Circulating inflammatory mediators in patients with fever: predicting bloodstream infection.

The systemic host response to microbial infection involves clinical signs and symptoms of infection, including fever and elevated white blood cell (WBC) counts. In addition, inflammatory mediators are released, including activated complement product C3a, interleukin 6 (IL-6), and the acute-phase reactant secretory phospholipase A(2) (sPLA(2)). To compare the value of the latter with the former in predicting (the degree of) microbial infection at the bedside, we determined clinical variables and took blood samples daily for 3 consecutive days in 300 patients with a new fever (>38.0 degrees C rectally or >38.3 degrees C axillary). Microbiological culture results for 7 days after inclusion were collected. Patients were divided into clinical and microbial categories: those without and with a clinical focus of infection and those with negative cultures, with positive local cultures or specific stains for fungal (n = 13) or tuberculous infections (n = 1), and with positive blood cultures, including one patient with malaria parasitemia. The area under the curve (AUC) of the receiver operating characteristic (ROC) for prediction of positive cultures was 0.60 (P < 0.005) for peak temperature and 0.59 (P < 0.01) for peak WBC count, 0.60 (P < 0.005) for peak C3a, 0.63 (P < 0.001) for peak IL-6, and 0.61 (P < 0.001) for peak sPLA(2). The AUC under the ROC curve for prediction of positive blood cultures was 0.68 (P < 0.001) for peak temperature and 0.56 for peak WBC count (P < 0.05). The AUC for peak C3a was 0.69, that for peak IL-6 was 0.70, and that for sPLA(2) was 0.67 (for all, P < 0.001). The degree of microbial invasion is thus a major determinant of the clinical and inflammatory host response in patients with fever. Moreover, circulating inflammatory mediators such as C3a and IL-6 may help to predict positive blood cultures, together with clinical signs and symptoms of the host response to microbial infection, even before culture results are available. This may help in the designing of entry criteria for therapeutic intervention studies.     

Circulating Inflammatory Mediators in Patients with Fever: Predicting Bloodstream Infection

The systemic host response to microbial infection involves clinical signs and symptoms of infection, including fever and elevated white blood cell (WBC) counts. In addition, inflammatory mediators are released, including activated complement product C3a, interleukin 6 (IL-6), and the acute-phase reactant secretory phospholipase A₂ (sPLA₂). To compare the value of the latter with the former in predicting (the degree of) microbial infection at the bedside, we determined clinical variables and took blood samples daily for 3 consecutive days in 300 patients with a new fever (>38.0°C rectally or >38.3°C axillary). Microbiological culture results for 7 days after inclusion were collected. Patients were divided into clinical and microbial categories: those without and with a clinical focus of infection and those with negative cultures, with positive local cultures or specific stains for fungal (n = 13) or tuberculous infections (n = 1), and with positive blood cultures, including one patient with malaria parasitemia. The area under the curve (AUC) of the receiver operating characteristic (ROC) for prediction of positive cultures was 0.60 (P < 0.005) for peak temperature and 0.59 (P < 0.01) for peak WBC count, 0.60 (P < 0.005) for peak C3a, 0.63 (P < 0.001) for peak IL-6, and 0.61 (P < 0.001) for peak sPLA₂. The AUC under the ROC curve for prediction of positive blood cultures was 0.68 (P < 0.001) for peak temperature and 0.56 for peak WBC count (P < 0.05). The AUC for peak C3a was 0.69, that for peak IL-6 was 0.70, and that for sPLA₂ was 0.67 (for all, P < 0.001). The degree of microbial invasion is thus a major determinant of the clinical and inflammatory host response in patients with fever. Moreover, circulating inflammatory mediators such as C3a and IL-6 may help to predict positive blood cultures, together with clinical signs and symptoms of the host response to microbial infection, even before culture results are available. This may help in the designing of entry criteria for therapeutic intervention studies.     

