Abstract 14551: Biomarkers Predicting the Treatment-Resistant Kawasaki Disease

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Yukako Yoshikane ◽  
Ryuji Fukazawa ◽  
Kyoko Imanaka-yoshida ◽  
Naho Kobayashi ◽  
Yasuhiro Katsube

Introduction: Kawasaki disease (KD), which is the most common multisystem vasculitis with unknown causes in childhood, causes coronary artery lesions (CALs). Treatment with a high dose of intravenous immunoglobulin (IVIG), plus steroids if needed, is the most effective therapy for the acute phase of KD. However, there are some very severe cases who need several times additional treatments and are at risk for CALs. In Japan, there are some scoring systems that initially predict IVIG-resistant patients. However, the problem is that these scoring systems fail in multiethnic populations. The aim of this study is to find universal biomarkers that predict treatment-resistant cases of KD. Methods: The subject was 276 KD patients, including Group 1 (n=214) who needed only 1 st line treatment, Group 2 (n=48) who needed 2 nd line treatment, Group 3 (n=14) who needed 3 rd line treatment or more. Tenascin C (TN-C), Pentraxin 3 (PTX3) and Procalcitonin (PCT) values, which were selected by systematic review, were measured before initial treatment in each group. Results: TN-C; 99.8±41.05 ng/ml in Group 1, 118.0±71.4 ng/ml in Group 2 and 183.0±25.0 ng/ml in Group 3. The TN-C level of Group 3 was significantly higher than that of all the others (p<0.01). The cutoff value for distinguishing Group 3 was 142.0 ng/ml (Area under the Curve (AUC)=0.81). PTX3; 16.2±9.0 ng/ml in Group 1, 31.4±19.7 ng/ml in Group 2 and 58.0±33.0 ng/ml in Group 3. The PTX3 level of Group 3 was significantly higher than that of all the others (p<0.01). The cutoff value for distinguishing Group 3 was 35.1 ng/ml (AUC=0.86). PCT; 0.79±0.77 ng/ml in Group 1, 2.55±3.01 ng/ml in Group 2 and 4.15±4.49 ng/ml in Group 3. The PCT level of Group 3 was significantly higher than that of all the others (p<0.01). The cutoff value for distinguishing Group 3 was 2.55 ng/ml (AUC=0.88). When those three biomarkers combined, Group 3 can be predicted with the sensitivity 79%, the specificity 96%, the positive predictive value 50% and the negative predictive value 99%. Conclusions: It may be possible to predict treatment-resistant KD cases with high sensitivity and specificity by combining the measurement from the universal biomarkers, TN-C, PTX3 and PCT, before initial treatment.

2019 ◽  
Vol 23 (5) ◽  
pp. 639-647 ◽  
Author(s):  
Nobuhito Morota

OBJECTIVEDespite the surge in the intraoperative use of the bulbocavernosus reflex (BCR) during lumbosacral surgeries, there are as yet no widely accepted BCR warning criteria for use with intraoperative neurophysiological monitoring (IONM). The author’s aim was to find clinically acceptable warning criteria for use in IONM of the BCR.METHODSRecords of IONM of the BCR in 164 operations in 163 patients (median age 5 months) with a conus spinal lipoma who underwent surgery between August 2002 and May 2016 were retrospectively analyzed. The outcomes of IONM of the BCR were grouped by the residual amplitude at the end of surgery: group 1, ≥ 50%; group 2, 25%–50% (including the lower bound, but not the upper); and group 3, < 25%. Cases in which the BCR was lost were separately assessed as a subgroup of group 3. The postoperative urinary complication rate was used to verify the warning criteria zones.RESULTSThe BCR could be monitored in 149 surgeries (90.9%). There were 118 surgeries (79.2%) in group 1, 18 (12.1%) in group 2, and 13 (8.7%) in group 3. Two surgeries (11.1%) in group 2 and 6 (46.2%) in group 3 resulted in urinary complications. In the group 3 subgroup (lost BCR), all 5 surgeries resulted in urinary complications. The cutoff value of the BCR amplitude reduction was placed between groups 1 and 2 (zone 1: cutoff 50%), groups 2 and 3 (zone 2: cutoff 25%), and group 3 and its subgroup (zone 3: cutoff zero, present or lost). In zone 1, the positive predictive value (PPV) was 25.8% and the negative predictive value (NPV) was 100%. In zone 2, the PPV was 53.8% and the NPV 98.5%. In zone 3, the PPV was 100% and the NPV 97.9%. The PPV was highest in zone 3. The NPV was highest in zone 1, but its PPV was low (25.8%).CONCLUSIONSThe “lost or remained” criterion of BCR amplitude (zone 3: cutoff zero) can be used as a predictor of postoperative urinary function. As a warning criterion, the cutoff value of the BCR amplitude reduction at 75% (zone 2) may be used. This preliminary clinical report on the warning criteria for the BCR may contribute to improving the safety of surgery for conus spinal lipoma.


