BACKGROUND AND OBJECTIVE:Alpha-ketoglutarate (AKG), is a major intermediate metabolite of the tricarboxylic acid cycle, and is closely associated with cardiometabolic disease prognosis. Previous studies indicated that AKG is related to myocardial energy expenditure levels and reflects adverse short-term outcomes in heart failure (HF) patients. In this prospective cohort study, we examined the long-term prognostic value of AKG levels in acute HF (AHF) patients. METHODS:Plasma AKG levels were assessed in patients hospitalized with AHF. Hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality were calculated via multiple Cox regression. All-cause mortality was compared between patients with NT-proBNP < 1000 pg/ml and those with NT-proBNP ≥ 1000 pg/ml via subgroup analysis. RESULTS:Patients with AKG ≥ 9.83 μg/ml had higher heart rates and NT-proBNP and lower left ventricular ejection fraction (LVEF) and systolic blood pressure (SBP). After multiple adjustment, higher AKG was associated with an increased all-cause mortality risk (HR = 1.078, p < 0.001). Compared with AKG < 9.83 μg/ml, AKG ≥ 9.83 μg/ml nearly doubled (HR = 1.929, p < 0.001) and quadrupled (HR = 4.160, p < 0.001) the all-cause mortality risk in patients with NT-proBNP ≥ 1000 pg/ml and those with NT-proBNP < 1000 pg/ml, respectively. CONCLUSIONS AND RELEVANCE:Plasma AKG was independently associated with greater all-cause mortality risk in patients with AHF. Higher AKG levels retained prognostic value for patients with relatively low NT-proBNP.

Heart failure is a complex and multifaceted disease resulting from a range of causes, including ischemic heart disease, hypertension, valvular heart disease, and arrhythmia. The pathogenesis of heart failure involves neuroendocrine activation, dysregulated myocardial metabolism, inflammation, and endothelial cell injury. The prevention of heart failure centers on managing the underlying diseases, mitigating risk factors, and preventing complications. This review mainly addresses the etiology, risk factors, and preventive approaches related to this condition.

Objective The triglyceride-glucose index (TyG), a reliable marker of insulin resistance (IR), has an unclear association with symptomatic intracranial atherosclerotic stenosis in the posterior circulation (POC-sICAS). This study aimed to investigate the association between the TyG index, associated metabolites, and POC-sICAS. Methods A total of 106 patients with POC-sICAS and 81 with asymptomatic intracranial atherosclerotic stenosis of the posterior circulation (POC-aICAS) were retrospectively enrolled. The TyG index was calculated using the formula: ln [fasting triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2]. Logistic regression analysis evaluated the correlation between the TyG index and POC-sICAS. Differential metabolic markers were identified using liquid chromatography-tandem mass spectrometry. The predictive value of the TyG index and differential metabolites for POC-sICAS was assessed through receiver operating characteristic (ROC) curve analysis. Results Patients with POC-sICAS had a significantly higher TyG index than those with POC-aICAS (9.25 [interquartile range {IQR} 8.79-9.92] vs 8.87 [IQR 8.83-9.26]; P<0.001). The TyG index was an independent risk factor for POC-sICAS (adjusted odds ratio [OR]: 2.20, 95% confidence interval [CI]: 1.09-4.42, P=0.027), particularly in patients with diabetes mellitus (adjusted OR: 14.39, 95% CI: 2.37-87.36, P=0.004). The association was stronger in patients younger than 65 years with a high TyG index (≥8.99) (adjusted OR: 4.35, 95% CI: 1.12-16.94, P=0.034). The TyG index positively correlated with 90-day poor prognosis in those with POC-sICAS (R=0.4042, P=0003), especially in those with diabetes mellitus (R=6405, P<00001) and those younger than 65 years (R=0.4628, P=0002). Moreover, 11 differential metabolites were significantly related to the TyG index. The TyG index combined with pregnanediol showed significant discrimination between patients with POC-sICAS and POC-aICAS (area under the curve [AUC]=1, 95% CI 1.000-1.000; P<0.001). Conclusions The TyG index and pregnanediol could help identify patients with a high risk of ischemic stroke in POC-ICAS. Moreover, the TyG index was associated with a poor 90-day prognosis in patients with POC-sICAS.

