Development Of Multiple Organ Dysfunction Syndrome Research Articles

Impact of interleukin 6 levels on acute lung injury risk and disease severity in critically ill sepsis patients.

Sepsis is a life-threatening condition characterized by a dysregulation of the host response to infection that can lead to acute lung injury (ALI) and multiple organ dysfunction syndrome (MODS). Interleukin 6 (IL-6) is a pro-inflammatory cytokine that plays a crucial role in the pathogenesis of sepsis and its complications. To investigate the relationship among plasma IL-6 levels, risk of ALI, and disease severity in critically ill patients with sepsis. This prospective and observational study was conducted in the intensive care unit of a tertiary care hospital between January 2021 and December 2022. A total of 83 septic patients were enrolled. Plasma IL-6 levels were measured upon admission using an enzyme-linked immunosorbent assay. The development of ALI and MODS was monitored during hospitalization. Disease severity was evaluated by Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores. Among the 83 patients with sepsis, 38 (45.8%) developed ALI and 29 (34.9%) developed MODS. Plasma IL-6 levels were significantly higher in patients who developed ALI than in those without ALI (median: 125.6 pg/mL vs 48.3 pg/mL; P < 0.001). Similarly, patients with MODS had higher IL-6 levels than those without MODS (median: 142.9 pg/mL vs 58.7 pg/mL; P < 0.001). Plasma IL-6 levels were strongly and positively correlated with APACHE II (r = 0.72; P < 0.001) and SOFA scores (r = 0.68; P < 0.001). Elevated plasma IL-6 levels in critically ill patients with sepsis were associated with an increased risk of ALI and MODS. Higher IL-6 levels were correlated with greater disease severity, as reflected by higher APACHE II and SOFA scores. These findings suggest that IL-6 may serve as a biomarker for predicting the development of ALI and disease severity in patients with sepsis.

Comparative analysis of computed tomography severity indices in predicting the severity and clinical outcome in patients with acute pancreatitis.

Background: Acute pancreatitis (AP) has unpredictable severity. Its management is based on initial assessment of disease severity. It ranges from mild interstitial to severe necrotic form; the latter is associated with poor prognosis. Contrast-enhanced computed tomography (CT) of the abdomen is the gold standard in early detection of pancreatic necrosis and inassessing the severity ofAP. Two CTgrading systems exist to assess theseverity of AP: CT severity Index (CSI) and modified CSI (MCSI). This study compares the usefulness of these two systems in predicting theseverity and clinical outcome in AP in comparisonwith Ranson's criteria and clinical outcome parameters. Methods: This is a prospective hospital-based screening study of 80 patients aged >12 years with clinical diagnosis of AP who underwent contrast-enhanced CT study of the abdomen. Comparative analysis between MCSI and CSI with Ranson's criteria and clinical outcome parameters was assessed by Chi-Squared test. Results: The accuracy ofCSI and MCSI in predicting the requirement of critical care, superadded infection, multiple organ dysfunction syndrome (MODS) and requirement of intervention were 73.0%, 64.5%, 69.8% 60.9% and 77.2%, 76.0%, 74.4% & 56.6% respectively. Area under the curve for MCSI score was significantly higher (AUC: 0.861; 95% CI: 0.736-0.986) than CSI score (AUC:0.815;95% CI:0.749-0.941). MCSI and CSI showed significant correlation with Ranson's criteria; however, MCSI correlation was better (r:0.53; p<0.01) than CSI (r:0.35;p:0.04). Conclusion: CSI and MCSI are better predictors of severity, clinical outcome and mortality compared with Ranson's criteria, with MCSI being more accurate and better predictor than CSI. The accuracy of MCSI is better than CSI for prediction of requirement of critical care, development of superadded infection and development of MODS in AP. However, CSI and MCSI have low accuracy in predicting intervention in AP.

