Oculogyric Crisis – Atypical Presentation in Patient with Dengue Fever

Here we are presenting a case of dengue fever presented with an atypical symptom of “oculogyric crisis” with features of multi organ dysfunction syndrome. Increased vascular permeability, plasma leakage, haemorrhagic manifestations, and thrombocytopenia are charecteristics of dengue fever. A 19 year old male patient, with no co-morbidity came to Dhiraj hospital with chief complaints of fever which was high grade & intermittent, it is associated with chills & rigours for 5 days. Also complain of abdominal pain over epigastric region, dull aching non radiating associated with decreased appetite since 5 days. Dengue infection has a wide range of clinical features. Neurological complications can occur in any spectrum of dengue infection. The diagnosis of oculogyric crisis is majorly clinical and it requires a focused detailed history and detailed physical examination to find out possible triggers for the crisis and to rule out other reasons for abnormal eye movements.

A CASE OF CLINICAL ITP IN A PATIENT WITH COVID19

Since December 2019, China has experienced an outbreak of SARS COV2 known as Coronavirus Disease or COVID19.Subsequently it led to pandemic all across the globe. SARS-COV-2 is known to present with a variety of manifestations ranging from a completely asymptomatic course or a mild URTI (Upper respiratory tract infection) to a full blown LRTI (Lower Respiratory Tract Infection) with ARDS (Acute Respiratory Disease Syndrome) like features, ALIs (Acute Lung Injury), Pulmonary or Pan-endothelitis, overwhelming rapidly escalating Cytokine Storm, Multi-Organ Dysfunction Syndrome (MODS), Stroke, Encephalitis, Myocarditis, Septicemia, Acute Kidney Injury, Septic shock and several other complications(2). Here we report a rare association of SARS-COV2 infection with Immune Thrombocytopenic Purpura.

The inhibition of Macrophage Migration Inhibitory Factor by ISO-1 attenuates trauma-induced multi organ dysfunction in rats

BackgroundMulti organ dysfunction syndrome caused by systemic inflammation after trauma is responsible for a high number of deaths worldwide. The cytokine Migration Inhibitory Factor (MIF) is recognized as a modulator of inflammatory response, however, its role in trauma is unknown. The aim of this study was to investigate (a) the levels of MIF in serum of trauma patients and of rats after hemorrhagic shock, (b) the potential of the MIF tautomerase activity inhibitor ISO-1 to reduce multi organ dysfunction syndrome in an acute and chronic hemorrhagic shock rat model and (c) whether treatment with ISO-1 attenuates NF-κB and NLRP3 activation in hemorrhagic shock.MethodsThe serum MIF-levels in trauma patients and rats with hemorrhagic shock were measured by Enzyme-Linked Immunosorbent Assays. Acute and chronic hemorrhagic shock rat models were performed to determine the influence of ISO-1 on multi organ dysfunction syndrome. The activation of NF-κB and NLRP3 pathways were analyzed by western blot.ResultsWe demonstrated that (a) MIF levels are increased in serum of trauma patients on arrival in the emergency room and in serum of rats after hemorrhagic shock, (b) hemorrhagic shock caused organ damage and low blood pressure (after resuscitation) in rats, while (c) treatment of hemorrhagic shock rats with ISO-1 attenuated organ injury and dysfunction in acute and chronic hemorrhagic shock rat models and (d) decreased the activation of NF-κB and NLRP3 pathways.ConclusionOur results point to a role of MIF in the pathophysiology of the organ injury and dysfunction caused by trauma/hemorrhage and indicate that MIF tautomerase activity inhibitors may have potential in the therapy of the multi organ dysfunction syndrome after trauma and/or hemorrhage.

Cytokine Storm: The Primary Determinant for the Pathophysiological Evolution of COVID-19 Deterioration

The coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing major threat to global health and has posed significant challenges for the treatment of severely ill COVID-19 patients. Several studies have reported that cytokine storms are an important cause of disease deterioration and death in COVID-19 patients. Consequently, it is important to understand the specific pathophysiological processes underlying how cytokine storms promote the deterioration of COVID-19. Here, we outline the pathophysiological processes through which cytokine storms contribute to the deterioration of SARS-CoV-2 infection and describe the interaction between SARS-CoV-2 and the immune system, as well as the pathophysiology of immune response dysfunction that leads to acute respiratory distress syndrome (ARDS), multi-organ dysfunction syndrome (MODS), and coagulation impairment. Treatments based on inhibiting cytokine storm-induced deterioration and occurrence are also described.

