Upregulated N‐cadherin expression is associated with poor prognosis in epithelial‐derived solid tumours: A meta‐analysis

Background

N‐cadherin is an important molecular in epithelial‐mesenchymal transition (EMT) and has been reported to be associated with aggressive behaviours of tumours. However, prognostic value of N‐cadherin in solid malignancies remains controversially.

Materials and Methods

The Pubmed/MELINE and EMBASE databases were used for a comprehensive literature searching. Pooled risk ratio (RR) and hazard ratio (HR) with their corresponding 95% confidence intervals (CIs) were employed to quantify the prognostic role.

Results

Involving 36 studies with 5705 patients were performed to investigate relationships between N‐cadherin upregulation and clinicopathological features, survival. Results suggested upregulated N‐cadherin was associated with lymph node metastasis (RR = 1.16, 95% CI [1.00, 1.35]), higher histological grade (RR = 1.36, 95%CI [1.14, 1.62]), angiolymphatic invasion (RR = 1.19, 95% CI [1.06, 1.34]) and advanced clinical stage (RR = 1.32, 95% CI [1.06, 1.64]), while upregulated N‐cadherin was apt to be associated with distant metastasis (RR = 1.43, 95% CI [0.99, 2.05]). Moreover, N‐cadherin was correlated with poor prognosis of 3‐year survival (HR = 1.78, 95% CI [1.51, 2.10]), 5‐year survival (HR = 1.57, 95% CI [1.17, 2.10]) and overall survival (OS) (HR = 1.32, 95% CI [1.20, 1.44]). Subgroup analyses according to cancer types were also conducted for applying these conclusions to some tumours more properly. No publication bias was found except subgroup analysis of distant metastasis (P = .652 for Begg's test and 0.023 for Egger's test).

Conclusions

Taken together, upregulation of N‐cadherin is associated with more aggressive behaviours of epithelial‐derived solid malignancies and can be regarded as a predictor of poor survival.     

The Brighton musculoskeletal Patient‐Reported Outcome Measure (BmPROM): An assessment of validity,reliability, and responsiveness

Background

In response for the need of a freely available, stand‐alone, validated outcome measure for use within musculoskeletal (MSK) physiotherapy practice, sensitive enough to measure clinical effectiveness, we developed an MSK patient reported outcome measure.

Objectives

This study examined the validity and reliability of the newly developed Brighton musculoskeletal Patient‐Reported Outcome Measure (BmPROM) within physiotherapy outpatient settings.

Methods

Two hundred twenty‐four patients attending physiotherapy outpatient departments in South East England with an MSK condition participated in this study. The BmPROM was assessed for user friendliness (rated feedback, N = 224), reliability (internal consistency and test–retest reliability, n = 42), validity (internal and external construct validity, N = 224), and responsiveness (internal, n = 25).

Results

Exploratory factor analysis indicated that a two‐factor model provides a good fit to the data. Factors were representative of “Functionality” and “Wellbeing”. Correlations observed between the BmPROM and SF‐36 domains provided evidence of convergent validity. Reliability results indicated that both subscales were internally consistent with alphas above the acceptable limits for both “Functionality” (α = .85, 95% CI [.81, .88]) and ‘Wellbeing’ (α = .80, 95% CI [.75, .84]). Test–retest analyses (n = 42) demonstrated a high degree of reliability between “Functionality” (ICC = .84; 95% CI [.72, .91]) and “Wellbeing” scores (ICC = .84; 95% CI [.72, .91]). Further examination of test–retest reliability through the Bland–Altman analysis demonstrated that the difference between “Functionality” and “Wellbeing” test scores did not vary as a function of absolute test score. Large treatment effect sizes were found for both subscales (Functionality d = 1.10; Wellbeing 1.03).

Conclusion

The BmPROM is a reliable and valid outcome measure for use in evaluating physiotherapy treatment of MSK conditions.     

