Exosomal mediators in sepsis and inflammatory organ injury: unraveling the role of exosomes in intercellular crosstalk and organ dysfunction.

Sepsis, a severe systemic inflammatory response to infection, remains a leading cause of morbidity and mortality worldwide. Exosomes, as mediators of intercellular communication, play a pivotal role in the pathogenesis of sepsis through modulating immune responses, metabolic reprogramming, coagulopathy, and organ dysfunction. This review highlights the emerging significance of exosomes in these processes. Initially, it provides an in-depth insight into exosome biogenesis and characterization, laying the groundwork for understanding their diverse and intricate functions. Subsequently, it explores the regulatory roles of exosomes in various immune cells such as neutrophils, macrophages, dendritic cells, T cells, and B cells. This analysis elucidates how exosomes are pivotal in modulating immune responses, thus contributing to the complexity of sepsis pathophysiology. Additionally, this review delves into the role of exosomes in the regulation of metabolism and subsequent organ dysfunction in sepsis. It also establishes a connection between exosomes and the coagulation cascade, which affects endothelial integrity and promotes thrombogenesis in sepsis. Moreover, the review discusses the dual role of exosomes in the progression and resolution of sepsis, exploring their complex involvement in inflammation and healing processes. Furthermore, it underscores their potential as biomarkers and therapeutic targets. Understanding these mechanisms presents new opportunities for novel interventions to mitigate the severe outcomes of sepsis, emphasizing the therapeutic promise of exosome research in critical care settings.

Pharmacological Inhibition of FAK-Pyk2 Pathway Protects Against Organ Damage and Prolongs the Survival of Septic Mice.

Sepsis and septic shock are associated with high mortality and are considered one of the major public health concerns. The onset of sepsis is known as a hyper-inflammatory state that contributes to organ failure and mortality. Recent findings suggest a potential role of two non-receptor protein tyrosine kinases, namely Focal adhesion kinase (FAK) and Proline-rich tyrosine kinase 2 (Pyk2), in the inflammation associated with endometriosis, cancer, atherosclerosis and asthma. Here we investigate the role of FAK-Pyk2 in the pathogenesis of sepsis and the potential beneficial effects of the pharmacological modulation of this pathway by administering the potent reversible dual inhibitor of FAK and Pyk2, PF562271 (PF271) in a murine model of cecal ligation and puncture (CLP)-induced sepsis. Five-month-old male C57BL/6 mice underwent CLP or Sham surgery and one hour after the surgical procedure, mice were randomly assigned to receive PF271 (25 mg/kg, s.c.) or vehicle. Twenty-four hours after surgery, organs and plasma were collected for analyses. In another group of mice, survival rate was assessed every 12 h over the subsequent 5 days. Experimental sepsis led to a systemic cytokine storm resulting in the formation of excessive amounts of both pro-inflammatory cytokines (TNF-α, IL-1ß, IL-17 and IL-6) and the anti-inflammatory cytokine IL-10. The systemic inflammatory response was accompanied by high plasma levels of ALT, AST (liver injury), creatinine, (renal dysfunction) and lactate, as well as a high, clinical severity score. All parameters were attenuated following PF271 administration. Experimental sepsis induced an overactivation of FAK and Pyk2 in liver and kidney, which was associated to p38 MAPK activation, leading to increased expression/activation of several pro-inflammatory markers, including the NLRP3 inflammasome complex, the adhesion molecules ICAM-1, VCAM-1 and E-selectin and the enzyme NOS-2 and myeloperoxidase. Treatment with PF271 inhibited FAK-Pyk2 activation, thus blunting the inflammatory abnormalities orchestrated by sepsis. Finally, PF271 significantly prolonged the survival of mice subjected to CLP-sepsis. Taken together, our data show for the first time that the FAK-Pyk2 pathway contributes to sepsis-induced inflammation and organ injury/dysfunction and that the pharmacological modulation of this pathway may represents a new strategy for the treatment of sepsis.

Progressive, refractory macrophage activation syndrome as the initial presentation of anti-MDA5 antibody positive juvenile dermatomyositis: a case report and literature review.

