BACKGROUND & AIMS: BACKGROUND:Children commonly present to Emergency Departments (ED) with a non-blanching rash in the context of a feverish illness. While most have a self-limiting viral illness, this combination of features potentially represents invasive serious bacterial infection, including meningococcal septicaemia. A paucity of definitive diagnostic testing creates diagnostic uncertainty for clinicians; a safe approach mandates children without invasive disease are often admitted and treated with broad-spectrum antibiotics. Conversely, a cohort of children still experience significant mortality and morbidity due to late diagnosis. Current management is based on evidence which predates (i) the introduction of meningococcal B and C vaccines and (ii) availability of point of care testing (POCT) for procalcitonin (PCT) and Neisseria meningitidis DNA. METHODS:This PiC study is a prospective diagnostic accuracy study evaluating (i) rapid POCT for PCT and N. meningitidis DNA and (ii) performance of existing clinical practice guidelines (CPG) for feverish children with non-blanching rash. All children presenting to the ED with a history of fever and non-blanching rash are eligible. Children are managed as normal, with detailed prospective collection of data pertinent to CPGs, and a throat swab and blood used for rapid POCT. The study is running over 2 years and aims to recruit 300 children. PRIMARY OBJECTIVE:Report on the diagnostic accuracy of POCT for (i) N. meningitidis DNA and (ii) PCT in the diagnosis of early MD Report on the diagnostic accuracy of POCT for PCT in the diagnosis of Invasive bacterial infection Secondary objectives: Evaluate the performance accuracy of existing CPGs Evaluate cost-effectiveness of available diagnostic testing strategies Explore views of (i) families and (ii) clinicians on research without prior consent using qualitative methodology Report on the aetiology of NBRs in children with a feverish illness DISCUSSION: The PiC study will provide important information for policy makers regarding the value of POCT and on the utility and cost of emerging diagnostic strategies. The study will also identify which elements of existing CPGs may merit inclusion in any future study to derive clinical decision rules for this population. TRIAL REGISTRATION:NCT03378258 . Retrospectively registered on December 19, 2017.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Rational prescription of antibiotics in acute exacerbations of COPD (AECOPD) requires predictive markers. We aimed to analyze whether markers of systemic inflammation can predict response to antibiotics in AECOPD. METHODS:We used data from 243 exacerbations out of 205 patients from a placebo-controlled trial on doxycycline in addition to systemic corticosteroids for AECOPD. Clinical and microbiologic response, serum C-reactive protein (CRP) level (cutoffs 5 and 50 mg/L), and serum procalcitonin level (PCT) (cutoffs 0.1 and 0.25 μg) were assessed. RESULTS:Potential bacterial pathogens were identified in the majority of exacerbations (58%). We found a modest positive correlation between PCT and CRP (r = 0.46, P < .001). The majority of patients (75%) had low PCT levels, with mostly elevated CRP levels. Although CRP levels were higher in the presence of bacteria (median, 33.0 mg/L [interquartile range, 9.75-88.25] vs 17 mg/L [interquartile range, 5.0-61.0] [P = .004]), PCT levels were similar. PCT and CRP performed similarly as markers of clinical success, and we found a clinical success rate of 90% in patients with CRP ≤ 5 mg/L. A significant effect of doxycycline was observed in patients with a PCT level < .1 μg/L (treatment effect, 18.4%; P = .003). A gradually increasing treatment effect of antibiotics (6%, 10%, and 18%), although not significant, was found for patients with CRP values of ≤ 5, 6-50, and > 50 mg/L, respectively. CONCLUSIONS:Contrary to the current literature, this study suggests that patients with low PCT values do benefit from antibiotics. CRP might be a more valuable marker in these patients.

