BACKGROUND

Acute migraine can be treated with rimegepant, an antagonist of the calcitonin gene-related peptide (CGRP) receptor. With a focus on the Asian population as a subgroup, this metaanalysis attempts to investigate the effectiveness and safety of rimegepant for individuals suffering from severe migraines.

PubMed, MEDLINE database and Cochrane Library were used to identify valid randomized controlled trials for this study. The primary endpoint investigated was freedom from pain and freedom from the most bothersome symptom 2 hours post dose. RevMan 5.4.1 software was used to perform a meta-analysis on each outcome measure.

A total of five randomized controlled trials were incorporated, with two of them being conducted on Asian populations and published between 2014 and 2024. There were 2,516 cases in the rimegepant group and 2,668 cases in the placebo group out of the total 5,184 patients that were included. Rimegepant was found to significantly reduce the primary endpoints in acute migraine patients (RR 1.58, 95% CI 1.42-1.75, P-value 0.0001; RR 1.34, 95% CI 1.08-1.66, Pvalue 0.0001), and in the acute migraine Asian patients (RR 1.79, 95% CI 1.47-2.19, P-valueCONCLUSION

The use of rimegepant is effective and safe for acute migraine patients, including the Asian subgroup.

OBJECTIVE: To investigate the effects of calcitonin gene-related peptide (CGRP) on autophagy in hypoxic/reoxygenated (H/R) cardiomyocytes and its relationship with the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway. METHODS: The rat cardiomyocyte cell line H9c2 was routinely cultured in vitro and passaged for experiments when the cells grew to 80% fusion. (1) CGRP dosage screening experiment: the cells were divided into blank control group, H/R group and different dosages of CGRP pretreatment groups. H9c2 cells were placed in a closed hypoxia chamber for 2 hours and then reoxygenated in a conventional incubator for 12 hours to prepare the H/R model. The CGRP pretreatment groups were pretreated with 0.01, 0.1, 0.5, 1, 5, and 10 μmol/L CGRP before the modeling process. The blank control group was not given any treatment. Cell counting kit-8 (CCK-8) was used to detect the cell survival rate, and the most suitable drug dosage was screened out. (2) Intervention experiment: H9c2 cells were divided into blank control group, H/R group, CGRP+H/R group, and CGRP+PI3K target inhibitor ly294002 (LY)+H/R group. H/R group was prepared as cellular H/R model. CGRP (1 μmol/L) alone or in combination with LY (10 μmol/L) was administered to CGRP+H/R group and CGRP+LY+H/R group, respectively, prior to the preparation of cellular H/R model. The blank control group was cultured routinely without treatment. The cell survival rate was detected by CCK-8. The level of lactate dehydrogenase (LDH) release was detected by colorimetric assay. The expressions of autophagy-related proteins [autophagy effector protein Beclin-1, microtubule-associated protein 1 light chain 3-II (LC3-II), autophagy protein p62] and PI3K/Akt/mTOR signaling pathway proteins [phosphorylated Akt (p-Akt), phosphorylated mTOR (p-mTOR)] were detected by Western blotting. RESULTS: (1) Results of CGRP dosage screening experiment: compared with the blank control group, the