Multiple Organ Dysfunction Syndrome Patients Research Articles

Treatment of patients with multiple organ dysfunction syndrome (MODS) with an electromagnetic field coupled to biorhythmically defined impulse configuration: the MicrocircMODS study

BackgroundTo potentially improve impaired vasomotion of patients with multiple organ dysfunction syndrome (MODS), we tested whether an electromagnetic field of low flux density coupled with a biorhythmically defined impulse configuration (Physical Vascular Therapy BEMER®, PVT), in addition to standard care, is safe and feasible and might improve disturbed microcirculatory blood flow and thereby improve global haemodynamics.MethodsIn a prospective, monocentric, one-arm pilot study, 10 MODS patients (APACHE II score 20–35) were included. Patients were treated, in addition to standard care, for 4 days with PVT (3 treatment periods of 8 min each day; day 1: field intensity 10.5 μT; day 2:14 μT, day 3:17.5 μT; day 4:21.0 μT). Primary endpoint was the effect of PVT on sublingual microcirculatory perfusion, documented by microvascular flow index (MFI). Patient safety, adverse events, and outcomes were documented.ResultsAn increase in MFI by approximately 25% paralleled 4-day PVT, with the increase starting immediately after the first PVT and lasting over the total 4-day treatment period. Concerning global haemodynamics (secondary endpoints), halving vasopressor use within 24 h, and haemodynamic stabilisation paralleled 4-day PVT with an increase in cardiac index, stroke volume index, and cardiac power index by 30%–50%. No adverse events (AEs) or serious adverse events (SAEs) were classified as causally related to the medical product (PVT) or study. Three patients died within 28 days and one patient between 28 and 180 days.ConclusionPVT treatment was feasible and safe and could be performed without obstruction of standard patient care. An increase in microcirculatory blood flow, a rapid reduction in vasopressor use, and an improvement in global haemodynamics paralleled PVT treatment. Findings of this pilot study allowed forming a concept for a randomized trial for further proof.Graphical abstract

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.

Complement Activation in Patients With Heat-Related Illnesses: Soluble CD59 Is a Novel Biomarker Indicating Severity of Heat-Related Illnesses.

OBJECTIVES:Although multiple organ dysfunction syndrome (MODS) is the main cause of death in patients with heat-related illnesses, its underlying pathophysiological mechanism remains elusive. Complement activation is considered one of the main causes of MODS in patients with sepsis and trauma. Considering the pathophysiological similarity of heat related-illnesses with sepsis and trauma, the complement system might be activated in patients with heat-related illnesses as well. Our aim was to investigate whether excessive complement activation occurs in patients with heat-related illnesses.DESIGN:Prospective observational study.SETTING:Emergency department in the university hospital.PATIENTS:Thirty-two patients with heat-related illnesses and 15 age-matched healthy controls were enrolled in this study.INTERVENTIONS:Blood samples were collected from the study subjects for the measurement of complement factors.MEASUREMENTS AND MAIN RESULTS:Complement component 3a (C3a), complement component 5a (C5a), C5b-9, complement factor B (Ba), Factor H, and soluble CD59 in plasma were measured. The levels of C3a, C5a, C5b-9, and Ba significantly increased in patients with heat-related illnesses on day 0 compared with those in the healthy controls. Soluble CD59 was significantly high in patients with heat-related illnesses on day 0 and showed a correlation with the severity of the condition (Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, and staging scores), Japanese Association for Acute Medicine disseminated intravascular coagulation scores, and the coagulation system (prothrombin time and fibrin degradation products).CONCLUSIONS:The complement system was activated in patients with heat-related illnesses, suggesting that it is one of the causes of MODS. Soluble CD59 may be a potent biomarker for the severity of heat-related illnesses.

Epidemiology and outcomes of multiple organ dysfunction syndrome following pediatric trauma.

