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Critical Care (London, England) Jan 2022A biomarker describes a measurable indicator of a patient's clinical condition that can be measured accurately and reproducibly. Biomarkers offer utility for diagnosis,... (Review)
Review
A biomarker describes a measurable indicator of a patient's clinical condition that can be measured accurately and reproducibly. Biomarkers offer utility for diagnosis, prognosis, early disease recognition, risk stratification, appropriate treatment (theranostics), and trial enrichment for patients with sepsis or suspected sepsis. In this narrative review, we aim to answer the question, "Do biomarkers in patients with sepsis or septic shock predict mortality, multiple organ dysfunction syndrome (MODS), or organ dysfunction?" We also discuss the role of pro- and anti-inflammatory biomarkers and biomarkers associated with intestinal permeability, endothelial injury, organ dysfunction, blood-brain barrier (BBB) breakdown, brain injury, and short and long-term mortality. For sepsis, a range of biomarkers is identified, including fluid phase pattern recognition molecules (PRMs), complement system, cytokines, chemokines, damage-associated molecular patterns (DAMPs), non-coding RNAs, miRNAs, cell membrane receptors, cell proteins, metabolites, and soluble receptors. We also provide an overview of immune response biomarkers that can help identify or differentiate between systemic inflammatory response syndrome (SIRS), sepsis, septic shock, and sepsis-associated encephalopathy. However, significant work is needed to identify the optimal combinations of biomarkers that can augment diagnosis, treatment, and good patient outcomes.
Topics: Biomarkers; Humans; Leukocytosis; Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome
PubMed: 34991675
DOI: 10.1186/s13054-021-03862-5 -
The New England Journal of Medicine May 2015The successful treatment of intraabdominal infection requires a combination of anatomical source control and antibiotics. The appropriate duration of antimicrobial... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The successful treatment of intraabdominal infection requires a combination of anatomical source control and antibiotics. The appropriate duration of antimicrobial therapy remains unclear.
METHODS
We randomly assigned 518 patients with complicated intraabdominal infection and adequate source control to receive antibiotics until 2 days after the resolution of fever, leukocytosis, and ileus, with a maximum of 10 days of therapy (control group), or to receive a fixed course of antibiotics (experimental group) for 4±1 calendar days. The primary outcome was a composite of surgical-site infection, recurrent intraabdominal infection, or death within 30 days after the index source-control procedure, according to treatment group. Secondary outcomes included the duration of therapy and rates of subsequent infections.
RESULTS
Surgical-site infection, recurrent intraabdominal infection, or death occurred in 56 of 257 patients in the experimental group (21.8%), as compared with 58 of 260 patients in the control group (22.3%) (absolute difference, -0.5 percentage point; 95% confidence interval [CI], -7.0 to 8.0; P=0.92). The median duration of antibiotic therapy was 4.0 days (interquartile range, 4.0 to 5.0) in the experimental group, as compared with 8.0 days (interquartile range, 5.0 to 10.0) in the control group (absolute difference, -4.0 days; 95% CI, -4.7 to -3.3; P<0.001). No significant between-group differences were found in the individual rates of the components of the primary outcome or in other secondary outcomes.
CONCLUSIONS
In patients with intraabdominal infections who had undergone an adequate source-control procedure, the outcomes after fixed-duration antibiotic therapy (approximately 4 days) were similar to those after a longer course of antibiotics (approximately 8 days) that extended until after the resolution of physiological abnormalities. (Funded by the National Institutes of Health; STOP-IT ClinicalTrials.gov number, NCT00657566.).
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Appendicitis; Drug Administration Schedule; Female; Fever; Humans; Intraabdominal Infections; Kaplan-Meier Estimate; Leukocytosis; Male; Medication Adherence; Middle Aged; Peritonitis; Recurrence; Sepsis; Surgical Wound Infection; Young Adult
PubMed: 25992746
DOI: 10.1056/NEJMoa1411162 -
American Family Physician Dec 2015An elevated white blood cell count has many potential etiologies, including malignant and nonmalignant causes. It is important to use age- and pregnancy-specific normal...
