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1.
The role of mitophagy in pulmonary sepsis.
Mohsin, M, Tabassum, G, Ahmad, S, Ali, S, Ali Syed, M
Mitochondrion. 2021;:63-75
Abstract
Sepsis is a systemic inflammatory disease with an unacceptably high mortality rate caused by an infection or trauma that involves both innate and adaptive immune systems. Inflammatory events activate different downstream pathways leading to tissue damage and ultimately multi-organ failure. Mitochondria are responsible for cellular energy, thermoregulation, metabolite biosynthesis, intracellular calcium regulation, and cell death. Damaged mitochondria induce the high Ca2+ influx through mitochondrial calcium uniporter (MCU). It also generates excessive Reactive oxygen species (ROS) and releases mtDNA into the cytoplasm, which causes induction of NLRP3 inflammasome and apoptosis. Mitophagy (Autophagy of damaged mitochondria) controls mitochondrial dynamics and function. It also maintains cellular homeostasis. This review is about how pulmonary sepsis affects the body. What is the aftermath of sepsis, and how mitophagy affects Acute Lung Injury and macrophage polarisation to overcome the damages.
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Serum trace element and heavy metal levels in patients with sepsis.
Akkaş, İ, Ince, N, Sungur, MA
The aging male : the official journal of the International Society for the Study of the Aging Male. 2020;(3):222-226
Abstract
Background and objectives: Sepsis is defined as a life-threatening organ dysfunction syndrome, which occurs when the body's immune response to infection is impaired. The aim of the present study was to investigate serum Iron, Copper, Zinco, Cobalt, Chromium, Selenium, Vanadium, Nickel, Cadmium, and Aliminium levels in patients with sepsis.Materials and methods: This prospective and observational study was conducted at a tertiary care university hospital of Turkey from 2015 to 2016, and comprised patients with sepsis. Serum concentrations of 10 elements were analyzed using inductively coupled plasma mass spectrometry. Analyses were performed at the laboratory of Düzce University Scientific and Technological Research Application and Research Center. A total of 87 participants (52 men, 35 women; average age, 74.11 ± 14.26) were enrolled.Results: When evaluated in terms of trace elements, a significant difference was noted between the sepsis and control groups in terms of the levels of the five elements. Chromium, Iron, Nickel, Copper, and Cadmium levels were significantly higher in the sepsis group.Conclusion: Our study indicated in particular, Iron, Copper, Chromium, Nickel, and Cadmium levels were elevated in patients with sepsis.
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Role of selenium supplementation in prevention of late onset sepsis among very low birth weight neonates: a systematic review of randomized controlled trials.
Garg, BD, Bansal, A, Kabra, NS
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2019;(24):4159-4165
Abstract
Background: Neonatal sepsis is one of the most common causes of neonatal morbidity and mortality. Selenium has antioxidant and immune-modulating properties.Aim: The aim of this systematic review is to evaluate role of selenium supplementation in the prevention of late onset sepsis (LOS) among very low birth weight (VLBW) neonates.Methods: We searched literature for this review by searching the Cochrane Central Register of Controlled Trials (CENTRAL) electronic PubMed, Embase, and Google Scholar. We also searched for ongoing clinical trials.Results: This review included two randomized controlled trials (RCTs) that fulfilled inclusion criteria. There was statistically significant reduction in the incidence of LOS in the intervention group [23.7 versus 35.6%; relative risk (RR) 0.67; 95% CI 0.52-0.86; p= .001; number needed to treat (NNT) 8.4; 95% CI 5.2-20.96]. However, mortality due to any cause prior to hospital discharge was not statistically significant in between the groups (6.1% intervention group versus 6.9% control group; RR 0.88; 95% CI 0.49-1.61; p= .68).Conclusions: Evidences from current systematic review revealed that selenium supplementation has some role in the prevention of LOS. However, due to limited evidences and heterogeneity between studies, large RCTs are recommended among VLBW neonates.
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4.
Application of dynamic pulse pressure and vasopressor tools for predicting outcomes in patients with sepsis in intensive care units.
Fang, WF, Huang, CH, Chen, YM, Hung, KY, Chang, YC, Lin, CY, Fang, YT, Chang, YT, Chen, HC, Huang, KT, et al
Journal of critical care. 2019;:156-162
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Abstract
PURPOSE We aimed to determine whether the combination of dynamic pulse pressure and vasopressor (DPV) use is applicable for mortality risk stratification in patients with severe sepsis. We proposed the use of the DPV tool and compared it with traditional sepsis severity indices. MATERIALS AND METHODS All adult patients who met the sepsis criteria of the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) between August 2013 and January 2017 were eligible for the study. Patients who expired within 3 days of admission to the intensive care unit (ICU) were excluded. The primary outcomes were 7-day and 28-day mortality. RESULTS The study participants included 757 consecutive adult patients. A subpopulation of 155 patients underwent immune profiling assays on days 1, 3, and 7 of ICU admission. The DPV tool had a better performance for predicting 7-day mortality (area under curve, AUC: 0.70), followed by the Sequential Organ Failure Assessment (SOFA) (AUC: 0.64), the plus pulse pressure (AUC: 0.64). For predicting 28-day mortality, the DPV tool was not inferior to the SOFA (AUC: 0.61), DPV tool (AUC: 0.59). CONCLUSIONS The DPV tool can be applied for 7-day and 28-day mortality risk prediction in patients with sepsis.