The role of ACE2 cause of death between COVID-19 and various complications

The COVID-19 pandemic has affected millions of people worldwide. While the virus primarily targets the respiratory system, it also affects other organs in the body, leading to multiple organ dysfunction syndrome (MODS) and death. Recent studies have shown that angiotensin-converting enzyme 2 (ACE2) plays a crucial role in pathogenesis of COVID-19 and development of MODS.&lt;br /&gt; Since its discovery in 2000, ACE2 has garnered widespread attention for its multiple physiological roles, leading to subsequent interest in the influence of the Renin-angiotensin system (RAS) on SARS-CoV-2 infection and COVID-19 during the pandemic.&lt;br /&gt; ACE2 is both an enzyme and a functional receptor on cell surfaces through which SARS-CoV-2 enters the host cells. Recent research has highlighted the multifaceted impact of the virus on various organs, showcasing its ability to induce severe multi-organ injuries. Understanding the intricate interplay between ACE2, RAS, and the pathophysiological changes associated with COVID-19 is crucial for the development of effective treatment strategies and preventative measures.&lt;br /&gt; This study investigates the differences in causes of death related to COVID-19 and its complications. Data from cumulative records for all age groups across the 50 states of the USA and the District of Columbia was retrospectively analyzed. The results revealed significant differences in the incidence of COVID-19 deaths associated with various medical conditions, with respiratory complications showing notably higher incidence compared to other medical conditions besides COVID-19, circulatory, and diabetes.

Risk Factors Associated With Development of Multiple-Organ Dysfunction Syndrome After Pediatric Drowning.

This study aimed to describe a single-center experience of pediatric drowning and to investigate risk factors associated with the development of pediatric multiple-organ dysfunction syndrome (MODS) after drowning events. A single-center retrospective case-control study was performed at a tertiary children's hospital examining patients aged 1 month to 25 years who were admitted to the pediatric intensive care unit after a drowning event. The study period was June 2016 to June 2021. Patients who developed MODS at day 1 of intensive care admission were compared with those who did not. A total of 48 patients with a median age of 2.3 years were included. Twenty-nine (60%) had MODS at 24 hours. Those with MODS at 24 hours were more likely to require cardiopulmonary resuscitation (CPR), required longer duration of CPR, and had longer submersion times; otherwise, there were no differences in baseline characteristics. Those who developed MODS at 24 hours had longer lengths of stays, longer lengths of mechanical ventilation, and higher mortality. Multiple admission parameters were evaluated based on MODS-free survival at 24 hours. On univariable analysis, patients without MODS-free survival at 24 hours had higher rates of CPR, higher blood glucose on admission, higher illness severity scores, higher lactates, and lower Glasgow Coma Scale scores. A multivariable model was constructed using risk factors at presentation that were significant on univariable analysis; blood glucose greater than 200 mg/dL was associated with decreased odds of MODS-free survival at 24 hours after controlling for CPR administration of greater than 5 minutes and body temperature. Development of MODS in pediatric drowning is associated with worse patient outcomes. Hyperglycemia was identified as a potentially modifiable risk factor for the development of MODS at 24 hours and could serve as a useful prognostic parameter in this unique patient population.

The Association of the Lactate-Albumin Ratio With Mortality and Multiple Organ Dysfunction in PICU Patients.