An elevated white blood cell count has many potential etiologies, including malignant and nonmalignant causes. It is important to use age- and pregnancy-specific normal ranges for the white blood cell count. A repeat complete blood count with peripheral smear may provide helpful information, such as types and maturity of white blood cells, uniformity of white blood cells, and toxic granulations. The leukocyte differential may show eosinophilia in parasitic or allergic conditions, or it may reveal lymphocytosis in childhood viral illnesses. Leukocytosis is a common sign of infection, particularly bacterial, and should prompt physicians to identify other signs and symptoms of infection. The peripheral white blood cell count can double within hours after certain stimuli because of the large bone marrow storage and intravascularly marginated pools of neutrophils. Stressors capable of causing an acute leukocytosis include surgery, exercise, trauma, and emotional stress. Other nonmalignant etiologies of leukocytosis include certain medications, asplenia, smoking, obesity, and chronic inflammatory conditions. Symptoms suggestive of a hematologic malignancy include fever, weight loss, bruising, or fatigue. If malignancy cannot be excluded or another more likely cause is not suspected, referral to a hematologist/oncologist is indicated.
Topics: Education, Medical, Continuing; Humans; Leukocyte Count; Leukocytes; Leukocytosis; Practice Guidelines as Topic
PubMed: 26760415
DOI: No ID Found -
Nature Medicine Nov 2019A sedentary lifestyle, chronic inflammation and leukocytosis increase atherosclerosis; however, it remains unclear whether regular physical activity influences leukocyte...
A sedentary lifestyle, chronic inflammation and leukocytosis increase atherosclerosis; however, it remains unclear whether regular physical activity influences leukocyte production. Here we show that voluntary running decreases hematopoietic activity in mice. Exercise protects mice and humans with atherosclerosis from chronic leukocytosis but does not compromise emergency hematopoiesis in mice. Mechanistically, exercise diminishes leptin production in adipose tissue, augmenting quiescence-promoting hematopoietic niche factors in leptin-receptor-positive stromal bone marrow cells. Induced deletion of the leptin receptor in Prrx1-creER; Lepr mice reveals that leptin's effect on bone marrow niche cells regulates hematopoietic stem and progenitor cell (HSPC) proliferation and leukocyte production, as well as cardiovascular inflammation and outcomes. Whereas running wheel withdrawal quickly reverses leptin levels, the impact of exercise on leukocyte production and on the HSPC epigenome and transcriptome persists for several weeks. Together, these data show that physical activity alters HSPCs via modulation of their niche, reducing hematopoietic output of inflammatory leukocytes.
Topics: Adipose Tissue; Animals; Atherosclerosis; Cardiovascular Diseases; Epigenome; Exercise; Hematopoiesis; Hematopoietic Stem Cells; Homeodomain Proteins; Humans; Inflammation; Leukocytes; Leukocytosis; Mice; Physical Conditioning, Animal; Receptors, Leptin; Sedentary Behavior; Transcriptome
PubMed: 31700184
DOI: 10.1038/s41591-019-0633-x -
American Journal of Hematology Apr 2022Chronic neutrophilic leukemia (CNL) is a rare, often aggressive myeloproliferative neoplasm (MPN) defined by persistent mature neutrophilic leukocytosis, bone marrow...
DISEASE OVERVIEW
Chronic neutrophilic leukemia (CNL) is a rare, often aggressive myeloproliferative neoplasm (MPN) defined by persistent mature neutrophilic leukocytosis, bone marrow granulocyte hyperplasia, and frequent hepatosplenomegaly. The 2013 seminal discovery of oncogenic driver mutations in colony-stimulating factor 3 receptor (CSF3R) in the majority of patients with CNL not only established its molecular pathogenesis but provided a diagnostic biomarker and rationale for pharmacological targeting.
DIAGNOSIS
In 2016, the World Health Organization (WHO) recognized activating CSF3R mutations as a central diagnostic feature of CNL. Other criteria include leukocytosis of ≥25 × 10 /L comprising >80% neutrophils with <10% circulating precursors and rare blasts, and absence of dysplasia or monocytosis, while not fulfilling criteria for other MPN.