Circulating lncRNA IFNG‐AS1 expression correlates with increased disease risk,higher disease severity and elevated inflammation in patients with coronary artery disease

Background

This study aimed to investigate the associations of circulating long, non‐coding (lncRNA) IFNG‐AS1, lncRNA ANRIL and lncRNA ITSN1 relative expressions with disease risk, severity and inflammatory cytokines levels in coronary artery disease (CAD) patients.

Methods

One hundred and ninety‐one patients suspected of CAD who underwent coronary angiography were consecutively enrolled in this casecontrol study, and divided into CAD patients (N = 102) and controls (N = 89) according to coronary angiographic results. Blood samples of all participants were collected. Plasma lncRNA IFNG‐AS1, lncRNA ANRIL and lncRNA ITSN1 expressions were detected using quantitative polymerase chain reaction (qPCR). Serum tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐1β (IL‐1β), IL‐6, IL‐8, IL‐10, and IL‐17 were assessed using enzyme‐linked immunosorbent assay (ELISA). Gensini Score was used to evaluate the disease severity of CAD patients.

Results

LncRNA IFNG‐AS1 relative expression in CAD patients was upregulated compared with that in controls (P < .001), and the receiver operating characteristic (ROC) curve showed that the area under curve (AUC) of lncRNA‐IFNG‐AS1 for predicting the risk of CAD was 0.755 (95% CI: 0.688‐0.821). lncRNA IFNG‐AS1 relative expression was remarkably associated with Gensini Score (r = .259, P = .009). Additionally, lncRNA IFNG‐AS1 relative expression was positively associated with high‐sensitivity C‐reactive protein (hs‐CRP) (r = .283, P = .004), TNF‐α (r = .269, P = .006), and IL‐6 levels (r = .425, P < .001), while it was negatively correlated with IL‐10 level (r = −.263, P = .008). lncRNA ANRIL or lncRNA ITSN1 was not correlated with CA D risk, Gensini Score, hs‐CRP, ESR, TNF‐α, IL‐1β, IL‐6, IL‐8, IL‐10, or IL‐17 levels (all P > .05).

Conclusion

Circulating lncRNA IFNG‐AS1 expression correlates with increased disease risk, higher disease severity and elevated inflammation in CAD patients.

     

Contribution of adiponectin polymorphisms to the risk of coronary artery disease in a North‐African Tunisian population

Background

Adiponectin, an adipocyte‐derived protein, is known to play a key role in the processes leading to atherosclerosis and coronary artery disease (CAD) through its anti‐atherogenic, anti‐inflammatory, antioxidative, and anti‐apoptotic properties. In the current study, we have studied the association of two single nucleotide polymorphisms (SNPs) +45 T>G (rs2241766) and +276 G>T (rs1501299) of the adiponectin gene with coronary artery disease (CAD) on an Arab/North‐African population from Tunisia.

Methods

Subjects comprised 277 patients with angiographically demonstrated CAD and 269 age‐ and gender‐matched control subjects. The adiponectin genotypes were performed by polymerase chain reaction‐restriction fragment length polymorphism analysis (PCR‐RFLP). The contribution of adiponectin variants to CAD was analyzed by haplotype and regression analysis.

Results

Adiponectin +45T>G and +276G>T genotypic and allelic distributions did not show a significant difference between cases and controls. Similarly, no association with CAD was observed for the haplotype analysis. Assuming dominant model of transmission for both polymorphisms and after adjustment of a number of traditional risk factors for CAD, logistic regression analysis showed an association of SNP +45 T>G with increased risk of developing CAD [adjusted OR (95% CI) = 2.59 (1.17‐5.70); P = .01]. However, SNP + 276 G>T is associated with decreased risk of developing CAD [adjusted OR (95% CI) = 0.47 (0.22‐0.97); P = .04].

Conclusion

There is no allelic or genotypic association of +45 T>G and +276 G>T of the adiponectin gene with CAD in the Tunisian population.

