• 【脑脊液降钙素原与儿童严重创伤性脑损伤。】 复制标题 收藏 收藏
    DOI:10.1097/00130478-200201000-00010 复制DOI
    作者列表:Han YY,Carcillo JA,Ruppel RA,Adelson PD,Wisniewski SR,Bell MJ,Janesko KL,Marion DW,Kochanek PM
    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:
  • 【“现实生活” 中降钙素原指导的抗生素治疗下呼吸道感染的有效性和安全性: 一项国际多中心研究后调查 (ProREAL)。】 复制标题 收藏 收藏
    DOI:10.1001/archinternmed.2012.770 复制DOI
    作者列表:
    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:
  • 【血清降钙素原浓度在原发性肺癌中的诊断和预后价值。】 复制标题 收藏 收藏
    DOI:10.1016/j.clinbiochem.2014.09.002 复制DOI
    作者列表:Patout M,Salaün M,Brunel V,Bota S,Cauliez B,Thiberville L
    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:
  • 【发热性中性粒细胞减少症癌症儿童降钙素原水平的前瞻性队列研究。】 复制标题 收藏 收藏
    DOI:10.1186/s12887-016-0766-8 复制DOI
    作者列表:Hemming V,Jakes AD,Shenton G,Phillips B
    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:
  • 【头颅MRI联合血清同型半胱氨酸和降钙素原对新生儿高胆红素血症并发脑损伤的诊断价值。】 复制标题 收藏 收藏
    DOI:10.3892/etm.2020.9179 复制DOI
    作者列表:Chang N,Wang G
    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。
  • 【降钙素原与C反应蛋白在儿科患者中的急性期反应物有关。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Somech R,Zakuth V,Assia A,Jurgenson U,Spirer Z
    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:
  • 【不同医疗急救患者人群的入院降钙素原水平是通用死亡率预测指标吗?来自多国、前瞻性、观察性分诊研究的结果。】 复制标题 收藏 收藏
    DOI:10.1515/cclm-2017-0144 复制DOI
    作者列表:Sager R,Wirz Y,Amin D,Amin A,Hausfater P,Huber A,Haubitz S,Kutz A,Mueller B,Schuetz P
    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:
  • 【C反应蛋白 (CRP) 的显着升高以及降钙素原 (PCT) 的低水平有助于免疫功能低下患者的真菌感染的诊断。】 复制标题 收藏 收藏
    DOI:10.1007/s00520-013-1844-1 复制DOI
    作者列表:Marková M,Brodská H,Malíčková K,Válková V,Cetkovský P,Kolář M,Haluzík M
    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:
  • 【白介素6,降钙素原和C反应蛋白水平在重症监护病房患者发热期间的预后价值。】 复制标题 收藏 收藏
    DOI:10.1097/01.shk.0000215319.06866.bd 复制DOI
    作者列表:Fraunberger P,Wang Y,Holler E,Parhofer KG,Nagel D,Walli AK,Seidel D
    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。
  • 【降钙素原和C反应蛋白在严重毛细支气管炎婴儿细菌感染诊断中的应用。】 复制标题 收藏 收藏
    DOI:10.1007/s00431-020-03790-6 复制DOI
    作者列表:Alejandre C,Guitart C,Balaguer M,Torrús I,Bobillo-Perez S,Cambra FJ,Jordan I
    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。
  • 【亚硒酸钠给药和降钙素原指导治疗对严重脓毒症或脓毒休克患者死亡率的影响: 一项随机临床试验.】 复制标题 收藏 收藏
    DOI:10.1001/jamainternmed.2016.2514 复制DOI
    作者列表:
    BACKGROUND & AIMS: IMPORTANCE:High-dose intravenous administration of sodium selenite has been proposed to improve outcome in sepsis by attenuating oxidative stress. Procalcitonin-guided antimicrobial therapy may hasten the diagnosis of sepsis, but effect on outcome is unclear. OBJECTIVE:To determine whether high-dose intravenous sodium selenite treatment and procalcitonin-guided anti-infectious therapy in patients with severe sepsis affect mortality. DESIGN, SETTING, AND PARTICIPANTS:The Placebo-Controlled Trial of Sodium Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis (SISPCT), a multicenter, randomized, clinical, 2 × 2 factorial trial performed in 33 intensive care units in Germany, was conducted from November 6, 2009, to June 6, 2013, including a 90-day follow-up period. INTERVENTIONS:Patients were randomly assigned to receive an initial intravenous loading dose of sodium selenite, 1000 µg, followed by a continuous intravenous infusion of sodium selenite, 1000 µg, daily until discharge from the intensive care unit, but not longer than 21 days, or placebo. Patients also were randomized to receive anti-infectious