BACKGROUND: Macrophage activation syndrome (MAS) is a severe and under-recognized complication of rheumatologic diseases. We describe a patient who presented with rapidly progressive, refractory MAS found to have anti-MDA5 antibody Juvenile Dermatomyositis (JDM) as her underlying rheumatologic diagnosis. CASE PRESENTATION: We describe a 14-year-old female who at the time of admission had a history of daily fevers for 6 weeks and an unintentional sixteen-pound weight loss. Review of systems was significant for cough, shortness of breath, chest pain, headaches, sore throat, muscle aches, rash, nausea, and loss of appetite. An extensive initial workup revealed findings consistent with an autoimmune process. While awaiting results of her workup she had clinical decompensation with multi-organ system involvement including pancytopenias, interstitial lung disease, hepatitis, cardiac involvement, gastrointestinal distension and pain, feeding intolerance, extensive mucocutaneous candidiasis, and neuropsychiatric decline. Due to her decompensation, significant interstitial lung disease, and likely underlying rheumatologic condition she was started on high dose pulse steroids and mycophenolate. An MRI was performed due to her transaminitis and shoulder pain revealing significant myositis. Intravenous immunoglobulin was then initiated. The myositis antibody panel sent early in her workup was significant for anti-MDA5 and anti-SSA-52 antibodies. Despite high dose pulse steroids, mycophenolate, and IVIG, her disease progressed requiring escalating therapies. Ultimately, she responded with resolution of her MAS as well as significant and steady improvement in her feeding intolerance, interstitial lung disease, cardiac dysfunction, myositis, arthritis, and cutaneous findings. CONCLUSIONS: JDM in the pediatric patient is rare, as is MAS. In patients with complex rheumatologic conditions and lack of response to treatment, it is important to continually assess the patient's clinical status with MAS in mind, as this may change the treatment approach. Without proper recognition of this complication, patients can have a significant delay in diagnosis leading to life-threatening consequences.

Effects of real-ambient PM2.5 exposure plus lipopolysaccharide on multiple organ damage in mice.

Background: The toxicological effects of fine particulate matter (PM2.5) on the cardiopulmonary and nervous systems have been studied widely, whereas the study of PM2.5 on systemic toxicity is not in-depth enough. Lipopolysaccharide (LPS) can cause multiple organ damage. The combined effects of co-exposure of PM2.5 plus LPS on the stomach, spleen, intestine, and kidney are still unclear. Purpose: This study was aimed to explore the toxicological effects of co-exposure of PM2.5 and LPS on the different organs of mice. Research Design and Study Sample Using a real-ambient PM2.5 exposure system and an intraperitoneal LPS injection mouse model, we investigated multiple organ damage effects on male BALB/c mice after co-exposure of PM2.5 plus LPS for 23 weeks in Linfen, a city with a high PM2.5 concentration in China. Data Collection: Eosin-hematoxylin staining, ELISA and the biochemical assay analysed the toxicological effects. Results: The pathological tissue injury on the four organs above appeared in mice co-exposed to PM2.5 plus LPS, accompanied by the body weight and stomach organ coefficient abnormality, and significant elevation of pro-inflammatory cytokines levels, oxidative stress in the spleen and kidney, and levels of kidney injury molecule (KIM-1) increase in the kidney. There were tissue differences in the pathological damage and toxicological effects on mice after co-exposure, in which the spleen and kidney were more sensitive to pollutants. In the PM2.5 + LPS group, the superoxide dismutase inhibition and catalase (CAT) activity promotion in the kidney or spleen of mice were significant relative to the PM2.5 group; the CAT and interleukin-6 (IL-6) levels in the spleen were raised considerably compared with the LPS group. Conclusions: These findings suggested the severity and sensitivity of multiple organ injuries in mice in response to PM2.5 plus LPS.

[The role of the microcirculation in the pathogenesis of organ dysfunction]. / Die Rolle der Mikrozirkulation in der Entstehung des Organversagens.

The microcirculation includes all blood and lymph vessels with a diameter < 100 µm. Microcirculatory dysfunction is common in critically ill patients and is closely associated with both the severity of (multi-)organ dysfunction and mortality. The nature and extent of microcirculatory dysfunction differ depending on the underlying disease and are most pronounced in patients with systemic inflammation (e. g. sepsis), specific infections (e. g. malaria, dengue) or thrombocytopenia-associated multiple organ failure. This manuscript provides an overview of the pathophysiology, monitoring and therapy of microcirculatory dysfunction in the critically ill patient.