     

A Large‐Scale Survey on Trauma,Burnout, and Posttraumatic Growth among Nurses during the COVID‐19 Pandemic

A large‐scale survey study was conducted to assess trauma, burnout, posttraumatic growth, and associated factors for nurses in the COVID‐19 pandemic. The Trauma Screening Questionnaire, Maslach Burnout Inventory, and Posttraumatic Growth Inventory‐Short Form were utilized. Factors associated with trauma, burnout, and posttraumatic growth were analysed using logistic and multiple regressions. In total, 12 596 completed the survey, and 52.3% worked in COVID‐19 designated hospitals. At the survey’s conclusion in April, 13.3% reported trauma (Trauma ≥ 6), there were moderate degrees of emotional exhaustion, and 4,949 (39.3%) experienced posttraumatic growth. Traumatic response and emotional exhaustion were greater among (i) women (odds ratio [OR]: 1.48, 95% CI 1.12–1.97 P = 0.006; emotional exhaustion OR: 1.30, 95% CI 1.09–1.54, P = 0.003), (ii) critical care units (OR: 1.20, 95% CI 1.06–1.35, P = 0.004; emotional exhaustion OR: 1.23, 95% CI 1.12–1.33, P < 0.001) (iii) COVID‐19 designated hospital (OR: 1.24, 95% CI 1.11–1.38; P < 0.001; emotional exhaustion OR: 1.26, 95% CI 1.17–1.36; P < 0.001) and (iv) COVID‐19‐related departments (OR: 1.16, 95% CI 1.04–1.29, P = 0.006, emotional exhaustion only). To date, this is the first large‐scale study to report the rates of trauma and burnout for nurses during the COVID‐19 pandemic. The study indicates that nurses who identified as women, working in ICUs, COVID‐19 designated hospitals, and departments involved with treating COVID‐19 patients had higher scores in mental health outcomes. Future research can focus on the factors the study has identified that could lead to more effective prevention and treatment strategies for adverse health outcomes and better use of resources to promote positive outcomes.     

The De Ritis ratio as prognostic biomarker of in‐hospital mortality in COVID‐19 patients

Increased concentrations of serum aspartate transaminase (AST) and alanine transaminase (ALT) are common in COVID‐19 patients. However, their capacity to predict mortality, particularly the AST/ALT ratio, commonly referred to as the De Ritis ratio, is unknown. We investigated the association between the De Ritis ratio on admission and in‐hospital mortality in 105 consecutive patients with coronavirus disease of 2019 (COVID‐19) admitted to three COVID‐19 referral centres in Sardinia, Italy. The De Ritis ratio was significantly lower in survivors than nonsurvivors (median: 1.25; IQR: 0.91‐1.64 vs 1.67; IQR: 1.38‐1.97, P = .002) whilst there were no significant between‐group differences in ALT and AST concentrations. In ROC curve analysis, the AUC value of the De Ritis ratio was 0.701 (95% CI 0.603‐0.787, P = .0006) with sensitivity and specificity of 74% and 70%, respectively. Kaplan‐Meier survival curves showed a significant association between the De Ritis ratio and mortality (logrank test P = .014). By contrast, no associations were observed between the ALT and AST concentrations and mortality (logrank test P = .83 and P = .62, respectively). In multivariate Cox regression analysis, the HR in patients with De Ritis ratios ≥1.63 (upper tertile of this parameter) remained significant after adjusting for age, gender, smoking status, cardiovascular disease, intensity of care, diabetes, respiratory diseases, malignancies and kidney disease (HR: 2.46, 95% CI 1.05‐5.73, P = .037). Therefore, the De Ritis ratio on admission was significantly associated with in‐hospital mortality in COVID‐19 patients. Larger studies are required to confirm the capacity of this parameter to independently predict mortality in this group.     

Predictors of Functional Recovery in Patients Admitted to Geriatric Postacute Rehabilitation

Objective

To examine characteristics associated with functional recovery in older patients undergoing postacute rehabilitation.

Design

Observational study.

Setting

Postacute rehabilitation facility.

Participants

Patients (N=2754) aged ≥65 years admitted over a 4-year period.

