Bacterial and fungal infections in acute-on-chronic liver failure: prevalence, characteristics and impact on prognosis

Gut, Год журнала: 2017, Номер 67(10), С. 1870 - 1880

Опубликована: Авг. 28, 2017

Bacterial infection is a frequent trigger of acute-on-chronic liver failure (ACLF), syndrome that could also increase the risk infection. This investigation evaluated prevalence and characteristics bacterial fungal infections causing complicating ACLF, predictors follow-up impact on survival. Patients 407 patients with ACLF 235 acute decompensation (AD). Results 152 (37%) presented at diagnosis; 46%(n=117) remaining 255 developed during (4 weeks). The corresponding figures in AD were 25% 18% (p<0.001). Severe (spontaneous peritonitis, pneumonia, severe sepsis/shock, nosocomial caused by multiresistant organisms) more prevalent ACLF. (either diagnosis or follow-up) showed higher grade systemic inflammation syndrome, worse clinical course (ACLF 2-3 final assessment: 47% vs 26%; p<0.001) lower 90-day probability survival (49% 72.5%;p<0.001) than without independently associated mortality ACLF-1 ACLF-2. Fungal 9 (2%) none AD, occurred mainly after (78%) had high (71%). Conclusion are extremely They intense inflammation, poor mortality. highly predisposed to develop within short period benefit from prophylactic strategies.

Язык: Английский

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Interplay Between NLRP3 Inflammasome and Autophagy

Frontiers in Immunology, Год журнала: 2020, Номер 11

Опубликована: Окт. 9, 2020

The NLRP3 inflammasome is cytosolic multi-protein complex that induces inflammation and pyroptotic cell death in response to both pathogen (PAMPs) endogenous activators (DAMPs). Recognition of PAMPs or DAMPs leads formation the complex, which results activation caspase-1, followed by cleavage release pro-inflammatory cytokines. Excessive can contribute development inflammatory diseases cancer. Autophagy vital intracellular process for recycling removal damaged proteins organelles, as well destruction pathogens. Cytosolic components are sequestered a double-membrane vesicle – autophagosome, then fuses with lysosome resulting degradation cargo. autophagy dysfunction lead hyperinflammation excessive thus acts major regulator inflammasomes. Autophagic activators, such DAMPs, cytokines reduce response. Likewise, signaling pathways regulate autophagic necessary balance between required host defense prevention detrimental inflammation. has protective role some associated inflammasome, including gouty arthritis, familial Mediterranean fever sepsis. Understanding interregulation these two essential biological processes comprehend mechanisms designing possible treatments multiple

Язык: Английский

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The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology

Journal of Hepatology, Год журнала: 2020, Номер 73(4), С. 842 - 854

Опубликована: Июль 13, 2020

•Patients with acutely decompensated cirrhosis without ACLF develop 3 different clinical courses.•Patients pre-ACLF within 90 days and have high systemic inflammation mortality.•Patients unstable suffer from complications of severe portal hypertension.•Patients stable less frequent lower 1-year mortality risk. Background & AimsAcute decompensation (AD) is defined as the acute development ascites, gastrointestinal hemorrhage, hepatic encephalopathy, infection or any combination thereof, requiring hospitalization. The presence organ failure(s) in patients AD defines acute-on-chronic liver failure (ACLF). PREDICT study a European, prospective, observational study, designed to characterize course identify predictors ACLF.MethodsA total 1,071 were enrolled. We collected detailed pre-specified information on 3-month period prior enrollment, laboratory data at enrollment. Patients then closely followed up for months. Outcomes (liver transplantation death) 1 year also recorded.ResultsThree groups identified. Pre-ACLF (n = 218) developed had rates 53.7% 67.4%, respectively. Unstable (UDC) 233) required ≥1 readmission but did not 21.0% 35.6%, Stable (SDC) 620) readmitted, rate only 9.5%. differed significantly regarding grade (high-grade enrollment aggravation during follow-up pre-ACLF; low-grade subsequent steady-course UDC; improvement SDC) prevalence surrogates hypertension throughout (high UDC vs. low SDC).ConclusionsAcute heterogeneous condition courses 2 major pathophysiological mechanisms: hypertension. Predicting remains future challenge.ClinicalTrials.gov numberNCT03056612.Lay summaryHerein, we describe, first time, after hospital admission. includes who (ACLF) short-term risk death – termed pre-ACLF. second (unstable cirrhosis) hospitalizations unrelated associated than Finally, third (stable cirrhosis), two-thirds all admitted this group rarely require admission much Acute ACLF. A recorded. Three SDC). challenge.

