Evaluation of left ventricular stiffness with echocardiography.

Half of patients with heart failure are presented with preserved ejection fraction (HFpEF). The pathophysiology of these patients is complex, but increased left ventricular (LV) stiffness has been proven to play a key role. However, the application of this parameter is limited due to the requirement for invasive catheterization for its measurement. With advances in ultrasound technology, significant progress has been made in the noninvasive assessment of LV chamber or myocardial stiffness using echocardiography. Therefore, this review aims to summarize the pathophysiological mechanisms, correlations with invasive LV stiffness constants, applications in different populations, as well as the limitations of echocardiography-derived indices for the assessment of both LV chamber and myocardial stiffness. Indices of LV chamber stiffness, such as the ratio of E/e' divided by left ventricular end-diastolic volume (E/e'/LVEDV), the ratio of E/SRe (early diastolic strain rates)/LVEDV, and diastolic pressure-volume quotient (DPVQ), are derived from the relationship between echocardiographic parameters of LV filling pressure (LVFP) and LV size. However, these methods are surrogate and lumped measurements, relying on E/e' or E/SRe for evaluating LVFP. The limitations of E/e' or E/SRe in the assessment of LVFP may contribute to the moderate correlation between E/e'/LVEDV or E/SRe/LVEDV and LV stiffness constants. Even the most validated measurement (DPVQ) is considered unreliable in individual patients. In comparison to E/e'/LVEDV and E/SRe/LVEDV, indices like time-velocity integral (TVI) measurements of pulmonary venous and transmitral flows may demonstrate better performance in assessing LV chamber stiffness, as evidenced by their higher correlation with LV stiffness constants. However, only one study has been conducted on the exploration and application of TVI in the literature, and the accuracy of assessing LV chamber stiffness remains to be confirmed. Regarding echocardiographic indices for LV myocardial stiffness evaluation, parameters such as epicardial movement index (EMI)/ diastolic wall strain (DWS), intrinsic velocity propagation of myocardial stretch (iVP), and shear wave imaging (SWI) have been proposed. While the alteration of DWS and its predictive value for adverse outcomes in various populations have been widely validated, it has been found that DWS may be better considered as an overall marker of cardiac function performance rather than pure myocardial stiffness. Although the effectiveness of iVP and SWI in assessing left ventricular myocardial stiffness has been demonstrated in animal models and clinical studies, both indices have their limitations. Overall, it seems that currently no echocardiography-derived indices can reliably and accurately assess LV stiffness, despite the development of several parameters. Therefore, a comprehensive evaluation of LV stiffness using all available parameters may be more accurate and enable earlier detection of alterations in LV stiffness.

Using nomogram scores to predict the early regression of coronary artery aneurysms of Kawasaki disease.

BACKGROUND: Coronary artery aneurysms have been considered the most serious complication of Kawasaki disease. However, some coronary artery aneurysms do regress. Therefore, the ability to predict the expected time of coronary artery aneurysm regression is critical. Herein, we have created a nomogram prediction system to determine the early regression (<1 month) among patients with small to medium coronary artery aneurysms. METHODS: Seventy-six Kawasaki disease patients identified with coronary artery aneurysms during the acute or subacute phase were included. All the patients who met inclusion criteria demonstrated regression of coronary artery aneurysms within the first-year post Kawasaki disease diagnosis. The clinical and laboratory parameters were compared between the groups of coronary artery aneurysms regression duration within and beyond 1 month. Multivariate logistic regression analysis was used to identify the independent parameters for early regression based on the results from the univariable analysis. Then nomogram prediction systems were established with associated receiver operating characteristic curves. RESULTS: Among the 76 included patients, 40 cases recovered within 1 month. Haemoglobin, globulin, activated partial thromboplastin time, the number of lesions, location of the aneurysm, and coronary artery aneurysm size were identified as independent factors for early regression of coronary artery aneurysms in Kawasaki disease patients. The predictive nomogram models revealed a high efficacy in predicting early regression of coronary artery aneurysms. CONCLUSION: The size of coronary artery aneurysms, the number of lesions, and the location of aneurysms presented better predictive value for predicting coronary artery aneurysms regression. The nomogram system created from the identified risk factors successfully predicted early coronary artery aneurysm regression.

Coronary artery dilation in children with febrile illnesses other than Kawasaki disease: A case report and literature review.

