People with COVID-19 might have sustained postinfection sequelae. Known by a variety of names, including long COVID or long-haul COVID, and listed in the ICD-10 classification as post-COVID-19 ...condition since September, 2020, this occurrence is variable in its expression and its impact. The absence of a globally standardised and agreed-upon definition hampers progress in characterisation of its epidemiology and the development of candidate treatments. In a WHO-led Delphi process, we engaged with an international panel of 265 patients, clinicians, researchers, and WHO staff to develop a consensus definition for this condition. 14 domains and 45 items were evaluated in two rounds of the Delphi process to create a final consensus definition for adults: post-COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset, with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include, but are not limited to, fatigue, shortness of breath, and cognitive dysfunction, and generally have an impact on everyday functioning. Symptoms might be new onset following initial recovery from an acute COVID-19 episode or persist from the initial illness. Symptoms might also fluctuate or relapse over time. A separate definition might be applicable for children. Although the consensus definition is likely to change as knowledge increases, this common framework provides a foundation for ongoing and future studies of epidemiology, risk factors, clinical characteristics, and therapy.
Sepsis biomarkers can have important diagnostic, therapeutic, and prognostic functions. In a previous review, we identified 3370 references reporting on 178 different biomarkers related to sepsis. In ...the present review, we evaluate the progress in the research of sepsis biomarkers.
Using the same methodology as in our previous review, we searched the PubMed database from 2009 until September 2019 using the terms "Biomarker" AND "Sepsis." There were no restrictions by age or language, and all studies, clinical and experimental, were included.
We retrieved a total of 5367 new references since our previous review. We identified 258 biomarkers, 80 of which were new compared to our previous list. The majority of biomarkers have been evaluated in fewer than 5 studies, with 81 (31%) being assessed in just a single study. Apart from studies of C-reactive protein (CRP) or procalcitonin (PCT), only 26 biomarkers have been assessed in clinical studies with more than 300 participants. Forty biomarkers have been compared to PCT and/or CRP for their diagnostic value; 9 were shown to have a better diagnostic value for sepsis than either or both of these biomarkers. Forty-four biomarkers have been evaluated for a role in answering a specific clinical question rather than for their general diagnostic or prognostic properties in sepsis.
The number of biomarkers being identified is still increasing although at a slower rate than in the past. Most of the biomarkers have not been well-studied; in particular, the clinical role of these biomarkers needs to be better evaluated.
Mesenchymal stromal cells (MSCs, "adult stem cells") have been widely used experimentally in a variety of clinical contexts. There is interest in using these cells in critical illness, however, the ...safety profile of these cells is not well known. We thus conducted a systematic review of clinical trials that examined the use MSCs to evaluate their safety.
MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (to June 2011), were searched. Prospective clinical trials that used intravascular delivery of MSCs (intravenously or intra-arterially) in adult populations or mixed adult and pediatric populations were identified. Studies using differentiated MSCs or additional cell types were excluded. The primary outcome adverse events were grouped according to immediate events (acute infusional toxicity, fever), organ system complications, infection, and longer term adverse events (death, malignancy). 2347 citations were reviewed and 36 studies met inclusion criteria. A total of 1012 participants with clinical conditions of ischemic stroke, Crohn's disease, cardiomyopathy, myocardial infarction, graft versus host disease, and healthy volunteers were included. Eight studies were randomized control trials (RCTs) and enrolled 321 participants. Meta-analysis of the RCTs did not detect an association between acute infusional toxicity, organ system complications, infection, death or malignancy. There was a significant association between MSCs and transient fever.
Based on the current clinical trials, MSC therapy appears safe. However, further larger scale controlled clinical trials with rigorous reporting of adverse events are required to further define the safety profile of MSCs.
Polycystic ovary syndrome (PCOS) is a heterogeneous and complex disorder that has both adverse reproductive and metabolic implications for affected women. However, there is generally poor ...understanding of its etiology. Varying expert-based diagnostic criteria utilize some combination of oligo-ovulation, hyperandrogenism, and the presence of polycystic ovaries. Criteria that require hyperandrogenism tend to identify a more severe reproductive and metabolic phenotype. The phenotype can vary by race and ethnicity, is difficult to define in the perimenarchal and perimenopausal period, and is exacerbated by obesity. The pathophysiology involves abnormal gonadotropin secretion from a reduced hypothalamic feedback response to circulating sex steroids, altered ovarian morphology and functional changes, and disordered insulin action in a variety of target tissues. PCOS clusters in families and both female and male relatives can show stigmata of the syndrome, including metabolic abnormalities. Genome-wide association studies have identified a number of candidate regions, although their role in contributing to PCOS is still largely unknown.
Infection is frequent among patients in the intensive care unit (ICU). Contemporary information about the types of infections, causative pathogens, and outcomes can aid the development of policies ...for prevention, diagnosis, treatment, and resource allocation and may assist in the design of interventional studies.
To provide information about the prevalence and outcomes of infection and the available resources in ICUs worldwide.