cell survival rate of the H/R group decreased significantly; and after giving 0.1, 0.5, 1, 5 μmol/L CGRP for pretreatment, the cell survival rate increased significantly, and intervention effect of 1 μmol/L CGRP was the best, and the difference was statistically significant when compared with that of the H/R group [(74.23±6.18)% vs. (23.43±4.09)%, P < 0.01], so it was used as the intervention dosage for the subsequent experiment. (2) Intervention experiment results: compared with the blank control group, the cell survival rate in the H/R group was significantly reduced, the level of LDH release was significantly increased, the protein expressions of Beclin-1 and LC3-II were significantly increased, and the protein expressions of p62, p-Akt and p-mTOR were significantly reduced, indicating that the death of cardiomyocytes occurred after the treatment of H/R and was accompanied by the elevation of autophagy level, and this process was associated with the activation of PI3K/Akt/mTOR signaling pathway. Compared with the H/R group, CGRP pretreatment increased cell survival rate [(76.02±2.43)% vs. (46.15±3.29)%, P < 0.01], decreased the level of LDH release (U/L: 169.83±11.65 vs. 590.17±34.50, P < 0.01), and down-regulated the protein expressions of Beclin-1 and LC3-II [Beclin-1 protein (Beclin-1/β-actin): 1.27±0.15 vs. 1.93±0.19, LC3-II protein (LC3-II/LC3-I): 1.27±0.13 vs. 1.98±0.18, both P < 0.01], up-regulated the protein expressions of p62, p-Akt, p-mTOR [p62 protein (p62/β-actin): 0.96±0.02 vs. 0.63±0.05, p-Akt protein (p-Akt/Akt): 0.76±0.04 vs. 0.48±0.02, p-mTOR protein (p-mTOR/mTOR): 1.13±0.09 vs. 0.68±0.15, all P < 0.05], suggesting that CGRP was able to reduce the H/R-induced cardiomyocyte injury, and this process was accompanied by a decrease in the level of cellular autophagy and activation of the PI3K/Akt/mTOR signaling pathway. Compared with the CGRP+H/R group, the cell survival rate was significantly lower than that in the CGRP+LY+H/R group [(56.95±6.63)% vs. (76.02±2.43)%, P < 0.01], LDH release level was significantly higher (U/L: 436.00±27.44 vs. 169.83±11.65, P < 0.01), and the protein expressions of Beclin-1 and LC3-II were significantly up-regulated [Beclin-1 protein (Beclin-1/β-actin): 1.63±0.12 vs. 1.27±0.15, LC3-II protein (LC3-II/LC3-I): 1.61±0.13 vs. 1.27±0.13, both P < 0.01], and significantly down-regulated p62, p-Akt, and p-mTOR protein expressions [p62 protein (p62/β-actin): 0.57±0.09 vs. 0.96±0.02, p-Akt protein (p-Akt/Akt): 0.45±0.01 vs. 0.76±0.04, p-mTOR protein (p-mTOR/mTOR): 0.66±0.06 vs. 1.13±0.09, all P < 0.05], suggesting that PI3K-targeted inhibitor was able to reverse the protective effect of CGRP on H/R cells. CONCLUSIONS CGRP pretreatment attenuated H/R-induced cardiomyocyte injury, increased cell survival rate, and reduced cellular LDH release. This effect may be achieved through inhibiting the activation of PI3K/Akt/mTOR signaling pathway.
Animals ; Myocytes, Cardiac/drug effects* ; Signal Transduction/drug effects* ; Rats ; TOR Serine-Threonine Kinases/metabolism* ; Calcitonin Gene-Related Peptide/pharmacology* ; Proto-Oncogene Proteins c-akt/metabolism* ; Autophagy/drug effects* ; Cell Line ; Cell Hypoxia ; Phosphatidylinositol 3-Kinases/metabolism*

