新生儿感染诊断中降钙素原及超敏C-反应蛋白检测的临床意义

目的 探讨采用超敏C-反应蛋白(hs-CRP)和降钙素原(PCT)作为检测指标在新生儿感染诊断中的临床价值.方法 选取本院新生儿科2014年9月至2016年10月期间所收治新生儿60例作为观察对象,所有患儿均经诊断确诊为感染性疾病,将其作为观察组,另选取同期本院体检健康新生儿60例作为对照组,对两组新生儿进行血清降钙素原、超敏C反应蛋白检测,其中超敏C反应蛋白行散射比浊法检测,降钙素原行双抗体夹心精标法检测,对两组新生儿相关指标检测结果进行对比分析.结果 观察组新生儿其白细胞计数、hs-CRP水平、PCT水平均明显高于对照组,差异具有统计学意义(P＜0.05);同PCT相比,hs-CRP对于新生儿感染性疾病的诊断灵敏度、特异性均处于较低水平;同单一指标检测相比,PCT联合hs-CPR检测对于新生儿感染性疾病的诊断灵敏度、特异性均处于较高水平.结论 在新生儿感染性疾病中,血清超敏C-反应蛋白、降钙素原均存在显著的特异性变化,可作为感染性疾病的鉴别、诊断指标,其中降钙素原对于新生儿感染性疾病的诊断灵敏度、特异性优于超敏C-反应蛋白,采用二者进行联合检测可有效提高对于此类患儿的临床诊断价值.     

Neonatal Sepsis and Neutrophil Insufficiencies

Sepsis has continuously been a leading cause of neonatal morbidity and mortality despite current advances in chemotherapy and patient intensive care facilities. Neonates are at high risk for developing bacterial infections due to quantitative and qualitative insufficiencies of innate immunity, particularly granulocyte lineage development and response to infection. Although antibiotics remain the mainstay of treatment, adjuvant therapies enhancing immune function have shown promise in treating sepsis in neonates. This article reviews current strategies for the clinical management of neonatal sepsis and analyzes mechanisms underlying insufficiencies of neutrophil defense in neonates with emphasis on new directions for adjuvant therapy development.     

降钙素原检测在新生儿败血症早期诊断中的应用

目的：探讨血清降钙素原(PCT)作为早期诊断新生儿败血症指标的应用价值。方法应用固相免疫测定法测定84例新生儿血清中降钙素原(PCT),C反应蛋白(CRP)水平,其中败血症组30例、一般感染组28例、非感染组26例。结果败血症组患儿血清PCT、CRP水平显著高于一般感染组和非感染组,差异有统计学意义(P<0.05);一般感染组与非感染组血清中PCT、CRP水平比较差异有统计学意义(P<0.05)。以0.5ng/mL为临界值,PCT诊断新生儿败血症的敏感度为93.3%,特异度为80.8%;以8.0mg/L为临界值,诊断败血症的敏感度为70.0%,特异度为69.2%。与CRP相比,PCT诊断败血症的敏感性、特异性更高。经抗生素有效治疗后,血清PCT下降幅度明显大于血清CRP下降幅度。结论新生儿血清PCT水平的检测对败血症的早期诊断与疗效评价具有重要价值。     

hs-CRP和PCT水平的检测在新生儿细菌性脑膜炎诊断中的应用

目的 探讨hs-CRP和PCT水平的检测在新生儿细菌性脑膜炎诊断中的应用.方法 选取2012年3月至2015年10月我院收治的40例急性细菌性脑膜炎新生儿和同期收治的40例病毒性脑膜炎作为研究对象,比较两组患儿治疗前后hs-CRP和PCT水平的变化,以及诊断的特异度、敏感度和误诊率.结果 治疗前,观察组患儿的血清hs-CRP和PCT水平明显高于对照组(P＜0.05);治疗后,两组患儿的血清hs-CRP水平差异无统计学意义(P＞0.05),观察组患儿的血清PCT水平显著低于治疗前(P＜0.05),且与对照组血清PCT水平差异无统计学意义(P＞0.05);观察组细菌性脑膜炎hs-CRP的特异度和敏感度分别为75.0％和97.2％,误诊率为25.0％,PCT的特异度和敏感度分别为66.7％和94.6％,误诊率为33.3％;对照组病毒性脑膜炎hs-CRP的特异度和敏感度分别为50.0％和77.8％,误诊率为50.0％,PCT的特异度和敏感度分别为40.0％和74.6％,误诊率为60.0％.结论 hs-CRP和PCT是临床上常用的感染性炎症标志物,因此联合检测hs-CRP和PCT在新生儿细菌性脑膜炎的诊断和治疗效果监测上有重要的应用价值.     