Cancer of unknown primary(CUP)is a rare disease char-acterized by metastases in which the primary tumor is of unknown origin.The cerebrospinal fluid(CSF)tumor microenvironment of CUP is still unknown.A Chinese male was diagnosed with leptomeningeal metastases from CUP(CUP-LM)based on the following medical examination re-sults:partial leptomeningeal enhancement by brain mag-netic resonance imaging,few malignant cells of diverse morphology in CSF,and no abnormalities or lymphadenop-athy by systemic examination.

A total of 162 non-small cell lung cancer (NSCLC) patients were divided into discovery (N = 68) and validation (N = 94) groups. Nine Janus kinase/Signal transducer and activator of transcription (JAK/STAT) pathway-related single nucleotide polymorphisms were selected to explore the potential associations between genetic polymorphisms and adverse drug reactions (ADRs). The TT genotype of STAT6 rs324011 was significantly associated with severe ADRs in the recessive genetic model (TT vs. CC + CT, OR = 13.5, 95% CI = 2.12-86.09, p = 0.006 in the discovery group; OR = 8.41, 95% CI = 1.95-36.19, p = 0.004 in the validation group). The T allele was associated with a higher incidence of severe ADRs than was the C allele of rs324011 (OR = 3.67, 95% CI = 1.46-9.19, p = 0.006 in the discovery group; OR = 3.17, 95% CI = 1.44-6.99, p = 0.004 in the validation group). Patients with the CC genotype in STAT3 rs1053023 (and rs1053005) or the TT genotype of STAT6 rs324011 were likely to experience severe epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) related ADRs.

Objective: This study aimed to evaluate the real-world clinical efficacy and safety, economic burdens and medical resource utilization (MRU) of toripalimab treatment patterns compared with bevacizumab plus chemotherapy (BCP) for patients with advanced non-squamous NSCLC in China.Methods: Progression-free survival (PFS), adverse drug reactions (ADR) and the costs of drugs, laboratory testing, imageology examinations (including CT, B ultrasound, MRI), medical service, nursing, treatment, genetic test and medical disposable material were compared between two groups. A retrospective observational study was conducted with electronic medical records from Fudan University Huashan hospital. Data was obtained from established electronic medical records (EMRs) and patient surveys. Survival time from the study enrollment to disease progression or death plus from 1st progression disease (PD) in the maintenance phase to 2nd PD (PFS II), adverse events (AE), direct medical costs, MRU and AE-related costs were collected and compared between toripalimab group and BCP group. A total of 246 patients were enrolled.Results: Toripalimab combination therapy has significantly prolonged PFS comparing with BCP (13.8 months vs. 6.2 months, p < .001). A statistically significant improvement in PFS was observed favoring all toripalimab regimen subgroups compared with the bevacizumab group. Patients in toripalimab group occupied more overall resource consumption, more direct medical costs ($47,056.9 vs. $29,951.0, p < .0001) and AE-related costs ($4,500.2 vs. $784.4, p < .0001) than BCP group. Although patients in the toripalimab group used more drugs to prevent AEs ($4,500.2 vs. $784.4, p < .0001), they still experienced more AEs than patients in BCP group (51.4% vs. 41.4%).Conclusion: Toripalimab combination therapy could significantly prolonged PFS for patients with advanced non-squamous NSCLC compared with BCP, but at the expense of more MRU, costs and AEs.