Interventions

Not applicable.

Main Outcome Measure

Functional status was assessed at admission and again at discharge. Functional recovery was defined as achieving at least 30% improvement on the Barthel Index score from admission compared with the maximum possible room for improvement.

Results

Patients who achieved functional recovery (70.3%) were younger and were more likely to be women, live alone, and be without any formal home care before admission, and they had fewer chronic diseases (all P<.01). They also had better cognitive status and a higher Barthel Index score both at admission (mean ± SD, 63.3±18.0 vs 59.6±24.7) and at discharge (mean ± SD, 86.8±10.4 vs 62.2±22.9) (all P<.001). In multivariate analysis, patients <75 years of age (adjusted odds ratio [OR]=1.51; 95% confidence interval [CI], 1.16–1.98; P=.003), women (adjusted OR=1.24; 95% CI, 1.01–1.52; P=.045), patients living alone (adjusted OR=1.61; 95% CI, 1.31–1.98; P<.001), and patients without in-home help prior to admission (adjusted OR=1.39; 95% CI, 1.15–1.69; P=.001) remained at increased odds of functional recovery. In addition, compared with those with moderate-to-severe cognitive impairment (Mini-Mental State Examination score <18), patients with mild-to-moderate impairment (Mini-Mental State Examination score 19–23) and those cognitively intact also had increased odds of functional recovery (adjusted OR=1.56; 95% CI, 1.13–2.15; P=.007; adjusted OR=2.21; 95% CI, 1.67–2.93; P<.001, respectively).

Conclusions

Apart from sociodemographic characteristics, cognition is the strongest factor that identifies older patients more likely to improve during postacute rehabilitation. Further study needs to determine how to best adapt rehabilitation processes to better meet the specific needs of this population and optimize their outcome.     

Pregabalin Vs. Opioids for the Treatment of Neuropathic Cancer Pain: A Prospective,Head‐to‐Head,Randomized, Open‐Label Study

Objectives

Neuropathic cancer pain (NCP) is a common manifestation of cancer and/or its treatment. Treatment following the WHO analgesic ladder provides relief for the majority of cancer pain patients; however, concern remains that opioids may be less efficacious for neuropathic pain (NP) compared with nociceptive pain, often necessitating the use of higher doses. Adjuvants, such as pregabalin, have shown to be efficacious for the treatment of NP, although data come mostly from noncancer studies. The comparative efficacy and safety of opioids versus adjuvants has not been studied for NCP. The aim of this study was to directly compare pregabalin versus a strong opioid for the treatment of NCP.

Methods

A total of 120 patients, diagnosed with “definite” NCP, were randomized into two groups and received increasing doses of either oral pregabalin or transdermal fentanyl for 28 days. VAS score, patient satisfaction, need for opioid rescue, and adverse events (AEs) were recorded.

Results

In the pregabalin group, a significantly higher proportion of patients achieved at least 30% reduction in VAS compared with the fentanyl group (73.3%, 95% CI: 60.3%–83.93 vs. 36.7%, 95% CI: 24.5%–50.1%, P < 0.0001, respectively), while the percentage mean change from baseline was also significantly different [46% (95% CI: 39.5%–52.8%) for pregabalin and 22% (95% CI: 14.9%–29.5%) for fentanyl (P < 0.0001)]. Patient‐reported satisfaction was more frequent with pregabalin, while AEs and treatment discontinuations were more frequent in the fentanyl group.

Discussion

Prompt use of a neuropathic pain‐specific adjuvant, such as pregabalin, in NCP may lead to better control of the neuropathic component, with opioid‐sparing effects.     

Evaluation of vitamin D receptor gene polymorphisms (Fok‐I and Bsm‐I) in T1DM Saudi children

Background

Vitamin D deficiency conferred strongest susceptibility to pathogenesis of type 1 diabetes mellitus (T1DM). Altered gene expression and function have strong effect on VDR gene polymorphism.