To compare the relative associations of lactate, albumin, and the lactate-albumin ratio (LAR) measured early in disease course against mortality and prevalence of multiple organ dysfunction syndrome (MODS) in a general sample of critically ill pediatric patients. Retrospective analysis of the Health Facts (Cerner Corporation, Kansas City, MO) national database. U.S. hospitals with PICUs. Children admitted to the ICU ( n = 648) from 2009 to 2018 who had lactate and albumin measured within 6 hours of admission. None. A total of 648 admissions were included, with an overall mortality rate of 10.8% ( n = 70) and a MODS prevalence of 29.3% ( n = 190). Compared with survivors, deaths had higher initial lactates (7.3 mmol/L [2.6-11.7 mmol/L] vs 1.9 mmol/L [1.2-3.1 mmol/L]; p < 0.01), lower initial albumins (3.3 g/dL [2.7-3.8 g/dL] vs 4.2 g/dL [3.7-4.7 g/dL]; p < 0.01), and higher LARs (2.2 [1.0-4.2] vs 0.5 [0.3-0.8]; p < 0.01), with similar trends in patients with MODS versus those without MODS. LAR demonstrated a higher odds ratio (OR) for death than initial lactate alone (2.34 [1.93-2.85] vs 1.29 [1.22-1.38]) and a higher OR for MODS than initial lactate alone (2.10 [1.73-2.56] vs 1.22 [1.16-1.29]). Area under the receiver operating characteristic (AUROC) curve of LAR for mortality was greater than initial lactate (0.86 vs 0.82; p < 0.01). The LAR AUROC for MODS was greater than the lactate AUROC (0.71 vs 0.66; p < 0.01). Trends of lactate, albumin, and LAR for mortality were consistent across several diagnostic subgroups (trauma, primary respiratory failure, toxicology), but not all. LAR measured early in the course of critical illness is significantly associated with mortality and development of MODS when compared with initial lactate or initial albumin alone in critically ill pediatric patients.

Pediatric Drowning: Prognostic Parameters of Multiorgan Dysfunction

Background/Objective: There are sparse data on the epidemiology of organ dysfunction in pediatric drowning and prognostic parameters are not well understood. The objective of our study was to investigate prognostic parameters and epidemiology of multiple organ dysfunction syndrome (MODS).&#x0D; Methods: This was a single center retrospective cohort study of drowning in patients 1 month to 25 years admitted to the pediatric intensive care unit at our institution from June 1, 2016-June 1, 2021. Organ dysfunction scores were assessed at distinct time points using Goldstein criteria for pediatric MODS. Risk factors for the development of MODS were then investigated. Inferential statistics were used to describe MODS. Logistic regression was used to determine the association of factors with the development of MODS at 24 hours.&#x0D; Results: Forty-eight patients were included. At 24 hours, 56.3% (n=27) had MODS which was associated with an increased risk for mortality (p=.002). There were no differences in demographics between those who developed MODS and those who did not. Of those who had MODS at 24 hours, 26% (n=7) had 2 organs involved, 41% (n=11) had 3 organs involved, 30% (n=8) had 4 dysfunctional organs and 1 child had 5 organs involved. Patients that developed MODS at 24 hours, had CPR prior to admission (p=0.038), lower body temperature on admission (p=0.049), and higher admission blood glucose (p=0.002). Adjusting for CPR and body temperature in a multivariable model, blood glucose ≥200 on admission was associated with development of MODS [OR 4.77 (95%CI: 1.13-20.137), p=0.033].&#x0D; Conclusion: Development of MODS in pediatric drowning is common and is associated with worse outcomes. Hyperglycemia on admission was identified as a risk factor for the development of MODS in this cohort.&#x0D; Scientific/Clinical/Policy Impact and Implications: Future study should address if tighter glycemic control in this at-risk patient population could lead to decreased MODS development.

Multiple Organ Dysfunction and Critically Ill Children With Acute Myeloid Leukemia: Single-Center Retrospective Cohort Study.