Coagulation Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference.

CONTEXT: Previous criteria for coagulation dysfunction in critically ill children were based mainly on expert opinion. OBJECTIVE: To evaluate current evidence regarding coagulation tests associated with adverse outcomes in children to inform criteria for coagulation dysfunction during critical illness. DATA SOURCES: Electronic searches of PubMed and Embase were conducted from January 1992 to January 2020 by using a combination of medical subject heading terms and text words to define concepts of coagulation dysfunction, pediatric critical illness, and outcomes of interest. STUDY SELECTION: Studies were included if critically ill children with coagulation dysfunction were evaluated, if performance characteristics of assessment and/or scoring tools to screen for coagulation dysfunction were evaluated, and if outcomes related to mortality or functional status, organ-specific outcomes, or other patient-centered outcomes were assessed. DATA EXTRACTION: Data were abstracted from each eligible study into a standard data extraction form, along with risk of bias assessment, by a task force member. RESULTS: The systematic review supports the presence of at least 2 of the following criteria reflecting coagulation dysfunction in the absence of liver dysfunction: platelet count <100 000 cells per µL, international normalized ratio >1.5, fibrinogen level <150 mg/dL, and D-dimer value above 10 times the upper limit of normal, or above the assay's upper limit of detection if this limit is below 10 times the upper limit of normal. LIMITATIONS: The proposed criteria for coagulation dysfunction are limited by the available evidence and will require future validation. CONCLUSIONS: Validation of the proposed criteria and identified scientific priorities will enhance our understanding of coagulation dysfunction in critically ill children.

Endocrine Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference.

CONTEXT: Endocrine dysfunction is common in critically ill children and is manifested by abnormalities in glucose, thyroid hormone, and cortisol metabolism. OBJECTIVE: To develop consensus criteria for endocrine dysfunction in critically ill children by assessing the association of various biomarkers with clinical and functional outcomes. DATA SOURCES: PubMed and Embase were searched from January 1992 to January 2020. STUDY SELECTION: We included studies in which researchers evaluated critically ill children with abnormalities in glucose homeostasis, thyroid function and adrenal function, performance characteristics of assessment and/or scoring tools to screen for endocrine dysfunction, and outcomes related to mortality, organ-specific status, and patient-centered outcomes. Studies of adults, premature infants or animals, reviews and/or commentaries, case series with sample size ≤10, and non-English-language studies were excluded. DATA EXTRACTION: Data extraction and risk-of-bias assessment for each eligible study were performed by 2 independent reviewers. RESULTS: The systematic review supports the following criteria for abnormal glucose homeostasis (blood glucose [BG] concentrations >150 mg/dL [>8.3 mmol/L] and BG concentrations <50 mg/dL [<2.8 mmol/L]), abnormal thyroid function (serum total thyroxine [T4] <4.2 µg/dL [<54 nmol/L]), and abnormal adrenal function (peak serum cortisol concentration <18 µg/dL [500 nmol/L]) and/or an increment in serum cortisol concentration of <9 µg/dL (250 nmol/L) after adrenocorticotropic hormone stimulation. LIMITATIONS: These included variable sampling for BG measurements, limited reporting of free T4 levels, and inconsistent interpretation of adrenal axis testing. CONCLUSIONS: We present consensus criteria for endocrine dysfunction in critically ill children that include specific measures of BG, T4, and adrenal axis testing.

Immune System Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference.

