Relationship between the magnitude of haemoglobin changes and long-term mortality in patients with sepsis: a retrospective cohort study.

BACKGROUND: Sepsis is a common and severe disease with a high mortality rate in intensive care unit (ICU). The hemoglobin (HGB) level is a key parameter for oxygen supply in sepsis. Although HGB is associated with the progression of inflammation in sepsis patients, its role as a marker following sepsis treatment remains unclear. Here, we studied the correlation between early temporal changes in HGB levels and long-term mortality rates in septic patients. METHOD: In this retrospective study of data on patients with sepsis from the Medical Information Mart for Intensive Care (MIMIC) IV database, the outcome was long-term mortality. Patients were divided based on the cut-off of the HGB percentage for receiver operating characteristic (ROC) curve calculation. Kaplan-Meier (KM) survival curves and Cox proportional hazards regression models were used to analyse the associations between groups and outcomes. Propensity score matching (PSM) was used to verify the results. RESULTS: In this study, 2042 patients with sepsis and changes in HGB levels at day 4 after admission compared to day 1 were enrolled and divided into two groups: group 1 (n = 1147) for those with reduction of HGB < 7% and group 2 (n = 895) for those with dropping ≥ 7%. The long-term survival chances of sepsis with less than a 7% reduction in the proportion of HGB at day four were significantly higher than those of patients in the group with a reduction of 7% or more. After adjusting for covariates in the Cox model, the hazard ratios (HRs) with 95% confidence intervals (CIs) for long-term all-cause mortality in the group with a reduction of 7% or more were as follows: 180 days [HR = 1.41, 95% CI (1.22 to 1.63), P < 0.001]; 360 days [HR = 1.37, 95% CI (1.21 to 1.56), P < 0.001]; 540 days [HR = 1.35, 95% CI (1.20 to 1.53), P < 0.001]; 720 days [HR = 1.45, 95% CI (1.29 to 1.64), P < 0.001]. Additionally, the long-term survival rates, using Kaplan-Meier analysis, for the group with a reduction of 7% or more were lower compared to the group with less than 7% reduction at 180 days (54.3% vs. 65.3%, P < 0.001), 360 days (42.3% vs. 50.9%, P < 0.001), 540 days (40.2% vs. 48.6%, P < 0.001), and 720 days (35.5% vs. 46.1%, P < 0.001). The same trend was obtained after using PSM. CONCLUSION: A ≥ 7% decrease in HGB levels on Day 4 after admission was associated with worse long-term prognosis in sepsis patients admitted to the ICU.

A nomogram for predicting the risk of heart failure with preserved ejection fraction.

BACKGROUND: This study purposed to design and establish a nomogram to predict the risk of having heart failure with preserved ejection fraction. METHOD: The clinical data of 1031 patients diagnosed with heart failure (HF) in the First Affiliated Hospital of Jinan University from January 2018 to December 2022 were retrospectively analyzed, among which 618 patients were diagnosed with heart failure with preserved ejection fraction (HFpEF). Patients were randomly divided into a training set (70%, n = 722) and a validation set (30%, n = 309). The prediction model of HFpEF was established by using clinical characteristic data parameters, and the risk of having HFpEF was predicted by using a nomogram. Single-factor analysis was used to select independent risk factors (P < 0.05), and then binary logistic regression was used to screen predictive variables (P < 0.05). The discrimination ability of the model was evaluated by the ROC curve and calculating the area under the curve (AUC). In addition, the predictive ability of the established nomogram was evaluated using calibration curves and the Hosmer-Lemeshow goodness of fit test (HL test), and the clinical net benefit was evaluated using decision curve analysis (DCA). RESULTS: The results of binary logistic regression analysis showed that age, gender, hypertension, coronary heart disease, glycosylated hemoglobin, serum creatinine, E/e' septal, relative wall thickness (RWT), left ventricular mass index (LVMI) and pulmonary hypertension (PH) were independent influencing factors for the risk of having HFpEF (P < 0.05). Based on the results of logistic regression analysis, a nomogram was established and calibration curves were made. The prediction model showed that the AUC of the training dataset was 0.876 (95%CI, 0.851-0.902), and 0.837 (95%CI, 0.791-0.883) in the validation set. According to the calibration curves and HL test, the nomogram shows good calibration, and DCA shows that our model is clinically useful. CONCLUSION: A nomogram prediction model was constructed to predict the patient's risk of having HFpEF. This prediction model indicated that the combination of creatinine, E/e', RWT, LVMI and PH may be valuable in the diagnosis of HFpEF.