背景与目标：

BACKGROUND & AIMS: :Discrimination between urosepsis and febrile urinary tract infections is important in therapeutic decision-making to indicate suitable treatments to avoid sepsis-related organ failure. Accurate diagnosis is time-consuming and susceptible to false-positive results. Moreover, patient responses to urosepsis are complex and varied. Therefore, this study aimed to develop a new, early diagnostic predictor that could discriminate between patients with urosepsis and those with febrile urinary tract infections using a combination of initial procalcitonin and albumin levels.We conducted a retrospective study involving 140 patients with febrile urinary tract infections from January 2013 to December 2017. Univariate and multivariate logistic analyses were performed to identify the independent risk factors for differentiating urosepsis from febrile urinary tract infection. A receiver operating characteristic (ROC) curve analysis was conducted to compare the predictive accuracy of the procalcitonin/albumin ratio.Patients in the urosepsis group had higher procalcitonin/albumin ratios compared to those in the febrile urinary tract infection group [2.254 (0.978, 6.299) vs 0.021 (0.004, 0.095); P < .001]. Based on multivariate logistic analysis, the procalcitonin/albumin ratio [adjusted odds ratio (OR) 1.029, 95% confidence interval (CI) 1.013-1.045, P < .001] was an independent predictor of urosepsis, which allowed for differentiation from patients with febrile urinary tract infections. The area under the ROC curve (AUC) for the procalcitonin/albumin ratio was 0.937 (95% CI, 0.894-0.980); P < .001. The sensitivity and specificity of the procalcitonin/albumin ratio cut-off values (>0.44) were 84.62% and 96.00%, respectively. Moreover, in the subset of 65 patients with urosepsis, the procalcitonin/albumin ratio in the uroseptic shock group was higher than in the group of patients without uroseptic shock [5.46 (1.43, 6.58) vs 1.24 (0.63, 4.38); P = .009].Our study demonstrates that the procalcitonin/albumin ratio is an early diagnostic predictor that can discriminate between urosepsis and febrile urinary tract infection. Additionally, in patients with urosepsis, those with higher procalcitonin/albumin ratios were more prone to uroseptic shock. Our findings suggest that the procalcitonin/albumin ratio is a rapid and relatively low-cost biomarker that can be used in clinical practice.

背景与目标： : 区分尿脓毒症和发热性尿路感染在治疗决策中很重要，以指示合适的治疗方法以避免脓毒症相关器官衰竭。准确的诊断是耗时的，并且容易受到假阳性结果的影响。此外，患者对尿脓毒症的反应复杂多样。因此，本研究旨在开发一种新的早期诊断预测因子，该预测因子可以结合初始降钙素原和白蛋白水平来区分尿脓毒症患者和发热性尿路感染患者。我们进行了一项回顾性研究，涉及从2013年1月到2017年12月的140例发热性尿路感染患者。进行单因素和多因素logistic分析，以确定区分尿脓毒症与发热性尿路感染的独立危险因素。进行受试者工作特征 (ROC) 曲线分析以比较降钙素原/白蛋白比值的预测准确性。尿脓毒症组患者的降钙素原/白蛋白比值高于热性尿路感染组 [2.254 (0.978、6.299) vs 0.021 (0.004、0.095); P  < .001]。基于多因素logistic分析，降钙素原/白蛋白比值 [调整比值比 (OR) 1.029，95% 置信区间 (CI) 1.013-1.045，p  < .001] 是尿脓毒症的独立预测因子，可与发热性尿路感染患者区分。降钙素原/白蛋白比值的ROC曲线下面积 (AUC) 为0.937 (95% CI，0.894-0.980); P  < .001。分别84.62% 和96.00% 降钙素原/白蛋白比值临界值 (>0.44) 的敏感性和特异性。此外，在65例尿毒症患者的亚组中，尿毒症休克组的降钙素原/白蛋白比值高于无尿毒症休克患者组 [5.46 (1.43，6.58) vs 1.24 (0.63，4.38); P   =  .009].我们的研究表明，降钙素原/白蛋白比值是一种早期诊断预测因子，可以区分尿脓毒症和发热性尿路感染。此外，在尿毒症患者中，降钙素原/白蛋白比值较高的患者更容易发生尿毒症休克。我们的发现表明，降钙素原/白蛋白比率是一种快速且相对低成本的生物标志物，可用于临床实践。

