scholarly journals Up-regulation of BTLA expression in myeloid dendritic cells in neonatal sepsis associated with the treatment outcome and down-regulation of DC function

2020 ◽  
Author(s):  
Wandang Wang ◽  
Xuran Yang ◽  
Mingfa Guo ◽  
Zhifeng Pan ◽  
Mingjin Qiu ◽  
...  
Keyword(s):  
Neonatal Sepsis ◽  
Myeloid Dendritic Cells ◽  
Hla Dr ◽  
Tnf Α ◽  
Threatening Condition ◽  
Duration Of Hospitalization ◽  
Inflammatory Phenotype ◽  
Life Threatening ◽  
Antigen Presenting

Abstract Background: Neonatal sepsis is an acute life-threatening condition in neonates, and a proper innate inflammatory is essential for prevention of the systemic inflammation associated with sepsis. As the most potential antigen-presenting innate immune cells, dentritic cells (DCs) dysfunction has been verified detrimental for sepsis. B and T lymphocyte attenuator (BTLA) is an immune-regulatory receptor shown to be associated with DCs dysfunction. However, the role of BTLA expression in myeloid DCs (mDCs) in neonatal sepsis is unknown. Methods: 61 of neonates with sepsis and 32 of neonates having no suspicion of sepsis as control were enrolled into this study. BTLA and HLA-DR expression in mDCs was measured by flow cytometry. To further study the role of BTLA in regulating mDCs function, BTLA+mDCs and BTLA-mDCs from septic neonates were sorted and utilized to evaluate the phagacytosis capacity, bactericidal ability as well as cytokine secretion of mDCs.Results: A higher percentage of BTLA+mDCs were observed in neonatal septic patients and the percentage was positively correlated to the duration of hospitalization of neonates as well as the severity of sepsis. Moreover, a decrease MFI expression of HLA-DR was found in mDCs in neonatal sepsis, which expression was negatively correlated with the percentage of BTLA+mDCs. When compared to BTLA-mDCs, sorted BTLA+mDCs exhibited lower FITC-dextran uptake capacity but more CFU E.coli number after cells challenged by E.coli. In addition, BTLA+mDCs comparatively secreted lower level of TNF-α and IL-12, but higher IL-10. Conclusions: A higher level of BTLA in mDCs in the observed septic neonates was associated to the severity of neonatal sepsis; therefore, BTLA expression in mDCs could be a useful biomarker help to determine the neonatal sepsis development. Additionally, BTLA negatively regulated the phagocytosis capacity and bactericidal ability of mDCs and lowered their antigen-presenting ability as well as altered cells into an anti-inflammatory phenotype. Thus, targeting BTLA in mDCs may be a new therapeutic strategy for neonatal sepsis.

Bacteriophages immunomodulate the response of monocytes

2021 ◽  
pp. 153537022199515
Author(s):  
Lídia Perea ◽  
Lorena Rodríguez-Rubio ◽  
Juan C Nieto ◽  
Carlos Zamora ◽  
Elisabet Cantó ◽  
...  
Keyword(s):  
Cytokine Production ◽  
Statistical Significance ◽  
Control Sample ◽  
Polymyxin B ◽  
Dependent Manner ◽  
Direct Role ◽  
Gram Positive Bacteria ◽  
Hla Dr ◽  
Tnf Α

Bacteriophages are present in fluids from cirrhosis patients. However, their effect on the immune response is unknown. In this work, we explore the role of phages in the phenotype, function, and cytokine production of monocytes. We stimulated healthy monocytes with five different butanol-purified phage suspensions infective for Gram-negative and Gram-positive bacteria. We studied the expression of the monocyte markers involved in lipopolysaccharide recognition (LPS; CD14), antigen presentation (HLA-DR) and co-stimulation (CD86), and the concentration of induced cytokines (TNF-α, IFN-α, and IL-10) by phages. To confirm the direct role of phages without the interference of contaminating soluble LPS in phage suspensions, polymyxin B was added to the cell cultures. Phagocytosis experiments were assessed by flow cytometry using labeled phage suspensions. We observed that butanol-purified phages reduced the surface levels of CD14 and CD86 in monocytes and increased the secreted levels of TNF-α and IL-10 compared with the control sample containing only butanol buffer. All phage suspensions showed downregulation of HLA-DR expression but only Staphylococcus aureus phage contaminated with Escherichia coli reached statistical significance. The addition of polymyxin B did not restore the monocytic response induced by phages, suggesting that the effect was not caused by the presence of LPS. Monocytes were able to phagocyte phages in a dose- and time-dependent manner. To conclude, the phagocytosis of butanol-purified phages altered the phenotype and cytokine production of monocytes suggesting they become tolerogenic.

