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Background: Non-Hodgkin lymphoma associated hemophagocytic lymphohistiocytosis (NHL-HLH) in adult secondary HLH (sHLH) is a common and universally highly lethal critical disorder. Hyponatraemia is the most common electrolyte disorder in the critical illness setting and acts as a negative prognostic factor. The aim of our study was to evaluate the prognostic role of hyponatraemia among patients with NHL-HLH. Methods: This retrospective study enrolled 153 newly diagnosed adult NHL-HLH patients, which were divided into 2 groups based on serum sodium concentration on admission, a hyponatraemia and a normonatraemia group. Univariate and multivariate Cox regression analysis were used to identify the prognostic factors associated with worse survival. The overall survival time of all the patients were compared using log rank tests. Restricted cubic splines were conducted to address the association between serum sodium concentration and the risk of mortality. Results: The results showed that 81 (52.9%) patients had hyponatraemia. After a median follow-up of 47 (range 14-180) days, there were 72 (88.9%) cumulative deaths in hyponatraemia group while 50 (69.4%) in normonatremia group. Univariate Cox regression analysis showed that hyponatraemia group demonstrated unfavourable overall survival (P = 0.002). After adjustment for confounders, multivariate analysis revealed that hyponatraemia was an independent prognostic factor for OS (Hazard ratio [HR]:1.51, 95% confidence interval [CI]: 1.03-2.20; P = 0.033). Restricted cubic spline confirmed a linear and positive association between serum sodium and the risk of mortality. Conclusions: Hyponatraemia is relatively frequent in NHL-HLH. As a readily available biomarker in clinical routine, it was a promising prognostic predictor for NHL-HLH.

The clinical features of patients with secondary hemophagocytic lymphohistiocytosis (sHLH) complicated with capillary leak syndrome (CLS) remain controversial. The data of 259 sHLH patients were retrospectively analyzed. The clinical manifestations, laboratory findings, treatment, and prognosis of the CLS-sHLH group and non-CLS-sHLH group were compared. The levels of fibrinogen, albumin, and serum calcium in the CLS-sHLH group were lower than in the non-CLS-sHLH group, and serum triglycerides in the CLS-sHLH group were higher than in the non-CLS-sHLH group (P 1.3 g/L (P 0.05). sHLH patients complicated with CLS had significantly worse prognosis than without CLS. Significant reduction in fibrinogen may be an independent prognostic factor for poor prognosis in sHLH patients complicated with CLS.

This study aimed to examine the association between low T3 syndrome and overall survival (OS) in patients with secondary hemophagocytic lymphohistiocytosis (sHLH). The study consisted of 111 consecutive patients hospitalized due to newly diagnosed sHLH with detailed thyroid hormone profiles on admission. Low T3 syndrome was found in 75.7% of the studied sHLH population. After a median follow-up of 83 (interquartile range 25-365) days, there were 60 (71.4%) cumulative deaths in the low T3 syndrome group and 13 (48.1%) in the euthyroid group. Survival analysis showed a lower survival probability for patients with low FT3 than for those with normal FT3 (median OS, 60 vs. 365 days

Background In adult patients with secondary hemophagocytic lymphohistiocytosis (sHLH), no valid immune biomarker has been available for predicting the prognosis of untreated sHLH patients. Methods Circulating plasma levels of fibrinogen (FIB) were measured at diagnosis in 293 cases of adult sHLH. We categorized FIB levels into tertiles. Multivariable Cox proportional hazards models were used to evaluate the relationship between FIB and survival. Restricted cubic spline models and two-piecewise Cox proportional hazards models were used to address the nonlinear association between FIB and mortality. Results During a median follow-up of 52 (interquartile ranges, 18–221) days, 208 deaths occurred, with 137 deaths in malignancy-associated hemophagocytic lymphohistiocytosis (MHLH) and 71 deaths in non-malignancy-associated hemophagocytic lymphohistiocytosis (non-MHLH). After multivariable adjustment, compared with the highest tertile of FIB, the hazard ratios (HRs) with 95% confidence intervals (CIs) of survival for tertile 2 and tertile 1 were 1.06 (0.90–1.24) and 0.84 (0.71–0.98), respectively. The restricted cubic spline curve displayed a nonlinear and inverse relationship between FIB and mortality. Furthermore, the threshold effect analysis demonstrated that the inflection point for the curve was at an FIB level of 1.76 g/L. The HRs (95% CIs) for survival were 0.68 (0.55–0.83) and 1.08 (0.96–1.21) on the left and right side of the inflection point, respectively. Conclusions These results suggest that plasma fibrinogen is nonlinearly and inversely associated with the risk of mortality in adult secondary hemophagocytic lymphohistiocytosis.