BACKGROUND & AIMS: :The aims of this study were twofold. The first was to investigate the diagnostic performance of two biochemical markers, procalcitonin (PCT) and lipopolysaccharide-binding protein (LBP), considering each individually and then combined, for the postmortem diagnosis of sepsis. We also tested the usefulness of pericardial fluid for postmortem LBP determination. Two study groups were formed, a sepsis-related fatalities group of 12 cases and a control group of 30 cases. Postmortem native CT scans, autopsy, histology, neuropathology, and toxicology as well as other postmortem biochemical investigations were performed in all cases. Microbiological investigations were also carried out in the septic group. Postmortem serum PCT and LBP levels differed between the two groups. Both biomarkers, individually considered, allowed septic states to be diagnosed, whereas increases in both postmortem serum PCT and LBP levels were only observed in cases of sepsis. Similarly, normal PCT and LBP values in postmortem serum were identified only in non-septic cases. Pericardial fluid LBP levels do not correlate with the presence of underlying septic states. No relationship was observed between postmortem serum and pericardial fluid LBP levels in either septic or non-septic groups, or between pericardial fluid PCT and LBP levels.

背景与目标： : 这项研究的目的是双重的。首先是研究两种生化标志物 (降钙素原 (PCT) 和脂多糖结合蛋白 (LBP)) 的诊断性能，分别考虑并结合起来，用于脓毒症的死后诊断。我们还测试了心包液对死后LBP测定的有用性。组成两个研究组，脓毒症相关死亡组12例，对照组30例。在所有情况下，均进行了死后自然ct扫描，尸检，组织学，神经病理学和毒理学以及其他死后生化检查。化粪池组也进行了微生物学研究。两组死后血清PCT和LBP水平不同。单独考虑的两种生物标志物都可以诊断出脓毒症状态，而死后血清PCT和LBP水平仅在脓毒症病例中观察到。同样，仅在非败血症病例中鉴定出死后血清中的正常PCT和LBP值。心包液LBP水平与潜在脓毒症状态的存在无关。在脓毒症或非脓毒症组中，死后血清与心包液LBP水平之间或心包液PCT与LBP水平之间均未观察到关系。

BACKGROUND & AIMS: BACKGROUND:Procalcitonin (PCT) has been considered a more reliable marker than others because of its specificity for bacterial infection. METHODS:Case report and review of the literature. RESULTS:A 50-year-old male was diagnosed with subarachnoid hemorrhage, intraventricular hemorrhage, and intracerebral hemorrhage. We performed a ruptured aneurysm clipping and left unilateral external ventricular drainage. We also performed ventriculoperitoneal (VP) shunt placement in the course; however, VP shunt infection was indicated by fever, increased C-reactive protein concentration and leukocytosis. The cerebrospinal fluid culture showed methicillin-resistant Staphylococcus epidermidis but the serum PCT concentration was quite low. CONCLUSIONS:Although PCT is considered a more reliable serological marker of bacterial meningitis in several reports, the serum PCT concentration did not reflect the bacterial VP shunt infection that was present in our case.