Amniotic Fluid Granulocyte Colony Stimulating Factor Levels in Chorioamnionitis Do Not Predict Neonatal Sepsis

PROBLEM: To assess the usefulness of amniotic fluid (AF) granulocyte colony-stimulating factor levels (G-CSF) in chorioamnionitis (CAM) to predict neonatal sepsis. METHOD OF STUDY: AF samples were obtained from term and preterm patients with (Group I) and without (Group II) CAM and were assayed for G-CSF levels. Patients with other infections were excluded. All AF samples were also tested for gram stain and cultures. The sensitivity, specificity, and predictive values of these parameters for diagnosing neonatal sepsis were assessed. RESULTS: Positive AF cultures were the best predictors of neonatal sepsis in CAM, with a sensitivity of 67% and a positive predictive value (PPV) of 80%. Elevated AF G-CSF levels (>1,000 pg/ml) were poor predictors of neonatal sepsis with a sensitivity of 29% and PPV of 39%. CONCLUSION: Even though AF G-CSF levels were markedly elevated in patients with CAM, they were poor predictors of subsequent neonatal sepsis.     

Maternal and neonatal risk factors of asthma in children: Nationwide population based study

BackgroundSmall population group-based cohorts have found that perinatal factors may contribute to the development of asthma in children. We aimed to investigate maternal and neonatal risk factors for the asthma phenotypes using two databases from the Taiwan's Maternal and Child Health Database (TMCHD) and the National Health Insurance Research Database (NHIRD).MethodsPerinatal data was obtained from 2004 to 2008 in the TMCHD and linked the NHIRD to obtain relevant medical information regarding maternal and neonatal risk factors of three asthma phenotypes which were identified as transient early asthma, persistent asthma, and late-onset asthma. A multivariate logistic regression analysis was conducted to adjust for covariates.ResultsThe percentage of non-asthmatic patients was 77.02% and asthmatic (transient early asthma, late onset asthma, and persistent asthma) patients were 8.96%, 11.64%, and 2.42%, respectively. Maternal risk factors—including Cesarean section, maternal asthma, maternal allergic rhinitis (AR), and premature rupture of membranes—and neonatal risk factors, such as male gender, gestational age 29–37 weeks, ventilator use, antibiotics use, AR, and atopic dermatitis, were associated with the development of these three asthma phenotypes. Twins and a gestational age of 28 weeks or less premature were associated with the development of transient early asthma and persistent asthma, but not late onset asthma. Triplets and above were associated with the development of transient early asthma, but not late onset or persistent asthma.ConclusionVarious asthma phenotypes have different risk factors; therefore, their distinct risk factors should be identified in order to early diagnosis and treatment.     

Effect of Maternal Protein Restriction During Pregnancy and Lactation on the Number of Cardiomyocytes in the Postproliferative Weanling Rat Heart

Maternal protein restriction leads to a reduction in the number of cardiomyocytes in the rat heart at birth. However, in rats, cardiomyocytes continue to proliferate until about 2 weeks after birth. Hence, this study aimed to examine the effect of maternal protein restriction, on the number of cardiomyocytes in the young rat heart at a time point when the cardiomyocytes have ceased proliferating and are terminally differentiated. Female Wistar Kyoto rats were fed either a normal protein diet (NPD; 20% casein) or a low protein diet (LPD; 8.7% casein) during pregnancy and lactation. Offspring (seven males and seven females per group) were perfusion fixed at 4 weeks of age. Heart volume and total cardiomyocyte number were determined using stereological techniques. At 4 weeks of age, body weights in both male and female LPD offspring were significantly reduced compared with NPD controls whereas relative heart volumes were significantly increased in LPD offspring. Total number of cardiomyocytes was not significantly different between groups. In both groups, there was a significant linear correlation between cardiomyocyte number and heart volume. In conclusion, total cardiomyocyte number in the postproliferative rat heart does not appear to be affected by maternal protein restriction per se but is directly related to heart size. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.     