Toxic vascular effects of polystyrene microplastic exposure.

Polystyrene microplastics (PSMPs) are some of the most common microplastic components, and the resulting pollution has become a global problem. Extensive studies have been conducted on the toxic effects of PSMPs on the heart, lungs, liver, kidneys, nerves, intestines and other tissues. However, the impact of PSMPs on vascular toxicity is poorly understood at present. The aim of this study was to reveal the vascular toxicity of microplastics (MPs). Patients were assigned to a calcification group (25 patients) or a non-calcification group (22 patients) based on the presence or absence of calcification in the thoracic aorta wall. We detected 7 polymer types in human feces. Patients with vascular calcification (VC) had higher levels of total MPs, polypropylene (PP) and polystyrene (PS) in feces than patients without VC. The thoracic aortic calcification score was significantly positively correlated with the total MP abundance (Spearman r = 0.8109, p < 0.0001), PP (Spearman r = 0.7211, p = 0.0160) and PS (Spearman r = 0.6523, p = 0.0471) in feces. We then explored the effects of PSMP exposure on normal and vitamin D3 + nicotine (VDN)-treated rats. PSMP exposure induced mild VC in normal rats and aggravated VC in VDN-treated rats. PSMP exposure disturbed the gut microbiota, causing Proteobacteria and Escherichia_Shigella to be the dominant phylum and genus, respectively. It also induced intestinal inflammatory responses in normal rats, aggravated intestinal inflammation in VDN-treated rats, impaired the intestinal mucosal barrier, and increased intestinal permeability. This study provides a theoretical basis for the risk assessment of MP-induced cardiovascular disease.

Beneficial effect of the short-chain fatty acid propionate on vascular calcification through intestinal microbiota remodelling.

BACKGROUND: Vascular calcification is a major cause of the high morbidity and mortality of cardiovascular diseases and is closely associated with the intestinal microbiota. Short-chain fatty acids (SCFAs) are derived from the intestinal microbiota and can also regulate intestinal microbiota homeostasis. However, it remains unclear whether exogenous supplementation with propionate, a SCFA, can ameliorate vascular calcification by regulating the intestinal microbiota. This study was conducted to explore the roles of propionate and the intestinal microbiota in the process of vascular calcification. METHODS: In total, 92 patients were enrolled consecutively as the observational cohort to analyse the relationship between SCFAs and vascular calcification in both blood and faecal samples. A rat model of vascular calcification was induced by vitamin D3 and nicotine (VDN) to validate the effect of propionate. Differences in the intestinal microbiota were analysed by 16S ribosomal RNA gene sequencing. Faecal microbiota transplantation and Akkermansia muciniphila transplantation experiments were performed to evaluate the functions of the intestinal microbiota. RESULTS: The results of the observational cohort study revealed that the levels of SCFAs (particularly propionate) in both blood and faecal samples independently correlated negatively with calcification scores (P < 0.01). To verify the activities of propionate, it was provided to VDN-treated rats, and oral or rectal propionate delivery reshaped the intestinal microbiota, resulted in elevated SCFA production, improved intestinal barrier function and alleviated inflammation, ultimately ameliorating vascular calcification. Furthermore, we demonstrated that transplantation of the propionate-modulated intestinal microbiota induced beneficial outcomes similar to those with oral or rectal propionate administration. Interestingly, linear discriminant analysis (LDA) effect size (LEfSe) revealed that oral or rectal propionate administration and propionate-modulated intestinal microbiota transplantation both enriched primarily Akkermansia. Subsequently, we demonstrated that Akkermansia supplementation could ameliorate VDN-induced vascular calcification in rats. CONCLUSIONS: Propionate can significantly ameliorate vascular calcification in VDN-treated rats, and this effect is mediated by intestinal microbiota remodelling. The findings in our study indicate that the intestinal tract-vessel axis is a promising target for alleviating vascular calcification. Video Abstract.

The effects of serum iron level without anemia on long-term prognosis of patients with coronary heart disease complicated with chronic heart failure: a retrospective cohort study.