CONTEXT: Immune system dysfunction is poorly represented in pediatric organ dysfunction definitions. OBJECTIVE: To evaluate evidence for criteria that define immune system dysfunction in critically ill children and associations with adverse outcomes and develop consensus criteria for the diagnosis of immune system dysfunction in critically ill children. DATA SOURCES: We conducted electronic searches of PubMed and Embase from January 1992 to January 2020, using medical subject heading terms and text words to define immune system dysfunction and outcomes of interest. STUDY SELECTION: Studies of critically ill children with an abnormality in leukocyte numbers or function that is currently measurable in the clinical laboratory in which researchers assessed patient-centered outcomes were included. Studies of adults or premature infants, animal studies, reviews and commentaries, case series (≤10 subjects), and studies not published in English with inability to determine eligibility criteria were excluded. DATA EXTRACTION: Data were abstracted from eligible studies into a standard data extraction form along with risk of bias assessment by a task force member. RESULTS: We identified the following criteria for immune system dysfunction: (1) peripheral absolute neutrophil count <500 cells/µL, (2) peripheral absolute lymphocyte count <1000 cells/µL, (3) reduction in CD4+ lymphocyte count or percentage of total lymphocytes below age-specific thresholds, (4) monocyte HLA-DR expression <30%, or (5) reduction in ex vivo whole blood lipopolysaccharide-induced TNFα production capacity below manufacturer-provided thresholds. LIMITATIONS: Many measures of immune system function are currently limited to the research environment. CONCLUSIONS: We present consensus criteria for the diagnosis of immune system dysfunction in critically ill children.

Hematologic Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference.

CONTEXT: Studies of organ dysfunction in children are limited by a lack of consensus around organ dysfunction criteria. OBJECTIVES: To derive evidence-informed, consensus-based criteria for hematologic dysfunction in critically ill children. DATA SOURCES: Data sources included PubMed and Embase from January 1992 to January 2020. STUDY SELECTION: Studies were included if they evaluated assessment/scoring tools to screen for hematologic dysfunction and assessed outcomes of mortality, functional status, organ-specific outcomes, or other patient-centered outcomes. Studies of adults or premature infants, animal studies, reviews/commentaries, small case series, and non-English language studies with inability to determine eligibility were excluded. DATA EXTRACTION: Data were abstracted from each eligible study into a standard data extraction form along with risk of bias assessment. RESULTS: Twenty-nine studies were included. The systematic review supports the following criteria for hematologic dysfunction: thrombocytopenia (platelet count <100000 cells/µL in patients without hematologic or oncologic diagnosis, platelet count <30000 cells/µL in patients with hematologic or oncologic diagnoses, or platelet count decreased ≥50% from baseline; or leukocyte count <3000 cells/µL; or hemoglobin concentration between 5 and 7 g/dL (nonsevere) or <5 g/dL (severe). LIMITATIONS: Most studies evaluated pre-specified thresholds of cytopenias. No studies addressed associations between the etiology or progression of cytopenias overtime with outcomes, and no studies evaluated cellular function. CONCLUSIONS: Hematologic dysfunction, as defined by cytopenia, is a risk factor for poor outcome in critically ill children, although specific threshold values associated with increased mortality are poorly defined by the current literature.

Endothelial Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference.

OBJECTIVES: To review, analyze, and synthesize the literature on endothelial dysfunction in critically ill children with multiple organ dysfunction syndrome and to develop a consensus biomarker-based definition and diagnostic criteria. DATA SOURCES: Electronic searches of PubMed and Embase were conducted from January 1992 to January 2020, using a combination of medical subject heading terms and key words to define concepts of endothelial dysfunction, pediatric critical illness, and outcomes. STUDY SELECTION: Studies were included if they evaluated critically ill children with endothelial dysfunction, evaluated performance characteristics of assessment/scoring tools to screen for endothelial dysfunction, and assessed outcomes related to mortality, functional status, organ-specific outcomes, or other patient-centered outcomes. Studies of adults or premature infants (≤36 weeks gestational age), animal studies, reviews or commentaries, case series with sample size ≤10, and non-English language studies with the inability to determine eligibility criteria were excluded. DATA EXTRACTION: Data were abstracted from each eligible study into a standard data extraction form along with risk of bias assessment. DATA SYNTHESIS: We identified 62 studies involving 84 assessments of endothelial derived biomarkers indirectly linked to endothelial functions including leukocyte recruitment, inflammation, coagulation, and permeability. Nearly all biomarkers studied lacked specificity for vascular segment and organ systems. Quality assessment scores for the collected literature were low. CONCLUSIONS: The Endothelial Subgroup concludes that there exists no single or combination of biomarkers to diagnose endothelial dysfunction in pediatric multiple organ dysfunction syndrome. Future research should focus on biomarkers more directly linked to endothelial functions and with specificity for vascular segment and organ systems.

Patterns of Organ Dysfunction in Critically Ill Children Based on PODIUM Criteria.