Maternal serum procalcitonin levels in prediction of chorioamnionitis in women with preterm premature rupture of membranes

IntroductionChorioamnionitis is one of the most important maternal complications in the expectant management of patients with preterm premature rupture of membranes (PPROM). Procalcitonin (proCT), the precursor of the hormone calcitonin, is used to differentiate bacterial infections from non-bacterial ones. The objective of the study was to determine the efficacy of maternal serum procalcitonin levels in the early prediction of chorioamnionitis in women with PPROM.Material and methodsThe study was conducted in 76 pregnant women hospitalized due to PPROM at the maternal-fetal medicine unit of a tertiary center in Istanbul. Patients were followed up with white blood cell (WBC), C-reactive protein (CRP) and proCT levels every 2 days. The values of investigated parameters were recorded at the diagnosis of PPROM and at the time of delivery. The maximum values during the follow-up period were also recorded.ResultsOut of the 76 patients with PPROM, 15 (19.73%) developed clinical chorioamnionitis. No significant difference could be detected in the gravidity, parity, duration of hospitalization and gestational week at diagnosis between those patients who developed clinical chorioamnionitis and those who did not. The WBC at the time of hospital admittance and before delivery, and CRP levels before delivery were statistically higher in the chorioamnionitis group (p < 0.05). No difference in the proCT levels could be detected either at the time of hospital admittance or before delivery between the two groups.ConclusionsMaternal proCT was not found to be predictive of chorioamnionitis. However, since there are reports in the literature that contradict these results, further studies are warranted to determine the true efficacy of proCT in the prediction of clinical chorioamnionitis.     

High-Sensitivity C-Reactive Protein Can Reflect Small Airway Obstruction in Childhood Asthma

PurposeHigh-sensitivity assays enabled the identification of C-reactive protein (hs-CRP) at levels that were previously undetectable. We aimed to determine if hs-CRP could reflect airway inflammation in children, by comparing hs-CRP with spirometry and impulse oscillometry (IOS) parameters and symptomatic severities.ResultsOf the 276 asthmatic children [median age 7.5 (5.9/10.1) years, 171 boys (62%)], 39 were hs-CRP positive and 237 were negative. Regarding spirometry parameters, we observed significant differences in maximum mid-expiratory flow, % predicted (FEF_25–75) (p=0.010) between hs-CRP positive and negative groups, and a negative correlation between FEF_25–75 and hs-CRP. There were significant differences in the reactance area (AX) (p=0.046), difference between resistance at 5 Hz and 20 Hz (R5–R20) (p=0.027), resistance at 5 Hz, % predicted (R5) (p=0.027), and reactance at 5 Hz, % predicted (X5) (p=0.041) between hs-CRP positive and negative groups. There were significant positive correlations between hs-CRP and R5 (r=0.163, p=0.008), and X5 (r=0.164, p=0.007). Spirometry and IOS parameters had more relevance in patients with higher blood neutrophil levels in comparison to hs-CRP.ConclusionHs-CRP showed significant correlation with FEF_25–75, R5, and X5. It can reflect small airway obstruction in childhood asthma, and it is more prominent in neutrophil dominant inflammation.     

Protein biomarker druggability profiling

Developing automated and interactive methods for building a model by incorporating mechanistic and potentially causal annotations of ranked biomarkers of a disease or clinical condition followed by a mapping into a contextual framework in disease-linked biochemical pathways can be used for potential drug-target evaluation and for proposing new drug targets. We demonstrate the potential of this approach using ranked protein biomarkers obtained in neonatal sepsis by enrolling 127 infants (39 infants with late onset neonatal sepsis and 88 control infants) and by performing a focused proteomic profile of the sera and by applying the interactive druggability profiling algorithm (DPA) developed by us.     