scholarly journals Role of SatO2, PaO2/FiO2 Ratio and PaO2 to Predict Adverse Outcome in COVID-19: A Retrospective, Cohort Study

2021 ◽  
Vol 18 (21) ◽  
pp. 11534
Author(s):  
Stefano Sartini ◽  
Laura Massobrio ◽  
Ombretta Cutuli ◽  
Paola Campodonico ◽  
Cristina Bernini ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Adverse Outcome ◽  
University Hospital ◽  
Rt Pcr ◽  
Threatening Condition ◽  
Life Threatening ◽  
Group A ◽  
Group B ◽  
The University

COVID-19 respiratory failure is a life-threatening condition. Oxygenation targets were evaluated in a non-ICU setting. In this retrospective, observational study, we enrolled all patients admitted to the University Hospital of Genoa, Italy, between 1 February and 31 May 2020 with an RT-PCR positive for SARS-CoV-2. PaO2, PaO2/FiO2 and SatO2% were collected and analyzed at time 0 and in case of admission, patients who required or not C-PAP (groups A and B) were categorized. Each measurement was correlated to adverse outcome. A total of 483 patients were enrolled, and 369 were admitted to hospital. Of these, 153 required C-PAP and 266 had an adverse outcome. Patients with PaO2 <60 and >100 had a higher rate of adverse outcome at time 0, in groups A and B (OR 2.52, 3.45, 2.01, respectively). About the PaO2/FiO2 ratio, the OR for < 300 was 3.10 at time 0, 4.01 in group A and 4.79 in group B. Similar odds were found for < 200 in any groups and < 100 except for group B (OR 11.57). SatO2 < 94% showed OR 1.34, 3.52 and 19.12 at time 0, in groups A and B, respectively. PaO2 < 60 and >100, SatO2 < 94% and PaO2/FiO2 ratio < 300 showed at least two- to three-fold correlation to adverse outcome. This may provide simple but clear targets for clinicians facing COVID-19 respiratory failure in a non ICU-setting.

scholarly journals Clinical significance of miR-129-5p in patients with neonatal sepsis and its regulatory role in the LPS-induced inflammatory response

2020 ◽  
Author(s):  
Meng Li ◽  
Xiaoyang Huang ◽  
Qingcui Zhuo ◽  
Jinghui Zhang ◽  
Xiuli Ju
Keyword(s):  
Inflammatory Response ◽  
Clinical Significance ◽  
Neonatal Sepsis ◽  
Close Association ◽  
Disease Diagnosis ◽  
Diagnostic Value ◽  
Regulatory Role ◽  
Value Analysis ◽  
Tnf Α

Neonatal sepsis (NS) occurs in neonates within 28 days, especially preterm infants. The dysregulation of miRNAs is widely detected in NS. The study investigated the expression changes and clinical significance of miR-129-5p in NS patients and further explored the regulatory role of miR-129-5p in the LPS-induced inflammatory response in monocytes. A total of 75 neonates with NS and 84 neonates without NS were recruited. qRT-PCR was used for the measurement of miR-129-5p expression. The receiver operating characteristic (ROC) curve was constructed for diagnostic value analysis. ELISA was used to detect the concentration of inflammatory cytokines. Monocytes were isolated from the blood of neonates to investigate the role of miR-129-5p in the LPS-induced inflammatory response in vitro. miR-129-5p was low expressed in the serum of NS cases compared with controls. Serum miR-129-5p had a diagnostic value for NS with a sensitivity of 82.7% and specificity of 79.8%. There was close association for serum miR-129-5p with TNF-α (r = -0.652, p < 0.001) and IL-8 (r = -0.700, p < 0.001) levels in NS patients. Overexpression of miR-129-5p reversed the increasing trend of TNF-α and IL-8 induced by LPS, whereas miR-129-5p downregulation aggravated the increase of TNF-α and IL-8 induced by LPS in monocytes. MiR-129-5p was downregulated in the serum of NS patients, and it might be a promising biomarker for disease diagnosis. Overexpression of miR-129-5p alleviated the inflammatory response of NS.