Circulation ◽  
2015 ◽  
Vol 131 (suppl_2) ◽  
Author(s):  
yeo hyang kim ◽  
Chae Ok Shin ◽  
Myung Chul Hyun ◽  
Dong Seok Lee

Purpose: Of the principal diagnostic criteria of Kawasaki disease (KD), cervical lymphadenopathy is the least common. However, it may be misdiagnosed as bacterial cervical lymphadenitis. We evaluated the characteristics of patients with KD presenting with only fever and cervical lymphadenopathy at admission. Methods: This study enrolled patients diagnosed KD from January 2013 to May 2014. All of patients were divided to three groups: group 1 had only fever and cervical lymphadenopathy at admission; group 2 had typical manifestations with cervical lymphadenopathy; group 3 had typical manifestations without cervical lymphadenopathy. Results: Ninety eight patients (group 1 in 13, group 2 in 31, group 3 in 54) were examined. The median age of group 1 was significantly older than group 2 and 3 ( P =0.001). The duration of fever before admission at our hospital was more prolonged in group 1 than in group 2 and 3 ( P =0.001). In comparison between groups, the laboratory results at the admission day were not significantly different. However, group 1 showed significantly elevated white blood cell counts, elevated neutrophil counts, and decreased lymphocyte counts after first intravenous immunoglobulin administration ( P =0.001, P =0.001, and P =0.003). The frequency of additional intravenous immunoglobulin treatment did not have significant difference. Group 1 had significantly increased duration of hospitalization, and frequency of second line treatment such as systemic steroid or infliximab than group 2 and 3 ( P =0.000, P =0.024, and P =0.007). The development of a coronary artery dilatation (z score >2.5) was higher in group 1 than in group 3 ( P =0.008). Conclusions: KD with cervical lymphadenopathy as main presentation indicates a severe form of KD associated with increased risks of second line treatment such as systemic steroid or infliximab and coronary artery dilatation. KD should be suspected in the older children with antibiotics non-responsive, prolonged fever and cervical lymphadenopathy. For differentiation between responder and non-responder for first line treatment, white blood cell counts and their subset after first intravenous immunoglobulin administration may be beneficial.


1980 ◽  
Vol 93 (1) ◽  
pp. 13-19 ◽  
Author(s):  
Reiko Demura ◽  
Hajime Yamaguchi ◽  
Ichiji Wakabayashi ◽  
Hiroshi Demura ◽  
Kazuo Shizume

Abstract. The effect of growth hormone (hGH) on the hypothalamic-pituitary-thyroid function was studied in patients with pituitary dwarfism. Twenty-six patients were given KABI hGH, 0.5 U/kg/week, for a period of 4—18 months. Three groups of patients were identified according to their T4 levels before and during the treatment. Group 1: T4 levels were initially normal and stayed in the normal range throughout a course of treatment. Group 2: T4 levels were initially normal but dropped to the subnormal range after hGH. Group 3: T4 levels were initially subnormal and decreased further after hGH. Changes in T4 levels after hGH in groups 2 and 3 were accompanied by a decrease in plasma T3RSU without concomitant decrease in plasma T3. Clinically, most of them lacked symptoms and signs of hypothyroidism and exhibited a good growth response to hGH. Plasma TSH response to TRH in these patients revealed a sustained delayed pattern, which was suggestive of hypothalamic hypothyroidism. This pattern of TSH response to TRH became further exaggerated after hGH therapy. In contrast, TSH response to TRH among patients in group 1 was normal and was not influenced by hGH. Administration of 4.0 U of KABI hGH daily for 21 consecutive days to 3 patients resulted in a shortened half-life of T4 and inversely prolonged that of T3. These results suggest that various degrees of TRH deficiency exist among patients with idiopathic pituitary dwarfism. Therapy with hGH discloses a mild TRH deficiency by accelerating the half-life of T4. This also causes a further drop in the T4 levels in those with marked TRH deficiency. The development of clinical hypothyroidism is not so obvious in these patients because of inverse delay in half-life of T3 by hGH.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3280-3280
Author(s):  
Johanna Haselboeck ◽  
Alexandra Kaider ◽  
Ingrid Pabinger ◽  
Simon Panzer