therapy guided by a procalcitonin algorithm or without procalcitonin guidance. MAIN OUTCOMES AND MEASURES:The primary end point was 28-day mortality. Secondary outcomes included 90-day all-cause mortality, intervention-free days, antimicrobial costs, antimicrobial-free days, and secondary infections. RESULTS:Of 8174 eligible patients, 1089 patients (13.3%) with severe sepsis or septic shock were included in an intention-to-treat analysis comparing sodium selenite (543 patients [49.9%]) with placebo (546 [50.1%]) and procalcitonin guidance (552 [50.7%]) vs no procalcitonin guidance (537 [49.3%]). The 28-day mortality rate was 28.3% (95% CI, 24.5%-32.3%) in the sodium selenite group and 25.5% (95% CI, 21.8%-29.4%) (P = .30) in the placebo group. There was no significant difference in 28-day mortality between patients assigned to procalcitonin guidance (25.6% [95% CI, 22.0%-29.5%]) vs no procalcitonin guidance (28.2% [95% CI, 24.4%-32.2%]) (P = .34). Procalcitonin guidance did not affect frequency of diagnostic or therapeutic procedures but did result in a 4.5% reduction of antimicrobial exposure. CONCLUSIONS AND RELEVANCE:Neither high-dose intravenous administration of sodium selenite nor anti-infectious therapy guided by a procalcitonin algorithm was associated with an improved outcome in patients with severe sepsis. These findings do not support administration of high-dose sodium selenite in these patients; the application of a procalcitonin-guided algorithm needs further evaluation. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT00832039.
    背景与目标:
  • 【降钙素原-中性粒细胞减少性癌症儿童发热发作的敏感炎症标志物。】 复制标题 收藏 收藏
    DOI:10.1007/BF02900739 复制DOI
    作者列表:Fleischhack G,Cipic D,Juettner J,Hasan C,Bode U
    BACKGROUND & AIMS: OBJECTIVE:Sensitive parameters of inflammations, are rare or of limited validity in neutropenic patients. Procalcitonin (PCT) proven to be a sensitive inflammatory marker in nonneutropenic patients was evaluated for its diagnostic relevance in febrile episodes of neutropenic patients with cancer METHODS:Plasma levels of PCT were determined by an immunoluminometric assay in children with febrile neutropenic episodes (n=376) starting at the date of admission until the resolution of fever and were correlated with serum levels of the C-reactive protein (CrP). Febrile episodes were classified as fever of unknown origin (FUO), microbiologically or clinically documented infections and were also differentiated according to the site of the infection (unknown, bacteremia, respiratory, soft tissue, gastrointestinal and urinary tract infection). RESULTS:Independently from the aetiology and the site of infection the PCT peak value occurred mostly on the second hospital day and decreased rapidly in cases of successful antibiotic therapy and with the resolution of fever to the normal range (0.1+/-0.5 microg/l). The highest PCT peak levels at the onset of fever and during the febrile course were observed in patients with gramnegative bacteremia (n = 22, median 12.1 microg/l, range 0.4+/-568.2 microg/l). There was a positive correlation between PCT peak levels and CrP peak levels (r = 0.48, p = 0.001) which mostly were observed 24 h later than for PCT. CONCLUSIONS:PCT is a sensitive and specific parameter in the diagnostic and in the sequential assessment of febrile neutropenic episodes, especially in gramnegative infections. Its diagnostic accuracy in neutropenic patients is clearly higher than that of CrP.
