Pathophysiology of Hemorrhage as It Relates to the Warfighter

Saving lives of wounded military Warfighters often depends on the ability to resolve or mitigate the pathophysiology of hemorrhage, specifically diminished oxygen delivery to vital organs that leads to multi-organ failure and death. However, caring for hemorrhaging patients on the battlefield presents unique challenges that extend beyond applying a tourniquet and giving a blood transfusion, especially when battlefield care must be provided for a prolonged period. This review will describe these challenges and potential strategies for treating hemorrhage on the battlefield in a prolonged casualty care situation.

Hyaluronan-coated Prussian blue nanoparticles relieve LPS-induced peritonitis by suppressing oxidative species generation in tissue-resident macrophages

Excessive inflammatory response during sepsis causes irreversible damage to healthy tissues and results in multi-organ failure. During infection, bacterial endotoxin-triggered inflammatory responses in macrophages facilitate the recruitment of circulating leukocytes,...

COVID-19: Multiorgan Dissemination of SARS-CoV-2 Is Driven by Pulmonary Factors

Multi-organ failure is one of the common causes of fatal outcome in COVID-19 patients. However, the pathogenetic association of the SARS-CoV-2 viral load (VL) level with fatal dysfunctions of the lungs, liver, kidneys, heart, spleen and brain, as well as with the risk of death in COVID-19 patients remains poorly understood. SARS-CoV-2 VL in the lungs, heart, liver, kidneys, brain, spleen and lymph nodes have been measured by RT qPCR using the following formula: NSARS-CoV−2/NABL1 × 100. Dissemination of SARS-CoV-2 in 30.5% of cases was mono-organ, and in 63.9% of cases, it was multi-organ. The average SARS-CoV-2 VL in the exudative phase of diffuse alveolar damage (DAD) was 60 times higher than in the proliferative phase. The SARS-CoV-2 VL in the lungs ranged from 0 to 250,281 copies. The “pulmonary factors” of SARS-CoV-2 multi-organ dissemination are the high level of SARS-CoV-2 VL (≥4909) and the exudative phase of DAD. The frequency of SARS-CoV-2 dissemination to lymph nodes was 86.9%, heart–56.5%, spleen–52.2%, liver–47.8%, kidney–26%, and brain–13%. We found no link between the SARS-CoV-2 VL level in the liver, kidneys, and heart and the serum level of CPK, LDH, ALP, ALT, AST and Cr of COVID-19 patients. Isolated detection of SARS-CoV-2 RNA in the myocardium of COVID-19 patients who died from heart failure is possible. The pathogenesis of COVID-19-associated multi-organ failure requires further research in a larger cohort of patients.

Successful Use of Plasma Exchange Preceding RBC Exchange in Sickle Cell Disease Hyperhemolytic Crisis with Hepatic Sequestration: A Case Report

Introduction Hyperhemolytic crisis is an uncommon complication of SCD that may cause multiorgan failure and lead to significant mortality. There are no current national or international guidelines for management of hyperhemolytic crisis and associated complications. There have been limited number of case reports and series that demonstrated utility of plasma exchange in the patients with multiorgan failure resulting from hemolysis complications (Zaidi GZ et al.,2020). We are presenting the case where hyperhemolytic crisis was complicated by hepatic sequestration and acute liver failure, that was dramatically reversed by 2 plasma exchange treatments followed by RBC exchange. Case report We present a case of a 35-year-old African American male with SCD and beta thalassemia trait with frequent hospitalizations for sickle cell pain crisis. He presented with pain typical for his acute pain crises and was admitted for intravenous hydration and pain control. The next morning, lab work showed bicytopenia with a drop in hemoglobin from 10.5 to 5.8 g/dL and platelets (PLT) from 100 to 22 X10E3/uL. Lactate dehydrogenase (LDH) increased from 434 to 2848 U/L, haptoglobin was 36 mg/dL, but disseminated intravascular coagulation (DIC) and Heparin-induced Thrombocytopenia (HIT) antibody panel were negative. The blood urea nitrogen (BUN) creatinine (Cr) ratio was also elevated (30.6) suggesting renal damage as well. He was transferred to the intensive care unit and started on Intravenous Immunoglobulin (IVIG) 0.4 grams/kilogram daily for 5 days and methylprednisolone 500 mg daily for 2 days followed by a prednisone taper. Liver enzymes continued to trend upward with AST of 19,866 U/L and ALT of 3,675 U/L on day 3 of hospitalization. Ultrasound of abdomen demonstrated mild splenomegaly with a spleen measuring 13.3 cm. The clinical presentation and hepatocellular pattern of injury was consistent with hepatic sequestration crisis. Despite receiving 1 unit of platelet 3 units of pRBC, there was little improvement and apheresis service was consulted. Plasma exchange was initiated for 2 procedures on consecutive days followed by RBC exchange with rapid improvement in clinical status and laboratory findings with a reduction of LDH (1304), AST (129), ALT (204), Hgb (8.0), PLT (41), BUN/Cr (20.0). He was discharged on day 7 at baseline status. Discussion Although the mechanism of development of hyperhemolysis in SCD is not fully understood, the hemolysis leads to release of free hemoglobin (Hb) and free heme that activate neutrophils, and vascular endothelial cells via TLR-4. This ultimately leads to inflammatory, coagulative, and cytotoxic damages and decreased nitric oxide (NO) bioavailability which further contributes to SCD complications such as pulmonary and systemic vasculopathy, pain crisis and acute chest syndrome and multi organ failure (Louie JE et al., 2018). This provides a rationale for plasma exchange - removal of free heme from the patient plasma and replenishing exhausted haptoglobin and hemopexin reserves from donor plasma. Hemolytic crisis causing visceral organ damage is relatively rare. There are no current guidelines for management of such patients. In 1996 Betrosian et al. discussed the first case of liver failure in a SCD with vasa-occlusive crisis treated with RBC and plasma transfusions (Betrosian A et al., 1996). Since then, there have been case reports/series of plasma exchange/plasma transfusions in SCD with multi organ failure (Geigel EJ et al., 1997, Louie JE et al., 2018) but reports about use of plasma exchange in SCD patients with hepatic sequestration have not been identified by our literature review. Our case demonstrates that plasma exchange in hyperhemolysis and hepatic sequestration is: Safe Leads to quick and significant improvement in hemolysis laboratory values. Results in quick and durable reversal of hepatic sequestration and associated liver failure. Adds plasma exchange as therapeutic apheresis modality in addition to previously accepted RBC exchange. Provides data about priority of plasma exchange over RBC exchange in this clinical situation. Disclosures No relevant conflicts of interest to declare.