OBJECTIVE: To investigate whether electroacupuncture (EA) at sensitized acupoints could reduce sympathetic-sensory coupling (SSC) and neurogenic inflammatory response by interfering with 5-hydroxytryptamine (5-HT)ergic neural pathways to relieve colitis and somatic referred pain, and explore the underlying mechanisms. METHODS: Rats were treated with 5% dextran sodium sulfate (DSS) solution for 7 days to establish a colitis model. Twelve rats were randomly divided into the control and model groups according to a random number table (n=6). According to the "Research on Rat Acupoint Atlas", sensitized acupoints and non-sensitized acupoints were determined. Rats were randomly divided into the control, model, Zusanli-EA (ST 36), Dachangshu-EA (BL 25), and Xinshu (BL 15) groups (n=6), as well as the control, model, EA, and EA + GR113808 (a 5-HT inhibitor) groups (n=6). The rats in the control group received no treatment. Acupuncture was administered on 2 days after modeling using the stimulation pavameters: 1 mA, 2 Hz, for 30 min, with sparse and dense waves, for 14 consecutive days. GR113808 was injected into the tail vein at 5 mg/kg before EA for 10 min for 7 consecutive days. Mechanical sensitivity was assessed with von Frey filaments. Body weight and disease activity index (DAI) scores of rats were determined. Hematoxylin and eosin staining was performed to observe colon histopathology. SSC was analyzed by immunofluorescence staining. Immunohistochemical staining was performed to detect 5-HT and substance P (SP) expressions. The calcitonin gene-related peptide (CGRP) in skin tissue and tyrosine hydroxylase (TH) protein levels in DRG were detected by Western blot. The levels of hyaluronic acid (HA), bradykinin (BK), prostaglandin I2 (PGI2) in skin tissue, 5-HT, tryptophan hydroxylase 1 (TPH1), serotonin transporters (SERT), 5-HT 3 receptor (5-HT3R), and 5-HT 4 receptor (5-HT4R) in colon tissue were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: BL 25 and ST 36 acupoints were determined as sensitized acupoints, and BL 15 acupoint was used as a non-sensitized acupoint. EA at sensitized acupoints improved the DAI score, increased mechanical withdrawal thresholds, and alleviated colonic pathological damage of rats. EA at sensitized acupoints reduced SSC structures and decreased TH and CGRP expression levels (P<0.05). Furthermore, EA at sensitized acupoints reduced BK, PGI2, 5-HT, 5-HT3R and TPH1 levels, and increased HA, 5-HT4R and SERT levels in colitis rats (P<0.05). GR113808 treatment diminished the protective effect of EA at sensitized acupoints in colitis rats (P<0.05). CONCLUSION EA at sensitized acupoints alleviated DSS-induced somatic referred pain in colitis rats by interfering with 5-HTergic neural pathway, and reducing SSC inflammatory response.
Rats ; Animals ; Electroacupuncture ; Rats, Sprague-Dawley ; Serotonin ; Acupuncture Points ; Pain, Referred ; Calcitonin Gene-Related Peptide ; Signal Transduction ; Colitis/therapy* ; Indoles ; Sulfonamides

Cancer pain is one of the most common symptoms in patients with advanced cancer. In this study, we aimed to investigate the effects of the Mas-related gene C (MrgC) receptors on bone cancer pain. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured after the inoculation of Walker 256 mammary gland carcinoma cells into the tibia of adult Sprague-Dawley rats. The effects of MrgC receptor agonist bovine adrenal medulla 8-22 (BAM8-22) on nociceptive behaviors were investigated after intrathecal injection on days 16 and 17. Glial fibrillary acidic protein (GFAP)-positive cells in the spinal dorsal cord, and calcitonin gene related peptide (CGRP)-, neuronal nitric oxide synthase (nNOS)- and IL-1β-positive neurons in the dorsal root ganglia (DRG) were examined by immunofluorescence staining. The expression of nNOS and IL-1β proteins in the spinal dorsal horn and the DRG was examined by Western blotting after treatment with (Tyr6)-γ2-MSH-6-12 (MSH), which was another MrgC receptor agonist. The results showed that intrathecal injection of BAM8-22 (30 nmol) attenuated mechanical allodynia in a rat model of bone cancer pain and the effects could last for about 60 min, and single administration of BAM8-22 for two consecutive days reduced mechanical allodynia by about half on the third day. Moreover, the number of GFAP-positive cells in the spinal dorsal horn, and the number of CGRP-, nNOS- and IL-1β-positive neurons in the DRG were decreased. Similarly, intrathecal administration of MSH (15 nmol) reduced the expression of nNOS and IL-1β in the spinal dorsal horn and the DRG. In conclusion, activation of MrgC receptors suppresses the activation of astrocytes in the spinal dorsal cord and the expression of CGRP, nNOS, and IL-1β in the spinal dorsal cord and/or DRG, which may underlie the inhibition of bone cancer pain. These findings provide a novel strategy for the treatment of bone cancer pain.
Animals ; Cancer Pain/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Bone Neoplasms/complications* ; Ganglia, Spinal/metabolism* ; Spinal Cord Dorsal Horn/metabolism* ; Receptors, G-Protein-Coupled/genetics* ; Female ; Calcitonin Gene-Related Peptide/genetics* ; Interleukin-1beta/metabolism* ; Peptide Fragments/metabolism* ; Nitric Oxide Synthase Type I/genetics* ; Disease Models, Animal