    背景与目标:
  • 【降钙素原在脓毒症治疗中的作用。】 复制标题 收藏 收藏
    DOI:10.21037/jtd.2019.11.63 复制DOI
    作者列表:Gregoriano C,Heilmann E,Molitor A,Schuetz P
    BACKGROUND & AIMS: :Important aspects of sepsis management include early diagnosis as well as timely and specific treatment in the first few hours of triage. However, diagnosis and differentiation from non-infectious causes often cause uncertainties and potential time delays. Correct use of antibiotics still represents a major challenge, leading to increased risk for opportunistic infections, resistances to multiple antimicrobial agents and toxic side effects, which in turn increase mortality and healthcare costs. Optimized procedures for reliable diagnosis and management of antibiotic therapy has great potential to improve patient care. Herein, biomarkers have been shown to improve infection diagnosis, help in early risk stratification and provide prognostic information which helps optimizing therapeutic decisions ("antibiotic stewardship"). In this context, the use of the blood infection marker procalcitonin (PCT) has gained much attention. There is still no gold standard for the detection of sepsis and use of conventional diagnostic approaches are restricted by some limitations. Therefore, additional tests are necessary to enable early and reliable diagnosis. PCT has good discriminatory properties to differentiate between bacterial and viral inflammations with rapidly available results. Further, PCT adds to risk stratification and prognostication, which may influence appropriate use of health-care resources and therapeutic options. PCT kinetics over time also improves the monitoring of critically ill patients with sepsis and thus influences decisions regarding de-escalation of antibiotics. Most importantly, PCT helps in guiding antibiotic use in patients with respiratory infection and sepsis by limiting initiation and by shortening treatment duration. To date, PCT is the best studied biomarker regarding antibiotic stewardship. Still, further research is needed to understand optimal use of PCT, also in combination with other remerging diagnostic tests for most efficient sepsis care.
    背景与目标: : 败血症管理的重要方面包括早期诊断以及在分诊的头几个小时内及时和具体的治疗。但是,与非感染性原因的诊断和区分通常会导致不确定性和潜在的时间延迟。正确使用抗生素仍然是一个重大挑战,导致机会性感染的风险增加,对多种抗菌药物的耐药性和毒副作用,进而增加死亡率和医疗保健成本。用于可靠诊断和管理抗生素治疗的优化程序具有改善患者护理的巨大潜力。在本文中,生物标记物已显示改善感染诊断,有助于早期风险分层并提供有助于优化治疗决策的预后信息 (“抗生素管理”)。在这种情况下,血液感染标志物降钙素原 (PCT) 的使用已引起广泛关注。目前尚无检测脓毒症的金标准,并且常规诊断方法的使用受到一些限制。因此,需要进行额外的检查以实现早期和可靠的诊断。PCT具有良好的区分特性,可区分细菌和病毒炎症,并可快速获得结果。此外,PCT增加了风险分层和预后,这可能会影响医疗保健资源和治疗选择的适当使用。随着时间的推移,PCT动力学也改善了对脓毒症重症患者的监测,从而影响了有关抗生素降级的决定。最重要的是,PCT通过限制开始治疗和缩短治疗时间,有助于指导呼吸道感染和败血症患者的抗生素使用。迄今为止,PCT是有关抗生素管理的最佳研究生物标志物。尽管如此,还需要进一步的研究来了解PCT的最佳使用,并与其他重新合并的诊断测试相结合,以实现最有效的败血症护理。
  • 【血清降钙素原对活动性系统性红斑狼疮的细菌感染具有阴性预测价值。】 复制标题 收藏 收藏
    DOI:10.1177/0961203312450085 复制DOI
    作者列表:Bador KM,Intan S,Hussin S,Gafor AH
    BACKGROUND & AIMS: BACKGROUND:Previous studies in systemic lupus erythematosus (SLE) patients have produced conflicting results regarding the diagnostic utility of procalcitonin (PCT). The aim of this study was to determine predictive values of PCT and C-reactive protein (CRP) for bacterial infection in SLE patients. MATERIALS AND METHODS:This was a cross-sectional study of clinic and hospitalized SLE patients with and without bacterial infection recruited over 18 months. Bacterial infection was defined as positive culture results. SLE disease activity was measured using SLEDAI. PCT and CRP were measured by automated immunoassays. RESULTS:Sixty-eight patients (57 females) were studied. Ten patients (15%) had infection. The areas under the receiver operating characteristic curves for PCT and CRP were not significantly different [0.797 (CI 0.614-0.979) versus 0.755 (CI 0.600-0.910)]. In lupus flare patients, PCT but not CRP was higher with infection (p = 0.019 versus 0.195). A PCT of <0.17 ng/ml ruled out infection with 94% negative predictive value (NPV). In remission patients, CRP but not PCT was elevated with infection (p = 0.036 versus 0.103). CRP < 0.57 mg/dl had 96% NPV. CONCLUSION:PCT may be a better marker to rule out bacterial infection in lupus flare but not in remission or general screening.
