Presepsin as a powerful monitoring tool for the prognosis and treatment of sepsis: a multicenter prospective study.

Presepsin is a protein whose levels increase specifically in the blood of patients with sepsis. It is proposed as a diagnostic and prognostic marker for assessing the degree of sepsis severity. The present multicenter prospective study compared the clinical utility of presepsin with other conventional sepsis biomarkers including procalcitonin, interleukin-6, and C-reactive protein for evaluating the severity of sepsis during follow-up. Patients with sepsis (n = 103) admitted to the emergency room or intensive care unit were enrolled in this study and classified into 3 diagnostic groups: sepsis, severe sepsis, and septic shock. Blood samples were obtained from each patient on admission and after 1, 3, 5, and 7 days. The patients were further divided into the favorable and unfavorable prognosis groups on the basis of several indicators of sepsis severity (i.e., Sequential Organ Failure Assessment score, and Acute Physiology and Chronic Health Evaluation II score). The patients in the favorable prognosis group exhibited significant decreases in all biomarker levels on days 3 and 7 after admission. In the unfavorable prognosis group, only presepsin levels did not decrease significantly during follow-up. The period of antibiotics treatment in the unfavorable prognosis group was significantly longer than those in the favorable prognosis group (P < 0.05). The unfavorable prognosis group had significantly higher 28-day mortality than the favorable prognosis group (P < 0.05). Therefore, the results suggest that presepsin levels correlated with the severity of sepsis during follow-up in comparison with other conventional sepsis biomarkers.

Usefulness of presepsin in the diagnosis of sepsis in a multicenter prospective study.

The clinical usefulness of presepsin for discriminating between bacterial and nonbacterial infections (including systemic inflammatory response syndrome) was studied and compared with procalcitonin (PCT) and interleukin-6 (IL-6) in a multicenter prospective study. Suspected sepsis patients (n = 207) were enrolled into the study. Presepsin levels in patients with systemic bacterial infection and localized bacterial infection were significantly higher than in those with nonbacterial infections. In addition, presepsin, PCT, and IL-6 levels in patients with bacterial infectious disease were significantly higher than in those with nonbacterial infectious disease (P < 0.0001, P < 0.0001, and P < 0.0001, respectively). The area under the receiver operating characteristic curve was 0.908 for presepsin, 0.905 for PCT, and 0.825 for IL-6 in patients with bacterial infectious disease and those with nonbacterial infectious disease. The cutoff value of presepsin for discrimination of bacterial and nonbacterial infectious diseases was determined to be 600 pg/ml, of which the clinical sensitivity and specificity were 87.8 % and 81.4 %, respectively. Presepsin levels did not differ significantly between patients with gram-positive and gram-negative bacterial infections. The sensitivity of blood culture was 35.4 %; that for presepsin was 91.9 %. Also there were no significant differences in presepsin levels between the blood culture-positive and -negative groups. Consequently, presepsin is useful for the diagnosis of sepsis, and it is superior to conventional markers and blood culture.

cAMP response element-binding protein (CREB) is required for epidermal growth factor (EGF)-induced cell proliferation and serum response element activation in neural stem cells isolated from the forebrain subventricular zone of adult mice.

Neurogenesis, which occurs not only in the developing brain but also in restricted regions in the adult brain including the forebrain subventricular zone (SVZ), is regulated by a variety of environmental factors, extracellular signals, and intracellular signal transduction pathways. We investigated whether the transcription factor cAMP response element (CRE)-binding protein (CREB) is involved in the regulation of cell proliferation of neural stem cells (NSCs) isolated from the SVZ of adult mice. Treatment of NSCs with the protein kinase A (PKA) inhibitors H89 and KT5720 inhibited epidermal growth factor (EGF)-stimulated NSC proliferation. Similar inhibition was observed when a dominant-negative mutant of CREB (MCREB) was expressed. EGF treatment increased CRE-mediated transcriptional activity, but this increase was much less than that caused by treatment with the adenylate cyclase activator forskolin, which changed neither basal nor EGF-stimulated proliferation of NSCs. Neither PKA inhibitors nor MCREB expression blocked EGF-induced phosphorylation of extracellular signal-regulated kinase (ERK), a protein kinase mediating EGF's mitogenic action. However, MCREB suppressed EGF-induced expression of several immediately early genes including c-fos, c-jun, jun-B, and fra-1 and subsequent AP-1 transcriptional activation. MCREB expression also inhibited the ability of EGF to stimulate transcriptional activation mediated by the serum response element (SRE), a promoter sequence regulating c-fos gene expression. These results suggest that basal activity of CREB is required for the mitogenic signaling of EGF in NSCs at a level between ERK activation and SRE-mediated transcriptional activation.

