Multiple Organ Dysfunction Syndrome Group Research Articles

Predictive Value of Lactate/Albumin Ratio for Death and Multiple Organ Dysfunction Syndrome in Patients with Sepsis

Introduction: Multiple organ dysfunction syndrome (MODS) is common after sepsis and increases mortality. Lactate (Lac) can assess the prognosis of patients. Albumin (Alb) is closely associated with inflammatory response in sepsis patients. This work evaluated the predictive value of Lac/Alb for prognosis of sepsis patients. Materials and Methods: data of 160 sepsis patients were retrospectively collected. Lac and Alb levels were measured upon admission, at 24 hours and 48 hours later. Using 0.45 as the cutoff value for Lac/Alb, patients were rolled into high-level (HL) and low-level (LL) groups. MODS rates and mortality rates were analyzed. Receiver operating characteristic (ROC) curves were utilized to evaluate the predictive value of 48-hour Lac/Alb for patient prognosis. Correlation between Lac/Alb and APACHE II and SOFA scores was assessed. Results: the 12-month follow-up revealed 52 deaths (32.5%), and MODS occurred in 49 cases (30.6%) on the 7th day. The MODS group possessed elevated Lac and Lac/Alb and decreased Alb to the N-MODS group (P<0.05), and similar results were observed by comparison the survival and death group (P<0.05). The sensitivity, specificity, and area under the ROC curve (AUC) of Lac/Alb in predicting MODS were 81.63%, 85.59%, and 0.89, respectively, while those in predicting death were 94.23%, 88.89%, and 0.91, respectively. Lac/Alb was positively correlated with APACHE II and SOFA scores (r=0.718 and 0.808, respectively). Conclusion: Lac/Alb was linked to MODS and mortality in sepsis patients and can be based to predict adverse outcomes.

Practical Effect of Cervical Softening Decoction Combined with Delivery Ball Approach in Promoting Vaginal Delivery in Primiparous Women

In Traditional Chinese Medicine, Cervical Softening Decoction is derived from a modified “Wan Bing Hui Chun” formulation and consists of natural herbal ingredients such as Angelica sinensis, Ligusticum chuanxiong, Leonurus heterophyllus, and Cortex Daphnes. The decoction regulates Qi, promotes blood circulation, and facilitates fetus descent. Genkwanin is an active compound in L. heterophyllus and previous studies identified this compound in ethanolic extracts from rat uterine smooth muscle cell membrane fractions. To further understand the pharmacological activities of Cervical Softening Decoction, we examined genkwanin effects on isolated rat uterine contractions and protein expression in rat tissue with postpartum hemorrhage complicated by multiple organ dysfunction syndrome (MODS). We also explored the practical effects of Cervical Softening Decoction combined with a birthing ball approach on promoting natural delivery in primiparous women. First, an isolated rat uterine smooth muscle contraction model was generated and three groups established: oxytocin group (0.002 U/mL), conventional genkwanin dose group (3 μg/mL), and high genkwanin dose group (6.0 μg/mL). Changes in uterine smooth muscle contraction and relaxation amplitudes were recorded before and after administration. Second, 50 rats were used to establish the following groups: (1) control group, (2) postpartum hemorrhage with MODS model group (MODS group), and (3) a postpartum hemorrhage with MODS treated with genkwanin group (genkwanin group). Western blotting was used to detect and compare tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 protein expression levels in lung tissue from groups. Finally, 84 primiparous women admitted to our hospital between January 2020 and December 2021 were selected and divided into two groups based on their obstetric interventions. The control group (n = 42) received routine obstetric intervention, while the observation group (n = 42) received Cervical Softening Decoction and delivery ball interventions. Delivery conditions were compared across groups. In basic studies, genkwanin doses significantly increased contraction and relaxation values in isolated rat uterine smooth muscle (P <0.05). Moreover, the genkwanin contractile effects at conventional and high doses were comparable with oxytocin. TNF-α and IL-6 protein expression in MODS group lung tissue was significantly higher when compared with the control group, while expression in the genkwanin group was significantly reduced when compared with the MODS group (P <0.05). In clinical studies, the observation group showed significantly higher natural delivery rates and Labor Agentry Scale (LAS) scores when compared with the control group. In contrast, cesarean section rates, first and second stage labor duration, total labor duration, and Facial Pain Scale (FPS) scores were significantly lower in the observation group when compared with the control group (P <0.05). In basic studies, genkwanin elicited significant contraction effects on isolated rat uterine smooth muscle and effectively inhibited inflammatory responses in rats with postpartum hemorrhage complicated by MODS. In clinical studies, combined Cervical Softening Decoction and delivery ball generated promising practical effects in promoting vaginal delivery in primiparous women. The intervention significantly increased the probability of a natural delivery, shortened labor duration, relieved maternal pain, and enhanced maternal control during delivery.