C-reactive protein as a marker of infection in critically ill patients

A prospective, observational study was conducted in a medico-surgical intensive care unit to assess the value of C-reactive protein (CRP), temperature and white cell count (WCC) measurements for the diagnosis of infection in critically ill patients. CRP, temperature and WCC were monitored daily in 76 infected and 36 non-infected patients. Multiple receiver-operating characteristics (ROC) curves were used to compare each parameter for infection diagnosis. The area under the curve (AUC) of CRP was significantly higher than that of temperature (0.93 and 0.75, respectively; p < 0.001). A CRP concentration of >8.7 mg/dL and a temperature of >38.2 degrees C were associated with infection, with a sensitivity of 93.4% and 54.8%, and a specificity of 86.1% and 88.9%, respectively. The ROC curve of WCC showed a poor diagnostic performance. The combination of CRP and temperature increased the specificity for infection diagnosis to 100%. In the subgroup of patients with ventilator-associated pneumonia (n = 48), CRP measurements were more reliable than temperature (AUC 0.92 and 0.78, respectively; p 0.006). The CRP levels in infected patients with sepsis, severe sepsis and septic shock were 15.2 +/- 8.2, 20.3 +/- 10.9 and 23.3 +/- 8.7 mg/dL, respectively (p 0.044). It was concluded that CRP was a better marker of infection than temperature. However, the combination of CRP and temperature measurements further increased the specificity for infection diagnosis, even in the subgroup of patients with VAP.     

PCT、CRP动力学评估脓毒血症预后及诊断意义的研究

目的 观察血清降钙素原(PCT)、C反应蛋白(CRP)及其动力学变化,评估其在严重脓毒症/感染性休克患者的诊断及预后价值.方法 本研究采用回顾性分析方法,2014年9月1日至2016年4月30日选择184例ICU中被诊断为严重脓毒症/感染性休克疾病患者,检测入院时血清PCT、CRP水平和治疗后第2,第3和第5天的PCT、CRP水平.结果 通过△PCT、△CRP评估PCT、CRP的动力学在存活者与死亡组中有显著性统计学意(△PCT2/0,P=0.0001;△PCT3/0,P=0.0001;△PCT5/0,P=0.0001;△CRP2/0,P=0.0069;△CRP3/0,P=0.0001;△CRP5/0,P=0.0001),在严重脓毒症和感染性休克组中也存在显著差异(PCT5,P=0.007;△PCT5/0,P=0.007).受试者工作特征曲线(ROC)模型显示,△PCT3/0(AUC=0.721)、△PCT5/0(AUC=0.77)、△CRP5/0(AUC=0.766)水平判断严重脓毒症/感染性休克患者预后有较好的临床意义.△PCT5/0 (0.619)对严重脓毒症或感染性休克有一定的辅助诊断效果,其在ROC曲线上灵敏度、特异性均较高的临界点为0.624,所以,以第5天的血清△PCT5/0水平＞0.624可作为预测感染性休克的临界点.结论 血清中PCT、CRP对严重脓毒症/感染性休克早期有较好的临床诊断及预后价值,其动力学研究可以提高对严重脓毒症/感染性休克诊断及预后评估的敏感性及准确性.     

Hypoalbuminemia,Low Base Excess Values,and Tachypnea Predict 28-Day Mortality in Severe Sepsis and Septic Shock Patients in the Emergency Department

PurposeThe objective of this study was to develop a new nomogram that can predict 28-day mortality in severe sepsis and/or septic shock patients using a combination of several biomarkers that are inexpensive and readily available in most emergency departments, with and without scoring systems.ResultsThe prediction model that included albumin, base excess, and respiratory rate demonstrated the largest area under the receiver operating characteristic curve (AUC) value of 0.8173 [95% confidence interval (CI), 0.7605–0.8741]. The logistic analysis revealed that a conventional scoring system was not associated with 28-day mortality. In the validation set, the discrimination of a newly developed nomogram was also good, with an AUC value of 0.7537 (95% CI, 0.6563–0.8512).ConclusionOur new nomogram is valuable in predicting the 28-day mortality of patients with severe sepsis and/or septic shock in the emergency department. Moreover, our readily available nomogram is superior to conventional scoring systems in predicting mortality.     