肠易激综合征早期生活事件模型下的大鼠结肠肠神经可塑性研究

目的从神经可塑性角度探讨肠易激综合征的可能发病机制、临床特征及治疗方法。方法雄性SD大鼠出生后连续13 d每天分离3 h。腹壁撤退反射实验用来检测内脏痛觉过敏。肠神经系统结构可塑性可以通过铺片技术和免疫荧光技术,比较近端结肠神经节(HuD阳性细胞)的大小和数目以及胶质细胞(GFAP)的变化来检测。检测近端结肠多组肌间神经丛和黏膜下神经丛肠神经递质类型(ChAT-、VIP-、nNOS-、calbindin-TrKA-、P75-阳性细胞),分析神经递质的可塑性变化。结果新生期应激可致成年鼠内脏敏感性增高,新生期母婴分离可以诱导肠神经结构改变,导致神经元肥大和增生、胶质细胞与神经元的比例增高。神经递质方面,新生期母婴分离组P75和TrkA表达(黏膜下神经丛、肌间神经丛)较正常组均明显增加。ChAT在肌间神经丛表达明显增加,VIP在黏膜下神经丛表达降低,nNOS在肌间神经丛表达增高,Cabindin表达未见明显异常。结论新生期母婴分离可以引起大鼠结肠肠神经可塑性的长期改变。新生期母婴分离诱导的内脏高敏感性中存在肠神经系统可塑性。早期生活事件是引起成年后肠神经系统可塑性改变的重要原因。     

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.     

Muscle Proteolysis and Weight Loss in a Neonatal Rat Model of Sepsis Syndrome

Our hypothesis is that nitrogen loss in septic neonates is caused by increased muscle proteolysis. Sprague–Dawley rat pups (P7) were injected intraperitoneally with NaCl or 4 mg/kg/BW lipopolysaccharide (LPS) and then sacrificed at 2, 4, 24, and 48 hr. Sepsis syndrome was confirmed by elevated serum tumor necrosis factor (24.6 ng/mL ± 18.4 [LPS] and <1.0 ng/mL [controls]; p < .05). Proteolysis in gastrocnemius/soleus muscle was analyzed by quantitation of tissue tyrosine loss. The neonatal rats injected with LPS had significant media tyrosine release at 24 hr compared to the controls (0.39 ± 0.14 versus 0.25 ± 0.11 mol tyrosine/g muscle; p < .05). At 48 hr, LPS-induced muscle tyrosine release ceased (0.24 ± 0.04 [control] versus 0.23 ± 0.03 mol tyrosine/g muscle [LPS]). After 48 hr, gastrocnemium/soleus weight was less in the LPS-injected rats (50.5 ± 4.8 to 31.2 ± 4.0 g; p < .0001). Similar changes were not seen in the extensor digitorum longus, suggesting that some muscles were relatively preserved. Also, LPS resulted in significant weight loss. We conclude that selective muscle proteolysis contributes to nitrogen loss in neonatal sepsis. Although proteolysis abates by 48 hr, short-term injury results in significant muscle-mass deficit.     

Neonatal Immunity and Somatic Mutation

Neonatal animals are able to mount an effective immune response, both humoral and cellular, when immunized using conditions that maximize stimulation of antigen presenting cells, T cells, and B cells. In adults, somatic mutation is a key feature of the humoral immune response because it contributes to the generation of high affinity memory B cells. Recent evidence that B cells in neonatal mice and human infants can somatically mutate their immunoglobulin heavy chains suggests that neonates can utilize somatic mutation not only to diversify their restricted germline antibody repertoire, but also to improve upon this repertoire by the generation of B cells which can produce higher affinity antibodies. By extrapolation, if vaccination of children early in life resulted in somatic mutation and affinity maturation, this could provide a more protective antibody response to childhood diseases.     

水通道蛋白在脓毒症中的作用

脓毒症是世界范围内重症监护病房常见的死亡原因.由于这种免疫综合征的复杂性,迫切需要开发新的治疗策略.水通道蛋白(aquaporins,AQPs)参与脓毒症的多种生理功能,其表达受到不同程度的调控.药物靶点或生物标记物可能存在水通道蛋白(AQPs)上,因为它们是调节脓毒症的关键.对水通道蛋白调节机制的进一步研究可能确定潜...     

C反应蛋白对促红素治疗维持性血透病人贫血的影响

目的　探讨不同浓度C反应蛋白对促红细胞生成素治疗维持性血透病人贫血的影响 .方法　选择 5 6例CRF维持性血液透析病人 ,根据CRP浓度分为高CRP组 (>2 0mg/L)和低CRP组 (<2 0mg/L) ,接受 8个月的rHuEpo治疗及常规治疗 ,分析了Epo用量、血HCT、血Hb、Kt/Vurea、血铁蛋白、血清铁、血清转铁蛋白饱和度、血甲状旁腺素和血白蛋白等指标 .结果　血CRP浓度与Epo治疗剂量成正相关 ;血清铁和血白蛋白与血CRP和Epo治疗剂量负相关 .结论　血CRP升高可致贫血的维持性血透病人对Epo表现为低反应性     