The predictive value of the systemic inflammatory response index for the occurrence of multiple organ dysfunction syndrome in patients with wasp sting injury

Wasp sting injuries pose a significant threat to public health, especially in areas with abundant trees. Mortality rates are alarmingly high, with reports indicating that up to 70% or more of cases result in multiple organ dysfunction syndrome (MODS). It is crucial for emergency and critical care physicians to promptly identify and implement effective measures to reduce the occurrence of MODS in patients who have been stung by wasps. Therefore, finding a reliable predictive indicator is of utmost importance. We conducted a retrospective study, and clinical data of 226 hospitalized patients with wasp sting from July 2013 to April 2023 in the First College of Clinical Medicine Science, China Three Gorges University were collected. The patients were divided into MODS group and non-MODS (NMODS) group, and the general data, clinical symptoms, laboratory indexes, and prognosis were compared between the two groups. The indicators with significant differences in univariate analysis were included in the multivariate Logistic regression analysis to analyze the independent risk factors for MODS. The value of systemic inflammatory response index (SIRI) in predicting the occurrence of MODS in wasp sting was analyzed by using the receiver operating characteristic curve (ROC curve). Of the 214 patients with wasp sting, 109 cases were in the NMODS group, and 105 cases were in the MODS group. The SIRI was 1.6 (0.7, 3.6) and 12.2 (5.2, 23.3) in the NMODS group and MODS group, respectively, with a significant difference between the two groups (P ＜ 0.001). SIRI was an independent risk factor for MODS in patients with wasp sting; the AUC of SIRI in predicting MODS in wasp sting was 0.886 (P ＜ 0.001), and the optimal cutoff value was 6.39, with a sensitivity of 71.43% and a specificity of 94.5%, which had prediction value. Allowing for early identification and enabling doctors to intervene and provide timely treatment. SIRI was defined as follows: SIRI = neutrophil count × monocyte count/lymphocyte count.

Neutrophil-to-lymphocyte ratio in relation to trauma severity as prognosis factors in patients with multiple injuries complicated by multiple organ dysfunction syndrome: A retrospective analysis.

This study aimed to explore potential risk factors for the occurrence of multiple organ dysfunction syndrome (MODS) in patients with multiple injuries by evaluating neutrophil-to-lymphocyte ratio (NLR)-associated trauma severity. This retrospective case-control study included 95 patients with multiple injuries, who were admitted to our hospital (between January 2018 and December 2020). Clinical data including gender, age, underlying disease, number of injury sites (NIS), injury severity score (ISS), hemoglobin level within 24 h of admission (HL-24h), neutrophil count (NC), white blood cell count, platelet count (PC), NLR, d-dimer level, activated partial thromboplastin time (APTT), complicated shock within 24 h of admission (CS-24h), length of stay, as well as prognostic outcome was systematically analyzed. According to MODS occurrence, patients were divided into a MODS group (n = 27) and a non-MODS group (n = 68). The risk factors affecting patients with multiple injuries complicated by MODS were identified using univariate and multivariate logistic regression analyses. Candidate risk factors were further analyzed using receiver operating characteristic (ROC) curves. Univariate analysis revealed a significant difference between the MODS and non-MODA groups in terms of NIS, ISS, HL-24h, PC, APTT, d-dimer level, CS-24h, NLR, NC, prognostic outcome, and other indicators (p < .05). Multivariate logistic regression analysis showed that d-dimer levels within 24 h of admission and ISS, NLR, and CS-24h were significantly associated with multiple injuries complicated by MODS. Compared with the non-MODS controls, the NLR in the MODS group showed a much higher level and tended to rise with the increase in ISS score, indicating a significant intergroup difference (p < .05). The ROC curve analysis results suggested that the NLR had good sensitivity and specificity for predicting the prognosis of patients with MODS with multiple injuries. d-dimer level, ISS, NLR, and CS-24h are important risk factors for MODS in patients with multiple injuries. Notably, NLR expression may be a good indicator of injury severity and predictor of the occurrence of MODS in patients with multiple injuries. Therefore, assessment of injury severity and coagulation function, active resuscitation, as well as prevention of infection should be emphasized during treatment of multiple injuries, to reduce and prevent the risk of MODS in patients with multiple injuries.

Value of vascular endothelial-cadherin in evaluating the severity of patients with sepsis

