This prospective study aimed to evaluate the diagnostic utilities of neutrophil CD64 expression for the identification of early-onset clinical infection and pneumonia in term infants and to define the optimal cutoff value so that it may act as a reference with which future studies can be compared. Term newborns in whom infection was suspected when they were Ͻ72 h of age were recruited into the study. C-reactive protein (CRP) and expression of CD64 on neutrophils were measured at 0 h (at the time of sepsis evaluation) and 24 h. The sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of CRP, CD64, and the combination of these two markers for predicting neonatal sepsis were determined. A total of 338 infants with suspected clinical sepsis were investigated, 115 of whom were found to be clinically infected. CRP and CD64 in infected infants were both significantly elevated at 0 and 24 h compared with noninfected infants (p Ͻ 0.001). The calculated optimal cutoff value for CD64 was 6136 antibody-phycoerythrin molecules bound/cell. CD64 has a very high sensitivity (96%) and NPV (97%) at 24 h. The addition of CRP only marginally enhanced the sensitivity and NPV (97 and 98%, respectively). In conclusion, neutrophil CD64 is a very sensitive diagnostic marker for the identification of early-onset clinical infection and pneumonia in term newborns. The results strongly suggest that measurement of neutrophil CD64 may allow neonatal clinicians to discontinue antibiotic treatment at 24 h in infants who are clinically stable and whose CD64 expressions are below the optimal cutoff level. Early-onset (Ͻ72 h of age) neonatal infection is associated with a high morbidity and mortality (1). Immature immunologic defenses in newborn infants, including low circulating levels of immunoglobulins, decrease in absolute number of T lymphocytes and neutrophils, and functionally impaired cytotoxic activity in leukocytes (2-4), are important risk factors that predispose these infants to life-threatening sepsis. Early clinical signs and symptoms of neonatal infection and pneumonia are often inconspicuous and can easily be confused with other noninfective causes, such as transient tachypnea of the newborns, meconium aspiration syndrome, congenital heart diseases, and hypoxic-ischemic encephalopathy (5). Thus, there is always a possibility that the attending neonatologists may overlook or miss subtle cases of early infection. In view of the potentially serious outcome associated with delayed treatment and the difficulty in distinguishing infected from noninfected cases, it has become common practice to prescribe broad-spectrum antibiotics for suspected infection that presents with nonspecific clinical features and maternal risk factors (5-7). Furthermore, as negative microbiologic culture results do not always suggest the absence of bacterial sepsis, continuation of antimicrobial therapy for presumptive infection frequently leads to unnecessary and prolonged treatment and increases in duration of hospitalizatio...

Summary Background Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. Methods We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. Findings Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1·34 years [IQR 0·19–2·44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1·35 (95% CI 1·20–1·50) for the composite outcome of intracranial haemorrhage and ischaemic stroke; 2·45 (1·82–3·29) for intracranial haemorrhage and 1·23 (1·08–1·40) for ischaemic stroke. The aHR increased with increasing cerebral microbleed burden for intracranial haemorrhage but this effect was less marked for ischaemic stroke (for five or more cerebral microbleeds, aHR 4·55 [95% CI 3·08–6·72] for intracranial haemorrhage vs 1·47 [1·19–1·80] for ischaemic stroke; for ten or more cerebral microbleeds, aHR 5·52 [3·36–9·05] vs 1·43 [1·07–1·91]; and for ≥20 cerebral microbleeds, aHR 8·61 [4·69–15·81] vs 1·86 [1·23–2·82]). However, irrespective of cerebral microbleed anatomical distribution or burden, the rate of ischaemic stroke exceeded that of intracranial haemorrhage (for ten or more cerebral microbleeds, 64 ischaemic strokes [95% CI 48–84] per 1000 patient-years vs 27 intracranial haemorrhages [17–41] per 10...

Very low birth weight (VLBW) infants with suspected late-onset infection requiring sepsis screening were enrolled in a prospective study to evaluate the diagnostic utilities of a comprehensive panel of key chemokines and cytokines, both individually and in combination, to identify diagnostic markers for early recognition of bacterial sepsis and necrotizing enterocolitis (NEC). Plasma chemokines interleukin (IL)-8, interferon-␥-inducible protein 10 (IP-10), monokine induced by interferon-␥ (MIG), monocyte chemoattractant protein 1 (MCP-1), growth-related oncogene-␣ (GRO-␣), and regulated upon activation of normal T cell expressed and secreted (RAN-TES) and cytokines IL-1␤, IL-6, IL-10, IL-12p70, and tumor necrosis factor ␣ (TNF-␣) were measured at the onset of sepsis (0 h) and 24 h later. Of 155 suspected infection episodes, 44 were classified as infected. Concentrations of all studied inflammatory mediators (except IL-1␤ and RANTES) were significantly higher in the infected than in the noninfected group at 0 h, but the levels decreased precipitously by 24 h. IP-10 with a plasma cutoff concentration Ն1250 pg/mL could identify all septicemic and NEC cases and had the highest overall sensitivity (93%) and specificity (89%) at 0 h. We conclude that preterm infants have the ability to induce a robust chemokine and cytokine response during sepsis, and IP-10 is a sensitive early marker of infection. and NEC are important risk factors that predispose to increased morbidity and mortality in preterm VLBW infants (1-4). A recent multicenter survey suggested that 21% of VLBW infants who survived Ͼ72 h of age had at least one episode of septicemia (1). Preterm infants who developed NEC had threefold increased risk of mortality (4). As the immunologic defense of preterm infants is considered to be immature and/or deficient (5), this category of patients is particularly vulnerable to developing severe and opportunistic infections in the immediate postnatal period (1,3,4). However, early warning signs and symptoms of systemic infection and NEC are often nonspecific and inconspicuous and can easily be confused with noninfective causes such as apnea of prematurity, gastrointestinal dysmotility, and acute exacerbation of bronchopulmonary dysplasia (6 -8). Thus, early identification of infants with bacterial sepsis and NEC has been recognized to be a major diagnostic challenge (7,8).Exposure to microorganisms and their derived products triggers a rapid and coordinated sequence of host reactions resulting in recruitment of leukocytes into areas of inflammation or sites of microbial invasion (9 -12). The regulation and trafficking of leukocytes into specific body tissues are principally controlled by chemoattractant cytokines or chemokines (10). The activation of leukocytes coupled with interaction of pro-and anti-inflammatory cytokines can influence the orchestration of the anti-infectious process and the magnitude of tissue damage and ultimately can determine the outcome of infection (13-16). Up-regulation (or down-regula...

Purpose: To examine the reproducibility of the single breathhold T2* technique from different scanners, after installation of standard methodology in five international centers. Materials and Methods:Up to 10 patients from each center were scanned twice locally for local interstudy reproducibility of heart and liver T2*, and then flown to a central MR facility to be rescanned on a reference scanner for intercenter reproducibility. Interobserver reproducibility for all scans was also assessed. Results:Of the 49 patients scanned, the intercenter reproducibility for T2* was 5.9% for the heart and 5.8% for the liver. Local interstudy reproducibility for T2* was 7.4% for the heart and 4.6% for the liver. Interobserver reproducibility for T2* was 5.4% for the heart and 4.4% for the liver. Conclusion:These data indicate that T2* MR may be developed into a widespread test for tissue siderosis providing that well-defined and approved imaging and analysis techniques are used.