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Life Sciences May 2021A novel infectious disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was detected in December 2019 and declared as a global... (Review)
Review
A novel infectious disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was detected in December 2019 and declared as a global pandemic by the World Health. Approximately 15% of patients with COVID-19 progress to severe pneumonia and eventually develop acute respiratory distress syndrome (ARDS), septic shock and/or multiple organ failure with high morbidity and mortality. Evidence points towards a determinant pathogenic role of members of the renin-angiotensin system (RAS) in mediating the susceptibility, infection, inflammatory response and parenchymal injury in lungs and other organs of COVID-19 patients. The receptor for advanced glycation end-products (RAGE), a member of the immunoglobulin superfamily, has important roles in pulmonary pathological states, including fibrosis, pneumonia and ARDS. RAGE overexpression/hyperactivation is essential to the deleterious effects of RAS in several pathological processes, including hypertension, chronic kidney and cardiovascular diseases, and diabetes, all of which are major comorbidities of SARS-CoV-2 infection. We propose RAGE as an additional molecular target in COVID-19 patients for ameliorating the multi-organ pathology induced by the virus and improving survival, also in the perspective of future infections by other coronaviruses.
Topics: Animals; COVID-19; Drug Discovery; Humans; Molecular Targeted Therapy; Multiple Organ Failure; Receptor for Advanced Glycation End Products; Renin-Angiotensin System; SARS-CoV-2; Signal Transduction; COVID-19 Drug Treatment
PubMed: 33636175
DOI: 10.1016/j.lfs.2021.119251 -
The Journal of Trauma and Acute Care... Dec 2022Existing studies have found a low prevalence of multiple organ dysfunction syndrome (MODS) in pediatric trauma patients, typically applying adult criteria to...
BACKGROUND
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.
METHODS
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.
RESULTS
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).
CONCLUSION
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.
LEVEL OF EVIDENCE
Prognostic and Epidemiological; Level III.
Topics: Adult; Child; Humans; Multiple Organ Failure; Retrospective Studies; Intensive Care Units, Pediatric; Risk Factors; Prognosis
PubMed: 35358103
DOI: 10.1097/TA.0000000000003616 -
Journal of Human Hypertension Jan 2020
Topics: Acute Kidney Injury; Antihypertensive Agents; Blood Pressure Determination; Diagnosis, Differential; Early Medical Intervention; Emergency Medical Services; Humans; Hypertension, Malignant; Hypertensive Encephalopathy; Hypertensive Retinopathy; Multiple Organ Failure; Practice Guidelines as Topic; Prognosis
PubMed: 31636349
DOI: 10.1038/s41371-019-0267-y -
Pediatrics Jan 2022Multiple scores exist to characterize organ dysfunction in children.
CONTEXT
Multiple scores exist to characterize organ dysfunction in children.
OBJECTIVE
To review the literature on multiple organ dysfunction (MOD) scoring systems to estimate severity of illness and to characterize the performance characteristics of currently used scoring tools and clinical assessments for organ dysfunction in critically ill children.
DATA SOURCES
Electronic searches of PubMed and Embase were conducted from January 1992 to January 2020.
STUDY SELECTION
Studies were included if they evaluated critically ill children with MOD, evaluated the performance characteristics of scoring tools for MOD, and assessed outcomes related to mortality, functional status, organ-specific outcomes, or other patient-centered outcomes.
DATA EXTRACTION
Data were abstracted into a standard data extraction form by a task force member.
RESULTS
Of 1152 unique abstracts screened, 156 full text studies were assessed including a total of 54 eligible studies. The most commonly reported scores were the Pediatric Logistic Organ Dysfunction Score (PELOD), pediatric Sequential Organ Failure Assessment score (pSOFA), Pediatric Index of Mortality (PIM), PRISM, and counts of organ dysfunction using the International Pediatric Sepsis Definition Consensus Conference. Cut-offs for specific organ dysfunction criteria, diagnostic elements included, and use of counts versus weighting varied substantially.
LIMITATIONS
While scores demonstrated an increase in mortality associated with the severity and number of organ dysfunctions, the performance ranged widely.
CONCLUSIONS
The multitude of scores on organ dysfunction to assess severity of illness indicates a need for unified and data-driven organ dysfunction criteria, derived and validated in large, heterogenous international databases of critically ill children.
Topics: Child; Critical Illness; Humans; Multiple Organ Failure; Organ Dysfunction Scores; Prognosis
PubMed: 34970683
DOI: 10.1542/peds.2021-052888D -
The Turkish Journal of Pediatrics 2022Thrombocytopenia-associated multiple organ failure (TAMOF) causes a high ratio of mortality in pediatric patients. Only anticoagulants and profibrinolytic molecules can...
BACKGROUND
Thrombocytopenia-associated multiple organ failure (TAMOF) causes a high ratio of mortality in pediatric patients. Only anticoagulants and profibrinolytic molecules can be replaced with plasma infusion (PI), while therapeutic plasma exchange (TPE) eliminates antifibrinolytic and thrombogenic molecules and charges inadequate anticoagulants and profibrinolytic molecules. This study aims to compare the efficacy of plasma exchange to plasma infusion in pediatric TAMOF patients.