Objectives

We aimed to check for the association of two single nucleotide polymorphisms (SNPs) in VDR gene (Fok‐I and Bsm‐I) with T1DM in Saudi children.

Subjects and Methods

Cross‐sectional study included 100 T1DM Saudi children, plus 102 unrelated healthy subjects. PCR technique was used for detection of Fok‐I and Bsm‐I SNPs in VDR gene.

Results

Regarding the Fok‐I polymorphisms, T1DM cases showed a significant increased frequency of the heterozygous genotype (Ff) than controls (33% vs 21%, OR = 1.9, 95% CI = 1.006‐3.587, P = .04). In the meantime, they showed significantly lower frequency of the homozygous (ff) genotype (64% vs 79%, OR = 0.51, 95% CI = 0.28‐0.96, P = .03). Cases showed also a significantly lower frequency of the (f) allele than controls (80.5% vs 87.7%, OR = 0.57, 95% CI = 0.33‐0.995, P = .04). On the other hand, cases showed significantly higher frequency of the Bsm‐I homozygous (bb) and heterozygous (Bb) genotypes (25% vs 11.8%, P = .01, OR = 2.5, 95% CI = 1.18‐5.31) & (45% vs 27.5%, P = .0, OR = 2.1, 95 % CI = 1.20‐3.89, respectively). Cases showed also significantly higher frequency of (b) allele compared to control (47.5% vs 25.5%, P = .0, OR = 2.6, 95% CI = 1.74‐4.02). Haplotype analysis showed an increased risk with the fB and fb haplotypes.

Conclusion

This study emphasizes a positive association between SNPs (Fok‐I and Bsm‐I) and T1DM among Saudi children with increased risk with the Fok‐I F and Bsm‐I b alleles.

     

E‐selectin gene in essential hypertension: a case‐control study

Background

Hypertension is associated with endothelial cell dysfunction. E‐selectin, an endothelial cell adhesion molecule, is specific for endothelial cell activation. Polymorphism in E‐selectin gene has recently been identified among which Leu554Phe E‐selectin gene polymorphism is least investigated in essential hypertension. This study reports the association of E‐selectin gene Leu554Phe polymorphism and the expression of E‐selectin gene in patients with essential hypertension.

Materials and methods

We analysed the Leu554Phe polymorphism and expression of E‐selectin gene in 250 patients with essential hypertension and 250 normal healthy controls. Genotyping of Leu554Phe polymorphism was performed by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP), and the expression of E‐selectin gene at mRNA and protein levels were carried out by real‐time PCR and Western blot, respectively.

Results

A significant association of E‐selectin genotypes (CT + TT) with essential hypertension (P < .0001, Odds ratio = 2.2 [1.58‐3.24] at 95% CI) was observed. The expression of mRNA for E‐selectin gene in patients with essential hypertension was ~12‐fold higher as compared to control. We observed an elevated level of E‐selectin protein expression (up to 1.9 times) in patients as compared to controls.

Conclusions

A significant association of E‐selectin (Leu554Phe) gene and increased expression of E‐selectin gene at mRNA and protein levels in patients might be related to the genetic predisposition to develop essential hypertension.     

Effect of Manual Therapy,Motor Control Exercise,and Inspiratory Muscle Training on Maximum Inspiratory Pressure and Postural Measures in Moderate Smokers: A Randomized Controlled Trial

Objective

The aim of this study is to assess whether adding manual therapy to motor control exercises protocol with inspiratory muscle training (IMT) (combined intervention) resulted in a greater effect than IMT alone in enhancing maximum inspiratory pressure (MIP) in the short term.

