preserved ejection fraction and low NT-proBNP levels.

The aim of this study was to investigate the clinical characteristics and prognosis of patients hospitalized with heart failure with preserved ejection fraction (HFpEF) and low N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Seven hundred ninety consecutive patients hospitalized with HFpEF from 2006 to 2017 were enrolled. Clinical characteristics and outcomes were compared between low NT-proBNP group (<300 ng/L) and elevated NT-proBNP group (≥300 ng/L). 108 HFpEF patients (13.7%) presented with low NT-proBNP levels. Age, body mass index, atrial fibrillation, New York Heart Association functional class, and albumin were independent predictors of low NT-proBNP levels in HFpEF patients. During the median follow-up duration of 1103 days, 11 patients (10.2%) in low NT-proBNP group suffered from primary endpoint event. Elevated NT-proBNP group had a higher risk of all-cause death or heart transplantation than low NT-proBNP group (adjusted HR [95%CI]: 2.36 [1.24,4.49], P = .009). Stratified analyses showed that the association between NT-proBNP (elevated NT-proBNP group vs low NT-proBNP group) and risk of all-cause death or heart transplantation was stronger in non-atrial fibrillation patients than in atrial fibrillation patients (P value for interaction = .025). Furthermore, the associations between NT-proBNP and risk of all-cause death or heart transplantation were stronger in younger and male patients than in older and female patients. However, both subgroups only reached borderline significant (P values for interaction = .062 and .084, respectively). Our findings suggest that low NT-proBNP levels were common in patients hospitalized with HFpEF. Patients with HFpEF and low NT-proBNP levels had a better prognosis than those with elevated NT-proBNP levels, particularly in younger, male, and non-atrial fibrillation patients.

Pregnancy Outcomes in Patients with Primary Sjögren's Syndrome Undergoing Assisted Reproductive Therapy: A Multi-center Retrospective Study.

INTRODUCTION: The aim of this work was to investigate the pregnancy outcomes in infertile patients with primary Sjögren's syndrome (pSS) undergoing assisted reproductive therapy (ART). METHODS: A multi-center retrospective study was performed in pregnant women with pSS and ART from five tertiary hospitals from Guangdong Province from 2013 to 2022. Natural planned pregnancy in pSS and healthy people undergoing ART were selected as controls. Pregnancy outcomes were collected from medical records and compared among groups. RESULTS: Twenty-four pregnancies in pSS with ART, 70 natural planned pregnancies in pSS, and 96 pregnancies in healthy people with ART were analyzed. More than half of the pSS mothers undergoing ART have a past history of adverse pregnancy and spontaneous abortion was the most common (10/24, 41.7%). Primary infertility (25.0%) and recurrent spontaneous abortion (16.7%) were the leading causes of infertility in pSS. The major maternal adverse pregnancy outcome (APO) in pSS patients with ART was premature delivery (11/24, 45.8%), likely attributed to twin gestation (4/11, 36.4%) and fetal distress (3/11, 27.3%). Twenty-seven live infants were born from 22 successful deliveries. The live birth rate was 93.1% (27/29). The average delivery time was 36.1 ± 3.3 weeks of gestation. The average birthweight was 2434.4 ± 722.1 g, compared with 2844.9 g in natural planned pregnancy in pSS, and 3072.1 g from healthy mothers with ART (P < 0.001). Seven (25.9%) low-birthweight (LBW) infants were born, and the incidence was comparable to the other two groups (22.2% in natural pregnancy, 13.0% in healthy people, P = 0.09). No infants developed congenital heart block (CHB). CONCLUSIONS: ART is an effective method for infertility in patients with pSS. Premature delivery is the leading maternal APOs. The incidence of fetal APOs does not increase, while birthweight is lower in offspring from pSS mothers with ART.

Tumor cell-induced platelet aggregation accelerates hematogenous metastasis of malignant melanoma by triggering macrophage recruitment.

BACKGROUND: Tumor cell-induced platelet aggregation (TCIPA) is not only a recognized mechanism for paraneoplastic thrombocytosis but also a potential breakthrough alternative for a low response to immune checkpoint inhibitors (ICIs) in hematogenous metastasis of malignant melanoma (MM). However, there is no TCIPA-specific model for further investigation of the relationship among TCIPA, the tumor immune microenvironment (TIME), and metastasis. METHODS: We developed a TCIPA metastatic melanoma model with advanced hematogenous metastasis and enhanced TCIPA characteristics. We also investigated the pathway for TCIPA in the TIME. RESULTS: We found that TCIPA triggers the recruitment of tumor-associated macrophages (TAMs) to lung metastases by secreting B16 cell-educated platelet-derived chemokines such as CCL2, SDF-1, and IL-1ß. Larger quantities of TAMs in the TCIPA model were polarized to the M2 type by B16 cell reprocessing, and their surface programmed cell death 1 ligand 1 (PD-L1) expression was upregulated, ultimately assisting B16 cells in escaping host immunity and accelerating MM hematogenous metastasis. CONCLUSIONS: TCIPA accelerates MM lung metastasis via tumor-educated platelets (TEPs), triggering TAM recruitment, promoting TAM polarization (M2), and remodeling the suppressive TIME in lung metastases.

