Sepsis is a severe and life-threatening systemic inflammatory response to infection that affects all populations and age groups. The pathophysiology of sepsis is associated with aberrant interaction between leukocytes and the vascular endothelium. As inflammation progresses, the adhesion molecules that mediate these interactions become shed from cell surfaces and accumulate in the blood as soluble isoforms that are being explored as potential prognostic disease biomarkers. We critically review the studies that have tested the predictive value of soluble adhesion molecules in sepsis pathophysiology with emphasis on age, as well as the underlying mechanisms and potential roles for inflammatory shedding. Five soluble adhesion molecules are associated with sepsis, specifically, E-selectin, L-selectin and P-selectin, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. While increased levels of these soluble adhesion molecules generally correlate well with the presence of sepsis, their degree of elevation is still poorly predictive of sepsis severity scores, outcome and mortality. Separate analyses of neonates, children and adults demonstrate significant age-dependent discrepancies in both basal and septic levels of circulating soluble adhesion molecules. Additionally, a range of both clinical and experimental studies suggests protective roles for adhesion molecule shedding that raise important questions about whether these should positively or negatively correlate with mortality. In conclusion, while predictive properties of soluble adhesion molecules have been researched intensively, their levels are still poorly predictive of sepsis outcome and mortality. We propose two novel directions for improving clinical utility of soluble adhesion molecules: the combined simultaneous analysis of levels of adhesion molecules and their sheddases; and taking age-related discrepancies into account. Further attention to these issues may provide better understanding of sepsis pathophysiology and increase the usefulness of soluble adhesion molecules as diagnostic and predictive biomarkers.
Acute Zika virus infection usually presents with a self-limiting triad of fever, rash and arthritis. There is limited information on severe or lethal cases. We report three cases of lethal acute Zika infection, confirmed with polymerase chain reaction, in adult patients with some co-morbidities. The patients showed rapid clinical deterioration with hemorrhagic and septic shock, and exaggerated acute and innate inflammatory responses with pronounced coagulopathy, and died soon after admission to the hospital. It remains unclear whether the fatal outcomes were due to acute Zika virus infection alone or to the combination with exacerbated underlying prior disease or co-infection. Nonetheless, the severity of these cases implies that increased awareness for atypical presentations of Zika virus infection, and careful clinical assessment of patients with symptoms of Zika, is warranted during current and future outbreaks.
Older age in women than in men who present to surgery for RCC was only prevalent in those older than 70 years. The male-to-female ratio was almost equal in patients older than 70 years compared to a 2:1 ratio at ages 41 to 60 years. Women presented with fewer pT3 tumors than men at age 41 years or greater. Missing pathological data decreased significantly between 1995 and 2005.
We propose that integration of features of neutrophil morphology, mechanics, and motility with these new analytical methods can be useful as markers for diagnosis, prognosis, and monitoring of sepsis and may even contribute to basic understanding of its pathophysiology.
BackgroundScaling up neonatal care facilities in developing countries can improve survival of newborns. Recently, the only tertiary neonatal care facility in Suriname transitioned to a modern environment in which interventions to improve intensive care were performed. This study evaluates impact of this transition on referral pattern and outcomes of newborns.MethodsA retrospective chart study amongst newborns admitted to the facility was performed and outcomes of newborns between two 9-month periods before and after the transition in March 2015 were compared.ResultsAfter the transition more intensive care was delivered (RR 1.23; 95% CI 1.07–1.42) and more outborn newborns were treated (RR 2.02; 95% CI 1.39–2.95) with similar birth weight in both periods (P=0.16). Mortality of inborn and outborn newborns was reduced (RR 0.62; 95% CI 0.41–0.94), along with mortality of sepsis (RR 0.37; 95% CI 0.17–0.81) and asphyxia (RR 0.21; 95% CI 0.51–0.87). Mortality of newborns with a birth weight <1000 grams (34.8%; RR 0.90; 95% CI 0.43–1.90) and incidence of sepsis (38.8%, 95% CI 33.3–44.6) and necrotizing enterocolitis (NEC) (12.5%, 95% CI 6.2–23.6) remained high after the transition.ConclusionsAfter scaling up intensive care at our neonatal care facility more outborn newborns were admitted and survival improved for both in- and outborn newborns. Challenges ahead are sustainability, further improvement of tertiary function, and prevention of NEC and sepsis.Electronic supplementary materialThe online version of this article (10.1186/s12887-017-0941-6) contains supplementary material, which is available to authorized users.
Background Viruses are the most frequent cause of severe acute respiratory infection (SARI) in children. It is currently unknown whether presence of a virus, the number of viruses, or type of virus, are associated with clinical outcomes of pediatric SARI in developing countries. Methods Between 2012 and 2014 nasopharyngeal swabs and demographic and clinical variables were prospectively collected for surveillance of viral causes of SARI in Surinamese children within 48 hours after hospitalization. These swabs were tested for 18 respiratory viruses using a multiplex polymerase chain reaction (PCR) panel to identify the specific viral causes of SARI, unknown to the treating physicians. In post hoc analyses we evaluated if the PCR results, and demographic and clinical characteristics, were associated with course of disease, duration of respiratory support, and length of stay (LOS). Results Of a total of 316 analyzed children, 290 (92%) had one or more viruses. Rhinovirus/enterovirus (43%) and respiratory syncytial virus (34%) were most prevalent. Course of disease was mild in 234 (74%), moderate in 68 (22%), and severe in 14 (4%) children. Neither presence of a single virus, multiple viruses, or the type of virus, were different between groups. Prematurity and lower weight-for-age-z-score were independent predictors of a severe course of disease, longer duration of respiratory support, and longer LOS. Conclusions Viruses are common causes of pediatric SARI in Suriname, yet not necessarily associated with clinical outcomes. In developing countries, demographic and clinical variables can help to identify children at-risk for worse outcome, while PCR testing may be reserved to identify specific viruses, such as influenza, in specific patient groups or during outbreaks.
Purpose:Vascular inflammation and leakage in sepsis is mediated by Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) and their phosphorylation of the endothelial Tie-2 receptor. This study investigates levels of Ang-1 and Ang-2 in newborns to gain insight in the vascular pathophysiology of early onset sepsis (EOS) within 72 h after birth.Methods:A prospective cohort study was performed among 71 Surinamese newborns treated with antibiotics for suspected EOS and 20 control newborns. Newborns with suspected EOS were divided in two groups: blood culture negative and positive EOS. Ang-1 and Ang-2 levels were measured in serum obtained at the start of antibiotic treatment and at re-evaluation after 48 to 72 h.Results:In this cohort 8.5% of newborns had a positive blood culture. At the start of antibiotic treatment Ang-1 serum levels were lower (P < 0.01), and Ang-2 and Ang-2/Ang-1 serum protein ratios were higher (P < 0.01 and P < 0.01, respectively) in newborns with blood culture positive EOS than in controls. These levels were not dependent on timing of first blood draw after birth. After 48 to 72 h levels of Ang-1 further decreased in blood culture positive EOS, while in the other groups no change was observed.Conclusions:Our findings support the hypothesis that a disbalance in the Angiopoietins plays a role in the vascular pathophysiology of EOS.
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