背景与目标：

BACKGROUND & AIMS: OBJECTIVE:To determine the relationship between cerebrospinal fluid procalcitonin concentration and severe traumatic brain injury in children. DESIGN:Prospective, observational clinical study. SETTING:A multidisciplinary, tertiary-care pediatric intensive care unit. PATIENTS:Twenty-eight patients who required external ventricular drainage for management of severe traumatic brain injury (Glasgow Coma Scale score of <8) and 22 control patients for whom lumbar cerebrospinal fluid evaluation excluded possible meningitis. INTERVENTIONS:Standard intracranial pressure-directed neurointensive care, including intraventricular catheter placement and continuous cerebrospinal fluid drainage, was used to manage patients with severe traumatic brain injury. MEASUREMENTS AND MAIN RESULTS:Demographic data including age, mechanism of injury, time of injury, initial Glasgow Coma Scale score, and outcome were collected. Cerebrospinal fluid procalcitonin concentration was determined by immunoluminometric assay. Initial cerebrospinal fluid procalcitonin concentration (median [range]) in patients with severe traumatic brain injury was increased greater than three-fold vs. controls (0.41 ng/mL [0.15-2.14] vs. 0.12 ng/mL [0.00-0.24], p <.001). Initial cerebrospinal fluid procalcitonin concentration among patients with abusive head trauma (0.31 ng/mL [0.29-0.50]) also was increased vs. controls (p <.05), although this increase was less robust than patients with accidental trauma (0.41 ng/mL [0.15-2.14], p <.001 vs. controls). Additional examination of key demographic and outcome variables with a generalized linear regression model was performed for patients with severe traumatic brain injury. Univariate analysis revealed that both time after injury (p <.01) and abusive head trauma as a mechanism of injury (p <.001) were associated with attenuation of the increased cerebrospinal fluid procalcitonin response after traumatic brain injury. CONCLUSION:Cerebrospinal fluid procalcitonin concentration is increased in children after traumatic brain injury. The attenuated increase in cerebrospinal fluid procalcitonin among victims of abusive head trauma warrants further study because it may reflect impairment of endogenous neuroprotective mechanisms or delay in seeking medical attention. The significance of these observations remains to be determined as future studies elucidate the physiologic and mechanistic properties of procalcitonin.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:In controlled studies, procalcitonin (PCT) has safely and effectively reduced antibiotic drug use for lower respiratory tract infections (LRTIs). However, controlled trial data may not reflect real life. METHODS:We performed an observational quality surveillance in 14 centers in Switzerland, France, and the United States. Consecutive adults with LRTI presenting to emergency departments or outpatient offices were enrolled and registered on a website, which provided a previously published PCT algorithm for antibiotic guidance. The primary end point was duration of antibiotic therapy within 30 days. RESULTS:Of 1759 patients, 86.4% had a final diagnosis of LRTI (community-acquired pneumonia, 53.7%; acute exacerbation of chronic obstructive pulmonary disease, 17.1%; and bronchitis, 14.4%). Algorithm compliance overall was 68.2%, with differences between diagnoses (bronchitis, 81.0%; AECOPD, 70.1%; and community-acquired pneumonia, 63.7%; P < .001), outpatients (86.1%) and inpatients (65.9%) (P < .001), algorithm-experienced (82.5%) and algorithm-naive (60.1%) centers (P < .001), and countries (Switzerland, 75.8%; France, 73.5%; and the United States, 33.5%; P < .001). After multivariate adjustment, antibiotic therapy duration was significantly shorter if the PCT algorithm was followed compared with when it was overruled (5.9 vs 7.4 days; difference, -1.51 days; 95% CI, -2.04 to -0.98; P < .001). No increase was noted in the risk of the combined adverse outcome end point within 30 days of follow-up when the PCT algorithm was followed regarding withholding antibiotics on hospital admission (adjusted odds ratio, 0.83; 95% CI, 0.44 to 1.55; P = .56) and regarding early cessation of antibiotics (adjusted odds ratio, 0.61; 95% CI, 0.36 to 1.04; P = .07). CONCLUSIONS:This study validates previous results from controlled trials in real-life conditions and demonstrates that following a PCT algorithm effectively reduces antibiotic use without increasing the risk of complications. Preexisting differences in antibiotic prescribing affect compliance with antibiotic stewardship efforts. TRIAL REGISTRATION:isrctn.org Identifier: ISRCTN40854211.