Observational 24-hour point prevalence study with longitudinal follow-up at 1150 centers in 88 countries. All adult patients (aged ≥18 years) treated at a participating ICU during a 24-hour period commencing at 08:00 on September 13, 2017, were included. The final follow-up date was November 13, 2017.
Infection diagnosis and receipt of antibiotics.
Prevalence of infection and antibiotic exposure (cross-sectional design) and all-cause in-hospital mortality (longitudinal design).
Among 15 202 included patients (mean age, 61.1 years SD, 17.3 years; 9181 were men 60.4%), infection data were available for 15 165 (99.8%); 8135 (54%) had suspected or proven infection, including 1760 (22%) with ICU-acquired infection. A total of 10 640 patients (70%) received at least 1 antibiotic. The proportion of patients with suspected or proven infection ranged from 43% (141/328) in Australasia to 60% (1892/3150) in Asia and the Middle East. Among the 8135 patients with suspected or proven infection, 5259 (65%) had at least 1 positive microbiological culture; gram-negative microorganisms were identified in 67% of these patients (n = 3540), gram-positive microorganisms in 37% (n = 1946), and fungal microorganisms in 16% (n = 864). The in-hospital mortality rate was 30% (2404/7936) in patients with suspected or proven infection. In a multilevel analysis, ICU-acquired infection was independently associated with higher risk of mortality compared with community-acquired infection (odds ratio OR, 1.32 95% CI, 1.10-1.60; P = .003). Among antibiotic-resistant microorganisms, infection with vancomycin-resistant Enterococcus (OR, 2.41 95% CI, 1.43-4.06; P = .001), Klebsiella resistant to β-lactam antibiotics, including third-generation cephalosporins and carbapenems (OR, 1.29 95% CI, 1.02-1.63; P = .03), or carbapenem-resistant Acinetobacter species (OR, 1.40 95% CI, 1.08-1.81; P = .01) was independently associated with a higher risk of death vs infection with another microorganism.
In a worldwide sample of patients admitted to ICUs in September 2017, the prevalence of suspected or proven infection was high, with a substantial risk of in-hospital mortality.
Pre‐B cell colony‐enhancing factor (PBEF), also known as visfatin, is a highly conserved, 52‐kDa protein found in living species from bacteria to humans. Originally a curiosity identified ...serendipitously in microarray studies but having no obvious functional importance, PBEF has now been shown to exert three distinct activities of central importance to cellular energetics and innate immunity. Within the cell, PBEF functions as a nicotinamide phosphoribosyl transferase, the rate‐limiting step in a salvage pathway of nicotinamide adenine dinucleotide (NAD) biosynthesis. By virtue of this role, it can regulate cellular levels of NAD and so impact not only cellular energetics but also NAD‐dependent enzymes such as sirtuins. Although it lacks a signal peptide, PBEF is released by a variety of cells, and elevated levels can be found in the systemic circulation of patients with a variety of inflammatory diseases. As an extracellular cytokine, PBEF can induce the cellular expression of inflammatory cytokines such as TNF‐α, IL‐1β, and IL‐6. Finally, PBEF has been shown to be an adipokine expressed by fat cells that exerts a number of insulin mimetic and antagonistic effects. PBEF expression is up‐regulated in a variety of acute and chronic inflammatory diseases including sepsis, acute lung injury, rheumatoid arthritis, inflammatory bowel disease, and myocardial infarction and plays a key role in the persistence of inflammation through its capacity to inhibit neutrophil apoptosis. This review summarizes the admittedly incomplete body of emerging knowledge about a remarkable new mediator of innate immunity.
Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, ...immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination.
To evaluate and, as needed, update definitions for sepsis and septic shock.
A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment).
Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant.
Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential Sepsis-related Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less.
These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis.
cGMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) sensing has emerged as a key regulator of innate immune responses to both exogenous and endogenous DNA. Recent studies reveal critical ...roles for this pathway in natural antitumor immunity across cancer types as well as in immune checkpoint blockade therapy. However, it is also clear that some tumors evade cGAS–STING-mediated immune responses, and immunomodulatory therapeutics are currently being explored to target this pathway. Finally, we also discuss recent observations that cGAS–STING-mediated inflammation may promote tumor initiation, growth, and metastasis in certain malignancies and how this may complicate the utility of this pathway in therapeutic development.
cGMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) recognizes cytosolic DNA and induces a type I interferon response in both tumor and phagocytic immune cells.
cGAS–STING-induced immunity has potent antitumor effects and magnifies the effects of a variety of anticancer therapeutics.
In certain tumor types, cGAS–STING promotes cancer growth and metastasis through modulation of the tumor microenvironment.
Sepsis definitions: time for change Vincent, Jean-Louis, Prof; Opal, Steven M, Prof; Marshall, John C, Prof ...
Lancet,
03/2013, Letnik:
381, Številka:
9868
Journal Article
Recenzirano
Odprti dostop
...some degree of host response is actually inherent to the infection; indeed, this is an important component of the difference between infection and mere colonisation. ...the 1991 criteria for ...sepsis continue to be used.
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