Existing studies have found a low prevalence of multiple organ dysfunction syndrome (MODS) in pediatric trauma patients, typically applying adult criteria to single-center pediatric cohorts. We used pediatric criteria to determine the prevalence, risk factors, and outcomes of MODS among critically injured children in a national pediatric intensive care unit (PICU) database. We conducted a retrospective cohort study of PICU patients 1 month to 17 years with traumatic injury in the Virtual Pediatric Systems, LLC database from 2009 to 2017. We used International Pediatric Sepsis Consensus Conference criteria to identify MODS on Day 1 of PICU admission and estimated the risk of mortality and poor functional outcome (Pediatric Overall/Cerebral Performance Category ≥3 with ≥1 point worsening from baseline) for MODS and for each type of organ dysfunction using generalized linear Poisson regression adjusted for age, comorbidities, injury type and mechanism, and postoperative status. Multiple organ dysfunction syndrome was present on PICU Day 1 in 23.1% of 37,177 trauma patients (n = 8,592), with highest risk among patients with injuries associated with drowning, asphyxiation, and abuse. Pediatric intensive care unit mortality was 20.1% among patients with MODS versus 0.5% among patients without MODS (adjusted relative risk, 32.3; 95% confidence interval, 24.1-43.4). Mortality ranged from 1.5% for one dysfunctional organ system to 69.1% for four or more organ systems and was highest among patients with hematologic dysfunction (43.3%) or renal dysfunction (29.6%). Death or poor functional outcome occurred in 46.7% of MODS patients versus 8.3% of patients without MODS (adjusted relative risk, 4.3; 95% confidence interval 3.4-5.3). Multiple organ dysfunction syndrome occurs more frequently following pediatric trauma than previously reported and is associated with high risk of morbidity and mortality. Based on existing literature using identical methodology, both the prevalence and mortality associated with MODS are higher among trauma patients than the general PICU population. Consideration of early organ dysfunction in addition to injury severity may aid prognostication following pediatric trauma. Prognostic and Epidemiological; Level III.

The relationship between transthoracic echocardiography and mortality in adult patients with multiple organ dysfunction syndrome: analysis of the MIMIC-III database.

BackgroundFor patients with multiple organ dysfunction syndrome (MODS), timely assessment of the condition and real-time adjustment of the treatment plan are of critical importance. To this end, transthoracic echocardiography (TTE) is widely used in clinical practice, but whether TTE can improve the short-term prognosis of MODS patients is currently unclear.MethodsWe extracted data of patients from the Medical Information Mart for Intensive Care III (MIMIC-III) database and included cases according to inclusion and exclusion criteria. The primary endpoint was the mortality within 28 days after admission to the intensive care unit (ICU), and multi-variate regression analysis was conducted to infer the risk factors associated death within 28 days after ICU admission. Double robust analysis was conducted to investigate the correlation between TTE and the endpoint. A gradient-boosted model (GBM) was constructed to calculate the propensity score (PS) of patients received TTE, so as to reduce the difference of variates between these two groups.ResultsA total of 13,844 MODS cases were included and were divided into a TTE group and a non-TTE group. There were 5,022 cases (36.28%) in the TTE group, 2,416 (48.10%) of whom were female; and 8,822 (63.72%) in the non-TTE group, 4,129 of whom (46.80%) were female. The covariates that contributed significantly to PS included chronic heart failure (CHF), creatine kinase (CK), troponin, partial pressure of oxygen (PO2), and sequential organ failure assessment (SOFA) scores. Double robust analysis showed that within 28 days after ICU admission, the TTE group had lower risk of death when compared with the non-TTE group. The adjusted odds ratio (OR) value of TTE for 28 days death was 0.73 [95% confidence interval (CI): 0.65–0.82; P<0.001]. The other 3 models had similar results, suggesting that conduct TTE for patients with MODS in ICU was associated with lower risk of 28 days mortality.ConclusionsTTE can reduce the mortality of MODS patients in the ICU.

MicroRNA-200b-3p as a biomarker for diagnosis and survival prognosis of multiple organ dysfunction syndrome caused by acute paraquat poisoning.