We aimed to investigate the prognostic role of genetic variants of VEGF in advanced NSCLC patients treated with platinum-based chemotherapy. A total of 196 patients with advanced NSCLC treated with first-line platinum-based chemotherapy were enrolled. We evaluated the relationship between VEGF polymorphisms and efficacy outcomes and chemotherapy toxicity. We found that rs699947, rs833061 and rs1005230 were in full linkage disequilibrium. Patients with CC genotype of rs833061 had a significant longer PFS than TT genotype (CC vs TT, HR = 1.67, 95%CI = 1.01-2.76, P = 0.043). Patients harbouring CC genotype had longer PFS compared with CT genotype (P < 0.001). Moreover, CC genotypes conferred a significantly increased PFS compared to CT and TT genotype in dominant model (CC vs CT + TT, HR = 1.95, 95%CI = 1.23-3.10, P = 0.005). Patients carrying TT genotype of rs833061 had improved both ORR (HR = 0.54, 95%CI = 0.30-0.98, P = 0.041) and DCR (HR = 0.37, 95%CI = 0.20-0.66, P = 0.001) than non-TT patients. Furthermore, no association was found between any rs833061 alleles and adverse events (P = 0.425), but patients carrying rs1570360 AA genotype were more likely to experience grade 3-4 toxicities (P = 0.004) (GG vs AA, HR = 3.16, 95%CI = 1.26-7.94, P = 0.015). In conclusion, the variant homozygote CC of rs833061 exhibited a better prognosis based on association analysis. The present study provides reference for the future study of platinum-based chemotherapy response and toxicity.

Programmed death-ligand 1 (PD-L1) has been widely used in immunotherapy evaluation of patients with nonsmall cell lung cancer (NSCLC). However, the effect is not particularly ideal, and the association between PDL1 and genetic alterations requires more exploration. Here, we performed targeted next-generation sequencing and PD-L1 immunohistochemistry (IHC) testing for PD-L1 expression on both tumor cells (TCs) and tumor-infiltrating immune cells (ICs) in 1549 patients. Our studies showed that surgical method of resection was positively correlated with IC+, and a low tumor mutation burden (TMB) was negatively correlated with TC+. Furthermore, we found that EGFR was mutually exclusive with both ALK and STK11. In addition, the features between PD-L1 expression status and genomic alterations were characterized. These results suggest that clinical characteristics and molecular phenotypes are associated with PD-L1 expression signatures, which may provide novel insights for improving the efficiency of immune checkpoint inhibitors (ICIs) in immunotherapy.

Background:Driver gene-positive non-small cell lung cancer (NSCLC) patients are prone to develop leptomeningeal metastasis (LM), leading to an extremely high mortality. The objective of this study was to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) treatments for patients with NSCLC and LM harboring targetable mutations. Methods:We retrospectively collected records of patients with NSCLC harboring targetable mutations and prescribed ICIs following the diagnosis of LM at Huashan Hospital, Fudan University. In addition, we reviewed relevant literature and enrolled patients who met the inclusion criteria. Clinical characteristics were statistically analyzed, and the Kaplan-Meier method and log-rank test were employed to assess the median progression-free survival (mPFS) and median overall survival (mOS). Results:A total of 37 patients with NSCLC harboring targetable mutations who received ICIs after LM diagnosis were included. The median age of the enrolled patients was 54 years (range, 33-70 years), and 62.2% were female. Following ICI administration, the intracranial objective response rate (iORR) and intracranial disease control rate (iDCR) for all enrolled patients were 18.9% and 62.2%, respectively. The mPFS of all patients was 2.5 months [95% confidence interval (CI): 2.166-2.834 months] and the mOS was 5.8 months (95% CI: 5.087-6.513 months). Both univariate and multivariate analyses revealed a significant increase in mOS or individuals who had previously undergone cranial radiation therapy compared to those who had not. Furthermore, different histology molecular types were found to be potentially associated with survival time. Conclusions:Some patients with NSCLC harboring targetable gene mutations following LM diagnosis may benefit from ICI treatment with relatively good tolerance. However, further screening of the most suitable patient populations for ICIs is required.