背景与目标：

BACKGROUND & AIMS: OBJECTIVES:Procalcitonin (PCT) is widely used for the diagnosis of bacterial infections. The aim of this study was to evaluate PCT as a tumor and as a prognostic marker in patients with primary lung cancer. DESIGN AND METHODS:We retrospectively performed a PCT dosage in the frozen serum samples of 147 patients with pulmonary neoplasia for whom a test of neuron-specific enolase (NSE) had been conducted at the time of diagnosis. RESULTS:We show that a PCT serum level above 0.15 ng/mL was independently linked to the presence of a neuroendocrine component in the tumor (HR=5.809 95% CI [1.695-19.908] p: 0005). Thus, median PCT serum levels were significantly more elevated in small-cell lung cancers than in pulmonary adenocarcinomas: 0.33 ng/mL versus 0.07 ng/mL (p<0.001). However, the diagnostic value of serum PCT levels for diagnosing carcinoma with a neuroendocrine component remains low (sensitivity 63.8%; specificity 71.9%). In this series, serum PCT levels were significantly more elevated in the presence of liver metastases: 0.37 ng/mL versus 0.09 ng/mL in the absence of liver metastasis (p<0.001). In uni- and multivariate analyses, a serum PCT level above 0.15n g/mL and the presence of metastases and of sepsis at the time of diagnosis were independent factors of unfavorable prognosis. CONCLUSIONS:Serum PCT is elevated in patients with lung cancer with neuroendocrine component or with liver metastases. As a consequence, in this population, PCT has a poor specificity for bacterial infection. At diagnosis, an elevated serum PCT is an independent predictive factor of bad prognosis.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Febrile neutropenia (FNP) causes significant morbidity and mortality in children undergoing treatment for cancer. The development of clinical decision rules to help stratify risks in paediatric FNP patients and the use of inflammatory biomarkers to identify high risk patients is an area of recent research. This study aimed to assess if procalcitonin (PCT) levels could be used to help diagnose or exclude severe infection in children with cancer who present with febrile neutropenia, both as a single measurement and in addition to previously developed clinical decision rules. METHODS:This prospective cohort study of a diagnostic test included patients between birth and 18 years old admitted with febrile neutropenia to the Paediatric Oncology and Haematology Ward in Leeds between 1st October 2012 and 30th September 2013. Each admission with FNP was treated as a separate episode. Blood was taken for a procalcitonin level at admission with routine investigations. 'R' was used for statistical analysis. Likelihood ratios were calculated and multivariable logistic regression. RESULTS:Forty-eight episodes from 27 patients were included. PCT >2 ng/dL was strongly associated with increased risk of severe infection (likelihood ratio of 26 [95% CI 3.5, 190]). The data suggests that the clinical decision rules are largely ineffective at risk stratification, frequently over-stating the risk of individual episodes. High procalcitonin levels on admission are correlated with a greatly increased risk of severe infection. CONCLUSIONS:This study does not show a definitive benefit in using PCT in FNP though it supports further research on its use. The benefit of novel biomarkers has not been proven and before introducing new tests for patients it is important their benefit above existing features is proven, particularly due to the increasing importance of health economics.

背景与目标：

BACKGROUND & AIMS: :The present study aimed to explore the diagnostic value of the combination of cranial magnetic resonance imaging (MRI), serum homocysteine (HCY) and procalcitonin (PCT) for hyperbilirubinemia complicated with brain injury in neonates. One hundred and forty-nine children with hyperbilirubinemia admitted to Shandong Medical Imaging Research Institute from January 2014 to April 2016 were collected as research subjects, and were divided into a brain injury group (n=67) and a non-brain injury group (n=82) according to whether children suffered from brain injury. PCT levels were detected by electrochemiluminescence (ECL), and HCY levels by enzymatic cycling assay (ECA). The combination of cranial MRI, HCY and PCT was used to diagnose hyperbilirubinemia complicated with brain injury in neonates. The concentrations of HCY and PCT in the brain injury group were significantly higher than those in the non-brain injury group (P<0.001). According to the MRI examination results, the patients were divided into an MRI normal group and an MRI abnormal group. In the brain injury group, the serum HCY and PCT levels of the MRI abnormal group were significantly higher than those of the MRI normal group, with a statistically significant difference (P<0.05). In the non-brain injury group, the serum HCY and PCT levels of the MRI abnormal group were significantly higher than those of the MRI normal group, with a statistically significant difference (P<0.05). The sensitivity of the combined detection was significantly higher than that of single detection (P<0.05); the specificity was significantly higher than that of HCY detection (P<0.05), and the accuracy was significantly higher than that of MRI and HCY single detection (P<0.05). In conclusion, the combination of cranial MRI, HCY and PCT, which has a high diagnostic value for hyperbilirubinemia complicated with brain injury in neonates, is conducive to the early diagnosis and timely treatment of the disease and the reduction of sequelae.