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Hydrocortisone, Ascorbic Acid and Thiamine (HAT Therapy) for the Treatment of Sepsis. Focus on Ascorbic Acid.
Marik, PE
Nutrients. 2018;(11)
Abstract
Sepsis is a devastating disease that carries an enormous toll in terms of human suffering and lives lost. Over 100 novel pharmacologic agents that targeted specific molecules or pathways have failed to improve the outcome of sepsis. Preliminary data suggests that the combination of Hydrocortisone, Ascorbic Acid and Thiamine (HAT therapy) may reduce organ failure and mortality in patients with sepsis and septic shock. HAT therapy is based on the concept that a combination of readily available, safe and cheap agents, which target multiple components of the host's response to an infectious agent, will synergistically restore the dysregulated immune response and thereby prevent organ failure and death. This paper reviews the rationale for HAT therapy with a focus on vitamin C.
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Prophylactic lactoferrin for preventing late-onset sepsis and necrotizing enterocolitis in preterm infants: A PRISMA-compliant systematic review and meta-analysis.
He, Y, Cao, L, Yu, J
Medicine. 2018;(35):e11976
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Abstract
BACKGROUND Currently, prophylactic use of drugs to promote a healthy gut microbiota and immune system in preterm infants is hot debated, among which lactoferrin is a promising supplementation. However, the effect and safety of lactoferrin to prevent late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in preterm infants remains controversial. METHODS Databases including Medline, Ovid-Embase, The Cochrane Library, CBM, CNKI, and VIP database of Chinese Journal were searched to collect randomized controlled trials (RCTs) about lactoferrin for preventing LOS and NEC in preterm infants. Languages of included RCTs were restricted to English and Chinese. Meta-analysis was conducted by Rev Man 5.3 software. The Mantel-Haenszel method with random-effects model was used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs). RESULTS A total of 9 RCTs, involving 1834 patients, were included. Pooled analysis showed that prophylactic lactoferrin could significantly reduce the incidence all culture-proven LOS (41/629 [6.5%] vs 96/659 [15.3%]; RR 0.47; 95% CI 0.33-0.67; P < .01) and NEC (stage II or more) (9/448 [2.0%] vs 26/462 [5.6%]; RR 0.40; 95% CI 0.18-0.86; P < .01). Lactoferrin was also associated with a significantly decreased hospital-acquired infection (16/139 [11.5%] vs 35/140 [25%]; RR 0.47; 95% CI 0.27-0.80; P < .01); and infection-related mortality (4/474 [0.8%] vs 25/505 [4.9%]; RR 0.24; 95% CI 0.04-1.32; P < .01, I = 53%). Lactoferrin could shorten time to reach full enteral feeding (weighted mean difference [WMD] = -2.11, 95% CI -3.12 to -1.10; P < .01) and showed a decreasing trend of duration of hospitalization (WMD = -1.69, 95% CI -6.87 to 3.50; P < .01; I = 95%). Lactoferrin did not have a significant effect on all-cause mortality (22/625 [3.5%] vs 35/647 [5.4%]; RR 0.70; 95% CI 0.38-1.30; P = .16; I = 13%). None of the included trials reported any confirmed adverse effects caused by the supplemented lactoferrin or probiotics. CONCLUSION Current evidence indicates that lactoferrin could significantly reduce the incidence of NEC and LOS, and decrease the risk of hospital-acquired infection and infection-related mortality in premature infants without obvious adverse effects.
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Applications of vitamin D in sepsis prevention.
Takeuti, FAC, Guimaraes, FSF, Guimaraes, PSF
Discovery medicine. 2018;(140):291-297
Abstract
Vitamin D (VD) is a steroid prohormone that regulates the body's calcium and phosphate levels in bone mineralization. It is also well described as a fat-soluble vitamin playing an important role in immunomodulation, regulation of cytokines, and cell proliferation. Thus, VD is a powerful hormone with pleiotropic effects, which acts to maintain optimal health. Recent studies demonstrate that VD deficiency is associated with the development of cardiovascular diseases, autoimmune disorders, and various types of cancer, each associated with increased mortality rates. VD deficiency is commonly seen in the intensive care unit (ICU); it aggravates the incidence and outcome of infectious complications in critically ill patients. In particular, VD deficiency is associated with an increased risk of sepsis and more severe clinical outcomes in patients with sepsis. These patients have dysregulated VD metabolism and frequently present insufficient plasma VD levels, which contribute to the deterioration of their clinical state. In this review, we summarize the role of VD in the immune system, the consequences of its deficiency and we discuss potential perspectives on VD supplementation in preventing sepsis and enhancing patient recovery. Although the relevance of the applications of VD in sepsis is stated, further studies are required to elucidate the optimal VD plasma levels and the recommended daily intake.
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[Probiotics: innocuousness, prevention and risks].