Abstract Abstract 3280 Background: Eltrombopag has recently been approved for treatment in immune thrombocytopenia (ITP). Studies on platelet function in eltrombopag-treated patients in comparison to steroid-treated or untreated ITP patients are not available. Objectives: To assess the function of eltrombopag-induced platelets, we compared platelets from eltrombopag-treated patients to those from ITP patients treated with steroids and a group of patients without treatment in a prospective study (ClinicalTrials.gov number NCT00888901). Patients/Methods: We compared platelet function in patients treated with eltrombopag after treatment-induced platelet rise (group 1) to those under steroid treatment (group 2) and ITP patients without treatment (group 3) in a non-randomized prospective study. Platelet function was assessed by adhesion under high shear conditions (surface coverage, SC), P-selectin expression, and formation of platelet-monocyte aggregates (PMA) after treatment induced platelet rise or, in group 3, in patients with ITP without treatment and platelet count between 50–100×109/L at the time of inclusion. Data are given as median [quartiles]. Correlations of the outcome measures are described by the Spearman correlation coefficient. In case of normally distributed data, analysis of variance (ANOVA) and of covariance (ANCOVA) models and in case of non-normally distributed parameters the nonparametric Kruskal-Wallis test were used to compare the groups Results: Eleven patients (female=9) were included in the treatment group with eltrombopag (group 1), thirteen (female=5) in the steroid treatment (group 2) and 6 patients as untreated controls (group 3). None of these patients developed severe bleeding during the study period, none received rescue medication. Four/30 patients were not included in the final analysis, three because they had no treatment induced platelet rise (1 on eltrombopag and 2 on steroids) and 1 because of aspirin medication. Thus, ten patients on eltrombopag, ten patients on steroid treatment and 6 untreated patients were evaluated in the comparative analyses of platelet function. Platelet counts [x109/L] were 48.25 [45.00–59.00] in group 1 after eltrombopag-induced platelet rise, 82.75 [78.50–112.00] in group 2 and 69.25 [65.00–73.00] in group 3. SC was highest in steroid-treated patients (11.25% [8.10–14.00%]) compared to eltrombopag-treated (5.80% [1.80–9.00%]) and untreated (5.03% [3.80–6.20%]) patients and correlated significantly with the platelet count (r=0.72, p<0.0001). There were no differences in P-selectin expression [GeoMFI] (1.15 [0.47–2.77] in group 1, 0.27 [0.10–0.99] in group 2 and 0.59 [0.47–1.44] in group 3; p=0.34) and PMA levels (6.19% [3.91–21.39%] in group 1, 9.73% [1.88–13.29%] in group 2, and 6.56% [4.82–8.43%] in group 3; p=0.93) between the groups. Two patients developed venous thromboses during eltrombopag treatment. No characteristic alteration of platelet function and activation was identified in those 2 patients when compared to the other eltrombopag-treated patients. Conclusions: We proofed a good functional competence of eltrombopag-induced platelets. No substantial hyper-reactivity of eltrombopag-induced platelets in comparison to those of steroid-treated and untreated patients was determined. Disclosures: Pabinger: GlaxoSmithKline: Research Funding, Speakers Bureau. Panzer:GlaxoSmithKline: Speakers Bureau.


2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Juliana Guarize ◽  
Monica Casiraghi ◽  
Stefano Donghi ◽  
Cristina Diotti ◽  
Nicolo Vanoni ◽  
...  

Background and Objective. EBUS-TBNA has revolutionized the diagnostic approach to thoracic diseases from a surgical to minimally invasive procedure. In non small-cell lung cancer (NCSLC) patients, EBUS-TBNA is able to dictate the consecutive therapy both for early and advanced stages, providing pathological diagnosis, mediastinal staging, and even adequate specimens for molecular analysis. This study reports on the ability of EBUS-TBNA to make different diagnoses and dictates the consecutive therapy in a large cohort of patients presenting different thoracic diseases. Methods. All procedures performed from January 2012 to September 2016 were reviewed. Five groups of patients were created according to the main indications for the procedure. Group 1: lung cancer staging; Group 2: pathological diagnosis in advanced stage lung cancer; Group 3: lymphadenopathy in previous malignancies; Group 4: pulmonary lesions; Group 5: unknown origin lymphadenopathy. In each group, the diagnostic yield of the procedure was analysed. Non malignant diagnosis at EBUS-TBNA was confirmed by a surgical procedure or clinical and radiological follow-up. Results. 1891 patients were included in the analysis. Sensitivity, negative predictive value, and diagnostic accuracy in each group were 90.7%, 79.4%, and 93.1% in Group 1; 98.5%, 50%, and 98.5% in Group 2; 92.4%, 85.1%, and 94.7% in Group 3; 90.9%, 51.0%, and 91.7% in Group 4; and 25%, 83.3%, and 84.2% in Group 5. Overall sensitivity, negative predictive value, and accuracy were 91.7%, 78.5%, and 93.6%, respectively. Conclusions. EBUS-TBNA is the best approach for invasive mediastinal investigation, confirming its strategic role and high accuracy in thoracic oncology.