BACKGROUND: Leptomeningeal metastasis (LM) is a severe complication in patients with non-small-cell lung cancer (NSCLC) and the optimal treatment strategy remains a challenge. This study aimed to investigate the treatment strategies and clinical outcomes in these patients.METHODS: We retrospectively reviewed the data of 44 patients with epidermal growth factor receptor (EGFR)-mutated NSCLC with LM between 2014 and 2020 at our institute. The patient characteristics, treatment ap-proaches, LM progression-free survival (LMPFS) and overall survival (OS) after the diagnosis of LM (OSLM) were analyzed. RESULTS: The median OSLM was 16.0 months and the 3 -year OS rate was 22.5%. The PFSLM in EGFR T790M-positive NSCLC patients with leptomeingeal disease was signifi-cantly improved by initiation of third-generation tyrosine kinase inhibitors (TKIs) compared with that of patients who were T790M negative (14.0 vs. 7.0 months; P = 0.030). A significantly higher LM disease control rate was shown in patients who received third-generation TKIs compared with previous generations of TKIs (90.1% vs. 60.0%; P = 0.024). Better Eastern Cooperative Oncology Group perfor-mance status, EGFR exon 19del, and clinical improvement of LM after therapy were independently associated with better OS.CONCLUSIONS: The survival of patients with NSCLC with LM has improved in the target therapy era. Our study provided real-world clinical evidence that patients with EGFR-mutated NSCLC who developed LM from previous TKIs can be benefit from third-generation EGFR-TKIs, especially for patients with EGFR T790M-positive.

INTRODUCTION:Patients whose solid tumors (ST) show leptomeningeal metastasis (LM) have very poor prognosis and short overall survival. The aim of this study was to evaluate the efficacy of first-line programed death-1(PD-1) monoclonal antibody (mAb) treatment in these patients.METHODS:We retrospectively evaluated patients diagnosed with LM from ST who were treated with first-line PD-1 mAb at our hospital between April 1 and November 30, 2019. We analyzed their clinicopathological characteristics and response to the treatment.RESULTS:We collected and analyzed data from 6 patients with different primary ST. 5 patients received PD-1 mAb combined with chemotherapy and/or anti-angiogenic drugs, while one received only PD-1 mAb. The median (range) number of treatment cycles was 5.5 (1-21). PD-1 mAb treatment did not cause neurotoxicity. The time period of first assessment varied from 21 to 65 days after treatment. Among 5 patients who got obvious symptoms relief, 4 patients persisted for > 3 months and even showed a reduction in the number of tumor cells in cerebrosprinal fluid. Ventriculoperitoneal (VP) shunt was used to treat hydrocephalus observed beneficial in 3 patients: 2 before and 1 after PD-1 mAb treatment. The median (range) follow-up time was 214 (57-460) days. 4 patients died. The overall survival ranged from 57 days to at least 460 days. 1 of the two alive patients continued to show no worsening of symptoms after 457 days.CONCLUSIONS:Patients with LM from ST can benefit from first-line PD-1 mAb combined treatment without additional neurotoxicity. Further research is required to validate the safety and efficacy.

目的:探讨心力衰竭(心衰)患者合并复杂室性心律失常(CVA)的相关因素. 方法:本研究为回顾性横断面研究.纳入 2019 年 1 月至 2022 年 8 月在南方医科大学南方医院心血管内科住院的303例心衰患者.收集心衰患者的临床资料、实验室检查、彩色多普勒超声心动图以及24小时动态心电图检查结果.CVA包括频发室性早搏(24 小时动态心电图监测中室性早搏比例>20％)、室性心动过速和心室颤动.根据 24 小时动态心电图检查结果将患者分为CVA组(n=167)和非CVA(NCVA)组(n=136).采用单因素及多因素Logistic回归分析心衰患者合并CVA的相关因素. 结果:单因素回归分析显示,左心室射血分数(LVEF)≤40％、左心室舒张末期内径(LVEDD)>55 mm、左心房内径(LAD)≥42 mm、心肌肌钙蛋白T(cTnT)>0.014 ng/ml、血K+≤3.5 mmol/L、男性、高血压、吸烟、饮酒和NYHA心功能分级Ⅳ级均与CVA风险增高相关(P均<0.05).校正混杂因素后,多因素Logistic回归分析显示,LVEDD>55 mm(OR=3.000,95％CI:1.680～5.358)、cTnT>0.014 ng/ml(OR=2.112,95％CI:1.141～3.907)、血K+≤3.5 mmol/L(OR=3.645,95％CI:1.663～7.990)、高血压(OR=1.841,95％CI:1.103～3.073)、饮酒(OR=1.931,95％CI:1.056～3.530)均与CVA风险增高相关(P均<0.05). 结论:LVEDD增大、cTnT升高、血K+水平降低、高血压和饮酒均与心衰患者CVA风险增高相关.