Acute paraquat poisoning-induced multiple organ dysfunction syndrome (MODS) leads to the high mortality. This study aimed to investigate the clinical significance of microRNA-200b-3p (miR-200b-3p), an upstream inhibitor of high-mobility group box 1 (HMGB1), in acute paraquat poisoning patients for the prediction of MODS and survival. This study enrolled 80 patients with MODS induced by paraquat and 94 healthy volunteers. The interaction between miR-200b-3p and HMGB1 was identified by luciferase reporter assay. miR-200b-3p levels were measured by quantitative real-time (QRT) PCR. High-mobility group box 1 levels were measured by enzyme-linked immune sorbent assay (ELISA). Receiver operating characteristic analysis was used to evaluate the diagnostic value of miR-200b-3p in screening MODS patients. The relationship between miR-200b-3p and the 28-day survival of MODS patients was evaluated by Kaplan-Meier curves and log-rank test. Cox regression analysis was used to assess the prognostic value of miR-200b-3p. Correlation between miR-200b-3p and HMGB1 was confirmed by Pearson's correlation analysis. miR-200b-3p directly target HMGB1. miR-200b-3p, decreased in MODS patients, had high diagnostic value to screen MODS patients from healthy controls. Additionally, serum miR-200b-3p was decreased in non-survivors, and patients with low miR-200b-3p level had poor 28-day survival. Serum miR-200b-3p could independently predict the survival prognosis. Moreover, serum HMGB1 level was increased in MODS patients, and was negatively correlated with miR-200b-3p level. Decreased miR-200b-3p may function as a biomarker for the diagnosis and survival prognosis of MODS patients, and miR-200b-3p may be involved in the progression of acute paraquat-induced MODS via regulating inflammatory responses by targeting HMGB1.

Cholinesterase level is a predictor of systemic inflammatory response syndrome and complications after cardiopulmonary bypass.

To study the changes of serum cholinesterase (S-ChE) levels in patients with systemic inflammatory response syndrome (SIRS) after cardiopulmonary bypass (CPB) and its predictive value for multiple organ dysfunction syndrome (MODS). Forty-two patients with SIRS after CPB were selected as the SIRS group. Another 42 patients who did not develop SIRS after CPB were selected as the control group. The S-ChE levels of patients were compared between the two groups at the time of intensive care unit (ICU) admission and 48 hours after admission to the ICU. The correlation between S-ChE levels and Acute Physiology and Chronic Health EvaluationII (APACHEII) score, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels was compared between the two groups at the time of ICU admission and 48 hours after ICU admission, and receiver operator characteristic (ROC) curve analysis was used to analyze the accuracy of S-ChE level in diagnosing MODS in patients with SIRS after CPB. There was no significant difference in the S-ChE levels among the non-SIRS patients between the time of admission to the ICU and 48 hours later. However, the S-ChE levels in SIRS patients exhibited a decreasing trend from 48 hours after ICU admission compared with those at the time of ICU admission. Meanwhile, the S-ChE levels were obviously lower in SIRS patients than in non-SIRS patients at those two time points. Furthermore, we found that S-ChE levels were negatively correlated with APACHEII scores as well as the levels of TNF-α and IL-6 at ICU admission and 48 hours after ICU admission in SIRS patients. Meanwhile, S-ChE levels were associated with the occurrence of MODS of SIRS patients. Subsequent ROC curve analysis revealed that early S-ChE levels could predict the occurrence of SIRS complicated by MODS after CBP. S-ChE was significantly decreased in patients with SIRS after CPB, and the decrease of S-ChE in the early stage was closely related to the severity of SIRS after CBP and the increase of inflammatory cytokines. Meanwhile, there was a close relationship between S-ChE activity and MODS in the early stage.

The clinical characters and prognosis of COVID-19 patients with multiple organ dysfunction.