    背景与目标:
  • 【抑制miR-497-3p会下调降钙素原的表达并改善小鼠的细菌性肺炎。】 复制标题 收藏 收藏
    DOI:10.1007/s10753-020-01279-w 复制DOI
    作者列表:Wang W,Zhu Y,Yin L,Deng Y,Chu G,Liu S
    BACKGROUND & AIMS: :Pneumonia is usually caused by a wide variety of pathogen infection. The underlying mechanism contributing to pneumonia remains elusive. Here, the role of microRNA-497-3p (miR-497-3p) was explored in bacterial pneumonia. The expression levels of miR-497-3p and procalcitonin (PCT) in patient serum were detected by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The interaction between miR-497-3p and PCT was further verified in A549 cell line. To further explore the role of miR-497-3p in pneumonia, mouse model of bacterial pneumonia was established via Sp TIGR4 strain (SpT4) infection. Subsequently, LV-miR-497-3p sponge was administrated in mice with bacterial pneumonia. The severity of pneumonia and inflammatory response were evaluated. Serum miR-497-3p and PCT levels increased in patients with bacterial pneumonia and miR-497-3p level positively corrected with the PCT level. The functional assay demonstrated that CALCA is the target of miR-497-3p in the A549 cell line. In mice with bacterial pneumonia, both miR-497-3p and PCT levels were upregulated after SpT4 infection. LV-miR-497-3p sponge administration attenuated pneumonia, accompanied with increasing gain of bodyweight and blood oxygen levels, as well as uninjured lungs. miR-497-3p inhibition attenuates the expression of C-reactive protein (CRP) and inflammatory cytokines in lung tissues of SpT4-infected mice, including nterleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). In conclusion, inhibition of miR-497-3p downregulates the expression of procalcitonin and ameliorates bacterial pneumonia in mice.
    背景与目标: : 肺炎通常是由多种病原体感染引起的。导致肺炎的潜在机制仍然难以捉摸。在这里,细菌性肺炎探讨了microRNA-497-3p (miR-497-3p) 的作用。采用实时聚合酶链反应 (rt-pcr) 和酶联免疫吸附试验 (ELISA) 分别检测患者血清中miR-497-3p和降钙素原 (PCT) 的表达水平。在A549细胞系中进一步验证了miR-497-3p与PCT之间的相互作用。为进一步探讨miR-497-3p在肺炎中的作用,通过Sp TIGR4株 (SpT4) 感染建立小鼠细菌性肺炎肺炎模型。随后,在具有细菌性肺炎的小鼠中施用LV-miR-497-3p海绵。评估肺炎的严重程度和炎症反应。细菌性肺炎患者的血清miR-497-3p和PCT水平升高,miR-497-3p水平与PCT水平呈正相关。功能测定表明CALCA是A549细胞系中miR-497-3p的靶标。在细菌性肺炎小鼠中,SpT4感染后miR-497-3p和PCT水平均上调。LV-miR-497-3p海绵给药可减轻肺炎,并伴有体重和血氧水平增加以及未受伤的肺部。miR-497-3p抑制抑制SpT4-infected小鼠肺组织中C反应蛋白 (CRP) 和炎性细胞因子的表达,包括nterleukin-6 (IL-6) 和肿瘤坏死因子-α (TNF-α)。总之,抑制miR-497-3p会下调降钙素原的表达并改善小鼠的细菌性肺炎。

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