Background: Catheter ablation for atrial fibrillation (AF) has been gaining popularity; however, the trend of inflammatory response markers in patients treated with different catheter ablation strategies over time and their predictability of AF recurrence remain unknown. Methods: A total of 210 patients with AF were enrolled and grouped according to surgical mode as follows: freeze group, RF group, and freeze3D group. The subjects were tested for related indexes before and after surgery. To determine AF recurrence during follow up, 24-h ambulatory electrocardiography was performed at two, three, six, and 12 months after surgery. Results: The inflammation indexes of the three groups peaked between one and three days after surgery but fell at different time points (P < .05). The recurrence rate of paroxysmal atrial fibrillation (PAF) was positively correlated with the increase in the percentage of white blood cells and neutrophils after surgery (P < .05). Conclusions: The postoperative inflammation indices peaked and fell at different time points after different catheter ablation methods. In addition, the recurrence rate of AF in patients treated with freeze3D is lower.

Circular RNAs (circRNAs) may be potential biomarkers or therapeutic targets of hemophagocytic syndrome (HPS) due to their high stability, covalently closed structure and implicated roles in gene regulation. The aim of the present study was to determine and characterize the circRNAs from natural killer (NK)/T-cell lymphoma-associated hemophagocytic syndrome (NK/T-LAHS). CircRNA in NK/T-LAHS and healthy control patient serum were assessed using next-generation sequencing (NGS). One hundred and forty-three differentially expressed circRNAs of which 114 were up-regulated and 29 were down-regulated in NK/T-LAHS patients were identified. Next, Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses to explore the roles of these circRNAs were utilized, and a microRNA (miRNA) target gene prediction software to predict the interaction of circRNAs and miRNAs was used. Moreover, five circRNAs were then selected as NK/T-LAHS candidate circRNAs which were related to tumors and contained NK/T-LAHS-related miRNA-binding sites. Using real-time PCR, the significant up-regulation of these five circRNAs in NK/T-LAHS patient serum were verified. Together these results show that circRNAs may serve as valuable diagnostic biomarkers of early NK/T-LAHS, with potential therapeutic targets in disease progression.

Purpose. Secondary hemophagocytic lymphohistiocytosis (sHLH) accompanied by liver involvement, characterized by hepatomegaly and increased liver enzymes, is usually associated with elevated mortality. However, the magnitude of these associations remains unknown. Our objective was to assess the associations of the aspartate transaminase/alanine transaminase (AST/ALT, De Ritis) ratio with overall survival among adult patients with sHLH. Methods. A retrospective analysis was performed on 289 patients aged 18–86 years with complete serum transaminase data at diagnosis of sHLH. Multivariate Cox regression analyses and restricted cubic splines were conducted to address the association between the De Ritis ratio and the risk of mortality. Results. The median De Ritis ratio for the entire study population was 1.34 (IQR: 0.84-2.29). After a median follow-up time of 60 (range 17-227.5) days, 205 deaths occurred. After fully adjusting for hepatomegaly, albumin, fibrinogen, EBV, ferritin, etiologies, and treatment strategies, the adjusted hazard ratios (HRs) with corresponding confidence intervals (CIs) of mortality for the 2 st tertile and 3 st tertile were 1.2 (0.8-1.7) and 1.6 (1.1-2.2), respectively ( P < 0.01 for trends). Restricted cubic spline confirmed a linear association between the log2-transformed De Ritis ratio and the risk of mortality. Moreover, this trend persisted in subgroups with MHLH, hyperferrinaemia, sCD 25 ≤ 20,000 ng / L , patients without EBV infection, and those received treatment. Conclusions. The De Ritis ratio is a strong and independent predictor for overall survival in patients with sHLH. As a readily available biomarker in routine clinical practice, it is used to identify patients with sHLH with inferior overall survival.