To explore the value of vascular endothelial-cadherin (VE-cad) in evaluating the severity of sepsis. A prospective study was conducted to select 85 patients with sepsis treated in the emergency ward of the First Affiliated Hospital of Wenzhou Medical University from June 1, 2015 to November 1, 2017. The gender, age, medical history, first infection site, number of affected organs, laboratory indexes, acute physiology and chronic health evaluation II (APACHE II), simplified acute physiology score II (SAPS II), sequential organ failure assessment (SOFA) and the total length of stay, emergency intensive care unit (EICU) length of stay, 28-day at admission and survival during hospitalization were measured, and the VE-cad level within 24 hours at admission was measured. The patients were divided into sepsis group and septic shock group according to the progress of the disease. The patients were divided into multiple organ dysfunction syndrome (MODS) group and non MODS group according to whether they were accompanied by MODS. The differences of the above indexes in patients with different disease progression, MODS and different prognosis were analyzed and compared. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the value of VE-cad in evaluating the severity of sepsis. A total of 85 patients were included, mainly respiratory tract infection. Among them, 38 cases were sepsis and 47 cases were septic shock, 39 cases had MODS, 46 cases had no MODS, 64 cases survived and 21 cases died within 28 days after admission. Compared with sepsis group, the number of affected organs in septic shock group was greater [3 (2, 4) vs. 1 (0, 2)], APACHE II score [13 (10, 21) vs. 7 (5, 12)], SAPS II score [35 (31, 55) vs. 7 (5, 12)], SOFA score [7.0 (5.0, 10.0) vs. 3.0 (0, 5.0)], blood lactic acid [Lac (mmol/L): 3.5 (2.4, 6.2) vs. 1.9 (1.2, 2.2)], C-reactive protein [CRP (mg/L): 90.0 (58.1, 90.0) vs. 50.5 (38.0,90.0)] and VE-cad levels [mg/L: 1.427 (1.141, 2.150) vs. 1.195 (0.901, 1.688)] were significantly increased, while platelet count [PLT (×109/L): 113.4±67.2 vs. 202.5±109.5] and hemoglobin (Hb) levels (g/L: 106.3±36.3 vs. 118.6±18.0) were significantly decreased (all P < 0.05). Compared with non MODS group, APACHE II score [14 (10, 22) vs. 8 (6, 13)], SAPS II score [36 (32, 56) vs. 29 (24, 35)], SOFA score (7.9±3.9 vs. 4.0±3.8), in-hospital mortality [53.8% (21/39) vs. 0% (0/46)], Lac [mmol/L: 3.1 (2.3, 6.3) vs. 2.1 (1.4, 4.6)] and VE-cad levels [mg/L: 1.427 (1.156, 1.937) vs. 1.195 (0.897, 1.776)] in MODS group were significantly higher, the length of stay in EICU was significantly longer [days: 6 (3, 12) vs. 3 (0, 7)], and the PLT level was significantly lower (×109/L: 118.2±80.0 vs. 182.5±104.0, all P < 0.05). Compared with the death group, the number of affected organs in the survival group was fewer [2 (1, 3) vs. 3 (1, 5)], APACHE II score [9 (6, 13) vs. 21 (13, 25)], SAPS II score [31 (25, 36) vs. 55 (35, 63)] and SOFA score (4.7±3.7 vs. 8.9±4.5) were significantly reduced, and the length of stay in EICU [days: 4 (1, 8) vs. 8 (3, 15)] was significantly shorter (all P < 0.05). ROC curve analysis showed that area under the ROC curve (AUC) of VE-cad, SOFA score and VE-cad combined with SOFA score in evaluating the severity of sepsis were 0.632 [95% confidence interval (95%CI) was 0.513-0.750], 0.830 (95%CI was 0.744-0.916) and 0.856 (95%CI was 0.779-0.933), respectively. When the cut-off value of VE-cad was 1.240 mg/L, the sensitivity was 68.1% and the specificity was 55.3%, the sensitivity of VE-cad combined with SOFA score was 85.1%, the specificity was 73.7%. VE-cad has a certain evaluation value for the severity of sepsis, and the evaluation value of VE-cad combined with SOFA score is better than that of VE-cad single index.

Association of Histones With Coagulofibrinolytic Responses and Organ Dysfunction in Adult Post-cardiac Arrest Syndrome.

BackgroundPatients successfully resuscitated from cardiac arrest often develop organ dysfunction caused by systemic inflammation and increased coagulation, leading to disseminated intravascular coagulation (DIC). The involvement of histones in DIC and organ dysfunction in patients with sepsis and trauma has been previously reported, raising the probability that histones may also be associated with pathophysiology in patients after cardiac arrest and resuscitation. This study evaluated the relationship between histones and organ dysfunction related to coagulofibrinolytic changes in patients with post-cardiac arrest syndrome (PCAS).MethodsThis prospective single-center observational study assessed 35 adult patients with PCAS who were divided into two groups, i.e., 15 patients with multiple organ dysfunction syndrome (MODS) and 20 patients without MODS. MODS was defined as a sequential organ failure assessment score of ≥12. The plasma levels of histones and coagulofibrinolytic markers, including soluble fibrin, tissue-type plasminogen activator, plasminogen activator inhibitor-1, plasmin-alpha 2-plasmin inhibitor complex (PIC), and soluble thrombomodulin, were measured in patients with PCAS immediately after admission to the emergency department, and 3 and 24 h after arriving at the hospital.ResultsPCAS patients with MODS had higher DIC scores [4 (3.0–5.0) vs. 1 (0.0–3.0), p = 0.012] and higher mortality rates (66.7% vs. 20.0%, p = 0.013) than those without MODS. Moreover, patients with MODS exhibited higher histone levels than those without MODS during the early phase of the post-resuscitation period. Severe endothelial injury and higher thrombin and plasmin generation were observed in the MODS group. Plasma levels of histones were positively correlated with those of soluble fibrin immediately after resuscitation (rho = 0.367, p = 0.030) and PIC 3 h after arriving at the hospital (rho = 0.480, p = 0.005). This correlation was prominent in the patient population with MODS (soluble fibrin: rho = 0.681, p = 0.005, PIC: rho = 0.742, p = 0.002).ConclusionsThis study demonstrated that elevated histone levels were associated with increased levels of thrombin, and subsequent plasmin generation in PCAS patients, especially those with MODS. Further studies are required to elucidate the causal relationship between histones and organ dysfunction related to DIC in PCAS.