软脑膜转移是晚期非小细胞肺癌（non-small-cell-lung-cancer，NSCLC）患者的严重并发症之一。患者一旦发生脑膜转移，预后差，治疗策略存在巨大挑战。本研究旨在探讨合并脑膜转移的表皮生长因子受体（epidermal growth factor receptor，EGFR）突变NSCLC患者在靶向治疗时代的生存情况。肺癌脑膜转移预后差，未经治疗的脑膜转移癌生存期仅1~3个月，在靶向药物面世之前放化疗对其生存期的延长非常有限 ［1］。随着靶向治疗时代的来临，第1代EGFR-TKI改善了EGFR突变肺癌患者的预后 ［2］，而随着患者生存期延长，脑膜转移的发生也明显增加 ［3］。肺癌合并脑膜转移的患者是否也能从TKI中获益？第1代TKI哪种疗效更好？第1代TKI使用过程中发生的脑膜转移换用第3代TKI疗效如何？这篇来自复旦大学附属华山医院单中心真实世界的回顾性分析数据给到了这些问题的部分答案。脑膜转移后中位生存时间达16.0个月，3年总生存率达23%，远远超越了靶向治疗前时代，并且同既往的研究报道相符 ［4］；而第3代TKI疗效优于第1代TKI也与既往临床研究结论相符 ［5, 6］；第1代TKI耐药后发生的脑膜转移，如果耐药原因是T790M突变，换用第3代TKI可以有效改善脑膜转移症状 ［7］。

Context Diabetes has a bidirectional association with nonalcoholic fatty liver disease (NAFLD) and increases the risk of cirrhosis and related complications. Objective To investigate the association between visit-to-visit fasting glucose (FG) variability in early adulthood and NAFLD in middle age. Methods This prospective cohort study included 2467 Black and White adults aged 18 to 30 years at baseline (1985-1986) who were followed over 25 years in the Coronary Artery Risk Development in Young Adults Study. FG variability measures included coefficient of variation about the mean FG (CV-FG), the SD of FG (SD-FG), and the average real variability of FG (ARV-FG) across 25 years (year 0, 7, 10, 15, 20, and 25 examinations). NAFLD was defined as liver attenuation <= 40 Hounsfield units on computed tomography scan at year 25 examination after excluding other causes of hepatic steatosis. Results Of the 2467 participants, 241 (9.8%) had NAFLD at year 25. In multivariate analysis, the odds ratio for NAFLD was 2.80 (95% CI, 1.69-4.64; P trend < 0.001) for the fourth quartile vs first quartile of CV-FG after adjusting for confounding variables, including mean FG. Similar results were observed for SD-FG and ARV-FG. Conclusion Greater visit-to-visit FG variability in early adulthood was associated with higher risk of NAFLD in middle age independent of mean FG level. FG variability may help identify individuals at high risk for NAFLD.