To describe the prevalence of multiple organ dysfunction syndrome (MODS) and critical care utilization in children and young adults with acute myeloid leukemia (AML) who have not undergone hematopoietic cell transplantation (HCT). Retrospective cohort study of MODS (defined as dysfunction of two or more organ systems) occurring any day within the first 72 hours of PICU admission. Large, quaternary-care children's hospital. Patients 1 month through 26 years old who were treated for AML from 2011-2019. None. Eighty patients with AML were included. These 80 patients had a total of 409 total non-HCT-related hospital and 71 PICU admissions. The majority 53 of 71 of PICU admissions (75%) were associated with MODS within the first 72 hours. MODS was present in 49 of 71 of PICU admissions (69%) on day 1, 29 of 52 (56%) on day 2, and 25 of 32 (78%) on day 3. The organ systems most often involved were hematologic, respiratory, and cardiovascular. There was an increasing proportion of renal failure (8/71 [11%] on day 1 to 8/32 [25%] on day 3; p = 0.02) and respiratory failure (33/71 [47%] to 24/32 [75%]; p = 0.001) as PICU stay progressed. The presence of MODS on day 1 was associated with a longer PICU length of stay (LOS) (β = 5.4 [95% CI, 0.7-10.2]; p = 0.024) and over a six-fold increased risk of an LOS over 2 days (odds ratio, 6.08 [95% CI, 1.59-23.23]; p = 0.008). Respiratory failure on admission was associated with higher risk of increased LOS. AML patients frequently require intensive care. In this cohort, MODS occurred in over half of PICU admissions and was associated with longer PICU LOS. Respiratory failure was associated with the development of MODS and progressive MODS, as well as prolonged LOS.

The Importance of Pore-Forming Toxins in Multiple Organ Injury and Dysfunction.

Multiple organ injury and dysfunction often occurs in acute critical illness and adversely affects survival. However, in patients who survive, organ function usually recovers without permanent damage. It is, therefore, likely that there are reversible mechanisms, but this is poorly understood in the pathogenesis of multiple organ dysfunction syndrome (MODS). Based on our knowledge of extracellular histones and pneumolysin, as endogenous and exogenous pore-forming toxins, respectively, here we clarify if the extent of cell membrane disruption and recovery is important in MODS. This is a combination of retrospective clinical studies of a cohort of 98 patients from an intensive care unit (ICU) in a tertiary hospital, with interventional animal models and laboratory investigation. In patients without septic shock and/or disseminate intravascular coagulation (DIC), circulating histones also strongly correlated with sequential organ failure assessment (SOFA) scores, suggesting their pore-forming property might play an important role. In vivo, histones or pneumolysin infusion similarly caused significant elevation of cell damage markers and multiple organ injury. In trauma and sepsis models, circulating histones strongly correlated with these markers, and anti-histone reagents significantly reduced their release. Comparison of pneumolysin deletion and its parental strain-induced sepsis mouse model showed that pneumolysin was not essential for sepsis development, but enhanced multiple organ damage and reduced survival time. In vitro, histones and pneumolysin treatment disrupt cell membrane integrity, resulting in changes in whole-cell currents and elevated intracellular Ca2+ to lead to Ca2+ overload. Cell-specific damage markers, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and cardiac troponin I (cTnI), were released from damaged cells. Once toxins were removed, cell membrane damage could be rapidly repaired and cellular function recovered. This work has confirmed the importance of pore-forming toxins in the development of MODS and proposed a potential mechanism to explain the reversibility of MODS. This may form the foundation for the development of effective therapies.

Mesenchymal stromal/stem cells: breaking the deadlock in the treatment of multiple organ dysfunction syndrome

Mesenchymal stromal/stem cells: breaking the deadlock in the treatment of multiple organ dysfunction syndrome

Comparative analysis of computed tomography severity indices in predicting the severity and clinical outcome in patients with acute pancreatitis