OBJECTIVES: The goal of this study was to determine the incidence, prognostic performance, and generalizability of the Pediatric Organ Dysfunction Information Update Mandate (PODIUM) organ dysfunction criteria using electronic health record (EHR) data. Additionally, we sought to compare the performance of the PODIUM criteria with the organ dysfunction criteria proposed by the 2005 International Pediatric Sepsis Consensus Conference (IPSCC). METHODS: Retrospective observational cohort study of critically ill children at 2 medical centers in the United States between 2010 and 2018. We assessed prevalence of organ dysfunction based on the PODIUM and IPSCC criteria for each 24-hour period from admission to 28 days. We studied the prognostic performance of the criteria to discriminate in-hospital mortality. RESULTS: Overall, 22 427 PICU admissions met inclusion criteria, and in-hospital mortality was 2.3%. The cumulative incidence of each PODIUM organ dysfunction ranged from 15% to 30%, with an in-hospital mortality of 6% to 10% for most organ systems. The number of concurrent PODIUM organ dysfunctions demonstrated good-to-excellent discrimination for in-hospital mortality (area under the curve 0.87-0.93 for day 1 through 28) and compared favorably to the IPSCC criteria (area under the curve 0.84-0.92, P < .001 to P = .06). CONCLUSIONS: We present the first evaluation of the PODIUM organ dysfunction criteria in 2 EHR databases. The use of the PODIUM organ dysfunction criteria appears promising for epidemiologic and clinical research studies using EHR data. More studies are needed to evaluate the PODIUM criteria that are not routinely collected in structured format in EHR databases.

Cardiovascular Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference.

CONTEXT: Cardiovascular dysfunction is associated with poor outcomes in critically ill children. OBJECTIVE: We aim to derive an evidence-informed, consensus-based definition of cardiovascular dysfunction in critically ill children. DATA SOURCES: Electronic searches of PubMed and Embase were conducted from January 1992 to January 2020 using medical subject heading terms and text words to define concepts of cardiovascular dysfunction, pediatric critical illness, and outcomes of interest. STUDY SELECTION: Studies were included if they evaluated critically ill children with cardiovascular dysfunction and assessment and/or scoring tools to screen for cardiovascular dysfunction and assessed mortality, functional status, organ-specific, or other patient-centered outcomes. Studies of adults, premature infants (≤36 weeks gestational age), animals, reviews and/or commentaries, case series (sample size ≤10), and non-English-language studies were excluded. Studies of children with cyanotic congenital heart disease or cardiovascular dysfunction after cardiopulmonary bypass were excluded. DATA EXTRACTION: Data were abstracted from each eligible study into a standard data extraction form, along with risk-of-bias assessment by a task force member. RESULTS: Cardiovascular dysfunction was defined by 9 elements, including 4 which indicate severe cardiovascular dysfunction. Cardiopulmonary arrest (>5 minutes) or mechanical circulatory support independently define severe cardiovascular dysfunction, whereas tachycardia, hypotension, vasoactive-inotropic score, lactate, troponin I, central venous oxygen saturation, and echocardiographic estimation of left ventricular ejection fraction were included in any combination. There was expert agreement (>80%) on the definition. LIMITATIONS: All included studies were observational and many were retrospective. CONCLUSIONS: The Pediatric Organ Dysfunction Information Update Mandate panel propose this evidence-informed definition of cardiovascular dysfunction.

Acute Neurologic Dysfunction in Critically Ill Children: The PODIUM Consensus Conference.

CONTEXT: Acute neurologic dysfunction is common in critically ill children and contributes to outcomes and end of life decision-making. OBJECTIVE: To develop consensus criteria for neurologic dysfunction in critically ill children by evaluating the evidence supporting such criteria and their association with outcomes. DATA SOURCES: Electronic searches of PubMed and Embase were conducted from January 1992 to January 2020, by using a combination of medical subject heading terms and text words to define concepts of neurologic dysfunction, pediatric critical illness, and outcomes of interest. STUDY SELECTION: Studies were included if the researchers evaluated critically ill children with neurologic injury, evaluated the performance characteristics of assessment and scoring tools to screen for neurologic dysfunction, and assessed outcomes related to mortality, functional status, organ-specific outcomes, or other patient-centered outcomes. Studies with an adult population or premature infants (≤36 weeks' gestational age), animal studies, reviews or commentaries, case series with sample size ≤10, and studies not published in English with an inability to determine eligibility criteria were excluded. DATA EXTRACTION: Data were abstracted from each study meeting inclusion criteria into a standard data extraction form by task force members. DATA SYNTHESIS: The systematic review supported the following criteria for neurologic dysfunction as any 1 of the following: (1) Glasgow Coma Scale score ≤8; (2) Glasgow Coma Scale motor score ≤4; (3) Cornell Assessment of Pediatric Delirium score ≥9; or (4) electroencephalography revealing attenuation, suppression, or electrographic seizures. CONCLUSIONS: We present consensus criteria for neurologic dysfunction in critically ill children.