目的:探讨抗程序性死亡受体配体1（PD-L1）单抗阿替利珠单抗联合抗血管生成药物及化疗治疗三阴性乳腺癌（TNBC）脑膜转移的效果。方法:回顾性分析复旦大学附属华山医院2020年11月收治的1例合并脑、脑膜转移TNBC患者的临床资料。治疗方案为阿替利珠单抗、贝伐珠单抗联合含铂双药化疗。按实体瘤疗效评价标准1.1以及患者中枢神经系统（CNS）症状的缓解情况及脑脊液细胞学评价临床疗效，并结合文献复习。结果:经过联合治疗，患者颅内病灶、CNS症状明显缓解，持续缓解时间达到7个月，超过了既往文献报道的TNBC脑膜转移患者的平均无进展生存时间，且未见明显不良反应。结论:对于合并脑、脑膜转移的TNBC患者，化疗基础上联合靶向PD-L1的免疫治疗及抗血管生成治疗有望改善患者的CNS症状，提高患者生命质量。

Objective To explore the association between dietary fiber and heart failure (HF). Methods Data were collected from the 2009–2018 National Health and Nutrition Examination Survey. Dietary fiber intake data were obtained from two 24-h dietary recall interviews. Logistic regression and restricted cubic spline models were used to explore the association of dietary intakes of total, cereal, fruit, and vegetable fiber with HF prevalence. Results A total of 21869 adults were included in this study. After adjusting for multiple confounding factors, the odds ratios (OR) and 95% confidence intervals (CI) for HF was 0.49 (0.28 to 0.87, P for trend = 0.016) for the highest tertile versus lowest tertile of total fiber intake. Similar results were observed for cereal but not fruit and vegetable fiber intake. Dose-response analysis indicated that dietary intake of total and cereal fiber were inversely associated with HF in a linear manner. Conclusion Intakes of total and cereal fiber were inversely associated with HF in adults.

目的 观察一线使用含纳武利尤单抗的方案联合治疗脑膜转移癌(meningeal carcinomatosis,MC)的临床效果.方法 收集2019年4月1日至10月1日在复旦大学附属华山医院肿瘤科经脑脊液(cerebrospinal fluid,CSF)细胞学确诊的4例MC患者,一线给予含纳武利尤单抗的联合治疗方案,总结CSF肿瘤负荷(tumor burden,TB)、软脑膜强化、脑积水和中枢神经系统(central nervous system,CNS)症状等临床特征,分析其与近期疗效和远期疗效的相关性.结果 原发灶包括2例多线靶向治疗后失败的肺癌、1例胆管细胞癌和1例原发灶不明.2例患者CSF TB低,2例CSF TB高且合并脑积水行CSF分流术挽救治疗.纳武利尤单抗联合化疗和/或抗血管生成药物治疗中位疗程5.5(5～33)个,截至2022年5月1日末次随访,4位患者中位随访610(153～947)天,1例无进展,2例仍存活,所有患者均未观察到CNS毒性.治疗后首次评估中位时间为46(37～65)天,4位患者CNS症状均缓解,3例CSF TB下降,CNS无进展生存期(progression free survival,PFS)分别为108天、134天和>944天;1例CSF TB无变化,PFS仅76天.CSF TB低相较于高的患者总生存期(overall survival,OS)更长(>947天和>944天vs.153天和275天).结论 一线含纳武利尤单抗联合治疗MC患者,CSF TB短期内下降可能预示CNS PFS更长,CSF TB低可能预示OS更长,其疗效值得进一步验证.

Exosomes are critical mediators of intercellular communication. Exosomal circular RNAs (circRNAs) have been reported to play critical roles in the development of chemoresistance in various tumors, including gastric cancer. However, the role of exosomal circ_0063526 in cisplatin (CDDP) resistance of gastric cancer is still unclear. The expression of circ_0063526, microRNA-449a (miR-449a) and serine hydroxymethyltransferase 2 (SHMT2) mRNA was determined by quantitative real-time PCR (qRT-PCR). Cell viability was assessed by the Cell Counting Kit-8 assay. Cell migration and invasion were evaluated by the transwell assay and wound healing assay. Western blot assay was used to measure the protein expression of light Chain 3 (LC3) I/II, p62 and SHMT2. Exosomes were detected using transmission electron microscopy. The size distribution of exosomes was analyzed by nanoparticle tracking analysis. The interaction between miR-449a and circ_0063526 or SHMT2 was confirmed by a dual-luciferase reporter and RNA pull-down assays. Circ_0063526 expression was increased in gastric cancer tissues and cells and CDDP-resistant cells. Extracellular circ_0063526 could be packaged into exosomes and transmitted to sensitive cells, thus disseminating CDDP resistance. Knockdown of exosomal circ_0063526 inhibited CDDP resistance via suppressing migration, invasion and autophagy in gastric cancer cells. Moreover, circ_0063526 was identified as a molecular sponge of miR-449a to upregulate SHMT2 expression. Further, exosomal circ_0063526 regulated SHMT2 expression to enhance CDDP resistance of gastric cancer cells. Additionally, high expression of exosomal circ_0063526 in serum was associated with poor response to CDDP treatment in gastric cancer patients. Exosomal circ_0063526 facilitated CDDP resistance in gastric cancer via regulating the miR-449a/SHMT2 axis.