Язык: Английский

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A Review of Persistent Post-COVID Syndrome (PPCS)

Clinical Reviews in Allergy & Immunology, Год журнала: 2021, Номер 64(1), С. 66 - 74

Опубликована: Фев. 20, 2021

Язык: Английский

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Interleukin-7 restores lymphocytes in septic shock: the IRIS-7 randomized clinical trial

JCI Insight, Год журнала: 2018, Номер 3(5)

Опубликована: Март 7, 2018

A defining pathophysiologic feature of sepsis is profound apoptosis-induced death and depletion CD4+ CD8+ T cells. Interleukin-7 (IL-7) an antiapoptotic common γ-chain cytokine that essential for lymphocyte proliferation survival. Clinical trials IL-7 in over 390 oncologic lymphopenic patients showed was safe, invariably increased counts, improved immunity.We conducted a prospective, randomized, double-blind, placebo-controlled trial recombinant human (CYT107) with septic shock severe lymphopenia. Twenty-seven at academic sites France the United States received CYT107 or placebo 4 weeks. Primary aims were to determine safety its ability reverse lymphopenia.CYT107 well tolerated without evidence inducing storm worsening inflammation organ dysfunction. caused 3- 4-fold increase absolute counts circulating cells persisted weeks after drug administration. also cell activation.This first immunoadjuvant therapy targeting defects adaptive immunity sepsis. reversed marked loss immune effector cells, hallmark likely key mechanism morbidity mortality. represents potential new way forward treatment by restoring immunity. Such immune-based should be broadly protective against diverse pathogens including multidrug resistant bacteria preferentially target impaired immunity.Trials registered clinicaltrials.gov: NCT02640807 NCT02797431.Revimmune, NIH National Institute General Medical Sciences GM44118.

Язык: Английский

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The systemic inflammation hypothesis: Towards a new paradigm of acute decompensation and multiorgan failure in cirrhosis

Journal of Hepatology, Год журнала: 2020, Номер 74(3), С. 670 - 685

Опубликована: Дек. 7, 2020

Acute decompensation (AD) of cirrhosis is defined by the development ascites, hepatic encephalopathy and/or variceal bleeding. Ascites traditionally attributed to splanchnic arterial vasodilation and left ventricular dysfunction, hyperammonaemia, haemorrhage portal hypertension. Recent large-scale European observational studies have shown that systemic inflammation a hallmark AD. Here we present working hypothesis, suggesting through an impairment functions one or more major organ systems may be common theme act synergistically with traditional mechanisms involved in Systemic impair system function which are not mutually exclusive. The first mechanism nitric oxide-mediated accentuation preexisting vasodilation, resulting overactivation endogenous vasoconstrictor elicit intense vasoconstriction hypoperfusion certain vascular beds, particular renal circulation. Second, cause immune-mediated tissue damage, process called immunopathology. Finally, induce important metabolic changes. Indeed, inflammatory responses energetically expensive processes, requiring reallocation nutrients (glucose, amino acids lipids) fuel immune activation. also inhibits nutrient consumption peripheral (non-immune) organs, effect provide prioritisation fuels for responses. However, decrease organs result decreased mitochondrial production ATP (energy) subsequently impaired function.

Язык: Английский

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Pathological alteration and therapeutic implications of sepsis-induced immune cell apoptosis

Cell Death and Disease, Год журнала: 2019, Номер 10(10)

Опубликована: Окт. 14, 2019

Sepsis is a life-threatening organ dysfunction syndrome caused by dysregulated host response to infection that leads uncontrolled inflammatory followed immunosuppression. However, despite the high mortality rate, no specific treatment modality or drugs with efficacy available for sepsis date. Although improved strategies have increased survival rate during initial state of excessive response, recent trends in show occurs at period continuous immunosuppressive which patients succumb secondary infections within few weeks months due post-sepsis "immune paralysis." Immune cell alteration induced apoptosis has been considered major cause significant Particularly, lymphocytes, including innate immune cells and adaptive cells, associated higher risk poor outcomes. Multiple postmortem studies confirmed sepsis-induced all age groups, neonates, pediatric, adult patients, it be primary contributing factor pathophysiology sepsis. Therapeutic perspectives targeting through various could improve In this review article, we will focus on describing process respect physiologic molecular mechanisms. Further, advances apoptosis-targeted modalities also discussed.

Язык: Английский

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Dynamic balance of pro‐ and anti‐inflammatory signals controls disease and limits pathology

Immunological Reviews, Год журнала: 2018, Номер 285(1), С. 147 - 167

Опубликована: Авг. 11, 2018

Abstract Immune responses to pathogens are complex and not well understood in many diseases, this is especially true for infections by persistent pathogens. One mechanism that allows long‐term control of infection while also preventing an over‐zealous inflammatory response from causing extensive tissue damage the immune system balance pro‐ anti‐inflammatory cells signals. This dynamic responds cues both host pathogen, maintaining a steady state across multiple scales through continuous feedback. Identifying signals, cells, cytokines, other factors mediate over time has been difficult using traditional research strategies. Computational modeling studies based on data systems can identify how contributes immunity. Here we provide evidence experimental mathematical/computational support concept operating during scenarios. We focus mainly tuberculosis, currently leading cause death due infectious disease world, infections. A better understanding dynamically balanced help shape treatment strategies utilize drugs host‐directed therapies.

Язык: Английский

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Surviving sepsis campaign: research priorities for sepsis and septic shock

Intensive Care Medicine, Год журнала: 2018, Номер 44(9), С. 1400 - 1426

Опубликована: Июль 3, 2018

Язык: Английский

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New pro-resolving n-3 mediators bridge resolution of infectious inflammation to tissue regeneration

Molecular Aspects of Medicine, Год журнала: 2017, Номер 64, С. 1 - 17

Опубликована: Сен. 2, 2017

Язык: Английский

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