Changes of serum procalcitonin level in patients with severe trauma and its relationship with multiple organ failure

Objective To investigate the changes of serum procalcitonin (PCT) level in patients with severe trauma, and to analyze its relationship with multiple organ failure (MODS). Methods From October 2013 to October 2018, the serum PCT levels were measured in 40 patients with severe trauma complicated with MODS (MODS group: 40 cases) and 62 patients without MODS (non-MODS group: 62 cases) in Yuncheng Central Hospital.The relationship between PCT and severity of trauma score (ISS), sequential organ failure (SOFA), acute physiology and chronic health status score (APACHE Ⅱ) and prognosis was analyzed.The predictive value of PCT in the prognosis of patients with MODS and severe trauma combined with MODS was analyzed by ROC. Results The serum PCT levels of the MODS group were (8.25±2.35)μg/L, (7.26±2.49)μg/L, (3.62±1.75)μg/L on the 1st, 3rd and 7th day after admission, respectively, which were higher than those of the control group (t=7.561, 9.561, 8.251, all P<0.05). The serum PCT level in the MODS group increased with the increase of APACHE Ⅱ score and ISS score (F=12.108, 9.173, all P<0.05). The serum PCT level in the death group was higher than that in the survival group[(11.82±3.75)μg/L vs.(4.92±1.26)μg/L], and the difference was statistically significant (t=7.959, P<0.05). The area under MODS curve predicted by PCT for severe trauma patients was 0.848, with sensitivity and specificity of 80.00%(32/40), 82.50%(33/40), respectively.The area under MODS curve predicted by PCT was 0.747, with sensitivity and specificity of 77.50%(31/40), 72.50%(29/40), respectively. Conclusion The serum PCT level in patients with severe trauma complicated with MODS is significantly higher than that in patients without MODS, and its level is closely related to trauma, disease progression and prognosis.It is of great value to predict the occurrence and prognosis of MODS. Key words: Wounds and injuries; Procalcitonin; Multiple organ failure; Injury severity score; ROC curve; Prognosis; Diagnosis

The predictive value of serum neopterin for multiple organ dysfunction syndrome in severe burn patients

Abstract Objective To investigate the predictive value of serum neopterin for multiple organ dysfunction syndrome (MODS) in severe burn patients. Methods Seventy-six severe burn patients with burns covering a total body surface area (TBSA) above 70% were included in this study. Of the 76 patients, 29 cases developed MODS (MODS group) and the remaining 47 subjects did not (non-MODS group). From the MODS group, 12 patients died (Death group) and 17 patients survived (Survive group). The serum level of neopterin in the MODS and non-MODS groups were examined by radioimmunoassay on following 1, 3 , 7 , 14 , 21 and 28 post-burn days (PBDs). A receiver operating characteristic (ROC) curve was used to analyse the predictive value of serum neopterin for MODS and death. Results The serum neopterin level in the MODS group was significantly higher than that of non-MODS group between 3~28 PBDs (p&lt;0.001). However, the serum neopterin levels between the MODS and non-MODS groups following 1 PBD were not statistically significant (p&gt;0.05). The best diagnostic performance of serum neopterin for MODS occurred 14 PBDs with the prediction sensitivity and specificity of 75.86% (56.46%~89.70%) and 85.11% (71.69%~93.80%) respectively. However, serum neopterin levels had no clinical value in predicting the death of MODS patients. The area under the ROC curve (AUC) was 0.72 (0.58~0.85), 0.81 (0.71~0.92) and 0.83 (0.72~0.94) for serum neopterin as biomarker in the prediction of MODS after 3, 7 and 14 PBDs, respectively. The AUCs were 0.50 (0.27~0.73), 0.53 (0.30~0.76) and 0.56 (0.33~0.79) for serum neopterin as biomarker in prediction of death for MODS patients after 3, 7 and 14 PBDs, respectively. Conclusion The persistent and significant increase of serum neopterin level is closely related to the development of MODS in patients with severe burns. Serum neopterin is therefore a promising serological marker for MODS early diagnosis, but has little efficacy in the prediction of the likelihood of death in severe burn patients with MODS.

Serum Neopterin and its Significance as Biomarker in Differentiation of Mods From Sepsis

Abstract Objective The aim of this study was to evaluate the dynamic changes of serum neopterin and its significance as biomarker in differentiation of MODS from sepsis. Methods Fifty eight critical illness patients and 21 healthy controls were included in the study. Of the included 58 critical illness patients, 37 cases were diagnosed of sepsis (sepsis group) and other 21 were non-sepsis subjects (non-sepsis group). Of the 37 sepsis patients, 17 were diagnosed of multiple organ dysfunction syndrome (MODS group). The serum level of neopterin of the above subjects were examined by enzyme linked immunosorbent assay and compared between groups. Results The serum level of neopterin were 0.885±0.34(ng/mL), 3.77±2.08(ng/mL), 14.80±6.78(ng/mL) and 23.90±11.26(ng/mL) for healthy control, non-sepsis, non-MODS and MODS groups respectively with significant statistical difference (F=52.71, p&lt;0.001). Serum neopterin level of non-sepsis, non-MODS and MODS groups were statistical different in the time points of 0, 24h, 48h, 72h, and 96h (p&lt;0.05). The serum neopterin level was significant higher in MODS group compared to nonsepsis and non-MODS groups (p&lt;0.05). Using the serum neopterin as biomarker in differentiation of MODS from sepsis, the diagnostic sensitivity, specificity and AUC were 70.59% (95%CI:44.04-89.69) %, 80.00% (95%CI:56.34- 94.27)% and 0.74(95%CI:0.57-0.91)% respectively. Conclusion Serum neopterin levels in patients with sepsis were elevated and can be used as a promising biomarker in differentiation of MODS from sepsis.