Background: Acute pancreatitis (AP) has unpredictable severity. Its management is based on initial assessment of disease severity. It ranges from mild interstitial to severe necrotic form; the latter is associated with poor prognosis. Contrast-enhanced computed tomography (CT) of the abdomen is the gold standard in early detection of pancreatic necrosis and in assessing the severity of AP. Two CT grading systems exist to assess severity of AP: CT severity Index (CSI) and modified CSI (MCSI). This study compares the usefulness of these two systems in predicting severity and clinical outcome in AP in comparison with Ranson’s criteria and clinical outcome parameters. Methods: This is a prospective hospital-based screening study of 80 patients aged &gt;12 years with clinical diagnosis of AP who underwent contrast-enhanced CT study of the abdomen. Comparative analysis between MCSI and CSI with Ranson’s criteria and clinical outcome parameters was assessed by Chi-Squared test. Results: The accuracy of CSI and MSCI in predicting the requirement of critical care, superadded infection, multiple organ dysfunction syndrome (MODS) and requirement of intervention were 73.0%, 64.5%, 69.8% 60.9% and 77.2%, 76.0%, 74.4% &amp; 56.6%, respectively. Area under the curve for MCSI score was significantly higher (AUC : 0.861; 95% CI: 0.736-0.986) than CSI score (AUC:0.815;95% CI:0.749-0.941). MCSI and CSI showed significant correlation with Ranson’s criteria; however, MCSI correlation was better (r:0.53; p&lt;0.01) than CSI (r:0.35;p:0.04). Conclusion: CSI and MCSI are better predictors of severity, clinical outcome and mortality compared with Ranson’s criteria, with MCSI being more accurate and better predictor than CSI. The accuracy of MCSI is better than CSI for prediction of requirement of critical care, development of superadded infection and development of MODS in AP. However, CSI and MCSI have low accuracy in predicting intervention in AP.

Predictive Value of Combination of Procalcitonin and Predisposition, Infection, Response, and Organ Dysfunction (PIRO) System in Septic Patients with Positive Blood Cultures in the Emergency Department.

PurposeProcalcitonin and predisposition, infection, response, and organ dysfunction (PIRO) system have high predictive value for the prognosis of critically ill patients. There are few studies on the predictive value of patients with positive blood cultures. The aim of the study was to evaluate risk stratification and sepsis-related mortality in patients with positive blood cultures via procalcitonin (PCT) combined with the PIRO system in emergency departments (ED).MethodsA total of 1074 patients with positive blood cultures were admitted to Beijing Chao-Yang Hospital ED from December 2017 to October 2020. Their serum PCT was recorded, along with a Sequential Organ Failure Assessment (SOFA) score, Mortality in Emergency Department Sepsis (MEDS) score, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and PIRO score to predict the prognosis of septic patients with positive blood culture in terms of ICU (intensive care unit) admission, multiple organ dysfunction syndrome (MODS) development, and 28-day mortality. Receiver operating characteristic (ROC) curves and logistic regression analysis were used to assess the prognostic value of the scoring systems.ResultsA total of 978 patients met the inclusion criteria. PCT, MEDS, APACHE II, and PIRO scores were found to independently predict ICU-admission, MODS development, and 28-day mortality (P<0.05), whereas SOFA did not. The AUC values of the PCT, MEDS, APACHE II, and PIRO scores for ICU-admission were 0.620, 0.740, 0.780, and 0.751, respectively. In the prediction of 28-day mortality, the AUC values of PCT, MEDS, APACHE II, and PIRO were 0.782, 0.745, 0.805, and 0.831, respectively. The AUC values combined PCT and PIRO system in predicting MODS and 28-day mortality were better than when predicting ICU-admission.ConclusionThis study indicates that PCT combined with the PIRO scoring system has a higher predictive value and is superior in predicting MODS and 28-day mortality in septic patients with positive blood cultures.

Chronic critical illness in polytrauma. Results of the Spanish trauma in ICU registry.

Chronic critical illness after trauma injury has not been fully evaluated, and there is little evidence in this regard. We aim to describe the prevalence and risk factors of chronic critical illness (CCI) in trauma patients admitted to the intensive care unit. Retrospective observational multicenter study (Spanish Registry of Trauma in ICU (RETRAUCI)). Period March 2015 to December 2019. Trauma patients admitted to the ICU, who survived the first 48h, were included. Chronic critical illness (CCI) was considered as the need for mechanical ventilation for a period greater than 14days and/or placement of a tracheostomy. The main outcomes measures were prevalence and risk factors of CCI after trauma. 1290/9213 (14%) patients developed CCI. These patients were older (51.2±19.4 vs 49±18.9); p<.01) and predominantly male (79.9%). They presented a higher proportion of infectious complications (81.3% vs 12.7%; p<.01) and multiple organ dysfunction syndrome (MODS) (27.02% vs 5.19%; p<.01). CCI patients required longer stays in the ICU and had higher ICU and overall in-hospital mortality. Age, injury severity score, head injury, infectious complications, and development of MODS were independent predictors of CCI. CCI in trauma is a prevalent entity in our series. Early identification could facilitate specific interventions to change the trajectory of this process.