The frequency and duration of exposure to acrylamide (AA) from the environment and diet are associated with a range of adverse health effects. However, whether long-term AA exposure is related to diabetes mellitus (DM) remains unknown. Data from 3577 adults in the National Health and Nutrition Examination Survey (NHANES) 2005-2006 and 2013-2016 aged ≥ 20 years was analysed. The main analyses applied multivariate logistic regression and restricted cubic spline models to investigate the associations between DM and AA haemoglobin biomarkers, including haemoglobin adducts of acrylamide and glycidamide (HbAA and HbGA), the sum of HbAA and HbGA (HbAA + HbGA), and the ratio of HbGA to HbAA (HbGA/HbAA) levels. After multivariable adjustment, the odds ratios (95% confidence intervals) for DM comparing the highest with the lowest AA haemoglobin biomarker quartiles were 0.71 (0.55, 0.93), 0.92 (0.71, 1.18), 0.80 (0.62, 1.03) and 1.95 (1.51, 2.51) for HbAA, HbGA, HbAA + HbGA and HbGA/HbAA, respectively. The restricted cubic spline model demonstrated that HbAA was linearly and inversely associated with risk of DM (P for trend = 0.013), while HbGA/HbAA was nonlinearly and positively associated with the prevalence of DM (P for trend0.001). These results support for epidemiological evidence that the HbAA and HbGA/HbAA are significantly associated with DM. Further studies are warranted to infer the causal role of AA exposure in the prevalence of DM.

MDR1 (multidrug resistance 1) encodes an adenosine triphosphate (ATP)-dependent efflux transporter that plays a fundamental role in transportation of harmful compounds outside cells to maintain optimal health. The present study was aimed to investigate whether the MDR1 gene single nucleotide polymorphisms (SNPs) were associated with the prognosis of diffuse large B cell lymphoma (DLBCL). Three common SNPs, including C1236T, G2677T/A, and C3435T were focused on, and a total of 150 DLBCL patients from Jiangsu Han population were successively genotyped by polymerase chain reaction-allele-specific primers (PCR-ASP) method or DNA direct sequencing. At locus C1236T, patients carrying T allele (genotype CT and TT) had a prolonged overall survival (OS) when compared with patients with CC genotype (2-year OS 82.6 vs. 60.0 %, respectively; hazard ratio (HR) = 0.1, 95 % confidence interval (CI) 0.01-0.6, p = 0.016). At locus C3435T, complete remission/ complete remission unconfirmed (CR/CRu) rate in C allele group was significantly higher than T allele group (66.7 vs. 51.9 %, respectively; p = 0.009). The progression-free survival (PFS) curves of with T (genotype CT and TT) and without T (genotype CC) were significantly different (2-year PFS 46.4 % in with T group vs. 73.7 % in without T group, respectively; HR = 1.9, 95 % CI 1.0-3.6, p = 0.045). At locus G2677T/A, the age for genotypes AG and AT groups was significantly younger than the other genotypes (51.1 ± 12.6 vs. 57.7 ± 13.4 years, respectively; p = 0.033). In the haplotype analysis of loci 1236-3435, compared with T-C group, the C-T group displayed an inferior PFS rate (2-year PFS 23.0 vs. 50.6 %, respectively; HR = 7.8, 95 % CI 1.9-32.6, p = 0.005), while C-C and T-T groups showed an intermediate PFS rate. Our findings demonstrate that genotype CT + TT at locus C1236T, allele C, and genotype CC at locus C3435T might contribute to a relatively superior prognosis in DLBCL, as well as haplotype of T-C in loci 1236-3435. Besides, genotypes at locus G2677T/A might affect age at diagnosis, which has important prognostic value for DLBCL.