scholarly journals HLA Class II-DRB,-DQA and –DQB Genotypes in Peripheral Blood Shows Shifts During the Course of Sepsis

2019 ◽  
Vol 73 (1) ◽  
pp. 10-16
Author(s):  
Linda Bāra ◽  
Jeļena Eglīte ◽  
Pēteris Ošs ◽  
Vinita Cauce ◽  
Vilnis Lietuvietis ◽  
...  
Keyword(s):  
Human Leukocyte ◽  
Class Ii ◽  
Hla Class Ii ◽  
University Hospital ◽  
Control Group ◽  
Hla Dr ◽  
Group Data ◽  
Threatening Condition ◽  
Life Threatening ◽  
Genetically Determined

Abstract Undeniably, sepsis is still a profoundly damaging and life-threatening condition for many individuals. With multiple changes in sepsis patients it is difficult to precisely classify an individual’s response in sepsis as proinflammatory or immunosuppressed. The aim of this study was to investigate genetically determined predisposition to developed sepsis by analysis of distribution of human leukocyte antigen (HLA) class II genes. Samples from patients with sepsis were collected at Pauls Stradiņš Clinical University Hospital, Latvia, in an intensive care unit between October 2016 and May 2017. The study group included 62 patients with sepsis, who were genotyped for HLA-DR; DQ using real time polymerase chain reaction – sequence specific primer (RT PCR-SSP). As a control group, data of 100 individuals were taken from the genetic bank of RSU Joint Laboratory of Clinical Immunology and Immunogenetics. The summarised results showed that the frequency of alleles DRB1*04:01 (OR = 5.54; 95% CI = 1.88–16.29); DRB1*07:01 (OR = 19.03; 95% CI = 2/37–152.82); DQA1*05:01 (OR = 14.17; 95% CI = 5.67–35.4); and DQB1*02:01 (OR = 50.00; 95% CI = 2.90–861.81) were significantly increased in patients with sepsis compared to the control group patients. The frequency of DRB1*16:01 (OR = 0.17, 95% CI = 0.04–0.59); DRB1*17:01 (OR = 0.04; 95% CI = 0.00–0.69); DQA1*01:01 (OR = 0.04; 95% CI = 0.00–0.31); DQA1*01:02 (OR = 0.03; 95% CI = 0.00–0.23); DQB1*02:02 (OR = 0.12; 95% CI = 0.03–0.42) alleles was lower in sepsis patients than in control subjects. The most frequent HLA-DRB1/DQA1/DQB1 haplotypes that was significantly increased in patients with sepsis were: DRB1*01:01/DQA1*05:01/DQB1*03:01 (OR = 12.6; 95% CI = 1.51–105.0; p < 0.003). Sepsis patients with pneumonia and alleles and DRB1 04:01; 07:01, DQB1 02:01 had the highest mortality rate. Undoubtedly, our preliminary data showed that development of sepsis can be associated with alleles and haplotypes of HLA class II genes. For more precise conclusion the research should be continued to include a larger patient group.

Sudden death due to ruptured oesophageal varices – autopsy-based case report

2020 ◽  
Vol 88 (4) ◽  
pp. 189-191
Author(s):  
Nagendra Singh Sonwani ◽  
Navneet Ateriya ◽  
Arvind Kumar ◽  
Anil Kohli ◽  
Kalyan Kumar Banerjee
Keyword(s):  
Chronic Alcoholism ◽  
Medical Emergency ◽  
Oesophageal Varices ◽  
High Morbidity ◽  
Forensic Pathologist ◽  
Threatening Condition ◽  
Life Threatening ◽  
Cirrhotic Patients ◽  
Acute Haemorrhage

Acute haemorrhage from ruptured oesophageal varices is a serious consequence of portal hypertension in cirrhotic patients. It represents a medical emergency with a high morbidity and mortality rate. Studies over the years have shown a direct link with chronic alcoholism in the development of such complications. Although the gastrointestinal system accounts for a few numbers of sudden deaths, bleeding through ruptured varices represent a life-threatening condition. The role of forensic pathologist is vital in dealing with sudden deaths. Here, we report a case of a 46-year-old man who died suddenly following the rupture of oesophageal varices.

scholarly journals Reduced Parasite Burden in Children with Falciparum Malaria and Bacteremia Coinfections: Role of Mediators of Inflammation