Multiple organ dysfunction syndrome prediction in newborn children

There are several directions for predicting multiple organ dysfunction syndrome (MODS), but almost all of them are poorly tested in neonatology. This review is presented to indicate the problem of the condition severity objectification of newborns and the possibility of predicting the development of MODS. Scales for assessing the severity of MODS in critically ill children have been developed and used since the end of the last century, but their validation in the newborns faces certain difficulties. Prognostic nosospecific scales: NICHD (National Institute of Child Health and Human Development) calculator, CRIB II (Clinical Risk Index for Babies), SNAPPE-II (Score for Neonatal Acute Physiology with Perinatal Extension II) are used in neonatology, however their comparison in this category of patients has not been carried out.Theoretical and practical issues of the short-term and long-term prediction of the MODS onset and its outcomes in newborns is a promising area of neonatology, since it allows a doctor to be warned about an impending catastrophe and opens a “window of opportunity” for timely correction of treatment tactics and complications prevention. Obtaining different phenotypes of critical illness and predicting their outcomes in children may have good predictive potential, but such studies have not been conducted in newborns. A promising direction in predicting MODS is the identification of biomarkers of inflammation, among which endocan, cluster of differentiation 64, cluster of differentiation molecules 11b, “pancreatic stone protein” (PSP), soluble intercellular adhesionmolecule-1 (sICAM-1), progranulin, neopterin, resistin (FIZZ3, presepsin (PSP)) carry a good potential, but their effectiveness in neonatology is still to be investigated.Thus, the prediction of MODS in children and newborns remains an unresolved problem. At the same time, several promising scientific directions are actively being developed today, which may lead to a significant breakthrough in predicting MODS in neonatology.

СИНДРОМ ПОЛИОРГАННОЙ ДИСФУНКЦИИ ПРИ ОСТРОМ НЕКРОТИЗИРУЮЩЕМ ПАНКРЕАТИТЕ

Acute necrotizing pancreatitis (ANP) is associated with significantlyhighermorbidity and mortality. It is still difficult for the surgeon to choose and schedule the most appropriate treatment.In the early phase of the disease, surgical activity is considered to be ineffective and is associated with high risks. The only chance to save the patient is to conduct the intensive therapy in the intensive care unit, based on current pathogenetic approaches. The present review analyzed the current understanding of the pathogenesis of multiple organ dysfunction syndrome (MODS) in acute necrotizing pancreatitis. The role of inflammatory mediators, cytokines, biogenic amines, bradykinins, and lipid peroxidation products in the development of organ hypoperfusion is reflected. It is shown that the violation of the intestinal barrier function with the translocation of microorganisms exacerbates endogenous intoxication and contributes to the development of MODS. The endothelial dysfunction that develops in acute necrotizing pancreatitis has a significant effect on hemostasis. The literature analysis revealed the contradictory data on the functional activity of the coagulation and anticoagulation systems at different stages of the disease. The mechanisms of development of intra-abdominal hypertension and its multisystem negative impact are reflected. There are still controversialquestionof appropriatetiming and indications for surgical decompression. The analysis of the available literature data showed the need for further study of the mechanisms of multiple organ dysfunction development in acute necrotizing pancreatitis to work out new pathogenetically justified methods of its intensive therapy with an assessment of their effectiveness.

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.

Predictors of Severity of Scrub Typhus in Children Requiring Pediatric Intensive Care Admission.