缺血性脑卒中患者急性期血清C反应蛋白水平与预后的关系

目的 探讨急性脑梗死患者血清C反应蛋白（CRP）水平与疾病预后的相关性方法。方法 对80例脑梗死患者（脑梗死组）、20例腔隙性脑梗死患者（腔梗组）和40名健康体检者（对照组）血清CRP含量进行测定，计算其异常率并进行比较。按脑卒中患者临床神经功能缺损程度评分（NHISS）标准对患者进行评分。结果 脑梗死组CRP含量高于腔梗组，腔梗组高于对照组（均P〈0.01）；脑梗死组中，CRP异常率高于腔梗组（P〈0．05）；CRP异常的患者NHISS的评分的改善低于CRP正常组，且CRP异常者预后中无变化和死亡明显高于正常对照者（均P〈0．01）。结论 CRP水平是临床评价脑梗死严重程度和预后的一个重要的生物学指标。     

Pediatric Sepsis Guidelines: Summary for resource-limited countries

Justification:

Pediatric sepsis is a commonly encountered global issue. Existing guidelines for sepsis seem to be applicable to the developed countries, and only few articles are published regarding application of these guidelines in the developing countries, especially in resource-limited countries such as India and Africa.

Process:

An expert representative panel drawn from all over India, under aegis of Intensive Care Chapter of Indian Academy of Pediatrics (IAP) met to discuss and draw guidelines for clinical practice and feasibility of delivery of care in the early hours in pediatric patient with sepsis, keeping in view unique patient population and limited availability of equipment and resources. Discussion included issues such as sepsis definitions, rapid cardiopulmonary assessment, feasibility of early aggressive fluid therapy, inotropic support, corticosteriod therapy, early endotracheal intubation and use of positive end expiratory pressure/mechanical ventilation, initial empirical antibiotic therapy, glycemic control, and role of immunoglobulin, blood, and blood products.

Objective:

To achieve a reasonable evidence-based consensus on the basis of published literature and expert opinion to formulating clinical practice guidelines applicable to resource-limited countries such as India.

Recommendations:

Pediatric sepsis guidelines are presented in text and flow chart format keeping resource limitations in mind for countries such as India and Africa. Levels of evidence are indicated wherever applicable. It is anticipated that once the guidelines are used and outcomes data evaluated, further modifications will be necessary. It is planned to periodically review and revise these guidelines every 3–5 years as new body of evidence accumulates.     

Elevated Levels of Lipopolysaccharide-Binding Protein and Soluble CD14 in Plasma in Neonatal Early-Onset Sepsis

No data on lipopolysaccharide-binding protein (LBP) in newborns with sepsis have been available up to now. We therefore determined levels of LBP and soluble CD14 (sCD14) in plasma of healthy and septic neonates in order to evaluate their potential diagnostic role. The study included prospectively collected patient samples of two recently published studies on cytokine expression in neonatal sepsis. Twenty-nine septic patients were enrolled in the present analysis. Samples—either cord blood or peripheral blood—from patients admitted within the first 24 h of life for suspicion of sepsis and cord blood samples of a control group of 40 healthy mature infants delivered spontaneously were analyzed. For seven patients of the septic group, a second sample collected between 24 and 48 h of life was available. Levels of sCD14 and LBP in plasma were determined by an enzyme immunoassay using recombinant CD14 and LBP as standards. LBP and sCD14 were correlated to cytokine plasma levels. In septic neonates, LBP (median, 36.6 versus 7.8 μg/ml; P < 0.001) and sCD14 (median, 0.42 versus 0.28 μg/ml; P < 0.001) levels were highly elevated when compared to those of healthy neonates and strongly correlated to granulocyte colony-stimulating factor (G-CSF), interleukin-1β (IL-1β), IL-6, and IL-8 levels. LBP levels in septic neonates analyzed between 24 and 48 h of life even increased when compared to samples obtained at or shortly after delivery (median, 36.6 versus 60 μg/ml; P = 0.038). In summary, levels of LBP in plasma of neonates with early-onset sepsis are significantly elevated; the elevated plasma levels seem to persist for more than 24 h, which could provide the clinician with a prolonged time period to identify the newborn with bacterial sepsis.