背景与目标： 本研究旨在探讨头颅磁共振成像 (MRI) 、血清同型半胱氨酸 (HCY) 和降钙素原 (PCT) 联合检测对新生儿高胆红素血症合并脑损伤的诊断价值。收集山东省医学影像研究所2014年1月至2016年4月收治的49例高胆红素血症患儿作为研究对象，根据患儿是否遭受脑损伤分为脑损伤组 (n = 67) 和非脑损伤组 (n = 82)。通过电化学发光 (ECL) 检测PCT水平，通过酶循环测定 (ECA) 检测HCY水平。头颅MRI，HCY和PCT联合用于诊断新生儿高胆红素血症并发脑损伤。脑损伤组的HCY和PCT浓度明显高于非脑损伤组 (P<0.001)。根据MRI检查结果将患者分为MRI正常组和MRI异常组。在颅脑损伤组中，MRI异常组的血清HCY和PCT水平明显高于MRI正常组，差异有统计学意义 (P<0.05)。在非脑损伤组中，MRI异常组的血清HCY和PCT水平明显高于MRI正常组，差异有统计学意义 (P<0.05)。联合检测的敏锐度显著高于单次检测 (P<0.05); 特异性显著高于HCY检测 (P<0.05)，准确性显著高于MRI和HCY单次检测 (P<0.05)。综上所述，头颅MRI、HCY和PCT联合应用对新生儿高胆红素血症并发脑损伤有较高的诊断价值，有利于疾病的早期诊断和及时治疗，减少后遗症。

BACKGROUND & AIMS: BACKGROUND:Previous reports on the behavior of procalcitonin blood levels in diverse clinical conditions suggest that it is part of the activation of cellular immunity and is another acute-phase reactant. OBJECTIVE:To compare procalcitonin with C-reactive protein, a well-known acute-phase reactant, in a series of acutely febrile pediatric patients and to review recent literature on procalcitonin. METHODS:Procalcitonin and CRP levels were evaluated in 38 blood samples of pediatric patients who were admitted to the Dana Children's Hospital for evaluation of unexplained fever or for sepsis work-up. RESULTS:The parallelism between procalcitonin and CRP was found to be highly significant (P < 0.01). CONCLUSION:The rise of procalcitonin blood levels in febrile pediatric patients suggests that it is part of the acute-phase reaction, parallel with the CRP reaction.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Procalcitonin (PCT), an inflammatory blood biomarker, is well studied in infectious diseases. Its prognostic value in unselected emergency department (ED) patients remains yet undefined. Herein, we investigated association of admission PCT levels and mortality in a large, international-multicenter ED patient cohort. METHODS:We prospectively enrolled 6970 unselected, consecutive, adult, medical patients seeking ED care in three tertiary-care hospitals in Switzerland, France and the USA. We used multivariable logistic regression models to examine association of admission PCT levels (as a continuous predictor and across cut-offs) and 30-day mortality. We also investigated subgroup effects by main diagnosis, comorbidities and clinical features at presentation. RESULTS:During the 30-day follow-up, 328 (4.7%) participants died. Mortality increased stepwise within higher PCT cut-offs (0.05, 0.1, 0.25, 0.5 ng/mL) from 1%, 3%, 7%, 13% to 15%, respectively. This association was also confirmed in a fully-adjusted model including age, gender, main symptom, main diagnosis and vital parameters on admission. Receiver operating characteristic (ROC) curve analysis showed that PCT differentiated well between survivors and non-survivors in the overall cohort (area under ROC curve [AUC] 0.75) with best results for patient with metabolic (AUC: 0.85) and cardiovascular disease (AUC: 0.82). Addition of PCT also improved the prognostic accuracy of the quick sequential organ failure assessment (qSOFA) score from an AUC of from 0.61 to 0.76 (p<0.001). Results were similar for other secondary endpoints including intensive care unit (ICU) admission and hospital readmission. CONCLUSIONS:In this large and heterogenous medical ED patient cohort, admission PCT was a strong and independent outcome predictor for 30-day mortality across different medical diagnoses independent of underlying infection. PCT may help to improve risk stratification in unselected medical ED patients.