Renal Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference.

CONTEXT: Renal dysfunction is associated with poor outcomes in critically ill children. OBJECTIVE: To evaluate the current evidence for criteria defining renal dysfunction in critically ill children and association with adverse outcomes. To develop contemporary consensus criteria for renal dysfunction in critically ill children. DATA SOURCES: PubMed and Embase were searched from January 1992 to January 2020. STUDY SELECTION: Included studies evaluated critically ill children with renal dysfunction, performance characteristics of assessment tools for renal dysfunction, and outcomes related to mortality, functional status, or organ-specific or other patient-centered outcomes. Studies with adults or premature infants (≤36 weeks' gestational age), animal studies, reviews, case series, and studies not published in English with inability to determine eligibility criteria were excluded. DATA EXTRACTION: Data were extracted from included studies into a standard data extraction form by task force members. RESULTS: The systematic review supported the following criteria for renal dysfunction: (1) urine output <0.5 mL/kg per hour for ≥6 hours and serum creatinine increase of 1.5 to 1.9 times baseline or ≥0.3 mg/dL, or (2) urine output <0.5 mL/kg per hour for ≥12 hours, or (3) serum creatinine increase ≥2 times baseline, or (4) estimated glomerular filtration rate <35 mL/minute/1.73 m2, or (5) initiation of renal replacement therapy, or (6) fluid overload ≥20%. Data also support criteria for persistent renal dysfunction and for high risk of renal dysfunction. LIMITATIONS: All included studies were observational and many were retrospective. CONCLUSIONS: We present consensus criteria for renal dysfunction in critically ill children.

Acute Liver Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference.

CONTEXT: Develop evidence-based criteria for individual organ dysfunction. OBJECTIVES: Evaluate current evidence and develop contemporary consensus criteria for acute liver dysfunction with associated outcomes in critically ill children. DATA SOURCES: Electronic searches of PubMed and Embase conducted from January 1992 to January 2020, used medical subject heading terms and text words to characterize acute liver dysfunction and outcomes. STUDY SELECTION: Studies evaluating critically ill children with acute liver dysfunction, assessed screening tools, and outcomes were included. Studies evaluating adults, infants ≤36 weeks gestational age, or animals or were reviews/commentaries, case series with sample size ≤10, or non-English language studies were excluded. DATA EXTRACTION: Data were abstracted from each eligible study into a data extraction form along with risk of bias assessment by a task force member. RESULTS: The systematic review supports criteria for acute liver dysfunction, in the absence of known chronic liver disease, as having onset of symptoms <8 weeks, combined with biochemical evidence of acute liver injury, and liver-based coagulopathy, with hepatic encephalopathy required for an international normalized ratio between 1.5 and 2.0. LIMITATIONS: Unable to assess acute-on-chronic liver dysfunction, subjective nature of hepatic encephalopathy, relevant articles missed by reviewers. CONCLUSIONS: Proposed criteria identify an infant, child, or adolescent who has reached a clinical threshold where any of the 3 outcomes (alive with native liver, death, or liver transplant) are possible and should prompt an urgent liaison with a recognized pediatric liver transplant center if liver failure is the principal driver of multiple organ dysfunction.

Hourly Kinetics of Critical Organ Dysfunction in Extremely Preterm Infants.