The effects of serum iron level without anemia on long-term prognosis of patients with coronary heart disease (CHD) complicated with chronic heart failure (CHF) is still unclear. The objective of this study was to explore the effects of serum iron level without anemia on long-term prognosis of patients with CHD complicated with CHF. In this retrospective cohort study, 221 patients with CHD complicated with CHF were consecutively investigated. These patients were divided into three groups according to the tertiles of the serum iron level: low-iron group (n = 71), medium-iron group (n = 76) and high-iron group (n = 74). The overall serum iron without anemia was 13.0 ± 5.50 µmol/L and serum iron in each group was 7.58 ± 1.63 µmol/L, 11.94 ± 1.79 µmol/L, and 19.37 ± 3.81 µmol/L, respectively. Composite endpoint events were composed of major adverse cardiovascular and cerebrovascular events (MACCE), including recurrent heart failure, all-cause death, acute coronary syndrome (ACS) and ischemic stroke. The median follow-up duration was 239 days. After adjusting relevant confounding risk factors, we found that excessively low or high serum iron level is correlated to the MACCE in patients with CHD complicated with CHF and that the prognosis of patients with excessively high serum iron level is poorer than that of patients with excessively low serum iron level. We further revealed the effect of serum iron level on MACCE is U-shaped, but not linear relationship. Sensitivity analysis showed that the correlation between serum iron level and MACCE is stable. In addition, according to the test for interaction, the variables that modify the effect including CRP (P for interaction < 0.0001), diuretics (P for interaction = 0.0212) and antiplatelet drugs (P for interaction = 0.0167). This study showed that excessively low or high serum iron level without anemia is an independent risk factor of MACCE in patients with CHD complicating with CHF.

Regulated preparation of Crocin-1 or Crocin-2' Triggered by the Cosolvent DMSO Using Bs-GT/At-SuSy One-Pot Reaction.

Crocins are the primary coloring ingredients of saffron. The low-glycosylated members of this compound family, such as crocin-1 (crocetin mono-glucosyl ester) and crocin-2' (crocetin di-glucosyl ester), are rarely distributed in nature and attracting interest for their therapeutic uses. In the present study, a one-pot reaction system was used for efficient preparation of crocin-1 and crocin-2' with in situ regeneration of UDP-Glc by coupling Bs-GT with At-SuSy, a sucrose synthase from Arabidopsis thaliana. Noticeably, DMSO was used as a cosolvent and resulted in improvement of the solubility of the substrate crocetin and regulation of the selectivity of glycosylation. With periodic addition of crocetin, the biosynthesis of crocin-2' was performed with a high yield of 3.25 g/L in 2% DMSO aqueous solution, whereas crocin-1 (2.12 g/L) was selectively obtained in a 10% DMSO aqueous solution. The present study provided a simple approach for the biosynthesis of crocin-1 and crocin-2'.

High Level of Lipoprotein(a) as Predictor for Recurrent Heart Failure in Patients with Chronic Heart Failure: a Cohort Study / Nível Alto de Lipoproteína (a) como Preditor de Insuficiência Cardíaca Recorrente em Pacientes com Insuficiência Cardíaca Crônica: um Estudo de Coorte

Abstract Background: Elevated plasma levels of Lipoprotein(a) [Lp(a)] are recognized as a significant risk factor for atherosclerotic vascular disease. However, there are limited data regarding association between Lp(a) and recurrent heart failure (HF) in patients with chronic HF caused by coronary heart disease (CHD). Objective: Elevated levels of Lp(a) might have a prognostic impact on recurrent HF in patients with chronic HF caused by CHD. Methods: A total of 309 patients with chronic HF caused by CHD were consecutively enrolled in this study. The patients were divided into 2 groups according to whether Lp(a) levels were above or below the median level for the entire cohort (20.6 mg/dL): the high Lp(a) group (n = 155) and the low Lp(a) group (n = 154). A 2-sided p < 0.05 was statistically considered significant. Results: During the median follow-up period of 186 days, 31 cases out of a total of 309 patients (10.03%) could not be reached during follow-up. A Kaplan-Meier analysis demonstrated that patients with higher Lp(a) levels had a higher incidence of recurrent HF than those with lower Lp(a) levels (log-rank < 0.0001). A multivariate Cox regression analysis revealed that Lp(a) levels were independently correlated with the incidence of recurrent HF after adjustment of potential confounders (hazard ratio: 2.720, 95 % confidence interval: 1.730-4.277, p < 0.0001). Conclusions: In Chinese patients with chronic HF caused by CHD, elevated levels of Lp(a) are independently associated with recurrent HF.