This study investigated the acute toxicity of fermented Platycodonis Radix on mice and its effect on coughing in mice infected with Mycoplasma pneumoniae. The maximum dosage(MAD) was used in the acute toxicity experiment on mice to observe the signs of mice. After 14 days, dissection, blood biochemical examination, and pathological tissue section observation were conducted. In the pharmacological experiment of fermented Platycodonis Radix, 60 healthy BALB/c mice, 30 males and 30 females, were randomly divided into a blank group, a model group, a carbetapentane group(0.013 g·kg~(-1)·d~(-1)), and high-, medium-, and low-dose fermented Platycodonis Radix groups(5.2, 2.6, and 1.3 g·kg~(-1)·d~(-1)), with 10 mice in each group. Except for the blank group, the mice in the other five groups underwent model induction by intranasally instilling 20 μL of 1×10~6 CCU M. pneumoniae for 3 days, and the mice in each group were orally administered the corresponding drugs for 7 days. Cough induction experiment was conducted to observe and record the cough latency and total cough count within 3 min for each group. Hematoxylin-eosin(HE) staining and Masson staining were used to observe the pathological changes in lung tissues. Immunohistochemistry was performed to observe the protein expression of transient receptor potential A1(TRPA1), calcitonin gene-related peptide(CGRP), and substance P(SP) in the lung tissues of mice in each group. Real-time fluorescence-based quantitative polymerase chain reaction(qRT-PCR) was used to elucidate the changes in the mRNA levels of cough-related factors TRPA1, CGRP, and SP in mice treated with fermented Platycodonis Radix. No mice died in the acute toxicity experiment, and there were no changes in general behavior and major organ histopathological examinations. Compared with the blank group, there were no statistically significant differences in blood biochemical indexes. In the pharmacological experiment of fermented Platycodonis Radix, compared with the model group, the high-and medium-dose fermented Platycodonis Radix groups showed improved lung tissue structure of mice, with clear structure and regular tissue morphology. The qRT-PCR and immunohistochemical detection showed a decrease in the expression of TRPA1, CGRP, and SP in the fermented Platycodonis Radix groups. Fermented Platycodonis Radix can exert an inhibitory effect on cough by suppressing the expression of TRPA1, CGRP, and SP in lung tissues, thereby identifying the target of the drug.
Animals ; Female ; Male ; Mice ; Calcitonin Gene-Related Peptide/analysis* ; Cough ; Drugs, Chinese Herbal/chemistry* ; Lung ; Plant Roots/chemistry*