Molecular Mechanisms of Multi-Organ Failure in COVID-19 and Potential of Stem Cell Therapy

As the number of confirmed cases and deaths occurring from Coronavirus disease 2019 (COVID-19) surges worldwide, health experts are striving hard to fully comprehend the extent of damage caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although COVID-19 primarily manifests itself in the form of severe respiratory distress, it is also known to cause systemic damage to almost all major organs and organ systems within the body. In this review, we discuss the molecular mechanisms leading to multi-organ failure seen in COVID-19 patients. We also examine the potential of stem cell therapy in treating COVID-19 multi-organ failure cases.

Hyperinflammatory Immune Response and COVID-19: A Double Edged Sword

The coronavirus disease-19 (COVID-19) elicited by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused devastating health, economic and social impact worldwide. Its clinical spectrum ranges from asymptomatic to respiratory failure and multi-organ failure or death. The pathogenesis of SARS-CoV-2 infection is attributed to a complex interplay between virus and host immune response. It involves activation of multiple inflammatory pathways leading to hyperinflammation and cytokine storm, resulting in tissue damage, acute respiratory distress syndrome (ARDS) and multi-organ failure. Accumulating evidence has raised concern over the long-term health effects of COVID-19. Importantly, the neuroinvasive potential of SARS-CoV-2 may have devastating consequences in the brain. This review provides a conceptual framework on how the virus tricks the host immune system to induce infection and cause severe disease. We also explore the key differences between mild and severe COVID-19 and its short- and long-term effects, particularly on the human brain.

Glucocorticoids in acute pancreatitis: a propensity score matching analysis

Background There are few reports about the effect of glucocorticoids in the treatment of acute pancreatitis in humans. This study aims to evaluate the effect of glucocorticoids in the treatment of acute pancreatitis by propensity score matching analysis. Results Acute pancreatitis patients admitted between 2014 and 2019 were collected from the database and analyzed. Included patients were divided into the glucocorticoids-used group (GC group) and the non-glucocorticoids-used group (NGC group) according to whether glucocorticoids were used. A total of 818 eligible patients were included in the final analysis. Seventy-six patients were treated with glucocorticoids, and 742 patients were treated without glucocorticoids. Before propensity score matching, the triglyceride levels (38.2 ± 18.5 vs. 20.2 ± 16.8, P < 0.05) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (7.1 ± 2.5 vs. 4.5 ± 2.1, P < 0.05) at admission were significantly higher in the GC group than in the NGC group. The incidence of multi-organ failure (33.3% vs. 11.9%, P < 0.05) was significantly higher in the GC group than in the NGC group. Patients in the GC group showed a positive balance of fluid intake and output over 72 h. After 1:1 propensity score matching, 59 patients from each group (GC and NGC) were included in the analysis. There were no significant differences in age, sex, body mass index, triglycerides, or APACHE II scores between the two groups (P > 0.05), and the patients’ clinical outcomes were reversed. The proportion of patients with organ failure (40.7% vs. 52.5%, p < 0.05) and multi-organ failure (35.0% vs. 67.7%, P < 0.05) was significantly lower in the GC group than in the NGC group. Furthermore, patients in the GC group had significantly shorter lengths of hospital stay (12.9 ± 5.5 vs. 16.3 ± 7.7, P < 0.05) and costs (25,348.4 ± 2512.6vs. 32,421.7 ± 2813.3, P < 0.05) than those in the NGC group. Conclusions This study presents preliminary confirmation of the beneficial effect of glucocorticoids in the treatment of acute pancreatitis. More high-quality prospective studies are needed in the future.