METHODS
Twenty-seven patients with TAMOF were included and the efficacy of PI and TPE was compared. The demographic data, admission laboratory values, Pediatric Logistic Organ Dysfunction (PELOD) scores before the beginning of treatment and PELOD at the end of treatment, and outcomes of groups were compared.
RESULTS
Sixteen children were in the plasma infusion group, eleven children were in the plasma exchange group. The total mortality rate of all patients was 37%. The PELOD scores were significantly reduced on the 5th day of treatment in both groups and also PELOD scores were significantly higher on the 5th day of study in the non-survivor group (p: < 0.001). The fifth day of PELOD scores and ferritin had a significant effect on mortality (OR: 1.85, 95% CI: 1.02-2.69; p: 0.04, OR: 1.43, 95% CI: 0.97-2.03; p: 0.05). The overall mortality ratio was not different between TPE and PI groups (p: 0.12).
CONCLUSIONS
Although there was no difference in mortality rates in children who received plasma exchange compared to children who received plasma infusion, mechanical ventilation and length of pediatric intensive care unit (PICU) day were shorter in the TPE group. The small patient population may be the major cause for the lack of significant statistical difference.
Topics: Child; Humans; Multiple Organ Failure; Plasma Exchange; Survival Rate; Thrombocytopenia; Intensive Care Units, Pediatric
PubMed: 36583890
DOI: 10.24953/turkjped.2022.494 -
Journal of Hepatology Jul 2021The syndrome of acute-on-chronic liver failure combines deterioration of liver function in a patient with chronic liver disease, with the development of extrahepatic... (Review)
Review
The syndrome of acute-on-chronic liver failure combines deterioration of liver function in a patient with chronic liver disease, with the development of extrahepatic organ failure and high short-term mortality. Its successful management demands a rapid and coherent response to the development of dysfunction and failure of multiple organ systems in an intensive care unit setting. This response recognises the features that distinguish it from other critical illness and addresses the complex interplay between the precipitating insult, the many organ systems involved and the disordered physiology of underlying chronic liver disease. An evidence base is building to support the approaches currently adopted and outcomes for patients with this condition are improving, but mortality remains unacceptably high. Herein, we review practical considerations in critical care management, as well as discussing key knowledge gaps and areas of controversy that require further focussed research.
Topics: Acute-On-Chronic Liver Failure; Critical Care; Disease Management; Humans; Multiple Organ Failure; Needs Assessment
PubMed: 34039487
DOI: 10.1016/j.jhep.2020.10.024 -
Pharmaceutical Biology Dec 2023Plantamajoside (PMS) possesses rich pharmacological characteristics that have been applied to remedy dozens of diseases. However, the understanding of PMS in sepsis...
CONTEXT
Plantamajoside (PMS) possesses rich pharmacological characteristics that have been applied to remedy dozens of diseases. However, the understanding of PMS in sepsis remains insufficient.
OBJECTIVE
Role of PMS in sepsis-regulated organ dysfunction and potential mechanisms were investigated.
MATERIALS AND METHODS
Thirty C57BL/6 male mice were adaptive fed for three days and used to establish acute sepsis model by caecal ligation and perforation (CLP). These experimental mice were divided into Sham, CLP, CLP + 25 mg PMS/kg body weight (PMS/kg), CLP + 50 mg PMS/kg and CLP + 100 mg PMS/kg ( = 6). The pathological and apoptotic changes of lung, liver and heart tissues were observed via HE and TUNEL staining. The injury-related factors of lung, liver and heart were detected by corresponding kits. ELISA and qRT-PCR were applied to assess IL-6/TNF-α/IL-1β levels. Apoptosis-related and TRAF6/NF-κB-related proteins were determined using Western blotting.
RESULTS
All doses of PMS enhanced the survival rates in the sepsis-induced mouse model. PMS remitted sepsis-mediated lung, liver and heart injury through prohibiting MPO/BALF (70.4%/85.6%), AST/ALT (74.7%/62.7%) and CK-MB/CK (62.3%/68.9%) levels. Moreover, the apoptosis index (lung 61.9%, liver 50.2%, heart 55.7% reduction) and IL-6/TNF-α/IL-1β levels were suppressed by PMS. Furthermore, PMS lowered TRAF6 and p-NF-κB p65 levels, whereas TRAF6 overexpression reversed the protective influences of PMS in organ injury, apoptosis and inflammation triggered by sepsis.
DISCUSSION AND CONCLUSIONS
PMS suppressed sepsis-induced organ dysfunction by regulating the TRAF6/NF-κB axis, and PMS treatment may be considered as a novel strategy for sepsis-caused damage in future.