2014 ◽  
Vol 10 (2) ◽  
Author(s):  
Febiola Rama Sari ◽  
Yudha Fahrimal ◽  
Ummu Balqis ◽  
Didik T Subekti ◽  
Aprilia Wardana

This study aimed to find out the parasitemia of DDY white mice infected with T. evansi of Pidie and Pemalang isolates obtained from Bbalitvet Bogor. A total of 12 mice were divided into 3 treatment groups. Group 1 (K1) without any treatment, group 2 (K2) was inoculated with 104 T. evansi Pidie isolate, and group 3 (K3) was inoculated with 104 T. evansi Pemalang isolate. Parasitemia examination was carried out every two days and the level of parasitemia was observed as well. Parasitemia examination was conducted until all mice died. Parasitemia of mice infected with Pidie isolate was characterized by rapid rise of parasitemia in blood (107-108/mL of blood) in a short time (2-4 days) since first parasitemia was detected and followed by death at day 4. The parasitemia of mice infected with Pemalang isolate increased in the blood (108-109/mL of blood) on day 4 and maintained for a few more days and then fluctuated for a few more days before the animal was dead. In conclusion, there was the difference in parasitemia level between Pidie and Pemalang isolates. Key words: Trypanosoma evansi, parasitemia, Pidie isolate, Pemalang isolate


2020 ◽  
Vol 66 (8) ◽  
pp. 1116-1121 ◽  
Author(s):  
Ertuğrul Güçlü ◽  
Mehmet Koroglu ◽  
Yusuf Yürümez ◽  
Hande Toptan ◽  
Elif Kose ◽  
...  

SUMMARY BACKGROUND Healthcare personnel are at risk of becoming infected while taking upper and/or lower respiratory tract specimens. Therefore, there is a need for sampling methods that do not risk infecting them. In this study, we aimed to compare the saliva and Oro-Nasopharyngeal Swab (ONS) sampling methods. METHODS Patients were divided into three groups. Group 1 included patients whose diagnosis of COVID-19 was confirmed by polymerase chain reaction (PCR). Group 2 included patients with COVID-19 compatible findings in lung computed tomography (CT), but with a negative PCR. Group 3 included patients who presented to the emergency department with COVID-19 compatible complaints but had normal CT. Saliva and ONS samples were taken on the third day of hospitalization in groups 1 and 2, whereas in group 3, they were taken at the time of admission to the hospital. RESULTS A total of 64 patients were included in the study. The average age was 51.04 ± 17.9 years, and 37 (57.8%) were male. SARS-CoV-2 was detected in 27 (42.2%) patients’ saliva samples. While the sensitivity and positive predictive value of saliva samples were 85.2%, specificity and negative predictive value were 89.2%. The value of kappa was in substantial agreement (0.744), and it was found statistically significant (<0.001). CONCLUSIONS Saliva samples can be used instead of ONS samples in detecting SARS-CoV-2. Investigating SARS-CoV-2 with saliva is cheaper, easier for the patient and overall, and, most importantly, it poses much less risk of SARS-CoV-2 contamination to healthcare personnel.