Resumo Fundamento: Níveis plasmáticos elevados de lipoproteína (a) [Lp(a)] são reconhecidos como um fator de risco significativo para doença vascular aterosclerótica. No entanto, existem dados limitados sobre a associação entre a Lp(a) e insuficiência cardíaca (IC) recorrente em pacientes com IC crônica causada por doença arterial coronariana (DAC). Objetivo: Níveis elevados de Lp(a) podem ter um impacto prognóstico na IC recorrente em pacientes com IC crônica por DAC. Métodos: Um total de 309 pacientes com IC crônica causada por DAC foram consecutivamente incluídos neste estudo. Os pacientes foram divididos em 2 grupos de acordo com os níveis de Lp(a), acima ou abaixo do nível mediano de toda a coorte (20,6 mg/dL): o grupo Lp(a) alto (n = 155) e o grupo Lp ( a) baixo (n = 154). Um p < 0,05 bicaudal foi considerado estatisticamente significativo. Resultados: Durante a mediana do período de seguimento de 186 dias, 31 casos de um total de 309 pacientes (10,03%) não puderam ser contatados durante o acompanhamento. A análise de Kaplan-Meier demonstrou que pacientes com níveis mais elevados de Lp(a) apresentavam maior incidência de IC recorrente do que aqueles com níveis mais baixos de Lp(a) (log-rank < 0,0001). Uma análise de regressão multivariada de Cox revelou que os níveis de Lp(a) foram independentemente correlacionados com a incidência de IC recorrente após ajuste de potenciais fatores de confusão (hazard ratio 2,720, intervalo de confiança de 95%: 1,730-4,277, p < 0,0001). Conclusões: Em pacientes chineses com IC crônica causada por DAC, níveis elevados de Lp(a) estão associados de forma independente à IC recorrente.

High Level of Lipoprotein(a) as Predictor for Recurrent Heart Failure in Patients with Chronic Heart Failure: a Cohort Study.

BACKGROUND: Elevated plasma levels of Lipoprotein(a) [Lp(a)] are recognized as a significant risk factor for atherosclerotic vascular disease. However, there are limited data regarding association between Lp(a) and recurrent heart failure (HF) in patients with chronic HF caused by coronary heart disease (CHD). OBJECTIVE: Elevated levels of Lp(a) might have a prognostic impact on recurrent HF in patients with chronic HF caused by CHD. METHODS: A total of 309 patients with chronic HF caused by CHD were consecutively enrolled in this study. The patients were divided into 2 groups according to whether Lp(a) levels were above or below the median level for the entire cohort (20.6 mg/dL): the high Lp(a) group (n = 155) and the low Lp(a) group (n = 154). A 2-sided p < 0.05 was statistically considered significant. RESULTS: During the median follow-up period of 186 days, 31 cases out of a total of 309 patients (10.03%) could not be reached during follow-up. A Kaplan-Meier analysis demonstrated that patients with higher Lp(a) levels had a higher incidence of recurrent HF than those with lower Lp(a) levels (log-rank < 0.0001). A multivariate Cox regression analysis revealed that Lp(a) levels were independently correlated with the incidence of recurrent HF after adjustment of potential confounders (hazard ratio: 2.720, 95 % confidence interval: 1.730-4.277, p < 0.0001). CONCLUSIONS: In Chinese patients with chronic HF caused by CHD, elevated levels of Lp(a) are independently associated with recurrent HF.

Efficient Synthesis of Crocins from Crocetin by a Microbial Glycosyltransferase from Bacillus subtilis 168.

Crocins are the most important active ingredient found in Crocus sativus, a well-known "plant gold". The glycosyltransferase-catalyzed glycosylation of crocetin is the last step of biosynthesizing crocins and contributes to their structural diversity. Crocin biosynthesis is now hampered by the lack of efficient glycosyltransferases with activity toward crocetin. In this study, two microbial glycosyltransferases (Bs-GT and Bc-GTA) were successfully mined based on the comprehensive analysis of the PSPG motif and the N-terminal motif of the target plant-derived UGT75L6 and Cs-GT2. Bs-GT from Bacillus subtilis 168, an enzyme with a higher activity of glycosylation toward crocetin than that of Bc-GTA, was characterized. The efficient synthesis of crocins from crocetin catalyzed by microbial GT (Bs-GT) was first reported with a high molecular conversion rate of 81.9%, resulting in the production of 476.8 mg/L of crocins. The glycosylation of crocetin on its carboxyl groups by Bs-GT specifically produced crocin-5 and crocin-3, the important rare crocins.