Brunser, O
Revista chilena de pediatria. 2017;(4):534-540
Abstract
Probiotics have been defined as live microorganisms which, when ingested in adequate numbers, confer health benefits to the host. They are currently consumed without any age restrictions and adverse effects such as sepsis, a marker of the risk of invasion of the bloodstream, are extremely infrequent. However, some health professionals express doubts about probiotics being truly innocuous. This review discusses the incidence of sepsis secondary to probiotics use, mainly lactobacilli and bifidobacteria, evaluated through molecular biology or classic culture techniques, showing that sepsis in large numbers of individuals along decennia is extremely low, of the order of 0,02% en some centers or as low as 1 case/million population in France. These data are important considering the use different species and strains of these microorganisms. Few studies which have reported other adverse effects but many of these have problems with their design that cast doubt about the validity of their results. On the contrary, it has been shown that probiotic microorganisms exert positive stimulatory effects on innate and acquired immunity, with decrease of the manifestations of atopy and eczema. These positive effects are further evidenced by the beneficial effects of many species of probiotics in preventing necrotizing enterocolitis in patients as functionally labile as premature-born babies.
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Oral lactoferrin to prevent nosocomial sepsis and necrotizing enterocolitis of premature neonates and effect on T-regulatory cells.
Akin, IM, Atasay, B, Dogu, F, Okulu, E, Arsan, S, Karatas, HD, Ikinciogullari, A, Turmen, T
American journal of perinatology. 2014;(12):1111-20
Abstract
OBJECTIVE Lactoferrin (LF) is effective in the prevention of sepsis in very low birth weight (VLBW) neonates. T-regulatory cells (Tregs) are important subsets of T lymphocytes that control pathogen-specific immune responses and are essential for intestinal immune homoeostasis. The aim of the present study is to determine whether oral LF at a dosage of 200 mg/d reduces nosocomial sepsis episodes and necrotizing enterocolitis (NEC) in premature infants and to evaluate the possible effects of LF on Treg levels. STUDY DESIGN In this prospective, placebo-controlled, double-blind, randomized trial, infants either VLBW or born before 32 weeks were assigned to receive either placebo (n = 25), or 200 mg LF (n = 25) daily throughout hospitalization. Episodes of culture proven nosocomial sepsis and NEC were recorded. The level of FOXP3 + CD4 + CD25hi lymphocytes was studied by flow cytometry at birth and discharge. A third comparison was made with healthy term neonates (n = 16). RESULTS Fewer sepsis episodes were observed in LF-treated infants (4.4 vs. 17.3/1,000 patient days, p = 0.007) with none developing NEC, without statistical significance. Treg levels at birth and discharge were similar, while preterm infants showed significantly lower levels than term controls. However, individual increases in Treg levels were higher in the LF group. CONCLUSION LF prophylaxis reduced nosocomial sepsis episodes. Treg levels in preterm infants were lower than in term infants and an increase of Treg levels under LF prophylaxis was observed. Increase in Treg levels can be the mechanism for protective effects of LF on nosocomial sepsis.
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Pathogen specific cytokine release reveals an effect of TLR2 Arg753Gln during Candida sepsis in humans.
Woehrle, T, Du, W, Goetz, A, Hsu, HY, Joos, TO, Weiss, M, Bauer, U, Brueckner, UB, Marion Schneider, E
Cytokine. 2008;(3):322-9
Abstract
Toll-like receptors (TLRs) are crucial pattern-recognition receptors (PRRs) for activation of innate and adapted immunity. TLR2 heterodimerizes with TLR1 or TLR6 to recognize multiple pathogen-associated molecular patterns (PAMPs) of fungi, Gram-positive pathogens, and mycobacteria. Receptor activation culminates in monocyte, T-helper (Th)1, and Th2 cytokine release. Single nucleotide polymorphisms (SNPs) Arg753Gln and Arg677Trp affect TLR2 responsiveness and may contribute to the course of sepsis, which is associated with substantial morbidity and mortality during intensive care treatment. We genotyped 325 critically ill patients with septic shock, and performed a detailed clinical follow-up with 47 of these patients. Here, we investigated whether distinct sepsis episodes result in defined plasma cytokine patterns, and whether cytokine profiles may be linked to the TLR2 polymorphisms. Blood sampling was done daily and microbiological testing was performed on a routine basis. DNA was extracted from whole blood and TLR2 SNPs were typed by pyrosequencing. Cytokines were measured by multiplexed array technologies and the leukocyte phenotype was determined by flow cytometry. Among the 325 ICU patients, 17 individuals (5.2%) were heterozygous for Arg753Gln. The SNP Arg677Trp was not found in any patient. Episodes of Gram-negative, Gram-positive, and Candida sepsis were recorded. During Gram-positive sepsis, the cytokine pattern did not differ between Arg753Gln heterozygous patients and wild type patients. By contrast, during Candida sepsis, the Arg753Gln heterozygous patients showed biomarker patterns that differed from wild type patients with elevated TNF-alpha plasma concentrations, but reduced IFN-gamma and IL-8 levels. In conclusion, TLR2 SNP Arg753Gln results in altered cytokine release in response to Candida but not to Gram-positive sepsis.