Interleukin‐18 gene 105A/C genetic polymorphism is associated with the susceptibility of Kawasaki disease

Interleukin‐18 (IL‐18)‐656T/G, ‐607A/C, and ‐137C/G promoter polymorphisms had been reported associated with Kawasaki disease (KD). An IL‐18 genetic A/C polymorphism at coding position 105 (rs549908) has been linked with asthma, rheumatoid, and systemic lupus erythematosus. We tested a hypothesis that the IL‐18 105A/C genetic polymorphism confers KD susceptibility. Study participants were Taiwanese KD patients and a healthy control group. Our data indicated that the frequency of C allele was significantly higher in the patient group (13.9%) than in the control group (2.7%; P<0.0001, odds ratio [OR]=5.93; 95% confidence interval [CI]=2.57–13.73). Therefore, persons with the C allele may have higher risk of deve loping KD. In addition, compared with the haplotype frequencies between case and control groups, the KD patients with TACC haplotype appeared to be a significant “at‐risk” haplotype compared with other haplotypes (OR: 4.62, 95% CI: 1.71–12.43; P=0.001). KD patient with the TAGA haplotype appeared to be a significant “protective” haplotype compared with other haplotypes (OR: 0.51, 95% CI:0.29–0.89; P=0.017). Our results suggest that 105A/C polymorphism and the haplotypes in IL‐18 gene are associated with the risk of KD in Taiwanese population. Clin. Lab. Anal. 23:71–76, 2009. © 2009 Wiley‐Liss, Inc.     

Plasma CXCL1 levels and TRAF3IP2 variants in patients with myocardial infarction

Background

IL‐17A plays an important role in inflammatory responses in myocardial infarction (MI). IL‐17A signals through its receptor, for which, Act1 (TRAF3IP2) functions as a key upstream adaptor in the pathway.

Aim

To compare frequencies of functional polymorphisms of TRAF3IP2 (rs13210247, rs33980500) between patients with MI and healthy controls.

Methods

The selected SNPs were studied in 201 Iranian MI patients and 201 healthy blood donors from Fars Province by PCR‐RFLP in association with clinicopathologic criteria of patients. CXCL1 plasma levels in 126 MI patients and 50 normal subjects were measured by ELISA.

Results

A significant increase in the mutant (T) allele of TRAF3IP2 rs33980500 in patients with diastolic dysfunction of the heart (P = .01) was observed. The highest correlation, however, was observed between the TRAF3IP2 rs33980500 TT genotype and T allele with left main coronary artery stenosis (P = .01, P < .001; OR = 31.03). T allele of TRAF3IP2 rs33980500 was also associated with female gender, family history of cardiovascular disease, and mechanical complications of heart (P = .04, P = .02, and P = .01, respectively). Moreover, TRAF3IP2 rs13210247 (G) correlated with mechanical complications of the heart (P = .01). A significant increase in the plasma levels of CXCL1 chemokine in patients (P = .0006) associated with TT genotype of TRAF3IP2 (rs33980500) was observed (P = .04).

Conclusion

The gene variants of Act1 adaptor are associated with correlates of poor outcome in patients with MI and plasma CXCL1 levels.

     

Variants at the promoter of the interleukin-6 gene are associated with severity and outcome of pneumococcal community-acquired pneumonia

Purpose

Conflicting results about the role of genetic variability at IL6, particularly the -174 G/C single nucleotide polymorphism (SNP), in sepsis have been reported. We studied the genetic variability at IL6 in patients with community-acquired pneumonia (CAP) and pneumococcal CAP (P-CAP).

Methods

This was a multicenter, prospective observational study. IL6 -174 was analyzed in 1,227 white Spanish patients with CAP (306 with P-CAP). IL6 1753 C/G (N?=?750), 2954 G/C (N?=?845), and haplotypes defined by these SNPs were also studied.

Results

In CAP patients the genotype -174 GG were associated with protection against acute respiratory distress syndrome (ARDS) (p?=?0.008, OR?=?0.4, 95% CI 0.2?C0.8). No other significant associations were observed. However, in patients with P-CAP multivariate analysis adjusted for age, gender, co-morbidity, hospital of origin, and severity (pneumonia severity index, PSI) showed that the IL6 -174 GG genotype was protective against the development of ARDS (p?=?0.002, OR?=?0.25, 95% CI 0.07?C0.79), septic shock (p?=?0.006, OR?=?0.46, 95% CI 0.18?C0.79), and multiple organ dysfunction syndrome (p?=?0.02, OR?=?0.53, 95% CI 0.27?C0.89). P-CAP patients homozygous for IL6 -174 G also showed a higher survival in a logistic regression analysis adjusted for age, gender, co-morbidity, hospital of origin, and PSI (p?=?0.048, OR?=?0.27, 95% CI 0.07?C0.98).