To depict the clinical characters and prognosis of coronavirus disease 2019 patients who developed multiple organ dysfunction syndrome (MODS).A cohort consisted of 526 patients, which including 109 patients complicated MODS, was retrospectively analyzed to examine the clinical characteristics and risk factors of MODS.Among the 526 novel coronavirus-infected pneumonia patients, 109 patients developed multiple organ failure, the incidence rate was 20.7%. Among all 109 patients with MODS, 81.7% were over 60 years old, and 63.3% were male. The most common symptoms were fever (79.8%), dyspnea (73.4%), and fatigue (55.0%). Compared with patients non-MODS patients, there were 70 cases of MODS patients with one or more underlying diseases (64.2% vs 41.0%, P < .001). Respiratory failure (92.7%), circulatory failure (52.0%), and liver function injury (30.9%) were the most common symptoms within the spectrum of MODS. Invasive ventilator, noninvasive ventilator, and high-flow respiratory support treatment for patients in MODS patients were higher than those in the non-MODS group (P < .001). The antiviral therapy and 2 or more antibacterial drug treatments in MODS patients were higher than those in the non-MODS group (P < .001). The median hospital stay of all patients was 16 days (interquartile range [IQR], 9-26), of which 20 days (IQR, 11.5-30.5) in the MODS patients, which was approximately 4 days longer than that of non-MODS patients. In addition, our data suggested that lymphocyte counts <1.0 ∗ 109/L, Troponin T > 0.014 ng/mL and lower oxygenation index were risk factors for MODS. In the early stage of hospital admission, higher inflammatory indexes and lactic acid concentration were associated with increased risk of death.MODS often leads to poor prognosis in coronavirus disease 2019. Our data suggested the importance of early identification of MODS. We recommend close monitoring and timely supportive therapy for patients with high risks, stopping the disease progression before it was too late.

Development of multiple organ dysfunction syndrome in patients with Coronavirus Disease 2019: clinical characteristics and risk factors

Objective: To explore the clinical characteristics and risk factors of patients with Coronavirus Disease 2019 (COVID-19) when developing multiple organ dysfunction syndrome (MODS). Methods: Data from 458 inpatients of confirmed COVID-19 in Wuhan, Shanghai and Tongling from December 29, 2019 to March 24, 2020 were retrospectively collected. COVID-19 was confirmed by real-time RT-PCR of throat swab samples. Data of demographics, clinical presentation, laboratory tests, imaging findings, treatment and prognosis were obtained from medical record and compared between COVID-19 patients with and without MODS. Risk factors for the development of MODS were analyzed by univariate and multivariate logistic regression analysis. Results: Of the 458 COVID-19 patients (266 from Wuhan, 208 from Shanghai, and 24 from Tongling), 103 developed transient or persistent MODS in the course. More male patients were found in those with MODS (72.8% vs 54.6%, P=0.001). And MODS patients were of older age (72.8% vs 54.6%, P=0.001), more chronic comorbidities (68.0% vs 43.4%, P<0.001), and longer onset-to-admission interval (9.0 vs 7.0 d, P<0.001). In addition, patients with MODS had more expectoration (45.6% vs 29.9%, P=0.003) and shortness of breath (52.4% vs 19.4%, P<0.001), dysfunction of various systems, decreased cellular immunity and elevated IL-6 (9.6 vs 7.6 g/L, P=0.015) in laboratory tests, isolation of other pathogens (18.4% vs 5.6%, P<0.001), and infiltration of all five lobes (75.3% vs 57.6%, P=0.003). During hospitalization, patients with MODS needed a higher proportion of comprehensive treatment and reached a mortality rate of 66.0%. Independents risk factors for development of MODS in COVID-19 patients were: onset-to-admission interval>7 days (OR=2.17, 95%CI: 1.11-4.22, P=0.023), shortness of breath (OR=3.19, 95%CI: 1.60-6.37, P=0.001), lymphocyte count<1×109/L (OR=2.67, 95%CI: 1.31-5.46, P=0.007), blood urea nitrogen>7mol/L (OR=6.27, 95%CI: 2.80-14.08, P<0.001), procalcitonin>0.1 ng/mL (OR=2.48, 95%CI: 1.20-5.13, P=0.014), and C-reactive protein>10 mg/L (OR=3.92, 95%CI: 1.41-10.89, P=0.009). Conclusions: COVID-19 patients with MODS were of higher severity and mortality. Early identification of high-risk groups with MODS according to risk factors may be helpful for early treatment.