Effects of bone marrow mesenchymal stem cells on the expressions of inflammatory factors in rats with multiple organ dysfunction syndrome

Objective To investigate the effects of bone marrow mesenchymal stem cells (BMSC) on the expression of inflammatory factors in rats with multiple organ dysfunction syndrome (MODS). Methods BMSC extracted from the 4-week-old Sprague-Dawley (SD) rats was cultivated and identified in vitro, then the 4th passage of which was used in the experimental study. Sixty SD rats were randomly(random number) divided into three groups (n=20 in each group): Sham group (SG), MODS group (MG) and BMSC group (BG). Rats in the MG was injected by 1 mg/kg lipopolysaccaride (LPS) via great saphenous vein, rats in the SG injected with the same volume sterile phosphate buffer saline and rats in the BG infused by 1×106/cells BMSCs through the tail vein at 2 h after LPS injection. The survival rate, tissue pathological changes of the lung, liver and heart by hematoxylin and eosin (HE) staining, organ dysfunction measurement by blood gas analysis and biochemical indicators as well as the related inflammatory factors by protein microarray and enzyme linked immunosorbent assay (ELISA), were detected 72 h post operation. Multi-group quantitative data was analyzed by one way ANOVA, paired-comparisons by LSD-t test and the comparisons of survival curves in the three groups by Log-rank test. The value of P<0.05 was considered statistically significant. Results The survival rate in SG, MG and BG was 100%, 60% and 80%, respectively. The survival curves showed that the survival rate of SG was higher than the MG and BG (SG vs. MG, χ2=9.798, P=0.001 7; SG vs. BG, χ2=4.333, P=0.037 4), but there was no significant difference comparing the BG to the MG (χ2=2.408, P=0.120 7). The tissue congestion and edema, and inflammatory cells infiltration in the lung, liver, and heart of the MG were observed by HE staining, while these changes reduced in the BG. Compared with the SG, the levels of pH and PaCO2 and lactic acid (Lac) increased significantly (all P<0.01), the level of total bilirubin (TB) significantly increased [(0.801±0.501)U/L vs. (2.533±0.382)U/L, P=0.003], while the albumin(ALB) level decreased significantly[(35.471±4.015)U/L vs. (23.202±4.872)U/L, P<0.01], and creatine kinase (CK) level increased significantly in MG [(315.670±41.402) vs. (708.250±219.201), P=0.042]. After BMSC treatment, the organ function improved significantly (all P<0.05). Gamma interferon (IFN-γ) and monocyte chemotactic protein 1 (MCP-1) were the differential expression factors in protein chips. The results of ELISA were similar to the protein chips: compared with the SG, IFN-γ and MCP-1 expressions in the MG increased significantly (P<0.01). Compared with MG, the expressions of IFN-γ and MCP-1 decreased significantly in the BG (P<0.01). Conclusion BMSC administration could modulate the inflammatory response of MODS rats by inhibiting the levels of IFN-γ and MCP-1, and improve the organ function and the survival rate. Key words: Multiple organ dysfunction syndrome; Bone marrow mesenchymal stem cells; Interleukin -γ; Monocyte chemoattractant protein-1; Inflammatory factor

Serum expression levels of Mb and NT-proBNP and NF-κB expression in neutrophils in patients with MODS and the clinical significance.

This study was designed to investigate the expression of myoglobin (Mb), N-terminal pro-brain natriuretic peptide (NT-proBNP) in serum and the expression of nuclear factor-κB (NF-κB) in neutrophils in patients with multiple organ dysfunction syndrome (MODS) and the clinical significance. From July 2014 to December 2015, 314 patients with severe disease were selected during their stays at the emergency ward of the Third People's Provincial Hospital of Henan Province (Zhengzhou, China). Seventy patients with MODS were selected as MODS group, 108 patients with single organ or system injury were selected as the key prevention group, and 136 patients without obvious organ or systemic injury were selected as prevention group. Serum levels of Mb and NT-proBNP were measured by ELISA. Neutrophils were isolated by flow cytometry, and the activity of NF-κB in neutrophils of MODS patients was measured by electrophoretic mobility shift assay (EMSA). At 1, 7 and 14 days after treatment, the levels of Mb, NT-proBNP and NF-κB in the three groups were significantly reduced compared with pretreatment levels (p<0.05). Logistic regression analysis showed that serum Mb, NT-proBNP and NF-κB activity were positively correlated with the progression of the disease (r=0.809, 0.785 and 0.833, p=0.012, 0.025 and 0.004), and negatively correlated with the treatment time (r=−0.773, −0.734 and −0.815; p=0.033, 0.041 and 0.078). Mb, NT-proBNP and NF-κB may be involved in the pathogenesis and development of MODS, and may play an important role in the prevention and treatment of MODS.

Diagnostic value of endogenous morphine in childhood sepsis

To investigate the plasma concentration of endogenous morphine and the value of endogenous morphine in predicting shock, death, and multiple organ dysfunction syndrome (MODS) in children with sepsis. A total of 31 children with sepsis who met the diagnostic criteria were enrolled. According to the presence or absence of shock, they were divided into non-shock group with 19 children and shock group with 12 children. According to the outcome, they were divided into survival group with 22 children and death group with 9 children. According to the presence or absence of MODS, they were divided into non-MODS group with 13 children and MODS group with 18 children. In addition, 16 children with common infection and 31 who underwent physical examination were enrolled as controls. High-performance liquid chromatography-mass spectrometry was used to measure the plasma concentration of endogenous morphine. The receiver operating characteristic (ROC) curve was used to evaluate the value of endogenous morphine in predicting shock, death, and MODS in children with sepsis. No endogenous morphine was detected in the healthy control group. Endogenous morphine was detected in 3 children from the common infection group and in all of 31 children with sepsis. The shock group had a significantly higher plasma concentration of endogenous morphine than the non-shock group (P<0.05). The death group had a significantly higher plasma concentration of endogenous morphine than the survival group (P<0.05). The MODS group had a significantly higher plasma concentration of endogenous morphine than the non-MODS group (P<0.05). The ROC curve showed that endogenous morphine had certain value in predicting shock, death, and MODS in children with sepsis (P<0.05). There is a significant increase in the plasma concentration of endogenous morphine in children with sepsis, and endogenous morphine has a good value in predicting the risk of shock, death, and MODS.