Author(s):  
Rajanna Ajumeera ◽  
Vijayalakshmi Venkatesan

Aims: To study the effects of pyridoxal phosphate (PLP) on oxidative stress in isolated pancreatic acinar cells. We have previously shown that PLP has cytoprotective and insulinotropic effects on mice islet cells in vivo and in vitro studies. Main methods: Acinar cells were isolated from three months old WNIN male rats and were cultured in vitro for a period of 24 h in CO2 incubator. Later the cells were divided into four groups as untreated (group 1), H2O2 treatment (group 2), PLP treatment (group 3) and PLP followed by H2O2 treatment (group 4). Cell viability was confirmed using MTT assays, oxidative stress levels were measured with ROS assay, change in different protein levels were recorded by flow cytometry. The acinar cells insulin secretion assay was performed with ELISA. The amylase protein expression was assessed using confocal microscopy. Key findings: The cell viability of acinar cell in group 1 was considered as 100%, while in group 2 it was reduced to 82% due to H2O2 effect, and in group 3 (99.8%) and group 4 (99.5%) were near to group 1 due to the cytoprotective effect of PLP. The ROS levels were increased by 1.47 folds in group 2, while PLP decreased to 1.02 fold in group 4, which was comparable with the changes in group 1. Beneficial effects of PLP were also observed from the increased expression levels of acinar cells are amylase -2.01, neurogenin-3-9.51, PDX-1- 23.6 and insulin-13.5 in group 3 compared to group 1. The specificity of PLP&rsquo;s response was confirmed by amino oxy acetic acid (AOAA), a specific PLP inhibitor. The increased amylase protein localization with PLP was confirmed by confocal microscopy. Insulin secretion efficiency of acinar cells was observed to be 6.13 folds higher at basal and 24.63 fold higher at stimulated levels in group3 compared to group1. Significance: Our results advocate the antioxidant and cytoprotective effects of PLP on the pancreatic acinar cell along with increased pancreatic marker expressions of amylase,PDX-1, neurogenin-3 and insulin proteins.


Author(s):  
Upender K. Munshi ◽  
Meredith Monaco Brown ◽  
Kate A. Tauber ◽  
Michael J. Horgan

Objective Elevation of serum troponin I has been reported in newborns with hypoxic ischemic encephalopathy (HIE), but it is diagnostic and prognostic utility for newborn under 6 hours is not clear. Study the predictive value of early serum troponin I levels in newborns with HIE undergoing therapeutic hypothermia (TH) for persistent residual encephalopathy (RE) at discharge. Study Design Retrospective chart review of newborns admitted with diagnosis of HIE to neonatal intensive care unit (NICU) for TH over a period of 3 years. Troponin levels were drawn with the initial set of admission laboratories while initiating TH. Newborns were followed up during hospital course and stratified into three groups based on predischarge examination and their electrical encephalography and cranial MRI findings: Group 1: no RE, Group 2: mild-to-moderate RE, and Group 3: severe RE or needing assisted medical technology or death. Demographic and clinical characteristics including troponin I levels were compared in each group. Results Out of 104 newborns who underwent TH, 65 infants were in Group 1, 26 infants in Group 2, and 13 newborns in Group 3. All groups were comparable in demographic characteristics. There was a significant elevation of serum troponin in group 2 (mild-to-moderate RE) and group 3 (severe RE) as compared with group 1 (no RE). Receiver operator curve analysis for any RE (groups 2 and 3) compared with group 1 (no RE as control) had 0.88 (0.81–0.95) area under curve, p < 0.001. A cut-off level of troponin I ≥0.12 µg/L had a sensitivity of 77% and specificity of 78% for diagnosis of any RE, positive predictive value of 68%, and a negative predictive value of 84%. Conclusion In newborns undergoing TH for HIE, the elevation of troponin within 6 hours of age predicts high risk of having RE at discharge. Key Points


2003 ◽  
Vol 17 (3) ◽  
pp. 212-216 ◽  
Author(s):  
Adriene Mara Souza Lopes-Silva ◽  
José Luiz Lage-Marques

The purpose of this study was to evaluate in vitro the dentin permeability of the deciduous pulp chamber floor after employing 2-octyl cyanoacrylate and Er:YAG laser. Twenty four deciduous molars were used, divided into four groups. After chemical-surgical preparation each group received a different treatment: Group 1 - control, without treatment; Group 2 - the floor of the pulp chamber was covered with a fine layer of 2-octyl cyanoacrylate; Group 3 - the floor of the pulp chamber was irradiated with Er:YAG laser (250 mJ, 10 Hz for 30 seconds, 80 J of energy and 320 pulses), and covered with a fine layer of 2-octyl cyanoacrylate; and Group 4 - the floor of the pulp chamber was irradiated with Er:YAG laser set at the parameters already described. After that the specimens received application of 0.5% methylene blue, for 15 minutes. The teeth were cut, photographed, and the digitalized images were analyzed using the ImageLab program. The results obtained were submitted to statistical analysis. Group 4 (Er:YAG) presented the largest averages in percentage of dye penetration area (19.5%), followed by Group 1 (11.1%), Group 3 (1.4%) and Group 2 (0.2%). The experimental model allowed to conclude that the specimens conditioned with 2-octyl cyanoacrylate (Group 2) and Er:YAG laser associated to 2-octyl cyanoacrylate (Group 3) presented a decrease in permeability, and the specimens treated with Er:YAG laser (Group 4) presented an increase in permeability of the analyzed area.


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