Estimated plasma volume status adds prognostic value to hemodynamic parameters in advanced heart failure.

BACKGROUND: Estimated plasma volume status (ePVS) is a marker of intravascular congestion and has prognostic value in patients with heart failure (HF). The elevation of intracardiac filling pressures is defined as hemodynamic congestion and is also associated with poor prognosis. However, the relationship between intravascular congestion and hemodynamic congestion remains unclear. This study sought to explore the correlation between ePVS and hemodynamic parameters and determine the association between ePVS and clinical outcomes in patients with advanced HF. METHODS: Patients with advanced HF underwent right heart catheterization (RHC) for hemodynamic profiles. The sum of right atrial pressure (RAP) and pulmonary arterial wedge pressure (PAWP) > 30 mmHg was considered to present with hemodynamic congestion. Blood tests were conducted within 24 h of RHC. We calculated ePVS using the Strauss-derived Duarte formula. The primary outcome was all-cause mortality. RESULTS: A total of 195 patients were divided into two groups based on the cut-off value of ePVS (4.08 dL/g) calculated from receiver operating characteristic analysis. Patients with ePVS > 4.08 dL/g were more likely to present with wet rales (21.2% vs. 9.9%, P = 0.032) and had a higher risk of death (HR 4.748, 95% CI 2.385-9.453), regardless of whether RAP + PAWP was normal or elevated (all P < 0.05). Hemodynamic parameters and ePVS were not correlated (all P > 0.05). High ePVS significantly improved the predictive value beyond the clinical plus hemodynamic prognostic model (area under the curve of 0.844, Delong test, P = 0.024). CONCLUSION: ePVS could additionally add prognostic value to hemodynamic parameters in advanced heart failure, although not correlated with hemodynamic parameters.

Obesity Paradox in Heart Failure Revisited: Etiology as Effect Modifier.

The prognostic value of overweight/obesity in heart failure (HF) may vary according to HF etiologies. We aim to determine whether body mass index has differential impacts on survival among hospitalized HF patients with varying etiologies. Consecutive hospitalized HF patients between December 2006 and December 2017 were included. Multivariable analyses, including Cox proportional hazard models and restricted cubic splines, were used to investigate the impact of body mass index on mortality by HF etiology. Among the 3,836 patients included (mean age 57.1 years, 28.4% women), 1,475 (38.5%) were identified as having ischemic etiology. Of the remaining 2,361 patients with non-ischemic etiologies, dilated cardiomyopathy (DCM) accounted for 45.6% (n = 1,077). The rest of the patients were uniformly classified as having non-ischemic-non-DCM HF. The unadjusted data demonstrated an adiposity-related survival paradox in HF across all etiologies. However, the paradox holds only among non-ischemic-non-DCM HF patients after multivariate adjustment, wherein overweight patients exhibit the lowest mortality compared with their normal-weight counterparts (adjusted hazard ratio [aHR] 0.69, 95% confidence interval [CI] 0.52 to 0.91), with a nadir in mortality risk at 28.18 kg/m2. Similar survival benefits of overweight were not demonstrated in ischemic or DCM HF patients (ischemic etiology: aHR 1.07, 95% CI 0.84 to 1.36; DCM etiology: aHR 0.97, 95% CI 0.74 to 1.28). In conclusion, being overweight or obese does not confer better survival in HF patients of ischemic or DCM etiology, and the prognostic benefit of being overweight is maintained only in non-ischemic-non-DCM HF patients. Pathophysiologic interpretations are warranted, and whether patients of certain etiologies would benefit from weight reduction needs to be explored.

Improved Prognostic Performance of Right Atrial Pressure-Corrected Cardiac Power Output in Pulmonary Hypertension and Heart Failure with Preserved Ejection Fraction.

