The role of PD-L1 in the immune dysfunction that mediates hypoxia-induced multiple organ injury.

Hypoxia is a pathological condition common to many diseases, although multiple organ injuries induced by hypoxia are often overlooked. There is increasing evidence to suggest that the hypoxic environment may activate innate immune cells and suppress adaptive immunity, further stimulating inflammation and inhibiting immunosurveillance. We found that dysfunctional immune regulation may aggravate hypoxia-induced tissue damage and contribute to secondary injury. Among the diverse mechanisms of hypoxia-induced immune dysfunction identified to date, the role of programmed death-ligand 1 (PD-L1) has recently attracted much attention. Besides leading to tumour immune evasion, PD-L1 has also been found to participate in the progression of the immune dysfunction which mediates hypoxia-induced multiple organ injury. In this review, we aimed to summarise the role of immune dysfunction in hypoxia-induced multiple organ injury, the effects of hypoxia on the cellular expression of PD-L1, and the effects of upregulated PD-L1 expression on immune regulation. Furthermore, we summarise the latest information pertaining to the involvement, diagnostic value, and therapeutic potential of immunosuppression induced by PD-L1 in various types of hypoxia-related diseases, including cancers, ischemic stroke, acute kidney injury, and obstructive sleep apnoea. Video Abstract.

Combined Hemorrhagic Shock and Unilateral Common Carotid Occlusion Induces Neurological Injury in Adult Male Rats.

Background: Clinical assessment reveals that patients after surgery of cardiopulmonary bypass or coronary bypass experience postoperative cognitive dysfunction. This study aimed to investigate whether resuscitation after a hemorrhagic shock (HS) and/or mild cerebral ischemia caused by a unilateral common carotid artery occlusion (UCCAO) can cause brain injury and concomitant neurological dysfunction, and explore the potential mechanisms. Methods: Blood withdrawal (6 mL/100 g body weight) for 60 min through the right jugular vein catheter-induced an HS. Immediately after the termination of HS, we reinfused the initially shed blood volumes to restore and maintain the mean arterial blood pressure (MABP) to the original value during the 30-min resuscitation. A cooling water blanket used to induce whole body cooling for 30 min after the end of resuscitation. Results: An UCCAO caused a slight cerebral ischemia (cerebral blood flow [CBF] 70%) without hypotension (MABP 85 mmHg), systemic inflammation, multiple organs injuries, or neurological injury. An HS caused a moderate cerebral ischemia (52% of the original CBF levels), a moderate hypotension (MABP downed to 22 mmHg), systemic inflammation, and peripheral organs injuries. However, combined an UCCAO and an HS caused a severe cerebral ischemia (18% of the original CBF levels), a moderate hypotension (MABP downed to 17 mmHg), systemic inflammation, peripheral organs damage, and neurological injury, which can be attenuated by whole body cooling. Conclusions: When combined with an HS, an UCCAO is associated with ischemic neuronal injury in the ipsilateral hemisphere of adult rat brain, which can be attenuated by therapeutic hypothermia. A resuscitation from an HS regards as a reperfusion insult which may induce neurological injury in patients with an UCCAO disease.

Reduction of lymphocyte count at early stage elevates severity and death risk of COVID-19 patients: a hospital-based case-cohort study.

Introduction: Several reports have noted that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) induced lymphopenia in coronavirus disease 2019 (COVID-19) patients. However, the clinical significance of lymphopenia remains unclear. The objective of this study was to analyze the association between lymphopenia at an early stage and the prognosis of COVID-19 patients. Material and methods: All 192 hospitalized patients with COVID-19 were enrolled. Demographic data and clinical characteristics were collected and patient's prognosis was followed up. Results: On admission, 84 (43.8%) patients suffered from lymphopenia among COVID-19 patients. The count and percentage of lymphocytes on admission were lower among patients over 70 years old than those of younger patients. Multivariate logistic regression revealed that older age was a risk factor of lymphopenia. Of interest, chest CT score, a key marker of lung injury, was increased among COVID-19 patients with lymphopenia. By contrast, PaCO2, SpO2 and oxygenation index, several respiratory function markers, were decreased in COVID-19 patients with lymphopenia. Moreover, total bilirubin (TBIL) and direct bilirubin (DBIL), two markers of hepatic injury, creatinine and urea nitrogen, two indices of renal function, and creatine kinase, AST and LDH, three myocardial enzymes, were elevated in COVID-19 patients with lymphopenia. Among 84 COVID-19 patients with lymphopenia, 32.1% died. The fatality rate was obviously higher in COVID-19 patients with lymphopenia. Conclusions: Older COVID-19 patients are more susceptible to lymphopenia. Multiple organ injuries were more serious in COVID-19 patients with lymphopenia. Lymphopenia at an early stage aggravates the severity and elevates the death risk of COVID-19 patients.

Long non-coding RNA plasmacytoma variant translocation 1 correlates with higher inflammation, multiple organ injury and mortality risk in acute pancreatitis, especially in severe acute pancreatitis.