Serum caspase-cleaved cytokeratin-18 fragment as a prognostic biomarker in hematological patients with febrile neutropenia

The study aim was to determine the benefit of the measurement of serum caspase-cleaved cytokeratin-18 (CK-18) fragment as a prognostic marker of febrile neutropenia (FN) in hematological patients. The study population consisted of 86 consecutive patients with FN who received intensive chemotherapy for hematological malignancy at the adult hematology ward of Kuopio University Hospital. Twenty-three patients (27%) had acute myeloid leukemia, and 63 patients (73%) were autologous stem cell transplant recipients. Serum caspase-cleaved CK-18 fragment M30, C-reactive protein (CRP) and procalcitonin (PCT) were measured at the onset of FN (d0), on day 1 (d1), and on day 2 (d2). Eight patients (9%) developed severe sepsis, including three patients with septic shock. Eighteen patients (21%) had a blood culture-positive infection. Serum CK-18 fragment peaked on the first day after fever onset in patients with severe sepsis. Higher CK-18 level was associated with severe sepsis, intensive care unit treatment, and fatal outcome, but not with blood culture positivity. In ROC curve analysis, d1 serum CK-18 fragment predicted severe sepsis with an area under the curve (AUC) of 0.767, CRP with an AUC of 0.764, and PCT with an AUC of 0.731. On d2, the best predictive capacity was observed for CRP with an AUC of 0.832. The optimal cutoff of caspase-cleaved CK-18 fragment M30 for predicting severe sepsis was 205 U/L on d1. In hematological patients, serum CK-18 fragment was found to be a potential prognostic marker of severe sepsis at early stages of FN.

     

Can hantavirus infections be predicted on admission to hospital?

The aim of this study was to investigate the predictive factors which contribute to diagnosis of hantavirus infection. One hundred patients from rural areas hospitalized with a preliminary diagnosis of hantavirus infection from different hospitals in Turkey were investigated. Hantavirus infection was confirmed in 20 patients (Group 1) using immunofluorescence and immunoblot assays at the Refik Saydam National Public Health Agency. Hantaviruses were not detected in the serum of the remaining 80 patients, other infectious and non‐infectious diseases being diagnosed in this group (Group 2). Patients' demographic characteristics and clinical and laboratory data on admission were examined and compared between the two groups. Fever, proteinuria, hematuria, lethargy‐weakness, and nausea‐vomiting were the most frequent symptoms and findings in Group 1, seen in almost all patients. Proteinuria, hematuria, muscle pain, diarrhea/abdominal pain, hypotension, shock, and sweating were observed at significantly higher levels in Group 1 compared to Group 2. Serum urea, creatinine, uric acid, lactate dehydrogenase (LDH), aspartate transaminase (AST), alkaline phosphatase (ALP), and C‐reactive protein (CRP) were significantly higher, but serum platelet counts were lower in Group 1 patients. Area beneath the receiver operating characteristics (ROC) curve analysis was used to calculate the discriminative ability of various laboratory values to identify patients with hantavirus infection. This analysis revealed that, serum CRP had a 100% negative predictive value, whilst, platelet, and creatinine had 75% and 70% positive predictive values for the diagnosis of hantavirus infection. In summary, laboratory markers used in clinical practice are of great importance predicting hantavirus infections. J. Med. Virol. 84:1790–1796, 2012. © 2012 Wiley Periodicals, Inc.     

Multiplex cytokine profiling in patients with sepsis

A major goal for the clinical research in sepsis is mapping the various mediators driving the systemic manifestations of infection. Identifying relevant mediators responsible for the physiological alterations during sepsis may offer diagnostic and therapeutic opportunities. We aimed to explore the novel approach of simultaneously measuring several biomolecules using the multiplex technique and to study its relevance in diagnosing and monitoring septic patients. In 30 patients fulfilling American College of Chest Physicians and the Society of Critical Care Medicine sepsis criteria, we simultaneously measured 17 cytokines during the first 7 days after admission. We analysed the results with respect to the presence of septic shock and survival. Five patients died during the study. We found a significant positive correlation between the monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1β and interleukin (IL)-8 levels in the first 3 days and Sepsis-related Organ Failure Assessment score on day 1. Most cytokines showed no significant difference between patients with mild or severe sepsis. The initial levels of MIP-1β and granulocyte macrophage colony-stimulating factor were lower in patients with septic shock than in patients without shock. IL-8 and MCP-1 early after admission were higher in the non-survivors (p < 0.05). In the multivariate logistical regression, the initial levels of IL-8 were the most predictive for fatal outcome. Moreover, IL-1β, IL-6, IL-8, IL-12, interferon-γ, granulocyte colony-stimulating factor and tumour necrosis factor-α exhibited persistent increases in non-survivors. The simultaneous evaluation of multiple cytokines in sepsis may identify complex cytokine patterns that reflect the systemic response associated with shock and mortality.     