Aberrant miR-219-5p is correlated with TLR4 and serves as a novel biomarker in patients with multiple organ dysfunction syndrome caused by acute paraquat poisoning.

This study aimed to investigate the clinical significance of serum microRNA-219-5p (miR-219-5p) in patients with multiple organ dysfunction syndrome (MODS) caused by acute paraquat (PQ) poisoning, and its correlation with Toll-like Receptor 4 (TLR4). Luciferase reporter assay was used to investigate in vitro the correlation of miR-219-5p with TLR4. Serum miR-219-5p levels were evaluated by quantitative real-time polymerase chain reaction. Serum levels of TLR4, IL-1β, and TNF-α were measured by Enzyme-linked immune sorbent assay (ELISA). ROC analysis was performed to assess the diagnostic significance, Kaplan-Meier survival curves and Cox regression analysis were used to evaluate the prognostic value of miR-219-5p in MODS patients. TLR4 was a target gene of miR-219-5p and was increased in MODS patients. Serum miR-219-5p level was decreased and negatively correlated with TLR4 level in MODS patients (r = −0.660, P < 0.001), which had important diagnostic value and negatively correlated with APACHE II score in MODS patients. The miR-219-5p expression was markedly associated with the WBC, ALT, AST, PaCO2, Lac, and APACHE II score. Non-survivals had more patients with low miR-219-5p expression. Patients with low miR-219-5p expression had shorter survival time. MiR-219-5p and APACHE II score were two independently prognostic factors for 28-day survival. MiR-219-5p was negatively correlated with, while TLR4 was positively correlated with the levels of IL-1β and TNF-α. The serum miR-219-5p level may be a potential biomarker for acute PQ-induced MODS diagnosis and prognosis. Furthermore, miR-219-5p may be associated with the progression of MODS by regulating TLR4-related inflammatory response.

Outcomes Associated With Multiple Organ Dysfunction Syndrome in Critically Ill Children With Hyperglycemia.

Patterns and outcomes of multiple organ dysfunction syndrome are unknown in critically ill children with hyperglycemia. We aimed to determine whether tight glycemic control to a lower vs. higher range influenced timing, duration, or resolution of multiple organ dysfunction syndrome as well as characterize the clinical outcomes of subgroups of multiple organ dysfunction syndrome in children enrolled in the Heart And Lung Failure-Pediatric INsulin Titration trial. Planned secondary analysis of the multicenter Heart And Lung Failure-Pediatric INsulin Titration trial. Thirty-five PICUs. Critically ill children with hyperglycemia who received the Heart And Lung Failure-Pediatric INsulin Titration protocol from 2012 to 2016. Randomization to a lower versus higher glucose target group. Of 698 patients analyzed, 48 (7%) never developed multiple organ dysfunction syndrome, 549 (79%) had multiple organ dysfunction syndrome without progression, 32 (5%) developed new multiple organ dysfunction syndrome, and 69 (10%) developed progressive multiple organ dysfunction syndrome. Of those whose multiple organ dysfunction syndrome resolved, 192 (34%) experienced recurrent multiple organ dysfunction syndrome. There were no significant differences in the proportion of multiple organ dysfunction syndrome subgroups between Heart And Lung Failure-Pediatric INsulin Titration glucose target groups. However, patients with new or progressive multiple organ dys function syndrome had fewer ICU-free days through day 28 than those without new or progressive multiple organ dysfunction syndrome, and progressive multiple organ dysfunction syndrome patients had fewer ICU-free days than those with new multiple organ dysfunction syndrome: median 25.1 days for never multiple organ dysfunction syndrome, 20.2 days for multiple organ dysfunction syndrome without progression, 18.6 days for new multiple organ dysfunction syndrome, and 0 days for progressive multiple organ dysfunction syndrome (all comparisons p < 0.001). Patients with recurrent multiple organ dysfunction syndrome experienced fewer ICU-free days than those without recurrence (median, 11.2 vs 22.8 d; p < 0.001). Tight glycemic control target range was not associated with differences in the proportion of new, progressive, or recurrent multiple organ dysfunction syndrome. New or progressive multiple organ dysfunction syndrome was associated with poor clinical outcomes, and progressive multiple organ dysfunction syndrome was associated with worse outcomes than new multiple organ dysfunction syndrome. In future studies, new multiple organ dysfunction syndrome and progressive multiple organ dysfunction syndrome may need to be considered separately, as they represent distinct subgroups with different, potentially modifiable risk factors. Patients with recurrent multiple organ dysfunction syndrome represent a newly characterized, high-risk group which warrants attention in future research.