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Gregory C. Davenport ◽  
James B. Hittner ◽  
Vincent Otieno ◽  
Zachary Karim ◽  
Harshini Mukundan ◽  
...  
Keyword(s):  
Geometric Mean ◽  
Parasite Burden ◽  
Sub Saharan Africa ◽  
Mediation Model ◽  
Multiple Mediation ◽  
Mediators Of Inflammation ◽  
Threatening Condition ◽  
Life Threatening ◽  
Sub Saharan

Bacteremia and malaria coinfection is a common and life-threatening condition in children residing in sub-Saharan Africa. We previously showed that coinfection with Gram negative (G[−]) enteric Bacilli andPlasmodium falciparum(Pf[+]) was associated with reduced high-density parasitemia (HDP, >10,000 parasites/μL), enhanced respiratory distress, and severe anemia. Since inflammatory mediators are largely unexplored in such coinfections, circulating cytokines were determined in four groups of children (n=206, aged <3 yrs): healthy;Pf[+] alone; G[−] coinfected; and G[+] coinfected.Staphylococcus aureusand non-TyphiSalmonellawere the most frequently isolated G[+] and G[−] organisms, respectively. Coinfected children, particularly those with G[−] pathogens, had lower parasite burden (peripheral and geometric mean parasitemia and HDP). In addition, both coinfected groups had increased IL-4, IL-5, IL-7, IL-12, IL-15, IL-17, IFN-γ, and IFN-αand decreased TNF-αrelative to malaria alone. Children with G[−] coinfection had higher IL-1βand IL-1Ra and lower IL-10 than thePf[+] group and higher IFN-γthan the G[+] group. To determine how the immune response to malaria regulates parasitemia, cytokine production was investigated with a multiple mediation model. Cytokines with the greatest mediational impact on parasitemia were IL-4, IL-10, IL-12, and IFN-γ. Results here suggest that enhanced immune activation, especially in G[−] coinfected children, acts to reduce malaria parasite burden.

PS02.056: TIMELY LIGATION OF THORACIC DUCT IN POST ESOPHAGECTOMY CHYLE LEAK: KEY TO SUCCESSFUL MANAGEMENT

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 136-136
Author(s):  
Sanjeev Parshad ◽  
Parvinder Sandu ◽  
Shekar Gogna ◽  
Abhijeet Beniwal ◽  
Rajendra Karwasra
Keyword(s):  
Mortality Rate ◽  
Thoracic Duct ◽  
Conflicts Of Interest ◽  
Surrounding Tissue ◽  
Chyle Leak ◽  
Threatening Condition ◽  
Life Threatening ◽  
Carcinoma Esophagus ◽  
Esophagectomy For Cancer

Abstract Background Chyle leak after esophagectomy for carcinoma esophagus is a rare but life threatening condition with reported an incidence of 1–6%. Mortality rate of up to 50% have been reported. Management of chyle leak is controversial. We reviewed our experience with iatrogenic chylothorax after esophagectomy for carcinoma esophagus. Methods From 2003 to 2017, 560 patients underwent esophagectomy for cancer at our department of oncosurgery. Eight patients developed post operative chyle leak. Transthoracic or transabdominal ligation of duct was done in six patients with in first week. 100 ml of cream was given 30 min before induction to visualize the leak intraoperatively. We used 4–0 prolene pledgeted suture to ligate the duct. Results Six patients who underwent early ligation could be salvaged and the two who were managed conservatively succumbed. Oringer et al. pointed towards conservative treatment having little place in the management of chylothorax in nutritionally depleted patients. Hence, prompt ligation of thoracic duct decreases morbidity and mortality of chylothorax. Thus the role of early surgery needs to stressed. There is a wide difference of mortality rate of conservative management of 82% with respect to the mortality rate of surgery of 10–16%. Though no conclusion data are available regarding the indication and time point of surgical ligation of the thoracic duct, it is important not to procrastinate while the condition deteriorates to a level at which surgery would be detrimental.Administration of cream to the patient (through feeding jejunostomy) around half an hour before surgery makes identification of site of leak simpler.The importance of pledgeted sutures cannot be denied as the thoracic duct is paper thin and chyle contains no fibrin. Thus non pledgeted sutures will tear it further. Infact, stitching should not be done through the duct but into the surrounding tissue around the duct and should allow the pledgets to close the duct. Conclusion Disclosure All authors have declared no conflicts of interest.