BACKGROUND: Long non-coding RNA plasmacytoma variant translocation 1 (lnc-PVT1) possesses a good ability to regulate inflammation as well as multiple organ injury via multiple pathways, and clinically exacerbates severe acute pancreatitis (SAP) via autophagy. This study aimed to further assess the correlation of lnc-PVT1 with inflammation, multiple disease assessment scales, and prognostication in acute pancreatitis (AP) patients. METHODS: Peripheral blood mononuclear cell (PBMC) samples were collected from 98 AP patients (within 24 h after admission) and 50 healthy controls (HCs). lnc-PVT1 in PBMC samples was examined by reverse transcription-quantitive polymerase chain reaction. Multiple AP assessments, C-reactive protein (CRP) level, and in-hospital deaths were evaluated or recorded. RESULTS: lnc-PVT1 was overexpressed in AP patients compared with HCs; it was also positively correlated with Ranson's score, acute pathologic and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, and CRP level in AP patients. Besides, lnc-PVT1 disclosed a good predictive value for higher in-hospital mortality in AP patients (the area under the curve: 0.838, 95% confidence interval: 0.708-0.968). Lastly, lnc-PVT1 was generally correlated with CRP level as well as SOFA score among mild AP, moderate-severe AP, and SAP subgroups, especially in SAP subgroup; it was also correlated with higher mortality risk in SAP subgroup, but not in mild AP or moderate-severe AP subgroup. CONCLUSION: lnc-PVT1 is associated with CRP level, SOFA score, and higher mortality risk in AP patients, especially in SAP patients, indicating its potential as a biomarker for AP.

[Treatment and nursing of one patient with burns on perineal region and complicated by secondary multiple organ injuries by exposing to paraquat fluid].

On March 18, 2016, one 53 years old man with burns on perineal region and complicated by secondary multiple organ injuries by exposing to paraquat fluid was admitted to our department. Comprehensive treatment measures including protective mechanical ventilation, intensive care, vacuum sealing drainage, anti-infection, and organ protection were conducted sequentially. Through 33 days of comprehensive treatment and nursing, the patient's condition substantially improved and he left hospital. This case presents that paraquat fluid absorption through skin and mucosa can also lead to severe systemic poisoning, and multiple organ protection is the key to improve the prognosis of this patient.

Intravenous injection of post-hemorrhagic shock mesenteric lymph induces multiple organ injury in rats.

Post-hemorrhagic shock mesenteric lymph (PHSML) has an important role in the multiple organ injuries caused by severe shock. The current study investigated whether intravenous injection of PHSML induces organ injury in normal rats. Following the establishment of hemorrhagic shock in donor rats (40±2 mmHg, 3 h), PHSML was drained during hypotension at 1-3 h and then injected to normal rats through the femoral vein within 30 min. The mean arterial pressure (MAP) was measured, and samples were obtained for analysis of histology and biochemical indices at 2.5 h post-PHSML administration. PHSML administration resulted in a significant decrease in MAP at the early and late stage of the experiment. Structural damage of the lung, kidney, heart and liver was also observed, and the levels of urea, creatinine, aspartate aminotransferase, total bile acid and creatine kinase MB isoenzyme were increased in the plasma. Additionally, PHSML injection significantly increased the levels of trypsin, tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 and receptor of advanced glycation end-products in the plasma, malondialdehyde in the lung and myocardium, and TNF-α in the lung, kidney, myocardium and liver. Intravenous injection of PHSML induced multiple organ injury in normal rats via increases in trypsin activity, inflammatory factors and free radical production. The findings indicate that PHSML return is an important contributor to organ damage following hemorrhagic shock.

Comparison of American guidelines for field triage and Polish criteria as qualification to a trauma center.

INTRODUCTION: Trauma is the third cause of death among the general population in Poland, and the first in people aged 1-44 years. Trauma centers are hospitals dedicated to treating patients with multiple organ injuries, in a complex way that endeavours to ensure a lower mortality rate, shorter hospital stay and better outcomes if the patients are transferred to such a center. Worldwide, there are many models on how to treat a trauma patient, but them to be qualified for the procedure, the selection of potential patients is crucial. OBJECTIVE: The aim of the study was to compare the Polish model for qualification to a trauma center and American Guidelines for Field Triage. MATERIAL AND METHODS: Retrospective analysis of medical documentation recorded between 1 January 2014 - 31 December 2014 was undertaken. The study concerned trauma patients admitted to the Emergency Department of the Regional Trauma Center at the Copernicus Memorial Hospital in Lódz, Poland. Inclusion criterion was initial diagnosis 'multiple-organ injury' among patients transported by the Emergency Medical Service (EMS). RESULTS: In the period indicated, 3,173 patients were admitted to the Emergency Department at the Copernicus Memorial Hospital. From among them, 159 patients were included in the study. Only 13.2% of the patients fulfilled the Polish Qualification Criteria to Trauma Center in comparison to 87.4% who fulfilled the American Guidelines for Field Triage. CONCLUSIONS: Polish qualification criteria do not consider the large group of patients with severe injuries (ISS>15), but indicate patients with minimal chance of survival. Polish criteria do not consider the mechanism of injury, which is a relevant predictive indicator of severe or extremely severe injuries (ISS>15). Further studies should be undertaken to improve the qualification and treatment of trauma patients in Poland.