Rationale: Use of severity of illness scores to classify patients for clinical care and research is common outside of the neonatal ICU. Extremely premature (<29 weeks' gestation) infants with extremely low birth weight (<1,000 g) experience significant mortality and develop severe pathology during the protracted birth hospitalization. Objectives: To measure at high resolution the changes in organ dysfunction that occur from birth to death or discharge home by gestational age and time, and among extremely preterm infants with and without clinically meaningful outcomes using the neonatal sequential organ failure assessment score. Methods: A single-center, retrospective, observational cohort study of inborn, extremely preterm infants with extremely low birth weight admitted between January 2012 and January 2020. Neonatal sequential organ failure assessment scores were calculated every hour for every patient from admission until death or discharge. Measurements and Main Results: Longitudinal, granular scores from 436 infants demonstrated early and sustained discrimination of those who died versus those who survived to discharge. The discrimination for mortality by the maximum score was excellent (area under curve, 0.91; 95% confidence intervals, 0.88-0.94). Among survivors with and without adverse outcomes, most score variation occurred at the patient level. The weekly average score over the first 28 days was associated with the sum of adverse outcomes at discharge. Conclusions: The neonatal sequential organ failure assessment score discriminates between survival and nonsurvival on the first day of life. The major contributor to score variation occurred at the patient level. There was a direct association between scores and major adverse outcomes, including death.

The early prediction of mortality in acute cholecystitis: Temperature, Neutrophils and Multiple organ failure (TNM) score.

OBJECTIVE: Acute Cholecystitis (AC) accounts for a significant proportion of patients presenting to the Emergency Department with abdominal pain. We suggest grading the severity of AC with a simple system: TNM, an acronym borrowed by cancer staging where T indicated Temperature, N neutrophils and M Multiple organ failure. This retrospective-prospective observational study evaluates the predictive value of TNM score on mortality of patients with AC. PATIENTS AND METHODS: TNM was developed in a training cohort of 178 patients with AC who underwent cholecystectomy from February 2005 to December 2012 (retrospectives data). To verify the prognostic value of TNM score, we prospectively recruited 172 patients who were consecutively included and treated from January 2013 to July 2020 as the validation cohort. After defining the categories T, N and M, patients were grouped in stages. The variables analyzed were age, sex, American Society of Anesthesiologists (ASA) score, blood transfusion, temperature, neutrophils count, preoperative organ failure, immune-compromised status, stage. RESULTS: In the training cohort TNM staging was: none patient at stage 0; 6 patients at stage I; 71 patients at stage II; 71 patients at stage III; 30 patients at stage IV. Death occurred in 51 patients. ASA score, neutrophils count, preoperative organ failure, stage III-IV emerged as statistically significant different prognostic factors. ASA score (III-IV) and stage (III-IV) were significant independent predictors of post-operative mortality in multivariate analysis. Comparable results were observed in the validation cohort. CONCLUSIONS: TNM classification is very easy to use; it helps to define the mortality risk and it is useful to objectively compare patients with AC.

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

ABSTRACT: 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.

A mini-review on the impact of COVID 19 on vital organs.

COVID-19 (Corona Virus Disease-2019) is an infectious disease caused by a novel coronavirus, known as the acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This is a highly contagious disease that has already affected more than 220 countries globally, infecting more than 212 million people and resulting in the death of over 4.4 million people. This review aims to highlight the pertinent documentary evidence upon the adverse effects of the SARS-CoV-2 infection on several vital human organs. SARS-CoV-2 primarily targets the lung tissue by causing diffuse alveolar damage and may result in Acute Respiratory Distress Syndrome (ARDS). SARS-CoV-2 infects the cell via cell surface receptor, angiotensin-converting enzyme 2 (ACE2). Besides lungs, SARS-CoV-2 critically damage tissues in other vital human organs such as the heart, kidney, liver, brain, and gastrointestinal tract. The effect on the heart includes muscle dysfunction (acute or protracted heart failure), myocarditis, and cell necrosis. Within hepatic tissue, it alters serum aminotransferase, total bilirubin, and gamma-glutamyl transferase levels. It contributes to acute kidney injury (AKI). Localized infection of the brain can lead to loss or attenuation of olfaction, muscular pain, headaches, encephalopathy, dizziness, dysgeusia, psychomotor disorders, and stroke; while the gastrointestinal symptoms include the disruption of the normal intestinal mucosa, leading to diarrhea and abdominal pain. This review encompassed a topical streak of systemic malfunctions caused by the SARS-CoV-2 infection. As the pandemic is still in progress, more studies will enrich our understanding and analysis of this disease.