scholarly journals Genetic study of late-onset neonatal sepsis reveals significant differences by sex

2021 ◽  
Author(s):  
Timothy H. Ciesielski ◽  
Xueyi Zhang ◽  
Alessandra Tacconelli ◽  
Irja Lutsar ◽  
Vincent Meiffredy de Cabre ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Neonatal Sepsis ◽  
Genome Wide Association Study ◽  
Late Onset ◽  
Total Sample ◽  
Single Sex ◽  
A Genome ◽  
Threatening Condition ◽  
Life Threatening ◽  
Pathway Analyses

Late-Onset Neonatal Sepsis (LOS) is a rare, but life-threatening condition, involving widespread infection, immune disruption, organ dysfunction, and often death. Because exposure to pathogens is not 100% preventable, identifying susceptibility factors is critical to defining neonates at greater risk. Prior studies demonstrated that both genetics and infant sex influence susceptibility. We, therefore, performed a genome wide association study (GWAS) with 224 cases and 273 controls from six European countries to identify genetic risk factors. We tested for association with both autosomal and X-chromosome variants in the total sample and in the samples stratified by sex. In total 71 SNPs associated with neonatal sepsis at p<1x10-4 in at least one analysis. Most importantly, the sex stratified analyses revealed associations with multiple SNPs (28 SNPs in males and 16 in females), but none of 44 SNPs from single-sex analyses associated with sepsis in the other sex at p<0.05, and the vast majority showed significant SNPxsex interactions (17 of 28 from the male-only analyses and all 16 from the female-only study). Pathway analyses showed that NOTCH signaling is over-represented among loci identified by the analyses. Our results indicate that susceptibility to LOS is genetically sexually dimorphic, and suggest that NOTCH signaling is likely to play a role in it.

scholarly journals Critical Care COVID-19 Patient with a Picture of Thrombotic Thrombocytopenic Purpura

2020 ◽  
Author(s):  
Rehab AL-Ansari ◽  
Mohanad Bakkar ◽  
Leena Abdalla ◽  
Khaled Sewify
Keyword(s):  
Mechanical Ventilation ◽  
Critical Care ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Kidney Injury ◽  
Therapeutic Plasma Exchange ◽  
Thrombocytopenic Purpura ◽  
Threatening Condition ◽  
Life Threatening

Background: Thrombotic thrombocytopenic purpura (TTP) is an uncommon haematological disease which can occur at any age and may present with COVID-19. This case describes a COVID-19 complication associated with a presentation resembling TTP. Case description: A 51-year-old man who had received a kidney transplant and was on immunosuppressant medication, was admitted to a critical care unit with severe COVID-19 pneumonia/acute respiratory distress syndrome (ARDS) which required intubation, mechanical ventilation and inotropic support. The course was complicated by the classic pentad of thrombocytopenia, intravascular haemolysis, acute kidney injury, neurological symptoms and fever, which prompted the diagnosis of probable TTP. After five sessions of therapeutic plasma exchange, the patient’s general status improved, he was weaned off mechanical ventilation and his renal panel and haemolytic markers normalized. Conclusion: TTP is a life-threatening condition which requires urgent management with therapeutic plasma exchange. This case highlights some possible complications of COVID-19 generally and in immunocompromised patients specifically. The potential role of plasma exchange in COVID-19 patients without a positive diagnosis of TTP (the so-called ‘TTP resembling presentation’) is an area of further research.

scholarly journals The Role of TNF-α as a Proinflammatory Cytokine in Pathological Processes

2019 ◽  
Vol 13 (1) ◽  
pp. 332-338
Author(s):  
Luciano B. Silva ◽  
Alexandrino P. dos Santos Neto ◽  
Sandra M.A.S. Maia ◽  
Carolina dos Santos Guimarães ◽  
Iliana L. Quidute ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Literature Review ◽  
Adaptive Immunity ◽  
Proinflammatory Cytokine ◽  
Antigen Presenting Cells ◽  
Tnf Α ◽  
Antigen Presenting

TNF-α is a member of the vast cytokine family being considered a proinflammatory substance produced many by macrophages and other cells belonging to the innate immunity, many of them classified as indeed Antigen Presenting Cells (APCs) involved in the complex chemotactic process of activation of the adaptive immunity. The aim of this work was to accomplish a literature review concerning the main pathologies that have TNF-α as a modulating agent in other to bring light to the main interactions present in the inflammation installed.

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