MANAGEMENT
There is currently no standard of care for management of CNL, due in large part to the rarity of disease and dearth of formal clinical trials. Most commonly used therapeutic agents include conventional oral chemotherapy (e.g., hydroxyurea), interferon, and Janus kinase (JAK) inhibitors, while hematopoietic stem cell transplant remains the only potentially curative modality.
DISEASE UPDATES
Increasingly comprehensive genetic profiling in CNL, including new data on clonal evolution, has disclosed a complex genomic landscape with additional mutations and combinations thereof driving disease progression and drug resistance. Although accurate prognostic stratification and therapeutic decision-making remain challenging in CNL, emerging data on molecular biomarkers and the addition of newer agents, such as JAK inhibitors, to the therapeutic arsenal, are paving the way toward greater standardization and improvement of patient care.
Topics: Genomics; Humans; Leukemia, Neutrophilic, Chronic; Leukocytosis; Mutation; Prognosis
PubMed: 35089603
DOI: 10.1002/ajh.26481 -
The Journal of the American Osteopathic... Apr 2020
Topics: Biomechanical Phenomena; Humans; Lymphocytosis; Soccer
PubMed: 32227154
DOI: 10.7556/jaoa.2020.046 -
Gaceta Medica de Mexico 2018Los pacientes inmunocomprometidos presentan respuesta inflamatoria limitada que puede retrasar el diagnóstico de la apendicitis aguda (AA).
INTRODUCCIÓN
Los pacientes inmunocomprometidos presentan respuesta inflamatoria limitada que puede retrasar el diagnóstico de la apendicitis aguda (AA).
OBJETIVO
Evaluar si el inmunocompromiso puede afectar el curso clínico y evolución de la AA.
MÉTODO
Análisis retrospectivo, comparativo, de pacientes sometidos a apendicectomía por AA: con VIH, diabetes mellitus tipo 2 (DM2) y sin otra patología.
RESULTADOS
Se revisaron 128 pacientes con AA intervenidos quirúrgicamente (53.6 % del sexo femenino), edad media de 42.5 años, 15 (11.7 %) tenían diagnóstico de VIH, 47 (36.7 %) de DM2 y 66 (51.6 %) no cursaban con otra enfermedad. La proporción de leucocitosis fue menor en el grupo con VIH (66.7 %; p = 0.007). En los pacientes con VIH y DM2 se registró mayor tiempo de evolución: 66.9 ± 61.2y 90.1 ± 144 horas (p ≤ 0.001), mayor tiempo de estancia hospitalaria: 11.1 ± 17.1 y 6.5 ± 4.1 días (p ≤ 0.0001), mayor tasa de complicaciones: 20 y 23.8 % (p = 0.036). La complicación más frecuente fue la infección del sitio quirúrgico superficial y profunda. La hemicolectomía derecha fue más frecuente en el grupo con VIH (20 %, p = 0.017). No se registró mortalidad.
CONCLUSIONES
La inmunodepresión afecta el curso clínico y evolución de la AA.
INTRODUCTION
Immunocompromised patients experience limited inflammatory response, which can delay acute appendicitis (AA) diagnosis.
OBJECTIVE
To assess if immunosuppression can affect AA clinical course and evolution.
METHOD
Comparative, retrospective analysis of patients with HIV or type 2 diabetes mellitus (DM2) or with no other pathology who underwent appendectomy for AA.
RESULTS
A total of 128 patients with AA who were surgically intervened were assessed (53.6% were of the female gender); mean age was 42.5 years, 15 (11.7%) had been diagnosed with HIV infection, 47 (36.7%) with DM2 and 66 (51.6%) had no other disease. The proportion of leukocytosis was lower in the HIV group (66.7%; p = 0.007). Patients with HIV and DM2 had longer evolution time (HIV 66.9 ± 61.2, DM2 90.1 ± 144 hours; p ≤ 0.001), longer hospital length of stay (HIV 11.1 ± 17.1, DM2 6.5 ± 4.1 days; p ≤ 0.0001), and a higher rate of complications (HIV 20%, DM2 23.8%; p = 0.036). The most common complication was superficial and deep surgical site infection. Right hemicolectomy was more common in the HIV group (20%; p = 0.017). There was no mortality registered.