This study investigated the neuroprotective effects and underlying mechanism of Liujing Toutong Tablets(LJTT) on a rat model of permanent middle cerebral artery occlusion(pMCAO). The pMCAO model was established using the suture method. Eighty-four male SPF-grade SD rats were randomly divided into a sham operation group, a model group, a nimodipine group(0.020 g·kg~(-1)), and high-, medium-, and low-dose LJTT groups(2.8, 1.4, and 0.7 g·kg~(-1)). The Longa score, adhesive removal test and laser speckle contrast imaging technique were used to evaluate the degree of neurological functional impairment and changes in local cerebral blood flow. The survival and mortality of rats in each group were recorded daily. After seven days of continuous administration following the model induction, the rats in each group were euthanized, and brain tissue and blood samples were collected for corresponding parameter measurements. Nissl staining was used to examine pathological changes in brain tissue neurons. The levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), IL-1β, vascular endothelial growth factor(VEGF), calcitonin gene-related peptide(CGRP), beta-endorphin(β-EP), and endogenous nitric oxide(NO) in rat serum were measured using specific assay kits. The entropy weight method was used to analyze the weights of various indicators. The protein expression levels of nuclear factor kappa-B(NF-κB), inhibitor kappaB alpha(IκBα), phosphorylated IκBα(p-IκBα), and phosphorylated inhibitor of NF-κB kinase alpha(p-IKKα) in brain tissue were determined using Western blot. Immunohistochemistry was used to detect the protein expression of chemokine-like factor 1(CKLF1) and C-C chemokine receptor 5(CCR5) in rat brain tissue. Compared with the sham operation group, the model group showed significantly higher neurological functional impairment scores, prolonged adhesive removal time, decreased cerebral blood flow, increased neuronal damage, reduced survival rate, significantly increased levels of TNF-α, IL-1β, IL-6, CGRP, and NO in serum, significantly decreased levels of VEGF and β-EP, significantly increased expression levels of NF-κB p65, p-IκBα/IκBα, and p-IKKα in rat brain tissue, and significantly upregulated protein expression of CKLF1 and CCR5. Compared with the model group, the high-dose LJTT group significantly improved the neurological functional score of pMCAO rats after oral administration for 7 days. LJTT at all doses significantly reduced adhesive removal time and restored cerebral blood flow. The high-and medium-dose LJTT groups significantly improved neuronal damage. The LJTT groups at all doses showed reduced levels of TNF-α, IL-1β, IL-6, CGRP, and NO in rat serum, increased VEGF and β-EP levels, and significantly decreased expression levels of NF-κB p65, p-IκBα/IκBα, p-IKKα, and CCR5 protein in rat brain tissue. The entropy weight analysis revealed that CGRP and β-EP were significantly affected during the model induction, and LJTT exhibited a strong effect in reducing the release of inflammatory factors such as TNF-α and IL-1β. LJTT may exert a neuroprotective effect on rats with permanent cerebral ischemia by reducing neuroinflammatory damage, and its mechanism may be related to the inhibition of the NF-κB signaling pathway and the regulation of the CKLF1/CCR5 axis. Additionally, LJTT may exert certain analgesic effects by reducing CGRP and NO levels and increasing β-EP levels.
Rats ; Male ; Animals ; NF-kappa B/metabolism* ; NF-KappaB Inhibitor alpha/metabolism* ; Vascular Endothelial Growth Factor A/genetics* ; I-kappa B Kinase/pharmacology* ; Tumor Necrosis Factor-alpha/pharmacology* ; Interleukin-6/genetics* ; Calcitonin Gene-Related Peptide/pharmacology* ; Rats, Sprague-Dawley ; Signal Transduction ; Brain Ischemia/drug therapy* ; Tablets