Pathogens and outcomes in pediatric septic shock patients supported by extracorporeal membrane oxygenation

Background

Refractory septic shock is the leading cause of mortality in children. There is limited evidence to support extracorporeal membrane oxygenation (ECMO) use in pediatric septic shock. We described the etiology and outcomes of septic patients in our institution and attempted to find predictive factors.

Factors associated with mortality in patients with bloodstream infection and pneumonia due to Stenotrophomonas maltophilia

Severe infections caused by Stenotrophomonas maltophilia are associated with high mortality, and strategies to improve the clinical outcome for infected patients are needed. A retrospective cohort study of patients with bloodstream infection (BSIs) and pneumonia caused by S. maltophilia was conducted. Multivariate analysis was performed to access factors associated with 14-day mortality. A total of 60 infections were identified. Among these, eight (13%) were pneumonias and 52 were BSIs; 33.3% were primary, 13% were central venous catheter (CVC)-related and 40% were secondary BSIs. Fifty-seven (85%) patients had received previous antimicrobial therapy; 88% had CVC, 57% mechanical ventilation and 75% were in the intensive care unit at the onset of infection. Malignancy (45%) was the most frequent underlying disease. The mean of the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores was 17 and for the Sepsis-related Organ Failure Assessment (SOFA) score, it was 7 points. The overall and 14-day mortality were, respectively, 75% and 48%. Forty-seven (78%) patients were treated and, of these, 74% received trimethoprim-sulfamethoxazole. Independent risk factors associated with mortality were SOFA index >6 points (0.005) and septic shock (0.03). The Kaplan-Meier estimations curves showed that patients with APACHE II score >20 and SOFA score >10 had a survival chance of, respectively, less than 8% and less than 10% (P≤0.001) at 21 days after the first positive S. maltophilia culture. Our results suggest that the independent factors associated with outcome in patients with infection caused by S. maltophilia are septic shock and higher SOFA index.     

Plasma PTX3, MCP1 and Ang2 are early biomarkers to evaluate the severity of sepsis and septic shock

Sepsis is associated with significant mortality. Early diagnosis and prognosis of patients with sepsis is still a difficult clinical challenge. In this study, the ability of plasma PTX3 (pentraxin 3), MCP1 (monocyte chemoattractant protein 1) and Ang (angiopoietin)1/2 was investigated to evaluate the severity of sepsis. Blood samples were obtained from 43 patients with sepsis. A total of 33 post‐surgery patients with infections and 25 healthy individuals served as controls. The results showed that plasma PTX3, MCP1 and Ang2 significantly increased in patients on the first day of septic shock onset, while sepsis patients had significantly higher Ang2 level, compared with controls. Furthermore, PTX3, MCP1 and Ang2 had high AUROC values in patients with septic shock on the first day of sepsis onset. The findings suggest that PTX3, MCP1 and Ang2 maybe early predictors to evaluate the severity of sepsis and septic shock with the latest Sepsis 3.0 definitions.     

Elevated soluble urokinase plasminogen activator receptor (suPAR) predicts mortality in Staphylococcus aureus bacteremia