Phenotyping Multiple Organ Dysfunction Syndrome Using Temporal Trends in Critically Ill Children.

Multiple organ dysfunction syndrome (MODS) is one of the most common causes of death in critically ill children. However, despite decades of clinical trials, there are no comprehensive approaches to the management of MODS or effective targeted therapies that have consistently improved outcomes. Better understanding the heterogeneity of MODS and characterizing subgroups of MODS patients could improve our understanding of the syndrome and help us develop new management strategies. We analyzed a cohort of 5,297 children with MODS from two children's hospitals and used subgraph-augmented non-negative matrix factorization (SANMF) to identify unique temporal patterns in organ dysfunction across four novel subgroups. We demonstrate that these subgroups are composed of patients with distinct clinical characteristics and are independently predictive of clinical outcomes. Our work suggests that these subgroups represent four relevant phenotypes of pediatric MODS that could be used to identify novel management strategies.

Outcomes of Day 1 Multiple Organ Dysfunction Syndrome in the PICU.

We sought to describe current outcomes of Multiple Organ Dysfunction Syndrome present on day 1 of PICU admission. Retrospective observational cohort study. Virtual Pediatric Systems, LLC, database admissions, January 2014 and December 2015. We analyzed 194,017 consecutive PICU admissions, (age 1 mo to 18 yr) from the 2014-2015 Virtual Pediatric Systems database. We identified day 1 Multiple Organ Dysfunction Syndrome by International Pediatric Sepsis Consensus Conference criteria with day 1 laboratory and vital sign values. Functional status was evaluated by Pediatric Overall Performance Category and Pediatric Cerebral Performance Category scores from PICU admission and discharge. Overall, PICU mortality was 2.1%. We identified day 1 Multiple Organ Dysfunction Syndrome in 14.4% of admissions. Patients with Multiple Organ Dysfunction Syndrome had higher mortality than those without Multiple Organ Dysfunction Syndrome (10.3% vs 0.7%; p < 0.0001), and a higher percentage of survivors had greater than or equal to 2 category worsening in Pediatric Cerebral Performance Category score (3.6% vs 0.5%; p < 0.0001) or Pediatric Overall Performance Category score (6.0% vs 1.8%; p < 0.0001). The odds of death with day 1 Multiple Organ Dysfunction Syndrome was 14.3 (95% CI, 13-15.7), while the odds of death or discharge with Pediatric Overall Performance Category/Pediatric Cerebral Performance Category score greater than or equal to 3 (poor functional outcome) was 6.7 (95% CI, 6-7.4). In a subset of 148,188 patients from hospitals where limitation of support decisions were recorded, 5.8% patients with Multiple Organ Dysfunction Syndrome had limitation of support decisions in place, compared with 0.8% of patients without Multiple Organ Dysfunction Syndrome (p < 0.0001). Of day 1 Multiple Organ Dysfunction Syndrome patients who died, 43.1% had limitation of support decisions in place, and 41.6% had withdrawal of life-sustaining therapies (p < 0.0001). Multiple Organ Dysfunction Syndrome present on day 1 of admission continues to be a major source of morbidity and mortality in the PICU, but risk of poor neurologic outcome may be improved. Further research is needed to understand decisions regarding limitation of support and withdrawal of life-sustaining therapy decisions in patients admitted with day 1 Multiple Organ Dysfunction Syndrome.