Cardiac power output (CPO) is a powerful predictor of adverse outcomes in heart failure (HF). However, the original formula of CPO included the difference between mean arterial pressure and right atrial pressure (RAP). The prognostic performance of RAP-corrected CPO (CPORAP) remains unknown in heart failure with preserved ejection fraction (HFpEF). We studied 101 HF patients with a left ventricular ejection fraction > 40% who had pulmonary hypertension due to left heart disease. CPORAP was significantly more discriminating than CPO in predicting outcomes (Delong test, P = 0.004). Twenty-five (24.8%) patients presented with dis-concordantly high CPORAP and low CPO when stratified by the identified CPORAP threshold of 0.547 W and the accepted CPO threshold of 0.803 W. These patients had the lowest RAP, and their cumulative incidence was comparable with those with concordantly high CPO and CPORAP (P = 0.313). CPORAP might identify patients with right ventricular involvement, thereby providing better prognostic performance than CPO in HFpEF.

Clinical Profile, Treatment, and Prognosis of Left Ventricular Thrombus in Dilated Cardiomyopathy.

Despite the emerging prevalence of left ventricular (LV) thrombus in dilated cardiomyopathy (DCM), clinical characteristics, management, and disease prognosis are poorly studied. We aim to assess the efficacy/safety profile of direct oral anticoagulants (DOACs) compared to warfarin by evaluating thrombus evolution, risk for stroke and systemic embolism (SSE), heart failure (HF) rehospitalization, all-cause mortality, and major adverse cardiovascular events (MACEs), and determine the impact of thrombus evolution on adverse events. We performed a historical cohort study of patients with a primary diagnosis of DCM and LV thrombus. Relationships between anticoagulants and thrombus resolution were analyzed with the Kaplan-Meier method and Cox regression. Associations between longitudinal thrombus evolution and adverse event hazard were measured with joint modeling. Among 122 patients included, 58.0% were prescribed warfarin, and 42.0% DOACs. Complete thrombus resolution at 90-day-after-index and 180-day-after-index was observed in 93 and 111 patients, with no difference in cumulative resolution between DOACs and warfarin. During a median follow-up of 12.5 months, MACE, all-cause death, SSE, and HF rehospitalization occurred in 42.6%, 27.9%, 4.1%, and 13.9% of patients, comparable in warfarin and DOACs groups. Thrombus persistence was associated with a higher risk of HF rehospitalization. Thrombus progression was associated with poor prognosis, with per unit increment in square-root-transformed thrombus-area resulting in a 1.0691-fold increase in MACE risk and a 1.0546-fold increase in death risk. This study suggests that in DCM patients with LV thrombus, DOACs were comparable to warfarin in thrombus resolution and safety profile. Thrombus persistence or progression was associated with an increased risk of HF rehospitalization, MACE, and mortality.

Afterload-related cardiac performance is a powerful hemodynamic predictor of mortality in patients with chronic heart failure.

Background: Afterload-related cardiac performance (ACP), a diagnostic parameter for septic cardiomyopathy, integrates both cardiac performance and vascular effects and could predict prognosis in septic shock. Objectives: We hypothesized that ACP would also correlate with clinical outcomes in patients with chronic heart failure (HF). Design: A retrospective study. Methods: We retrospectively studied consecutive patients with chronic HF who underwent right heart catheterization and established an expected cardiac output-systemic vascular resistance (CO-SVR) curve model in chronic HF for the first time. ACP was calculated as COmeasured/COpredicted × 100%. ACP > 80%, 60% < ACP ⩽ 80%, and ACP ⩽ 60% represented less impaired, mildly impaired, and severely impaired cardiovascular function, respectively. The primary outcome was all-cause mortality, and the secondary outcome was event-free survival. Results: A total of 965 individual measurements from 290 eligible patients were used to establish the expected CO-SVR curve model (COpredicted = 53.468 × SVR -0.799). Patients with ACP ⩽ 60% had higher serum NT-proBNP levels (P < 0.001), lower left ventricular ejection fraction (P = 0.001), and required dopamine more frequently (P < 0.001). Complete follow-up data were available in 263 of 290 patients (90.7%). After multivariate adjustment, ACP remained associated with both primary outcome (hazard ratio (HR) 0.956, 95% confidence interval (CI) 0.927-0.987) and secondary outcome (HR 0.977, 95% CI 0.963-0.992). Patients with ACP ⩽ 60% had the worst prognosis (all P < 0.001). ACP was significantly more discriminating (area under the curve of 0.770) than other conventional hemodynamic parameters in predicting mortality (Delong test, all P < 0.05). Conclusion: ACP is a powerful independent hemodynamic predictor of mortality in patients with chronic HF. ACP and the novel CO-SVR two-dimensional graph could be useful in assessing cardiovascular function and making clinical decisions. Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02664818.