Objective of our study was to determine the clinical characteristics and laboratory profile of scrub typhus patients requiring pediatric intensive care admission and to find out risk factors for the severity of illness. This was a cross-sectional observational study conducted on 1-month to 12-year-old children admitted with scrub typhus in a tertiary care pediatric intensive care unit (PICU). Relevant demographic, clinical, laboratory, treatment, and outcome-related data were documented. The severity of the disease was measured in the form of multiple organ dysfunction syndrome (MODS). With further correlation, and univariate and multivariate analyses, factors associated with severe disease were identified. During the study period, out of 586 PICU admission, 62 patients (10.6%) were diagnosed with scrub typhus. The mean age was 63.85 ± 52.78 months, where infants constituted 32.3% of the total population. Fever was present in 100% of the cases. Common indications of PICU admission were: respiratory distress 42 (67.7%), altered sensorium 41 (66.1%), convulsion 37 (59.7%), and shock 31 (50%). Total number of patients with MODS was 40 (64.5%). The case fatality rate was 8%. On multivariate analysis, infant age group ( p = 0.02), altered sensorium ( p = 0.001), reduced urine output ( p = 0.02), thrombocytopenia ( p = 0.001), raised C-reactive protein ( p = 0.004), hyponatremia ( p = 0.005), hypoalbuminemia ( p = 0.01), deranged international normalized ratio ( p = 0.02), and hyperferritinemia ( p = 0.02) came out to be independent factors in predictability for development of MODS. Multiorgan dysfunction is a life-threatening manifestation of scrub typus in children, which necessitates PICU admission. Infant age group, presence of altered sensorium, reduced urine output, thrombocytopenia, elevated inflammatory markers, coagulopathy, hypoalbuminemia, and hyponatremia predict risk for MODS.

The role of IL-6/lymphocyte ratio in the peripheral blood of severe patients with COVID-19

BackgroundTo investigate the prognostic value of a novel immune-inflammatory index, the interleukin-6-to-lymphocyte ratio (IL-6/LY), with the clinical outcomes of severe coronavirus disease 2019 (COVID-19) cases. MethodsA cohort study of COVID-19 patients in Tongji Hospital, from January 2020 to February 2020, was evaluated. Kaplan–Meier method and the log-rank test was performed to analyze survival data. Univariate and multivariate analyses were performed with COX proportional hazard regression model. The primary and secondary outcomes were in-hospital mortality and multiple organ dysfunction syndrome (MODS), respectively. ResultsTotal 320 adult patients were enrolled in our analyses. Patients were divided into low IL-6/LY group and high IL-6/LY group based on the cutoff value with 2.50. The Kaplan-Meier survival curves showed that high-value group (IL-6/LY ≥ 2.50) had a greater risk of poor prognosis (P < 0.001, respectively). Multivariate analysis indicated that IL-6/LY was the independent risk predictor for in-hospital mortality (hazard ratio [HR], 3.404; 95% confidence interval [CI], 1.090–10.633, P = 0.035) and MODS development (HR, 4.143; 95%CI, 1.321–12.986, P = 0.015). Meanwhile, IL-6/LY was positively correlated with the MuLBSTA score (r = 0.137, P = 0.031), suggesting that IL-6/LY was associated with long-term mortality (90-day). Furthermore, kinetic analysis revealed that the dynamic changes of inflammatory immune indexes were related to the severity of the disease. ConclusionsThe elevated IL-6/LY was related with the increased risk of poor prognosis. Not only that, IL-6/LY could be used for risk stratification and early clinical identification of high-risk patients.

The Critical Roles and Mechanisms of Immune Cell Death in Sepsis.

Sepsis was first described by the ancient Greek physicians over 2000 years ago. The pathophysiology of the disease, however, is still not fully understood and hence the mortality rate is still unacceptably high due to lack of specific therapies. In the last decade, great progress has been made by shifting the focus of research from systemic inflammatory response syndrome (SIRS) to multiple organ dysfunction syndrome (MODS). Sepsis has been re-defined as infection-induced MODS in 2016. How infection leads to MODS is not clear, but what mediates MODS becomes the major topic in understanding the molecular mechanisms and developing specific therapies. Recently, the mechanism of infection-induced extensive immune cell death which releases a large quantity of damage-associated molecular patterns (DAMPs) and their roles in the development of MODS as well as immunosuppression during sepsis have attracted much attention. Growing evidence supports the hypothesis that DAMPs, including high-mobility group box 1 protein (HMGB1), cell-free DNA (cfDNA) and histones as well as neutrophil extracellular traps (NETs), may directly or indirectly contribute significantly to the development of MODS. Here, we provide an overview of the mechanisms and consequences of infection-induced extensive immune cell death during the development of sepsis. We also propose a pivotal pathway from a local infection to eventual sepsis and a potential combined therapeutic strategy for targeting sepsis.