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.

Effect of Strontium Ranelate on Multiple Organ Damage in a Rat Sepsis Model

Background: Sepsis and multiple organ dysfunction syndrome (MODS) are life-threatening conditions common in intensive care units. In this regard, studies have shown that Strontium ranelate has anti-inflammatory activity by blocking tumor necrosis factor-alpha (TNFα). Objectives: This study aimed to investigate the effect of Strontium ranelate on MODS in an experimental sepsis model. Methods: The study protocol was approved by Cumhuriyet University Institutional Ethics Committee for Animal Experiments (Sivas-Turkiye, date 07/12/2017). Twenty female Wistar-Albino rats were randomly divided into four groups of sham operation, cecal ligation and perforation (CLP), CLP + Strontium (S) (oral 40 mg/kg for 7 days), and S (40 mg/kg oral preoperative 5 days) + CLP + S (oral 40 mg/kg for 7 days). Blood samples were taken, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine were studied. Tissues were removed, and inflammation scores were determined. Results: The mean inflammation scores of lung, liver, and renal tissues were found to be the lowest in the sham group (0.8 ± 0.45), and they increased in the S + CLP + S (1.6 ± 0.55) and CLP + S (3.4 ± 0.55) groups, respectively, with the highest score in the CLP (3.8 ± 0.45) group. It was found that there was no statistical difference between the sham and S + CLP + S groups (P > 0.05); however, there was a significant difference between the other groups (P 0.05); however, there was a significant difference between the other groups in terms of mean ALT, and there was a significant difference between all the groups in terms of mean AST, BUN, and creatinine (P < 0.05). Conclusions: It was concluded that Strontium ranelate reduced the development of life-threatening MODS in patients with sepsis, especially when it was administered before the development of sepsis, by suppressing inflammatory mediators.

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.

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.

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.

Expression and relationship of PPARγ and COX-2 in Peripheral Blood Mononuclear Cells of Multiple Organ Dysfunction Syndrome Patients

To study the expression and relationship of cyclooxygenase-2(COX-2) and peroxisome proliferators activated receptor-γ (PPARγ) in peripheral blood monouclear cells (PBMCs) of multiple organ dysfunction syndrome patients. In the emergency department and intensive care unit (ICU) of our hospital, 60 MODS patients were divided into three groups with 20 cases in each group. They were MODS1 group (APACHE II score 0-10 points), MODS 2 groups (APACHE II score 11-20 points), MODS 3 groups (APACHE II score> 20 points) and control groups of 20 healthy subjects. Venous blood were sampled 1d, 3d, 6d after diagnosis of MODS, reverse transcriptase -polymerase chain reaction (RT-PCR) were used to detect the expression of PPARγ, COX-2 in PBMCs. The expression of PPARγ, COX-2 in the same period were compared between the MODS groups and the healthy control group. The study fond that the expression of COX-2 and PPARγ were low in vehicle control group. In MODS1 group the expression of PPARγ and COX-2 was higher than in vehicle control group; during the treatment period, PPARγ was significantly increased (P <0.05), but the expression of COX-2 was significantly lower (P <0.05). PPARγ expression in MODS 2 group and MODS 3group was lower than that in vehicle control group, and its expression was progressively decreased during the treatment (P <0.05);in contrast, Expression of COX-2 in MODS2 and MODS3 group was higher than that in vehicle control group, and its level was progressively increased during the treatment (P <0.05). The study revealed a significant negative correlation between COX-2 and PPARγ in MODS1 group, MODS2 group and MODS3 group. (MODS1 group r=-0.761, P<0.01; MODS2 group: r=-0.782, P<0.01; MODS3 group: r=-0.791, P<0.01). There was no significant correlation in vehicle control group (r = -0.185, P >0.05). Thus, PPARγ may protect the MODS patients by repressing the expression of cox-2 therefore it can be used as an important indicator and potential target to determine the condition and treatment of MODS.