Objective To investigate the effect of calcitonin gene-related peptide (CGRP) on the regulation of group 2 innate lymphoid cells (ILC2) in the peripheral blood of patients with allergic rhinitis (AR). Methods Peripheral blood mononuclear cells (PBMCs) were extracted from normal healthy individuals and AR patients, then stimulated with CGRP, interleukin 33 (IL-33) and CGRP combined with IL-33 for 3 days, with blank stimulus as control. The percentage of ILC2 in the four groups was measured by flow cytometry. After being sorted, ILC2 was given to CGRP, IL-33 and CGRP combined with IL-33 stimulation for 3 days, with blank stimulus as control. The percentage of IL-5 and IL-13 positive cells in ILC2 was detected by flow cytometry, and the levels of IL-5 and IL-13 in ILC2 supernatant were measured by ELISA. Results The percentage of ILC2 in the peripheral blood of AR patients was significantly higher than that of the control group. The levels of IL-5⁺ILC2 and IL-13⁺ILC2 were significantly increased by IL-33 single stimulation after culturing PBMCs. After adding IL-33 combined with CGRP stimulation, the levels of IL-5⁺ILC2 and IL-13⁺ILC2 in PBMCs were significantly reduced; after CGRP single stimulation, the levels of IL-5⁺ILC2 and IL-13⁺ILC2 in PBMCs were further decreased. After ILC2 was sorted and cultured, the levels of IL-5⁺ILC2 and IL-13⁺ILC2 showed significant increase after IL-33 single stimulation. The levels of IL-5⁺ILC2 and IL-13⁺ILC2 were decreased by IL-33 and CGRP co-stimulation, and they were further reduced after CGRP single stimulation. Compared to IL-33 single stimulation, IL-5 and IL-13 levels dropped significantly due to the IL-33 and CGRP co-stimulation. The levels of IL-5 and IL-13 were further reduced by CGRP single stimulation. Conclusion CGRP inhibits the proliferation and activation of peripheral blood ILC2 in AR and exert anti-inflammatory effects in AR.
Humans ; Calcitonin Gene-Related Peptide/pharmacology* ; Leukocytes, Mononuclear ; Immunity, Innate ; Interleukin-33/pharmacology* ; Interleukin-13 ; Lymphocytes ; Interleukin-5/pharmacology* ; Rhinitis, Allergic ; Cell Proliferation

Objective: To explore the reasonable time of prophylactic thyroidectomy for RET gene carriers in multiple endocrine neoplasia(MEN) 2A/2B families. Methods: From May 2015 to August 2021, RET gene carriers in MEN2A/MEN2B families were dynamically followed up at the Department of Thyroid Head and Neck Surgery, Beijing Tongren Hospital of Capital Medical University. The high-risk patients were encouraged to undergo prophylacitc total thyroidectomy according to the principle of "graded early warning system", namely the evaluation of gene detection, calcitonin value and ultrasound examination successively. Seven cases underwent the surgery, including 3 males and 4 females, aged from 7 to 29 years. According to the risk stratification listed in the guidelines of the American Thyroid Association in 2015, there were 2 cases of the highest risk, 2 cases of the high risk and 3 cases of the modest risk. Calcitonin index remained within the normal range in 3 cases and elevated in 4 cases before operation. All 7 patients underwent thyroidectomy with lymph node dissection of the level Ⅵ performed in 4 patients. Results: The time from suggestion to operation was 2 to 37 months, with an average of 15.1 months. The 6 patients were medullary thyroid carcinoma and 1 case with C-cell hyperplasia. The follow-up time was 2 to 82 months, with an average of 38.4 months. Postoperative serum calcitonin levels of all cases decreased to normal level, with biochemical cure. There was no sign of recurrence on ultrasound examination. All 7 patients had no serious complications, no obvious thyroid dysfunction. Their height, weight and other indicators of pediatric patients were similar to those of their peers, with normal growth and development. Conclusion: For healthy people with MEN2A/MEN2B family history, prophylactic thyroidectomy can be carried out selectively based on the comprehensive evaluation of "graded early warning system" with strict screening and close monitoring.
Female ; Male ; Humans ; Child ; Adolescent ; Young Adult ; Adult ; Multiple Endocrine Neoplasia Type 2b/surgery* ; Thyroidectomy ; Multiple Endocrine Neoplasia Type 2a/surgery* ; Calcitonin ; Germ-Line Mutation ; Proto-Oncogene Proteins c-ret/genetics*