Objective To evaluate the association between serum galectin-3 and all-cause death (ACD) and cardiovascular death (CVD) in patients with chronic heart failure (CHF). Methods The PubMed and Embase databases and Clinical Trials Registry (www.clinicaltrials.gov) were searched for studies with data on serum galectin-3 and ACD and CVD in CHF patients. The hazard ratios (HRs) of ACD and CVD were calculated and presented with 95% CIs. HRs were pooled using fixed effects or random effects models when appropriate. Sensitivity analysis, meta-regression and subgroup analysis were applied to find the origin of heterogeneity. Visual inspection of Begg's funnel plot and Egger's test were performed to assess the possibility publication bias. Results Pooled data included the results from 6,440 patients from 12 studies in the meta-analysis. Higher serum galectin-3 was associated with a higher risk of ACD (HR, 1.38; 95% CI, 1.14–1.67) and CVD (HR, 1.13; 95% CI, 1.02–1.25) in CHF patients. In the subgroup analyses, higher serum galectin-3 was associated with an increased risk of ACD in all subgroups. The pooled HR of the shorter follow-up group (1.78; 95% CI, 1.50–2.11) was significantly higher than the pooled HR of the longer follow-up group (1.15; 95% CI, 1.05–1.25). Sensitivity analysis of eliminating one study in each turn indicated that Koukoui et al.'s study had the largest influence on the risk of all-cause death. All-cause death publication bias was not detected (Pr>|z| = 0.35 for Begg's test and P>|t| = 0.15 for Egger's test). Conclusions Serum galectin-3 has prognostic value of both all-cause death and cardiovascular death in CHF. Serum galectin-3 could be useful for risk classification in patients with CHF. Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=193399.

Abstract Aims This study sought to investigate the association between blood pressure (BP) trajectories from early to middle adulthood and echocardiographic indices of structure and function in middle age. Methods and results This prospective cohort study included 4717 black and white adults aged 18–30 years at baseline (1985–86) who were followed over 30 years in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Trajectories of systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) from the Year 0 examination to Year 30 examination were identified using latent mixture modelling. Echocardiographic indices of myocardial structure, systolic function, and diastolic function were assessed at the Year 30 examination. Five distinct SBP trajectory groups were identified: low‐stable [1110 participants (23.5%)], moderate‐stable [2188 (46.4%)], high‐stable [850 (18.0%)], moderate‐increasing [416 (8.8%)], and high‐increasing [153 (3.2%)]. After adjustment for clinical variables, a significant decreasing trend was observed from the high‐increasing and moderate‐increasing groups through to the low‐stable group for left ventricular (LV) mass index [mean (SE): high‐increasing, 112.3 (3.4); moderate‐increasing, 99.3 (2.6); high‐stable, 88.9 (2.5); moderate‐stable, 86.1 (2.3); low‐stable, 82.1 (2.4), P trend < 0.01], as well as LV end‐diastolic dimension, left atrial volume index, and E/e′, while an increasing trend was apparent for LV longitudinal strain, E/A ratio, and average e′ velocities. Results were generally consistent for trajectories of DBP and PP. Conclusions Higher BP trajectories from early to middle adulthood were associated with worse indices of myocardial modelling and LV systolic and diastolic function at middle age.