Topics: Mice; Male; Animals; NF-kappa B; TNF Receptor-Associated Factor 6; Tumor Necrosis Factor-alpha; Interleukin-6; Multiple Organ Failure; Mice, Inbred C57BL; Sepsis
PubMed: 37288729
DOI: 10.1080/13880209.2023.2215849 -
Peptides Oct 2020The family of natriuretic peptides (NPs) discovered in mammalian tissues including cardiac atrium and brain consists of three members, namely, atrial, B- and C-type... (Review)
Review
The family of natriuretic peptides (NPs) discovered in mammalian tissues including cardiac atrium and brain consists of three members, namely, atrial, B- and C-type natriuretic peptides (ANP, BNP, CNP). Since the discovery, basic and clinical studies have been vigorously performed to explore the biological functions and pathophysiological roles of NPs in a wide range of diseases including hypertension and heart failure. These studies revealed that ANP and BNP are hormones secreted from the heart into the blood stream in response to pre- or after-load, counteracting blood pressure (BP) elevation and fluid retention through specific receptors. Meanwhile, CNP was found to be produced by the vascular endothelium, acting as a local mediator potentially serving protective functions for the blood vessels. Because NPs not only exert blood pressure lowering actions but also alleviate hypertensive organ damage, attempts have been made to develop therapeutic agents for hypertension by utilizing this family of NPs. One strategy is to inhibit neprilysin, an enzyme degrading NPs, thereby enhancing the actions of endogenous peptides. Recently, a dual inhibitor of angiotensin receptor-neprilysin was approved for heart failure, and neprilysin inhibition has also been shown to be beneficial in treating patients with hypertension. This review summarizes the roles of NPs in regulating BP, with special references to hypertension and hypertensive organ damage, and discusses the therapeutic implications of neprilysin inhibition.
Topics: Animals; Antihypertensive Agents; Blood Pressure; Humans; Hypertension; Multiple Organ Failure; Natriuretic Peptides; Neprilysin; Receptors, Atrial Natriuretic Factor
PubMed: 32610060
DOI: 10.1016/j.peptides.2020.170352 -
Deutsche Medizinische Wochenschrift... Sep 2021Several inflammatory rheumatic diseases can severely affect any organ system and require immediate intervention and intensive care admission. The early detection of... (Review)
Review
Several inflammatory rheumatic diseases can severely affect any organ system and require immediate intervention and intensive care admission. The early detection of impending organ failure and the underlying rheumatic disease is of paramount importance for the prognosis and outcome of affected patients. Therefore, a thorough knowledge of the potential life threatening organ manifestations of systemic rheumatic diseases is of particular interest for clinicians working in intensive care. This paper provides an overview of diagnostic steps and therapy of organ manifestations in critically ill patients with underlying systemic rheumatic diseases. The presentation of the relevant systemic rheumatic diseases is structured according to the most important organ systems, i. e. the respiratory system, the kidney and the cardiovascular system. Furthermore, there is a focus in this paper on macrophage activation syndrome (MAS) as a potentially lethal complication of several rheumatic diseases and the catastrophic antiphospholipid syndrome (CAPS) as a rare cause of multi organ failure.
Topics: Antiphospholipid Syndrome; Critical Care; Critical Illness; Humans; Intensive Care Units; Macrophage Activation Syndrome; Multiple Organ Failure; Prognosis; Rheumatic Diseases
PubMed: 34448191
DOI: 10.1055/a-0949-4889 -
The British Journal of Surgery Mar 2020The nature of multiple organ dysfunction syndrome (MODS) after traumatic injury is evolving as resuscitation practices advance and more patients survive their injuries...
BACKGROUND
The nature of multiple organ dysfunction syndrome (MODS) after traumatic injury is evolving as resuscitation practices advance and more patients survive their injuries to reach critical care. The aim of this study was to characterize contemporary MODS subtypes in trauma critical care at a population level.
METHODS
Adult patients admitted to major trauma centre critical care units were enrolled in this 4-week point-prevalence study. MODS was defined by a daily total Sequential Organ Failure Assessment (SOFA) score of more than 5. Hierarchical clustering of SOFA scores over time was used to identify MODS subtypes.
RESULTS
Some 440 patients were enrolled, of whom 245 (55·7 per cent) developed MODS. MODS carried a high mortality rate (22·0 per cent versus 0·5 per cent in those without MODS; P < 0·001) and 24·0 per cent of deaths occurred within the first 48 h after injury. Three patterns of MODS were identified, all present on admission. Cluster 1 MODS resolved early with a median time to recovery of 4 days and a mortality rate of 14·4 per cent. Cluster 2 had a delayed recovery (median 13 days) and a mortality rate of 35 per cent. Cluster 3 had a prolonged recovery (median 25 days) and high associated mortality rate of 46 per cent. Multivariable analysis revealed distinct clinical associations for each form of MODS; 24-hour crystalloid administration was associated strongly with cluster 1 (P = 0·009), traumatic brain injury with cluster 2 (P = 0·002) and admission shock severity with cluster 3 (P = 0·003).
CONCLUSION
Contemporary MODS has at least three distinct types based on patterns of severity and recovery. Further characterization of MODS subtypes and their underlying pathophysiology may lead to future opportunities for early stratification and targeted interventions.
Topics: Adult; Aged; Cluster Analysis; Crystalloid Solutions; Female; Humans; Male; Middle Aged; Multiple Organ Failure; Organ Dysfunction Scores; Time Factors; Wounds and Injuries
PubMed: 31691956
DOI: 10.1002/bjs.11361