OBJECTIVES: To study the association between functional dyspepsia (FD) and serum levels of brain-gut peptides including calcitonin gene-related peptide (CGRP), nesfatin-1, and ghrelin in children. METHODS: A total of 38 children with FD who attended Shengjing Hospital of China Medical University from November 2019 to December 2020 were enrolled as the FD group. Thirty-four healthy children were enrolled as the control group. Serum samples were collected from all of the children. Enzyme-linked immunosorbent assay was used to measure serum levels of CGRP, ghrelin, and nesfatin-1 for comparison between the two groups. The scores of clinical symptoms were determined for the children with FD. Spearman rank correlation analysis was used to investigate the correlation of symptom scores with the serum levels of brain-gut peptides. RESULTS: The FD group had significantly higher serum levels of nesfatin-1 and CGRP than the control group (P<0.05), while there was no significant difference in the serum level of ghrelin between the two groups (P>0.05). The serum level of nesfatin-1 was positively correlated with the symptom score of early satiety (r_s=0.553, P<0.001), but was not significantly correlated with the total score of FD (r_s=0.191, P=0.250). The serum level of CGRP was positively correlated with the scores of abdominal pain (r_s=0.479, P=0.002) and belching (r_s=0.619, P<0.001) and the total score of FD (r_s=0.541, P<0.001). CONCLUSIONS CGRP and nesfatin-1 may play an important role in the pathophysiological process of FD.
Abdominal Pain ; Brain ; Calcitonin Gene-Related Peptide ; Child ; Dyspepsia/diagnosis* ; Ghrelin ; Humans

INTRODUCTION: Differentiating infants with serious bacterial infections (SBIs) or invasive bacterial infections (IBIs) from those without remains a challenge. We sought to compare the diagnostic performances of single biomarkers (absolute neutrophil count [ANC], C-reactive protein [CRP] and procalcitonin [PCT]) and 4 diagnostic approaches comprising Lab-score, Step-by-Step approach (original and modified) and Pediatric Emergency Care Applied Research Network (PECARN) rule. METHOD: This is a prospective cohort study involving infants 0-90 days of age who presented to an emergency department from July 2020 to August 2021. SBIs were defined as bacterial meningitis, bacteraemia and/or urinary tract infections. IBIs were defined as bacteraemia and/or bacterial meningitis. We evaluated the performances of Lab-score, Step-by-Step (original and modified) and PECARN rule in predicting SBIs and IBIs. RESULTS: We analysed a total of 258 infants, among whom 86 (33.3%) had SBIs and 9 (3.5%) had IBIs. In predicting SBIs, ANC ≥4.09 had the highest sensitivity and negative predictive value (NPV), while PCT ≥1.7 had the highest specificity and positive predictive value (PPV). CRP ≥20 achieved the highest area under receiver operating characteristic curve (AUC) of 0.741 (95% confidence interval [CI] 0.672-0.810). The Step-by-Step (original) approach had the highest sensitivity (97.7%). Lab-score had the highest AUC of 0.695 (95% CI 0.621-0.768), compared to PECARN rule at 0.625 (95% CI 0.556-0.694) and Step-by-Step (original) at 0.573 (95% CI 0.502-0.644). In predicting IBIs, PCT ≥1.7 had the highest sensitivity, specificity, PPV and NPV. The Step-by-Step (original and modified) approach had the highest sensitivity of 100%. Lab-score had the highest AUC of 0.854 (95% CI 0.731-0.977) compared to PECARN rule at 0.589 (95% CI 0.420-0.758) and Step-by-Step at 0.562 (95% CI 0.392-0.732). CONCLUSION CRP strongly predicted SBIs, and PCT strongly predicted IBI. The Step-by-Step approach had the highest sensitivity and NPV, while Lab-score had the highest specificity and AUC in predicting SBIs and IBIs.
Infant ; Humans ; Child ; Calcitonin ; Prospective Studies ; Emergency Service, Hospital ; Bacterial Infections/diagnosis* ; Fever/diagnosis* ; C-Reactive Protein/analysis* ; Meningitis, Bacterial/diagnosis* ; Bacteremia ; Biomarkers ; Emergency Medical Services ; Procalcitonin