We investigated whether the MDR1 (multidrug resistance 1) gene single nucleotide polymorphism (SNP) and haplotype variants were associated with the susceptibility to diffuse large B-cell lymphoma (DLBCL). A total of 129 DLBCL patients and 208 healthy controls from Jiangsu Han population were enrolled in this study. They were genotyped by polymerase chain reaction-allele specific primers (PCR-ASP) method or DNA direct sequencing at three common loci: C1236T, G2677T/A and C3435T. At locus G2677T/A, allele G and genotype GT were significantly more common in DLBCL (G: OR=1.48, 95% CI: 1.08-2.02, Pc=0.03; GT: OR=1.96, 95% CI: 1.25-3.07, Pc0.01), while genotype AT in this locus seemed to be protective (OR=0.29, 95% CI: 0.02-0.72, Pc=0.03). TT genotype at locus C3435T showed a risk factor in DLBCL (OR=2.38, 95% CI: 1.52-3.74, Pc0.01). The frequency of T-G-T haplotype was significantly increased in DLBCL group (OR=5.21, 95% CI: 2.58-10.54, Pc0.01); haplotype of G-T in 2677-3435 and diplotype of 2677GT/3435TT were significantly more frequent in DLBCL group (G-T: OR=3.97, 95% CI: 2.31-6.85, Pc0.01; 2677GT/3435TT: OR=4.55, 95% CI: 2.02-10.22, Pc0.01). Our findings demonstrate that G, GT at locus G2677T/A, and TT at locus C3435T might contribute to the susceptibility to DLBCL, as well as haplotype of T-G-T, G-T in 2677-3435 and diplotype of 2677GT/3435TT, while AT at locus G2677T/A might be a protective genotype. These findings could provide evidence that the MDR1 SNPs may modify the susceptibility to DLBCL and shade new lights in disease association studies.

Background: The conversion of atrial fibrillation (AF) to sinus rhythm is associated with transient dysfunction of the left atrium (LA). This study aimed to investigate the time course of LA function and inflammation after radiofrequency (RF) ablation for paroxysmal AF. Methods: Fifty-three patients with paroxysmal AF undergoing RF ablation were recruited. White blood cells were counted and high-sensitivity C-reactive protein (hs-CRP), fibrinogen, and D-dimer levels were measured. LA emptying fraction, strain, and strain rate were evaluated before RF ablation and at 1, 2, 3, and 4 weeks and 2 and 3 months after ablation using conventional Doppler echocardiography and two-dimensional speckle-tracking echocardiography. Results: LA emptying fraction sharply decreased at day 7 after ablation and then slowly increased (p

Objective To illustrate the association of MDR1 (Multidrug Resistance 1) polymorphisms at loci 1236, 2677, 3435 and the prognosis of multiple myeloma (MM) in Jiangsu population. Methods A total of 129 MM patients were recruited from Jiangsu Province, China. The DNA was extracted from white blood cells (WBC) of peripheral blood and was amplified by polymerase chain reaction-allele specific primers (PCR-ASP). MDR1 polymorphisms at 3 loci were analyzed by electrophoresis followed by photograph or DNA direct sequencing. The association between the MDR1 and clinical outcomes were calculated by Graphpad and SPSS. Results MDR1 alleles at locus C1236T with T had significant lower calcium level in MM patients compared with C. The genotype CT had a significantly prolonged progress free survival (PFS) compared genotype CC at locus C1236T (median time: 48 months vs. 28 months, respectively; p = 0.0062; HR = 0.21; 95%CI0.061–0.715) while patients carrying T allele (CT and TT) at locus C3435T had a longer PFS than patients without T allele (CC) (median time: 60 months vs. 29 months, respectively; p = 0.038; HR = 0.508; 95%CI 0.264–0.978). And a borderline significance was found in haplotype at loci 2677-3435 and PFS. No significant findings were revealed between OS and MDR1 polymorphisms. Conclusion MDR1 polymorphisms could affect the prognosis of multiple myeloma whereas more samples and a longer follow-up are also needed.