Background: Coronary artery dilation (CAD) had rarely been described as a cardiac complication of febrile disease other than Kawasaki disease (KD). There are rare cases complicated by CAD reported in patients with Mycoplasma pneumoniae (MP) infection. Case presentation: A 6-year-old boy with severe Mycoplasma pneumoniae pneumonia (MPP) was transferred to our hospital due to significant respiratory distress on the 11th day from disease onset. Nadroparin, levofloxacin, and methylprednisolone followed by oral prednisone were aggressively prescribed. His clinical condition gradually achieved remission, and the drugs were withdrawn on the 27th day. Regrettably, the recurrent fever attacked him again in the absence of infection-toxic manifestations. Necrotizing pneumonia (NP) was found on chest CT. And echocardiography revealed right CAD (diameter, 3.40mm; z-score, 3.8), however, his clinical and laboratory findings did not meet the diagnostic criteria of KD. CAD was proposed to result from MP infection, and aspirin was prescribed. Encouragingly, the CAD regressed one week later (diameter, 2.50mm; z-score, 1.4). Additionally, the child defervesced seven days after the initiation of prednisone and Nadroparin treatment. The patient was ultimately discharged home on the 50th day. During follow-up, the child was uneventful with normal echocardiography and fully resolved chest CT lung lesions. Conclusions: CAD can develop in patients with severe MP infection. Pediatricians should be alert to the possibility of CAD in patients with severe MP infection and recognize that CAD might also develop in febrile disease rather than KD.

Development of a nomogram prediction model for early identification of persistent coronary artery aneurysms in kawasaki disease.

BACKGROUND: Coronary artery aneurysms (CAA) persistence prediction is critical in evaluating Kawasaki disease (KD). This study established a nomogram prediction system based on potential risk factors for assessing the risk of CAA persistence in a contemporary cohort of patients with KD. METHODS: This cohort comprised 105 patients with KD who had been diagnosed with CAA during the acute or subacute phase by echocardiography. The follow-up duration was at least 1 year. The clinical and laboratory parameters were compared between the CAA regression and persistence groups. Multivariable logistic regression analysis was used to identify the independent risk factors for CAA persistence, which were subsequently used to build the nomogram predictive model. Decision curve analysis was used to assess the net benefits of different nomogram scores. RESULTS: Of these patients with CAA, 27.6% of patients presented with persistent lesions. The incidences of CAA persistence were 14.1%, 81.3%, and 100.0% in patients with small, medium, and large aneurysms, respectively. The ratio of neutrophils to lymphocytes, γ-GT, and CAA size at diagnosis were considered as the independent risk factors for CAA persistence in patients with KD. The nomogram predictive models yielded a high capability in predicting CAA persistence, based on either univariable or multivariable analyses-identified parameters, compared with using CAA size as a single predictor. CONCLUSION: The initial ratio of neutrophils to lymphocytes, γ-GT, and CAA size were the independent risk factors for CAA persistence in patients with KD. Nomogram scores could help elevate predictive efficacy in detecting CAA persistence.

Long noncoding RNA UCA1 promotes the expression and function of P-glycoprotein by sponging miR-16-5p in human placental BeWo cells.

Investigations on placental P-glycoprotein (P-gp) regulation could provide more therapeutic targets for individualized and safe pharmacotherapy during pregnancy. The role of long noncoding RNA (lncRNA) on placental P-gp regulation is lacking. The present study was carried out to investigate the regulation and underlying mechanisms of lncRNA urothelial carcinoma associated 1 (UCA1) on P-gp in Bewo cells. lncRNA UCA1 inhibition or overexpression could decrease or increase ABCB1 mRNA expression, P-gp expression and its cellular efflux function, respectively. RNA-FISH revealed that lncRNA UCA1 was mainly located in the cytoplasm of Bewo cells. MicroRNA array was applied and 10 significant miRNAs was identified after lncRNA UCA1 inhibition. Databases of LncTarD, LncRNA2Target, and miRcode were further used to search potential target miRNAs of lncRNA UCA1 and miR-16-5p was screened out. Thereafter, we confirmed that miR-16-5p expression was significantly upregulated or reduced after lncRNA UCA1 knockdown or overexpression, respectively. Furthermore, we also proved that ABCB1 mRNA expression, P-gp expression and its cellular efflux function was enhanced or reduced after miR-16-5p inhibition or overexpression, respectively. The rescue experiment further indicated that miR-16-5p was involved in the positive regulation of lncRNA UCA1 on the expression and function of P-gp. Lastly, dual-luciferase reporter system, RNA-binding protein immunoprecipitation and RNA pull-down assays were performed to explore the relationships among lncRNA UCA1, miR-16-5p, and ABCB1. It was found that lncRNA UCA1(1103-1125) could directly interact with miR-16-5p and miR-16-5p could directly target ABCB1 coding DNA sequence region (882-907). In conclusion, LncRNA UCA1 could promote the expression and function of P-gp by sponging miR-16-5p in BeWo cells.

Electrocardiographic features of children with Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a clinically common X-linked recessive myopathy, which is caused by mutation of the gene encoding dystrophin on chromosome Xp21. The onset of heart injury in children with DMD is inconspicuous, and the prognosis is poor once it develops to the stage of heart failure. Cardiovascular complications remain an important cause of death in this patient population. At present, population and animal studies have suggested that Electrocardiogram (ECG) changes may be the initial manifestation of cardiac involvement in children with DMD. Relevant clinical studies have also confirmed that significant abnormal ECG changes already exist in DMD patients before cardiomegaly and/or LVEF decrease. With increases in age and decreases in cardiac function, the proportion of ECG abnormalities in DMD patients increase significantly. Some characteristic ECG changes, such as ST-segment changes, T wave inversion, Q wave at the inferolateral leads, LBBB and SDANN, have a certain correlation with the indexes of cardiac remodeling or impaired cardiac function in DMD patients, while VT and LBBB have demonstrated relatively good predictive value for the occurrence of long-term DCM and/or adverse cardiovascular events or even death in DMD patients. The present review discusses the electrocardiographic features in children with DMD.