Values of detection of NF-κB activation level combined with IL-6 and TNF-α levels in peripheral neutrophils in the prediction of multiple organ dysfunction syndrome in patients with severe multiple trauma.

The aim of this study was to analyze the dynamic changes and predictive values of nuclear factor-κB (NF-κB) combined with interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in peripheral blood in multiple organ dysfunction syndrome (MODS) in patients with severe multiple trauma. Seventy patients diagnosed with severe multiple trauma in Emergency Department of Sichuan Provincial People's Hospital (Chengdu, China) from April 2014 to April 2016 were selected and retrospectively analyzed. The patients enrolled were divided into the MODS group (n=25) and the non-MODS group (n=45). The injury severity scores (ISSs), acute physiology and chronic health evaluation II (APACHE II) scores, NF-κB, IL-6 and TNF-α levels in patients were detected at different time points (12, 24 and 48 h after admission), the changes in different indexes and the areas under the receiver operating characteristic (ROC) curve (AUC) were analyzed. The predictive values of different detection methods in MODS patients were discussed and compared. The ISS, APACHE II score, NF-κB, IL-6 and TNF-α levels in the MODS group at admission and 24 and 48 h after admission were higher than those in the non-MODS group (P<0.05). Those indexes in the deceased patients at 12, 24 and 48 h after admission were higher than those in survivors (P<0.05). The ISS, APACHE II score, NF-κB, IL-6 and TNF-α levels were not the risk factors of MODS in patients with severe multiple trauma (P>0.05). AUCs of ISS >22 points and APACHE II score >14 points in predicting MODS were lower than that of combined detection of NF-κB >1.20. In conclusion, the combined detection of NF-κB, IL-6 and TNF-α in peripheral blood of patients with acute multiple trauma is more helpful to predict the occurrence of MODS, which has a certain guiding significance for the prognosis of patients with MODS.

The role of HMGB1 in BMSC transplantation for treating MODS in rats.

The effect of bone marrow mesenchymal stem cells (BMSCs) in treatment for multiple organ dysfunction syndrome (MODS) remains unknown and the mechanism is still unclear. Therefore, the goal of this study is to investigate the effects of intracellular high mobility group box 1 protein (HMGB1) on BMSCs treating for MODS. The rats were given 15% blood loss plus 1mg/kg lipopolysaccharide (LPS) via lower extremity superficial venous, then randomly allocated into four groups: sham group, MODS group, MODS plus BMSC group, MODS plus ethyl pyruvate (EP) group, MODS plus BMSCs plus EP group. Twenty-four hours later, rats in groups were sacrificed and then the blood and tissues were collected to evaluate the changes of tissue histopathology, cell apoptosis, inflammation level and organ function. The HGMB1 expression was monitored by RT-qPCR and Western blot. The expression of RAGE/TLR2/TLR4 and NF-κB at the protein levels was also assessed. BMSCs and/or EP exhibits an outstanding protective effect against LPS-induced histopathological injury by improving cell apoptosis, inflammatory response and the organ dysfunction but no effect on BMSC homing to the injury site. Moreover, BMSCs and/or EP inhibited LPS-induced upregulation of HMGB1, RAGE, TLR2 and TLR4 expression at protein levels and compromised p65 phosphorylation in the rat model of MODS. These findings suggest that HMGB1 is involved in BMSC treatment for MODS, through regulation of the TLR2, TLR4-mediated NF-κB signal pathway. It suggests that HMGB1 is an attractive potential target for the development of new therapeutic strategies for MODS.

Establishment of multiple organ dysfunction syndrome early warning score in patients with severe trauma and its clinical significance: a multicenter study