The soluble form of urokinase-type plasminogen activator receptor (suPAR) is a new inflammatory marker. High suPAR levels have been shown to associate with mortality in cancer and in chronic infections like HIV and tuberculosis, but reports on the role of suPAR in acute bacteremic infections are scarce. To elucidate the role of suPAR in a common bacteremic infection, the serum suPAR levels in 59 patients with Staphylococcus aureus bacteremia (SAB) were measured using the suPARnostic™ ELISA assay and associations to 1-month mortality and with deep infection focus were analyzed. On day three, after the first positive blood culture for S. aureus, suPAR levels were higher in 19 fatalities (median 12.3; range 5.7–64.6 ng/mL) than in 40 survivors (median 8.4; range 3.7–17.6 ng/mL, p = 0.002). This difference persisted for 10 days. The presence of deep infection focus was not associated with elevated suPAR levels as compared to patients with no deep infection focus. suPAR was found to be prognostic for mortality in receiver operator characteristic (ROC) curve analysis, which was not observed for serum C-reactive protein (CRP); the area under the curve (AUC) for suPAR was 0.754 (95% confidence interval [CI], 0.615–0.894, p = 0.003) and for CRP, it was 0.596 (95% CI, 0.442–0.750, p = 0.253). The optimal suPAR cut-off value in predicting 1-month mortality was 9.25 ng/mL. In conclusion, our study demonstrates that the new promising biomarker, serum suPAR concentration, was able to predict mortality in SAB.     

Increasing the Efficacy of Anti-Inflammatory Agents Used in the Treatment of Sepsis

Excessive production of inflammatory mediators during invasive infection plays a key role in the pathogenesis of septic shock. In an attempt to improve survival of patients with this lethal syndrome, agents were developed to selectively inhibit mediators in this inflammatory response. Despite promising preclinical results, several different mediator-specific anti-inflammatory agents failed to demonstrate significant benefit in patients. There was, however, a significant difference in mortality between preclinical and clinical trials. The median control mortality in preclinical trials, performed almost uniformly in highly lethal sepsis models, was 88%. In clinical trials however, the median control mortality rate was much lower, at 41%. A recent meta-regression analysis of these preclinical and clinical trials in combination with prospective confirmatory studies demonstrated that risk of death as assessed by control group mortality rate significantly altered the treatment effect of these agents in both humans and animals. While anti-inflammatory agents were very beneficial in groups with high control mortality rates, they were ineffective or harmful in groups with low control mortality rates. Thus, variation in the risk of death due to sepsis provides a basis for the marked difference in the efficacy of these anti-inflammatory agents in preclinical and clinical trials over the last decade. In contrast to mediator-specific anti-inflammatory agents, glucocorticoids and activated protein C have recently demonstrated significant beneficial effects in individual clinical trials. However, glucocorticoids were studied only in patients with vasopressor-dependent septic shock, which is associated with a high control mortality rate (i.e. 61%) similar to the level at which mediator-specific agents would have been expected to be markedly beneficial. Furthermore, consistent with earlier findings for mediator-specific anti-inflammatory agents, analysis of the activated protein C study also demonstrated a relationship between risk of death and effect of treatment. Developing better methods to define high-risk septic populations for treatment with anti-inflammatory agents will increase the efficacy of this therapeutic approach and minimize its potential for harm. Electronic Publication     

外周血中性粒细胞/淋巴细胞比值在慢性阻塞性肺病相关肺动脉高压患者中的预后价值

目的：探讨外周血中性粒细胞/淋巴细胞比值(neutrophil/lymphocyte ratio,NLR)对慢性阻塞性肺病(chronic obstructive pulmonary disease,COPD)相关肺动脉高压患者预后的评判价值。方法：选择2013年1月至2014年3月收治入上海交通大学医学院附属新华医院急诊科的200例COPD相关肺动脉高压(pulmonary hypertension,PH)患者为研究对象,对其进行至少2年的生存随访,随访终点为全因死亡,按照生存情况分为生存组和死亡组;记录各组入院24 h的一般临床资料,血常规[C反应蛋白(C-reactive protein,CRP)、中性粒细胞计数(neutrophils count,NEU)及淋巴细胞计数(lymphocyte count,LYM)并计算两者间比值(NLR)]、肌酐、尿素氮、胆红素、WHO肺动脉高压功能分级、肺动脉收缩压等;绘制受试者工作特征(receiver operating characteristic,ROC)曲线,分析NLR预测患者预后的临床价值;并以Kaplan-Meier法绘制观察指标不同水平下的生存曲线,进行生存分析。COX回归分析各指标提示预后的价值。结果：死亡组患者NLR,CRP,WHO肺动脉高压功能分级、肺动脉收缩压、尿素氮、肌酐、中性粒细胞计数高于生存组,淋巴细胞计数低于生存组,差异均具有统计学意义(P<0.05)。根据ROC曲线分析,NLR的ROC曲线下面积(AUC)为0.720(P<0.01),高于肌酐(AUC=0.716)、中性粒细胞计数(AUC=0.655)、肺动脉收缩压(AUC=0.652)及CRP(AUC=0.643)。当NLR截断值为4.7时,其灵敏度为74.2%,特异度为72.0%。Kaplan-Meier生存曲线分析显示,NLR值水平较高组预后明显差于水平较低组(P<0.01)。单因素Cox回归分析提示NLR是提示患者不良预后的危险因素,多因素Cox回归分析(P>0.05)。结论：NLR水平与COPD相关肺动脉高压患者临床预后呈明显相关;NLR水平越高则提示病情较重,预后较差。     