CONCLUSIONS
Immunosuppression affects AA clinical course and evolution.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Appendectomy; Appendicitis; Colectomy; Diabetes Mellitus, Type 2; Female; HIV Infections; Hospitalization; Humans; Immunocompromised Host; Length of Stay; Leukocytosis; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Time Factors; Young Adult
PubMed: 30250334
DOI: 10.24875/GMM.17003839 -
Deutsches Arzteblatt International Mar 2018
Topics: Aged; Humans; Leukemia; Leukocytosis; Male; Skin Neoplasms
PubMed: 29607809
DOI: 10.3238/arztebl.2018.0189 -
Journal of Microbiology, Immunology,... Aug 2021Coronavirus disease 2019 (COVID-19) is an infectious disease caused by SARS-CoV-2, a newly discovered coronavirus that exhibits many similarities with the severe acute... (Comparative Study)
Comparative Study Review
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by SARS-CoV-2, a newly discovered coronavirus that exhibits many similarities with the severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (SARS-CoV and MERS-CoV, respectively). The definite pathogenesis and immunological influences of SARS-CoV-2 have not been fully elucidated. Therefore, we constructed a brief summary comparison of SARS-CoV-2, SARS-CoV, and MERS-CoV infections regarding their immunological changes. In addition, we further investigated the immunological differences between severe and nonsevere COVID-19 cases, and we searched for possible immunological predictors of the patient outcome by reviewing case series studies to date. Possible immunological predictors of a poor outcome are leukocytosis, neutrophilia, lymphopenia (both CD4 and CD8 T cells), an increased neutrophil-to-lymphocyte ratio (NLR), and increased levels of pro-inflammatory cytokines (IL-6 and TNF-α), Th1 cytokines (IL-2 and IFN-γ), regulatory T cell cytokines (IL-10) and Th17 cytokines (IL-17). A more precise immunological map needs to be established, which may assist in diagnosing this disease and facilitate immunological precision medicine treatment.
Topics: COVID-19; Cytokines; Humans; Leukocytosis; Lymphopenia; Middle East Respiratory Syndrome Coronavirus; Receptors, Virus; Severe acute respiratory syndrome-related coronavirus; SARS-CoV-2; Severe Acute Respiratory Syndrome
PubMed: 34023234
DOI: 10.1016/j.jmii.2021.04.006 -
European Heart Journal Apr 2016Atherosclerosis, the major underlying cause of cardiovascular disease, is characterized by a lipid-driven infiltration of inflammatory cells in large and medium... (Review)
Review
Atherosclerosis, the major underlying cause of cardiovascular disease, is characterized by a lipid-driven infiltration of inflammatory cells in large and medium arteries. Increased production and activation of monocytes, neutrophils, and platelets, driven by hypercholesterolaemia and defective high-density lipoproteins-mediated cholesterol efflux, tissue necrosis and cytokine production after myocardial infarction, or metabolic abnormalities associated with diabetes, contribute to atherogenesis and athero-thrombosis. This suggests that in addition to traditional approaches of low-density lipoproteins lowering and anti-platelet drugs, therapies directed at abnormal haematopoiesis, including anti-inflammatory agents, drugs that suppress myelopoiesis, and excessive platelet production, rHDL infusions and anti-obesity and anti-diabetic agents, may help to prevent athero-thrombosis.
Topics: Atherosclerosis; Blood Platelets; Cholesterol; Hematopoiesis; Hematopoiesis, Extramedullary; Hematopoietic Stem Cells; Humans; Leukocytosis; Metabolic Diseases; Monocytes; Myelopoiesis; Myeloproliferative Disorders; Neutrophils; Risk Factors; Thrombopoiesis; Thrombosis
PubMed: 26869607
DOI: 10.1093/eurheartj/ehv718