To explore the risk factors of multiple organ dysfunction syndrome (MODS) in severe trauma patients, put forward a new warning scoring system of MODS, and to provide a more accurate scoring method for doctors to judge the clinical condition and prognosis of patients. Clinical data of 342 patients with severe trauma admitted to intensive care unit (ICU) of the Affiliated Hospital of Zunyi Medical College and Daping Hospital of the Third Military Medical University from January 1st, 2015 to December 31st, 2016 were retrospectively analyzed. The patients were divided into MODS groups (n = 251) and non-MODS group (n = 91) according to clinical outcomes. The clinical data of patients, including gender, age, heart rate (HR) and blood pressure within 24 hours after admission to the hospital, indicators of blood routine and blood biochemistry, severity of disease, severity of trauma, whether received the emergency intubation or surgery within 24 hours or not, whether developed sepsis or acute respiratory distress syndrome (ARDS) during hospitalization, were recorded, and univariate analysis was conducted. The indicators with statistical significance found by univariate analysis were enrolled in multivariate Logistic regression analysis, and the risk factors for MODS in patients with severe trauma were screened and assigned, and the final total score was MODS warning score. Receiver operating characteristic (ROC) curve was plotted to evaluate MODS warning score for predicting the occurrence of MODS in patients with severe trauma. Compared with non-MODS group, HR, Na+, serum creatinine (SCr), activated partial thromboplastin time (APTT), injury severity score (ISS), new injury severity score (NISS), acute physiology and chronic health evaluation II (APACHE II) score and sequential organ failure assessment (SOFA) score in MODS group were significantly increased, pH value, red blood cell (RBC), platelet (PLT), albumin (Alb) and Glasgow coma score (GCS) were remarkably decreased, and multiple injury, the patients with shock at admission, blood transfusion, central venous catheter, emergency intubation and infection were also increased, and more patients suffered from sepsis and ARDS. Multivariate Logistic regression analysis showed that the number of injured places equal or more than 2, shock at admission, APACHE II score ≥ 15, SOFA score ≥ 4 and APTT > 40 s were risk factors for MODS in patients with severe trauma, with total MODS warning score of 7.5. ROC curve analysis showed that the area under ROC curve (AUC) of MODS warning score for predicting MODS in patients with severe trauma was 0.822, which was significantly higher than that of APACHE II score (AUC = 0.698, P < 0.001), APTT (AUC = 0.693, P < 0.001) and SOFA score (AUC = 0.770, P = 0.025). When the cut-off value of MODS warning score was 2.5, the sensitivity was 61.35%, the specificity was 90.11%, and Youden index was 0.515. MODS warning score is composed of five factors, including the number of injured places, shock at admission, APACHE II score, SOFA score and APTT, which could be regarded as early warning score system for predicting MODS in patients with severe trauma. MODS warning score can be more comprehensive and timely to assess the possibility of MODS and prognosis of patients with severe trauma, and the prediction result is better than the single use of APTT, APACHE II or SOFA score.

The analysis on the expression of gasotransmitters in early trauma patients.

Nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) were endogenously-generated molecules gas. They owned important biological activity and participated in many pathophysiological processes. This study aimed to examine the levels of three gasotransmitters in the early phase of trauma patients. Blood samples were collected from 60 trauma patients and ten healthy volunteers. Concentration of serum iNOS and HO-1 were analyzed by enzyme linked immunosorbent assay and plasma H2S was determined by colorimetric method. Meanwhile, the occurrence of multiple organ dysfunction syndrome (MODS) was also monitored. The levels of iNOS, HO-1 and endogenous H2S in the patients group were significantly different from the healthy control group, and the difference was more obvious with the increase of ISS score. iNOS levels were positively correlated with ISS scores and blood lactic acid values, and HO-1 and endogenous H2S were negatively correlated with ISS scores and blood lactic acid values. Of 60 trauma patients, eight (13.33%) developed MODS. The level of iNOS in the MODS group was higher than that in non-MODS group, while HO-1 and H2S were significant lower in the MODS group. The three gasotransmitters participated in systemic inflammatory responses during early trauma and could be used as important indicators for trauma severity. Their measurements were meaningful for evaluating the severity and prognosis of trauma.

Th17/regulatory T cell imbalance in sepsis patients with multiple organ dysfunction syndrome: attenuated by high-volume hemofiltration.

We assessed the Th17 (T-helper cell)/Treg (Regulatory T cell) imbalance in sepsis patients with multiple organ dysfunction syndrome (MODS) and the clinical benefits of continuous high-volume hemofiltration (HVHF). 48 sepsis patients, including 22 patients with MODS (MODS group, n = 22) and 26 without (non-MODS group, n = 26), and 20 healthy volunteer controls were enrolled. The patients in MODS group were randomly divided into the continuous blood purification (CBP) group (n = 11) receiving conventional comprehensive treatment plus high-volume hemofiltration and the non-CBP group (n = 11) receiving conventional comprehensive treatment only. At day 28, all 48 patients were divided into the survival group (n = 36) and the non-survival group (n = 12). Venous blood samples, collected at 0, 6, 12 and 24 hours during hemofiltration (or equivalent times in the non-CBP group), were assessed by flow cytometry to detect the Th17 and Treg cells in peripheral blood. Serum cytokines (such as IL-6, IL-17, IL-23, IL-10 and TGF-β1) were detected by enzyme-linked immune sorbent assay (ELISA). Th17%, Treg%, Th17/Treg, IL-6, IL-17, IL-23, IL-10 and TGF-β1 were significantly higher in MODS and non-MODS group than in the health control (p<0.05), while Th17%, Treg%, Th17/Treg and measured cytokines were significantly higher in the MODS group compared to the non-MODS group (p<0.05). After HVHF treatment, Th17%, Treg%, Th17/Treg, IL-6, IL-17, and IL-10 were significantly reduced (p<0.05), while there were no significant changes in the non-CBP group (p>0.05). In addition, APACHE II and SOFA scores decreased markedly after HVHF treatment. Baseline Th17%, Treg%, Th17/Treg, IL-6, IL-17, IL-23, IL-10 and TGF-β1 were significantly higher in the non-survival group compared to the survival group. Both Th17% and Th17/Treg were positivity correlated with concentration of IL-6 and APACHE II score (p<0.01). The level of Th17/Treg imbalance in sepsis is related to the occurrence and prognosis of MODS. High-volume hemofiltration can attenuate the Th17/Treg imbalance in sepsis patients, possibly by removing inflammatory mediators.

Necroptosis as a potential therapeutic target in multiple organ dysfunction syndrome.