Diagnostic and prognostic role of procalcitonin (PCT) and MR‐pro‐Adrenomedullin (MR‐proADM) in bacterial infections

Rapid diagnosis of bacterial infections is crucial for adequate antibiotic treatment. Serum molecules such as Procalcitonin (PCT) have been used as biomarkers of infection. Recently, the mid‐regional pro‐Adrenomedullin (MR‐proADM) has been evaluated in combination with PCT for sepsis diagnosis. The diagnostic role of PCT and MR‐proADM both in sepsis and in localized infections together with their contribution to effective antibiotic therapy has been evaluated. One hundred and eighty‐two patients with bacterial infection has been enrolled: PCT and MR‐proADM were measured at admission (T = 0), at 12–24 h (T = 1) and in the third or fifth day of antibiotic therapy (T = 3–5). ROC curve (receiver operating characteristic) and post‐test probability were calculated. MR‐proADM increased with the severity of the infection. PCT resulted significantly higher in sepsis than localized infection. After antibiotic therapy, PCT significantly decreased in localized respiratory infections and in sepsis, while MR‐proADM decreased significantly after antibiotic therapy only in patients with severe sepsis/septic shock. The threshold values of PCT and MR‐proADM were >0.1 ng/mL and >0.8 nmol/L, respectively. The combined use of PCT and MR‐proADM increased the post‐test probability of the diagnosis of bacterial infections compared to PCT alone. In conclusion, PCT and MR‐proADM combination improves the diagnosis of bacterial infection and contribute to prognosis and antibiotic therapy effectiveness.     

A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock

The use of high-dose corticosteroids in the treatment of severe sepsis and septic shock remains controversial. Our study was designed as a prospective, randomized, double-blind, placebo-controlled trial of high-dose methylprednisolone sodium succinate for severe sepsis and septic shock. Diagnosis was based on the clinical suspicion of infection plus the presence of fever or hypothermia (rectal temperature greater than 38.3 degrees C [101 degrees F] or less than 35.6 degrees C [96 degrees F]), tachypnea (greater than 20 breaths per minute), tachycardia (greater than 90 beats per minute), and the presence of one of the following indications of organ dysfunction: a change in mental status, hypoxemia, elevated lactate levels, or oliguria. Three hundred eighty-two patients were enrolled. Treatment--either methylprednisolone sodium succinate (30 mg per kilogram of body weight) or placebo--was given in four infusions, starting within two hours of diagnosis. No significant differences were found in the prevention of shock, the reversal of shock, or overall mortality. In the subgroup of patients with elevated serum creatinine levels (greater than 2 mg per deciliter) at enrollment, mortality at 14 days was significantly increased among those receiving methylprednisolone (46 of 78 [59 percent] vs. 17 of 58 [29 percent] among those receiving placebo; P less than 0.01). Among patients treated with methylprednisolone, significantly more deaths were related to secondary infection. We conclude that the use of high-dose corticosteroids provides no benefit in the treatment of severe sepsis and septic shock.     