Hexosylceramides and Glycerophosphatidylcholine GPC(36:1) Increase in Multi-Organ Dysfunction Syndrome Patients with Pediatric Intensive Care Unit Admission over 8-Day Hospitalization

Glycero- and sphingo-lipids are important in plasma membrane structure, caloric storage and signaling. An un-targeted lipidomics approach for a cohort of critically ill pediatric intensive care unit (PICU) patients undergoing multi-organ dysfunction syndrome (MODS) was compared to sedation controls. After IRB approval, patients meeting the criteria for MODS were screened, consented (n = 24), and blood samples were collected from the PICU at HDVCH, Michigan; eight patients needed veno-arterial extracorporeal membrane oxygenation (VA ECMO). Sedation controls were presenting for routine sedation (n = 4). Plasma lipid profiles were determined by nano-electrospray (nESI) direct infusion high resolution/accurate mass spectrometry (MS) and tandem mass spectrometry (MS/MS). Biostatistics analysis was performed using R v 3.6.0. Sixty-one patient samples over three time points revealed a ceramide metabolite, hexosylceramide (Hex-Cer) was high across all time points (mean 1.63–3.19%; vs. controls 0.22%). Fourteen species statistically differentiated from sedation controls (p-value ≤ 0.05); sphingomyelin (SM) [SM(d18:1/23:0), SM(d18:1/22:0), SM(d18:1/23:1), SM(d18:1/21:0), SM(d18:1/24:0)]; and glycerophosphotidylcholine (GPC) [GPC(36:01), GPC(18:00), GPC(O:34:02), GPC(18:02), GPC(38:05), GPC(O:34:03), GPC(16:00), GPC(40:05), GPC(O:36:03)]. Hex-Cer has been shown to be involved in viral infection and may be at play during acute illness. GPC(36:01) was elevated in all MODS patients at all time points and is associated with inflammation and brain injury.

Pediatric Multi-Organ Dysfunction Syndrome: Analysis by an Untargeted “Shotgun” Lipidomic Approach Reveals Low-Abundance Plasma Phospholipids and Dynamic Recovery over 8-Day Period, a Single-Center Observational Study

Lipids are molecules involved in metabolism and inflammation. This study investigates the plasma lipidome for markers of severity and nutritional status in critically ill children. Children with multi-organ dysfunction syndrome (MODS) (n = 24) are analyzed at three time-points and cross-referenced to sedation controls (n = 4) for a total of N = 28. Eight of the patients with MODS, needed veno-arterial extracorporeal membrane oxygenation (VA ECMO) support to survive. Blood plasma lipid profiles are quantified by nano-electrospray (nESI), direct infusion high resolution/accurate mass spectrometry (MS), and tandem mass spectrometry (MS/MS), and compared to nutritional profiles and pediatric logistic organ dysfunction (PELOD) scores. Our results show that PELOD scores were not significantly different between MODS and ECMO cases across time-points (p = 0.66). Lipid profiling provides stratification between sedation controls and all MODS patients for total lysophosphatidylserine (lysoPS) (p-value = 0.004), total phosphatidylserine (PS) (p-value = 0.015), and total ether-linked phosphatidylethanolamine (ether-PE) (p-value = 0.03) after adjusting for sex and age. Nutrition intake over time did not correlate with changes in lipid profiles, as measured by caloric and protein intake. Lipid measurement in the intensive care environment shows dynamic changes over an 8-day pediatric intensive care unit (PICU) course, suggesting novel metabolic indicators for defining critically ill children.