PurposeTo investigate how necroptosisis, i.e. programmed necrosis, is involved in MODS, and to examine whether Nec-1, a specific necroptosis inhibitor, ameliorates multiorgan injury in MODS.Experimental DesignA model of MODS was established in six-week old SD rats using fracture trauma followed by hemorrhage. Control animals received sham surgery. Cell death form and necrosome formation were measured by fluorescence-activated cell sorting and western blotting. MODS rats were randomly assigned to receive Nec-1 or saline with pretreatment and once daily. The first end-point was 72 hours survival. Organ injury and dysfunction, inflammatory cytokine levels, and necroptotic execution protein expression were also recorded.ResultsOrgan injury and dysfunction were significantly more severe in the MODS group than the sham group (all p<0.01). Furthermore, MODS-induced liver, lung and kidney tissue injury was characterized by necroptosis rather than apoptosis, and accompanied by necrosome formation. Compared to MODS group, Nec-1 administration significantly improved 72 hours survival (p<0.01). Nec-1 administration significantly reduced necroptosis-induced liver, lung and kidney injury and dysfunction, inhibited inflammatory cytokines production, inhibited release of necroptotic execution proteins such as high-mobility group box 1 and mixed-lineage kinase domain-like protein pseudokinase in MODS rats (all p<0.01).ConclusionsThese results suggest that necroptosis is involved the pathology of MODS. Further, a necroptotic inhibitor Nec-1 may be considered as an adjunct treatment for MODS.

Early Kinetics of Procalcitonin in Predicting Surgical Outcomes in Type A Aortic Dissection Patients.

Background:In cardiac surgery, elevation of procalcitonin (PCT) could be observed postoperatively in the absence of any evidence of infection and also seems to be a prognostic marker. PCT levels measured in patients undergoing Type A aortic dissection (TAAD) were used to determine prognostic values for complications and surgical outcomes.Methods:Measurements of PCT, C-reactive protein (CRP), and leukocyte count were observed in TAAD surgery patients (n = 251; average age: 49.02 ± 12.83 years; 78.5% male) at presurgery (T0) and 24 h (T1), 48 h (T2), and 7 days (T3) postsurgery. PCT clearance (PCTc) on days 2 and 7 was calculated: (PCTday1 − PCTday2/day7)/PCTday1 × 100%. Endotracheal intubation duration, length of stay (LOS) in the Intensive Care Unit (ICU)/hospital, and complications were recorded.Results:PCT peaked 24 h postsurgery (median 2.73 ng/ml) before decreasing. Correlation existed between PCT levels at T1 and duration of cardiopulmonary bypass (P = 0.001, r = 0.278). Serum PCT concentrations were significantly higher in nonsurvivor and multiple organ dysfunction syndrome groups on all postoperative days. PCT levels at T1 correlated with length of time of ventilation support and ICU/hospital LOS. Comparing PCT values of survivors versus nonsurvivors, a PCT cutoff level of 5.86 ng/ml at T2 had high sensitivity (70.6%) and specificity (74.3%) in predicting in-hospital death. PCTc-day 2 and 7 were significantly higher in survivor compared with nonsurvivor patients (38% vs. 8%, P = 0.012, 83% vs. −39%, P < 0.001). A PCTc-day 7 cutoff point of 48.7% predicted survival with high sensitivity (77.8%) and specificity (81.8%).Conclusions:PCT level and PCTc after TAAD surgery might serve as early prognostic markers to predict postoperative outcome. PCT measurement may help identify high-risk patients.

Relation of antioxidant status at admission and disease severity and outcome in dogs naturally infected with Babesia canis canis

BackgroundCanine babesiosis is caused by species of the Babesia genus and has become an emerging disease worldwide. To the authors’ knowledge there are no reports in which antioxidants have been analyzed in different presentations of canine babesiosis or in which the prognostic value of antioxidants has been studied. The aim of this study was to evaluate whether oxidative stress could be related to the severity and outcome of canine babesiosis. For this purpose a profile consisting of four antioxidant biomarkers (superoxide dismutase - SOD, glutathione peroxidase - GPx, catalase, total antioxidant status - TAS) and malondialdehyde - MDA as an oxidant biomarker (previously evaluated, here studied for comparative purposes) were evaluated in dogs with canine babesiosis of different clinical severity and outcomes.ResultsThe study was conducted with a sample of 40 dogs suffering from babesiosis (further divided into uncomplicated, one complication and multiple organ dysfunction syndrome - MODS group) and 30 healthy dogs (control group). Additionally, the babesiosis group was divided according to the anaemia into non-anaemic, mildly anaemic, moderately anaemic and severely anaemic dogs. The results of our study showed significantly decreased SOD, catalase and TAS values in diseased dogs compared to controls, while there were no significant differences in GPx between these groups. Dogs that developed MODS showed lower activities of SOD and GPx and higher MDA values compared to dogs with uncomplicated babesiosis as well as with dogs that developed one complication. Superoxide dismutase, catalase and GPx were negatively correlated whereas MDA was positively correlated with the lethal outcome of the disease. Furthermore, this study detected more pronounced decrease in antioxidant biomarkers (SOD, GPx and catalase) in dogs with moderate anaemia compared to those with mild anaemia.ConclusionsThe results of this study showed changes in biomarkers related to the antioxidant status of dogs naturally infected with B. canis canis. These biomarkers could be used as indicators of disease severity and outcome in dogs suffering from babesiosis.