Mannan binding lectin in febrile adults: no correlation with microbial infection and complement activation

AIMS: To study the role of the mannan binding lectin (MBL) pathway of complement activation in the host defence to microbial infection in vivo, and the role of MBL in infectious mortality in non-selected patients. METHODS: A prospective observational study on 177 hospitalised medical patients with new onset fever. The presence, origin, and microbial cause of infection, the circulating MBL and complement activation product 3a (C3a), and the 28 day hospital course were determined. RESULTS: The patients had median MBL values similar to healthy blood donors: 18% of the patients and 14% of the blood donors had MBL deficiency, with values below 0.1 microg/ml. Median C3a was higher in patients with microbiologically confirmed infection than in those without, whereas there was no difference in MBL values or frequency of deficiency among patient groups with or without positive local cultures or bacteraemia. The mortality rate was 8% and the outcome groups did not differ in MBL. In febrile adults hospitalised in internal medicine wards, microbial infection induces complement activation, independently of MBL. CONCLUSIONS: The results argue against a predominant role for the MBL pathway of complement activation and a deficiency of MBL predisposing to serious and invasive microbial infection in non-selected adults.     

Clinical significance of sirtuin 1 level in sepsis: correlation with disease risk,severity, and mortality risk

This study aimed to investigate the value of sirtuin 1 (SIRT1) in differentiating sepsis patients from healthy controls (HCs), and its correlation with inflammation, disease severity, as well as prognosis in sepsis patients. Serum samples were collected from 180 sepsis patients and 180 age- and gender-matched HCs. The SIRT1 level in the serum samples was detected by enzyme-linked immunoassay. The clinical data of the sepsis patients were documented, and their disease severity scores and 28-day mortality rate were assessed. SIRT1 was decreased in sepsis patients compared with HCs, and the receiver operating characteristic curve (ROC) showed that SIRT1 distinguished sepsis patients from HCs (area under the curve (AUC): 0.901; 95% confidence interval (CI): 0.868-0.934). In sepsis patients, SIRT1 negatively correlated with serum creatinine (Scr), white blood cells (WBC), C-reactive protein (CRP), acute physiology, and chronic health evaluation II (APACHE II) score, and sequential organ failure assessment (SOFA) score, while it positively correlated with albumin. No correlation of SIRT1 with primary infection site or primary organism was observed. Furthermore, SIRT1 was reduced in 28-day non-survivors compared with 28-day survivors, and subsequent ROC showed that SIRT1 predicted 28-day mortality of sepsis patients (AUC: 0.725; 95% CI: 0.651-0.800), and its prognostic value was not inferior to Scr, albumin, WBC, and CRP, but was less than SOFA score and APACHE II score. In conclusion, measurement of serum SIRT1 might assist with the optimization of disease assessment, management strategies, and survival surveillance in sepsis patients.     

Serum procalcitonin for differentiating bacterial infection from disease flares in patients with autoimmune diseases

Early differentiation between bacterial infections and disease flares in autoimmune disease patients is important due to different treatments. Seventy-nine autoimmune disease patients with symptoms suggestive of infections or disease flares were collected by retrospective chart review. The patients were later classified into two groups, disease flare and infection. C-reactive protein (CRP) and serum procalcitonin (PCT) levels were measured. The CRP and PCT levels were higher in the infection group than the disease flare group (CRP,11.96 mg/dL ± 9.60 vs 6.42 mg/dL ± 7.01, P = 0.003; PCT, 2.44 ng/mL ± 6.55 vs 0.09 ng/mL ± 0.09, P < 0.001). The area under the ROC curve (AUC; 95% confidence interval) for CRP and PCT was 0.70 (0.58-0.82) and 0.84 (0.75-0.93), which showed a significant difference (P < 0.05). The predicted AUC for the CRP and PCT levels combined was 0.83, which was not significantly different compared to the PCT level alone (P = 0.80). The best cut-off value for CRP was 7.18 mg/dL, with a sensitivity of 71.9% and a specificity of 68.1%. The best cut-off value for PCT was 0.09 ng/mL, with a sensitivity of 81.3% and a specificity of 78.7%. The PCT level had better sensitivity and specificity compared to the CRP level in distinguishing between bacterial infections and disease flares in autoimmune disease patients. The CRP level has no additive value when combined with the PCT level when differentiating bacterial infections from disease flares.