背景与目标：

BACKGROUND & AIMS: PURPOSE:Serum procalcitonin (PCT) has become a routinely utilized parameter with a high prediction value of the severity of bacterial infectious complications and their immediate outcomes. Whereas the utility of PCT in differentiating between bacterial and viral infection is generally accepted, its significance in fungal infections has yet to be determined. The aim of the study was to determine the role of PCT testing in patients at high risk for invasive fungal infections. METHODS:Immunocompromised hematological patients undergoing cyclic chemotherapy treatment or allogeneic hemopoietic stem cell transplantation with infectious complications in which the infectious agents were identified during the disease course were evaluated. In patients with bacterial infection, positive hemocultures were documented, and in patients with fungal infection, the presence of either proven or probable disease was confirmed according to Ascioglu criteria. C-reactive protein (CRP) and PCT were prospectively assessed from the day following fever onset, for four consecutive days. RESULTS:Overall, 34 patients were evaluated, 21 with bacterial and 13 with fungal infections. Significant elevations of CRP concentrations (i.e., above the upper normal limit) were observed in all patients, with a tendency toward higher levels in bacterial (both gram-positive [Gr+] and Gr-negative [Gr-]) than in fungal infections. PCT levels were significantly elevated in patients with bacterial infections (e.g., predominantly in Gr- compared to Gr+), whereas in patients with fungal infections, we identified minimal or no PCT elevations, p < 0.01. For the fungal infections, according to constructed receiver operating characteristic curves, a combination of PCT <0.5 μg/L and CRP 100-300 mg/L offers the best specificity, sensitivity and positive and negative predictive values (81, 85, 73, and 89 %, respectively). CONCLUSION:Altogether, our data suggest that the finding of substantially elevated CRP combined with low PCT in immunocompromised patients may indicate systemic fungal infection. The use of this combination might simplify the diagnostic process, which otherwise can often be lengthy and arduous.

背景与目标：

BACKGROUND & AIMS: :To investigate the prognostic value of interleukin 6 (IL-6), procalcitonin (PCT), and C-reactive protein (CRP) in critically ill patients during the first increase of fever, serum levels were measured in 38 patients admitted to intensive care unit of the Department of Medicine, Klinikum Grosshadern, University of Munich, immediately after increase of body temperature more than 38.3 degrees C. Ten healthy controls were also included for comparison. The onset of fever was accompanied by elevated circulating levels of all the 3 markers in comparison with healthy controls. However, only IL-6 levels were significantly higher (P < 0.05) in nonsurvivors (n = 21) compared with survivors. Sensitivity, specificity, positive, and negative predictive values calculated from median levels was higher for IL-6 compared with PCT and CRP. Areas under receiver characteristic operating curves revealed the highest area under the curve for IL-6 in contrast to PCT and CRP. These data suggest that IL-6 rather than PCT or CRP may be an early predictor of mortality in patients with onset of fever and identify patients, who need intensive monitoring to initiate appropriate therapy at an early stage.

背景与目标： : 为了研究白介素6 (IL-6)，降钙素原 (PCT) 和C反应蛋白 (CRP) 在重症患者发热期间的预后价值，对38例重症监护室患者的血清水平进行了测量。Klinikum grossadern，慕尼黑大学，体温升高后立即超过38.3 ℃。还包括10个健康对照进行比较。与健康对照组相比，发烧的发作伴随着所有3种标志物的循环水平升高。然而，与幸存者相比，非幸存者 (n = 21) 中只有IL-6水平显着更高 (P <0.05)。IL-6的敏感性、特异性、阳性和阴性预测值均高于PCT和CRP。与PCT和CRP相比，接收器特性操作曲线下的面积显示出IL-6曲线下的最高面积。这些数据表明，IL-6而非PCT或CRP可能是发热患者死亡率的早期预测指标，并确定需要强化监测以在早期启动适当治疗的患者。