Conclusions

Our results indicate that the IL-6 -174 GG genotype is associated with lower severity and mortality in patients with P-CAP. This effect was higher than that observed in patients with CAP irrespective of the causal pathogen involved. Our results highlight the importance of the causal pathogen in genetic epidemiological studies in sepsis.     

Relative hyperlactatemia and hospital mortality in critically ill patients: a retrospective multi-centre study

Introduction

Higher lactate concentrations within the normal reference range (relative hyperlactatemia) are not considered clinically significant. We tested the hypothesis that relative hyperlactatemia is independently associated with an increased risk of hospital death.

Methods

This observational study examined a prospectively obtained intensive care database of 7,155 consecutive critically ill patients admitted to the Intensive Care Units (ICUs) of four Australian university hospitals. We assessed the relationship between ICU admission lactate, maximal lactate and time-weighted lactate levels and hospital outcome in all patients and also in those patients whose lactate concentrations (admission n = 3,964, maximal n = 2,511, and time-weighted n = 4,584) were under 2 mmol.L^-1 (i.e. relative hyperlactatemia).

Results

We obtained 172,723 lactate measurements. Higher admission and time-weightedlactate concentration within the reference range was independently associated with increased hospital mortality (admission odds ratio (OR) 2.1, 95% confidence interval (CI) 1.3 to 3.5, P = 0.01; time-weighted OR 3.7, 95% CI 1.9 to 7.00, P < 0.0001). This significant association was first detectable at lactate concentrations > 0.75 mmol.L^-1. Furthermore, in patients whose lactate ever exceeded 2 mmol.L^-1, higher time-weighted lactate remained strongly associated with higher hospital mortality (OR 4.8, 95% CI 1.8 to 12.4, P < 0.001).

Conclusions

In critically ill patients, relative hyperlactataemia is independently associated with increased hospital mortality. Blood lactate concentrations > 0.75 mmol.L^-1 can be used by clinicians to identify patients at higher risk of death. The current reference range for lactate in the critically ill may need to be re-assessed.     

High‐density lipoprotein from end‐stage renal disease patients exhibits superior cardioprotection and increase in sphingosine‐1‐phosphate

Background

Chronic kidney disease (CKD) exacerbates the risk of death due to cardiovascular disease (CVD). Modifications to blood lipid metabolism which manifest as increases in circulating triglycerides and reductions in high‐density lipoprotein (HDL) cholesterol are thought to contribute to increased risk. In CKD patients, higher HDL cholesterol levels were not associated with reduced mortality risk. Recent research has revealed numerous mechanisms by which HDL could favourably influence CVD risk. In this study, we compared plasma levels of sphingosine‐1‐phosphate (S1P), HDL‐associated S1P (HDL‐S1P) and HDL‐mediated protection against oxidative stress between CKD and control patients.

Methods

High‐density lipoprotein was individually isolated from 20 CKD patients and 20 controls. Plasma S1P, apolipoprotein M (apoM) concentrations, HDL‐S1P content and the capacity of HDL to protect cardiomyocytes against doxorubicin‐induced oxidative stress in vitro were measured.

Results

Chronic kidney disease patients showed a typical profile with significant reductions in plasma HDL cholesterol and albumin and an increase in triglycerides and pro‐inflammatory cytokines (TNF‐alpha and IL‐6). Unexpectedly, HDL‐S1P content (P = .001) and HDL cardioprotective capacity (P = .034) were increased significantly in CKD patients. Linear regression analysis of which factors could influence HDL‐S1P content showed an independent, negative and positive association with plasma albumin and apoM levels, respectively.