The Feasibility of Studying Metabolites in PICU Multi-Organ Dysfunction Syndrome Patients over an 8-Day Course Using an Untargeted Approach

Metabolites are generated from critical biological functions and metabolism. This pediatric study reviewed plasma metabolites in patients suffering from multi-organ dysfunction syndrome (MODS) in the pediatric intensive care unit (PICU) using an untargeted metabolomics approach. Patients meeting the criteria for MODS were screened for eligibility and consented (n = 24), and blood samples were collected at baseline, 72 h, and 8 days; control patients (n = 4) presented for routine sedation in an outpatient setting. A subset of MODS patients (n = 8) required additional support with veno-atrial extracorporeal membrane oxygenation (VA-ECMO) therapy. Metabolites from thawed blood plasma were determined from ion pairing reversed-phase liquid chromatography–mass spectrometry (LC-MS) analysis. Chromatographic peak alignment, identification, relative quantitation, and statistical and bioinformatics evaluation were performed using MAVEN and MetaboAnalyst 4.0. Metabolite analysis revealed 115 peaks per sample. From the partial least squares-discriminant analysis (PLS-DA) with variance of importance (VIP) scores above ≥2.0, 7 dynamic metabolites emerged over the three time points: tauro-chenodeoxycholic acid (TCDCA), hexose, p-hydroxybenzoate, hydroxyphenylacetic acid (HPLA), 2_3-dihydroxybenzoic acid, 2-keto-isovalerate, and deoxyribose phosphate. After Bonferroni adjustment for repeated measures, hexose and p-hydroxybenzoate were significant at one time point or more. Kendall’s tau-b test was used for internal validation of creatinine. Metabolites may be benign or significant in describing a patient’s pathophysiology and require operator interpretation.

Hexosylceramides and glycerophosphatidylcholine GPC(36:1) increase in Multi-Organ Dysfunction Syndrome patients with Pediatric Intensive Care Unit Admission over 8-day hospitalization

Glycero- and sphingo-lipids are important in plasma membrane structure, caloric storage and signaling. An un-targeted lipidomics approach for a cohort of critically ill pediatric intensive care unit (PICU) patients, undergoing multi-organ dysfunction syndrome (MODS) was compared to sedation controls. After IRB approval, patients meeting criteria for MODS were screened, consented (n=24), and blood samples were collected from the PICU at HDVCH, Michigan; eight patients needed veno-arterial extracorporeal membrane oxygenation (VA ECMO). Sedation controls were presenting for routine sedation (n=4). Plasma lipid profiles were determined by nano-electrospray (nESI) direct infusion high resolution/accurate mass spectrometry (MS) and tandem mass spectrometry (MS/MS). Biostatistics analysis was performed using R v 3.6.0. 61 patient samples over 3 time points revealed a ceramide metabolite, hexosylceramide (Hex-Cer) was high across all time points (mean 1.63% - 3.19%; vs. controls 0.22%). Fourteen species statistically differentiated from sedation controls (P-value ≤0.05); sphingomyelin (SM) [SM(d18:1/23:0), SM(d18:1/22:0), SM(d18:1/23:1), SM(d18:1/21:0), SM(d18:1/24:0)]; and glycerophosphotidylcholine (GPC) [GPC(36:01), GPC(18:00), GPC(O:34:02), GPC(18:02), GPC(38:05), GPC(O:34:03), GPC(16:00), GPC(40:05), GPC(O:36:03)]. Hex-Cer has been shown to be involved in viral infection and may be at play during acute illness. GPC(36:01) was elevated in all MODS patients at all time points and is associated with inflammation and brain injury.

Parallels in Sepsis and COVID-19 Conditions: Implications for Managing Severe COVID-19

Sepsis is a life-threatening systemic illness attributed to a dysregulated host response to infection. Sepsis is a global burden killing ~11 million persons annually. In December 2019, a novel pneumonia condition termed coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged and has resulted in more than 1,535,982 deaths globally as of 8th December 2020. These two conditions share many pathophysiological and clinical features. Notably, both sepsis and COVID-19 patients experience consumptive thrombocytopenia, haemolytic anaemia, vascular microthrombosis, multi-organ dysfunction syndrome, coagulopathy, septic shock, respiratory failure, fever, leukopenia, hypotension, leukocytosis, high cytokine production and high predisposition to opportunistic infections. Considering the parallels in the immunopathogenesis and pathophysiological manifestations of sepsis and COVID-19, it is highly likely that sepsis care, which has a well-established history in most health systems, could inform on COVID-19 management. In view of this, the present perspective compares the immunopathogenesis and pathophysiology of COVID-19 and non-SARS-CoV-2 induced sepsis, and lessons from sepsis that can be applicable to COVID-19 management.