BACKGROUND & AIMS: :The objective was to evaluate the use of procalcitonin (PCT) and C-reactive protein (CRP) for the diagnosis of bacterial infection in bronchiolitis patients. A prospective, single-centre, descriptive, and comparative observational study was carried out on patients with severe bronchiolitis admitted to the paediatric intensive care unit (PICU), from January 2011 to July 2017. Two cohorts were compared: patients with invasive bacterial infection (IBI) and patients with no bacterial infection (NBI). We included 675 patients, 399 of whom were males (59.1%), with median age of 47 days (IQR 25-100.3). Of them, 181 patients were diagnosed with IBI (26.8%). Seventy-two had sepsis (10.7%), 106 had pneumonia (15.7%), and 41 had a urinary tract infection (6.1%). PCT and CRP values were significantly higher in patients with IBI. ROC curves compared the ability of PCT and CRP to diagnose IBI at admission, 24 h, and 48 h. PCT showed a better AUC for diagnosing IBI, with statistically significant differences at all time points (p < 0.001). The best PCT cut-off for IBI diagnosis at admission was 1.4 ng/mL, with a sensitivity of 69% (95% CI 58.4-74.9) and a specificity of 91% (95% CI 88.1-92.5). Procalcitonin showed a better AUC for diagnosing both sepsis and pneumonia, which makes it an excellent predictor.Conclusion: We present PCT as a novel test in comparison with the traditional CRP screening test to discern which bronchiolitis patients have IBI. We highlight the importance of PCT for the diagnosis of pneumonia and sepsis, as it proved to be more sensitive and specific than CRP, with statistically significant differences. What is Known: • Bronchiolitis should be treated with antibiotics only when a bacterial infection is present. • The rate of antibiotic prescription in severe bronchiolitis is extremely high, so diagnostic tools are needed. What is New: • PCT is a good biomarker to discern which bronchiolitis patients have IBI, specially for pneumonia and sepsis diagnoses. It is more sensitive and specific than CRP, with statistically significant differences. • Implementation of PCT cut-off values may prevent unnecessary antibiotic use.

背景与目标： : 目的是评估降钙素原 (PCT) 和C反应蛋白 (CRP) 在毛细支气管炎患者细菌感染诊断中的应用。从2011年1月到2017年7月，对儿科重症监护病房 (PICU) 的重症细支气管炎患者进行了一项前瞻性，单中心，描述性和对比观察性研究。比较了两个队列: 侵袭性细菌感染 (IBI) 患者和无细菌感染 (NBI) 患者。我们纳入了675例患者，其中399例为男性 (59.1%)，中位年龄为47天 (IQR 25-100.3)。其中，181例患者被诊断为IBI (26.8%)。72例患有败血症 (10.7%)，106例患有肺炎 (15.7%)，41例患有尿路感染 (6.1%)。IBI患者的PCT和CRP值明显较高。ROC曲线比较了PCT和CRP在入院，24 h和48 h诊断IBI的能力。PCT在诊断IBI时显示出更好的AUC，在所有时间点均具有统计学上的显着差异 (p <0.001)。入院时诊断IBI的最佳PCT临界点为1.4 ng/mL，敏感性为69% (95% CI 58.4-74.9)，特异性为91% (95% CI 88.1-92.5)。降钙素原显示出更好的AUC来诊断败血症和肺炎，这使其成为一个很好的预测指标。结论: 与传统的CRP筛查测试相比，我们提出了PCT作为一种新颖的测试方法，以识别哪些毛细支气管炎患者患有IBI。我们强调PCT对于肺炎和败血症的诊断的重要性，因为它被证明比CRP更敏感和特异性，具有统计学上的显着差异。已知情况: • 毛细支气管炎应仅在存在细菌感染时使用抗生素治疗。• 严重毛细支气管炎的抗生素处方率非常高，因此需要诊断工具。最新情况: • PCT是识别哪些毛细支气管炎患者患有IBI的良好生物标志物，特别是用于肺炎和败血症诊断。它比CRP更敏感和特异性，具有统计学上的显着差异。• 实施PCT临界值可能会防止不必要的抗生素使用。