Necrotizing fasciitis following primary peritonitis caused by Streptococcus pyogenes with covS mutation in a healthy woman: a case report.

BACKGROUND: Primary peritonitis due to Streptococcus pyogenes (S. pyogenes) is uncommon in patients without comorbid conditions such as immunosuppression, nephritic disease, or liver cirrhosis. Furthermore, it does not cause another infection at the same time in a healthy person. However, several S. pyogenes mutants have been reported, and some of them exhibit strong virulence. Mutation of the control of virulence (cov) S gene of Streptococcus enhances bacterium survival by repressing negative regulators of virulence, which causes bacterial invasion of aseptic tissues, such as the parenteral space. We report a case of primary peritonitis and subsequent necrotizing fasciitis by the same S. pyogenes species with mutated covS in a previously healthy woman. CASE PRESENTATION: We present the case of a 55-year-old woman admitted to the hospital due to abdominal pain and nausea. She was treated for peritonitis. A few days later, she became hypotensive and tachycardic and was transferred to the intensive care unit (ICU) for the treatment of septic shock with primary peritonitis. On the second day of her ICU stay, both of her forearms developed swelling and redness around the peripheral injection site. The patient had developed necrotizing fasciitis. Since her skin symptoms spread rapidly, urgent debridement was performed. Her condition improved with antibiotic treatment and multiple episodes of debridement. S. pyogenes was detected in cultures of the patient's blood, ascites, and skin. The identified strain was emm89 genotype and had a genetic mutation of covS. CONCLUSIONS: S. pyogenes with covS mutation may spread from a portal, such as the upper respiratory tract or digestive system, to all organs immediately, causing septic shock. Infection with S. pyogenes with mutated genes should be considered in the differential diagnosis of gastrointestinal symptoms, even in a previously healthy patient.

Suppression of cell proliferation by interferon-alpha through interleukin-1 production in adult rat dentate gyrus.

The therapeutic use of interferon-alpha (IFN-alpha), a proinflammatory cytokine, is known to cause various neuropsychiatric adverse effects. In particular, depression occurs in 30-45% of patients, frequently interrupting treatment. IFN-alpha-treated animals also show depression-like behaviors. However, mechanisms underlying the depression caused by IFN-alpha remain to be defined. Recently, a decrease in adult hippocampal neurogenesis was revealed as a possible neuropathological mechanism of depression. Therefore, we investigated the effect of subchronic IFN-alpha treatment on neurogenesis in the adult rat dentate gyrus (DG). Immediately after the administration of IFN-alpha for 1 week, a decrease in the number of 5-bromo-deoxyuridine-labeled proliferating cells was observed in the DG; however, no effect was detected on the expression of mature neuronal phenotype in the newly formed cells 3 weeks later. Also, an increase in the level of interleukin-1beta (IL-1beta), a major proinflammatory cytokine, was observed in the hippocampus following the administration of IFN-alpha. Furthermore, coadministration of an IL-1 receptor antagonist completely blocked the IFN-alpha-induced suppression of the cell-proliferative activity in the DG. Our results indicate that IFN-alpha suppresses neurogenesis in the DG, and that IL-1beta plays an essential role in the suppression. The decreased cell proliferation caused by IFN-alpha-induced IL-1beta may be responsible, at least in part, for IFN-alpha-induced depression.

Orotracheal intubation with an AirWay Scope in a patient with Treacher Collins syndrome.

Treacher Collins syndrome (TCS) is a congenital malformation of craniofacial development; in these patients conventional direct laryngoscopy is very difficult and often unsuccessful because of the upper airway malformation. A 20-year-old man with TCS was scheduled for elective tympanoplasty. The patient showed the characteristic facial appearance of TCS, and a difficult airway was anticipated. After careful anesthesia induction, direct laryngoscopy with Macintosh blade no. 4 of a direct laryngoscope failed to visualize the epiglottis, even with cricoid pressure, resulting in a grade 4 Cormack and Lehane view. Next, the AirWay Scope was easily inserted, and his glottic opening was clearly visualized. An 8.0-mm-internal-diameter tracheal tube was then advanced into the trachea without any difficulty. The AirWay Scope is a very useful airway device for orotracheal intubation; it provides an excellent view of the glottis without requiring alignment of the oral, pharyngeal, and laryngeal axes, and appears to be promising for use in patients with a difficult airway.

Impairment of theory of mind in patients in remission following first episode of schizophrenia.

The aim of this study was to investigate theory of mind (ToM) ability in patients in remission after the first episode of schizophrenia. A ToM task which contained four pictures was given to 30 patients with schizophrenia in remission and 30 matched healthy controls. Patients with schizophrenia in remission showed statistically significant impairment in the ToM tasks. ToM impairment was not correlated with psychiatric symptoms. Thus, ToM deficit in schizophrenia may be a trait marker.