Discussion

The novel and unexpected observation in this study is that uremic HDL is more effective than control HDL for protecting cardiomyocytes against oxidative stress. It is explained by its higher S1P content which we previously demonstrated to be the determinant of HDL‐mediated cardioprotective capacity. Interestingly, lower concentrations of albumin in CKD are associated with higher HDL‐S1P.     

Rapid on‐site evaluation of routine biochemical parameters to predict right ventricular dysfunction in and the prognosis of patients with acute pulmonary embolism upon admission to the emergency room

Introduction

Patients with acute pulmonary embolism(APE)who present with right ventricular dysfunction (RVD) have a worse prognosis. This study aimed to evaluate the value of routine biochemical parameters in predicting RVD and 30‐day mortality in patients with APE.

Methods

We retrospectively collected the clinical data for 154 enrolled patients, including the neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), D‐dimer, cardiac troponin I (cTnI), and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP). We analyzed the correlation between RVD and the parameters and conducted a receiver operating characteristic (ROC) curve to confirm the cut‐off values for predicting RVD and 30‐day mortality. Formulas were built with relevant parameters to predict RVD and 30‐day mortality.

Results

Age, NLR, PLR, D‐dimer, the ratio of cTnI (+), and NT‐proBNP (+) were significantly higher in RVD (+) patients. The ratio of cTnI (+) and NT‐proBNP (+) in 30‐day mortality (+) patients was significantly higher than that in 30‐day mortality (−) patients. According to the logistic regression analysis, NLR, cTnI (+), and NT‐proBNP (+) correlated with RVD. The formula for the RVD risk score is 0.072 × NLR+1.460 × NT‐proBNP (+)+2.113 × cTnI (+), and the area under the curve (AUC) = 0.890 (95% CI: 0.839‐0.941, P = .001). The formula for the 30‐day mortality risk score is 0.115 × NLR + 2.046 × NT‐proBNP (+) + 1.946 × cTnI (+) −0.016 × PLR, and the AUC = 0.903 (95% CI: 0.829‐0.976, P = .001).

Conclusions

The rapid on‐site evaluation of routine biochemical parameters, including NLR, cTnI, and NT‐proBNP levels, and the formula developed using these parameters are valuable for predicting RVD and 30‐day mortality in patients with APE.

     

Serum lipoprotein and RBC rigidity index to predict cerebral infarction in patients with carotid artery stenosis

Objective

This study aims to determine the risk factors and to predict the occurrence of cerebral infarction in patients with carotid artery stenosis.

Methods

Two hundred and one subjects with carotid artery stenosis were retrospectively selected from Jinshan Branch of Shanghai Sixth People's Hospital, 115 cases of which with cerebral infarction and 86 without it. Clinical tests were performed including coagulation indices, fasting glucose, serum lipid, and blood rheology. Logistic regression analyses were used to identify the risk factors. Regression model was established, and receiver operating characteristic (ROC) curve was applied to analyze its diagnostic value.

Results

Our data indicated that apolipoprotein AI (OR = 0.051, 95% CI: 0.009‐0.295), lipoprotein (a) (OR = 1.003, 95% CI: 1.001‐1.005), and RBC rigidity index (OR = 0.383, 95% CI: 0.209‐0.702) were independent risk factors. Area under the curve (AUC) of the regression model = 0.78, with the sensitivity of 73.9% (95% CI: 64.9%‐81.7%) and specificity of 69.2% (95% CI: 52.4%‐83.0%). Prediction probability was determined while logistic regression score >0.748 defaulted as high‐risk status. High‐risk ratios were 80% in progressive cerebral infarction and 72% in nonprogressive cerebral infarction (P > .05), respectively, while significant differences were found when both compared with controls (P < .001).

Conclusions

We show herein that the regression model based on apolipoprotein AI, lipoprotein (a), and RBC IR is a promising tool to predict the occurrence of cerebral infarction in patients with carotid artery stenosis. However, identification of novel diagnostic markers for progressive cerebral infarction is still necessary.