Neutrophil-derived long noncoding RNA IL-7R predicts development of multiple organ dysfunction syndrome in patients with trauma.

Overactive neutrophils are thought to be key drivers in the development of post-traumatic multiple organ dysfunction syndrome (MODS). Little is known about the role of inflammation-related lnc-IL7R in trauma. Thus, we aimed to explore the association between neutrophil-derived lnc-IL7R and post-traumatic MODS. Total RNA was extracted from the isolated circulating neutrophils in 60 patients with trauma and 33 healthy volunteers for lnc-IL7R expression determination by real-time PCR. The correlation of lnc-IL7R expression with disease severity and the development of post-traumatic MODS was analyzed. The lnc-IL7R levels were significantly lower in trauma patients, especially in those with severe trauma [Injury Severity Score (ISS) ≥ 16], and correlated negatively with the ISS, Acute Physiology and Chronic Health Evaluation II score, and length of ICU stay. The lnc-IL7R levels were also significantly decreased in patients who developed MODS than in those who did not. Lnc-IL7R was an independent predictor of MODS [odds ratio (OR) 0.654, (0.435-0.982), p = 0.041]. The area under the curve for predicting post-traumatic MODS was 0.799 (sensitivity 76.9%, specificity 71.4%), with a cutoff value of 0.024. Neutrophil-derived lnc-IL7R is an independent predictor of post-traumatic MODS; therefore, it could be a useful predictive marker for MODS.

Cardiovascular Impairment in COVID-19: Learning From Current Options for Cardiovascular Anti-Inflammatory Therapy.

In December 2019, Coronavirus Disease 2019 (COVID-19) caused by SARS-CoV-2, occurred in China and has currently led to a global pandemic. In addition to respiratory involvement, COVID-19 was also associated with significant multiple organ dysfunction syndrome (MODS). Cardiovascular impairment has been observed and is now drawing growing attention. Cardiovascular protective strategies are urgent and of great significance to the overall prognosis of COVID-19 patients. Direct viral infection, cytokine storm, and aggravation of existing cardiovascular diseases were recognized as possible mechanisms of cardiovascular impairment in COVID-19. Hyperactivated inflammation plays an important role in all three mechanisms and is considered to be fundamental in the development of cardiovascular impairment and MODS in COVID-19. Therefore, in addition to conventional cardiovascular treatment, anti-inflammatory therapy is a reasonable strategy for severe cases to further enhance cardiovascular protection and potentially mitigate MODS. We reviewed the inflammatory features and current promising treatments of COVID-19 as well as cardiovascular anti-inflammatory therapies that have been verified in previous clinical trials with positive outcomes. We believe that targeting the central pathway (IL-1β, TNF-α, IL-6), balancing the Th1 and Th2 response, and administering long-term anti-inflammatory therapy might be promising prospects to reduce cardiovascular impairment and even MODS during the acute and recovery phases of COVID-19. The cardiovascular anti-inflammatory therapies might be of great application value to the management of COVID-19 patients and we further propose an algorithm for the selection of anti-inflammatory therapy for COVID-19 patients with or at high risk of cardiovascular impairment. We recommend to take the experiences in cardiovascular anti-inflammatory therapy as references in the management of COVID-19 and conduct related clinical trials, while the clinical translation of novel treatments from preclinical studies or in vitro drug screening should proceed with caution due to unguaranteed efficacy and safety profiles.