Sterile Pyuria in Kawasaki Disease: A Large Prospective Cohort Study.

Background: Kawasaki disease (KD) is an acute systemic vasculitis and is becoming the leading cause of acquired cardiac disease in Children. Sterile pyuria is a known complication of KD. However, its associations with the inflammatory reaction severity, IVIG resistance as well as coronary artery lesions (CALs) in KD remain elusive. Aims: We aimed to analyze the clinical profiles of sterile pyuria in KD, to determine whether sterile pyuria is an indicator of the disease severity in patients with KD, and to assess the associations between sterile pyuria and IVIG resistance as well as CALs. Methods: We prospectively collected data from 702 patients with KD between January 2015 and June 2020. Profiles of patients with sterile pyuria (group A, n = 63) were compared to those of patients without sterile pyuria (group B, n = 639). The associations between sterile pyuria and IVIG resistance as well as CALs in KD were further determined by univariate and/or multivariate logistic regression analysis. Results: Sterile pyuria was observed in 9.0% of patients with KD, without predominance in age spectrum and gender. The levels of neutrophil percentages, alanine transaminase, total bilirubin, blood urea nitrogen, creatinine, the incidence of initial IVIG resistance, and rate of moderate/giant coronary artery aneurysms (CAAs) were significantly higher in group A than that in group B. Sterile pyuria was identified as an independent risk factor for initial IVIG resistance, yielding high specificity (92.7%) and low sensitivity (18.5%). However, sterile pyuria was not associated with repeated IVIG resistance and persistence of CALs in KD. Conclusion: The incidence of sterile pyuria is relatively low in KD patients. Patients with sterile pyuria in KD exhibited a more severe inflammatory burden and were more likely to develop the initial IVIG resistance and moderate/giant CAAs. The overall prognosis of KD patients with sterile pyuria was satisfactory.

Predictive role of sampling-time specific prognostic nutritional index cut-off values for intravenous immunoglobulin resistance and cardiovascular complications in Kawasaki disease.

BACKGROUND: Intravenous immunoglobulin (IVIG) resistance and cardiovascular complications prediction are pivotal topic of interests in Kawasaki disease (KD). The prognostic nutritional index (PNI) has been proposed to be valuable in predicting the severity of inflammatory status and prognosis in clinical circumstances, with limited data in KD. Therefore, we prospectively investigated the role of sampling-time specific PNI cut-off values in predicting initial IVIG resistance as well as cardiovascular complications in patients with KD for the first time. METHODS: A total of 755 patients with KD were prospectively recruited between January 2015 and December 2019. Patients with KD were subgrouped based on the presence of IVIG resistance or cardiovascular complications. The clinical and laboratory parameters were compared. Multivariate logistic regression analysis was performed to identify the independent risk factors for IVIG resistance and cardiovascular complications. The receiver operating characteristic (ROC) curve was further applied to assess the predictive values of PNI in IVIG resistance and cardiovascular complications. RESULTS: The lower level of PNI was identified as independent risk factors for initial IVIG resistance and cardiovascular complications. The discriminating cut-off values of the PNI for IVIG resistance, all cardiovascular complications, CALs, KDSS and myocarditis were 47.8, 52.2, 38.6, 48.2 and 52.0, with the corresponding sensitivities of 0.573, 0.679, 0.174, 0.750, 0.851, and specificities of 0.753, 0.549, 0.957, 0.679 and 0.576, respectively. After sampling time stratification, the sensitivities and specificities of the PNI obtained at the sixth day from fever onset for prediction of both IVIG resistance (0.778, 0.787) and all cardiovascular complications (0.667, 0.753) remarkably improved. CONCLUSION: PNI may serve as a promising predictor for KDSS in patients with KD. PNI obtained at sixth day from fever onset possess good predictive power for both IVIG resistance and all cardiovascular complications in KD.

Transfemoral Occlusion of Doubly Committed Subarterial Ventricular Septal Defect Using the Amplatzer Duct Occluder-II in Children.

Backgrounds: The traditional treatment of doubly committed subarterial ventricular septal defect (dcVSD) is open-heart surgery. This study aimed to evaluate the feasibility, safety, and outcome of transcatheter closure of small dcVSD using Amplatzer duct occluder-II (ADO-II) in children. Methods: Between January 2016 and April 2021, 24 children (17 male and 7 female patients) with small dcVSD who received transfemoral closure with ADO-II were enrolled retrospectively. All of their available clinical and follow-up data were evaluated. Results: The patients' median age was 3.2 years (1.6-12.6 years, 4.2 ± 3.1 years) and body weight was 13.3 kg (10.0-38.5 kg, 16.5 ± 7.7 kg). Left ventricular angiography showed that the median dcVSD size was 2.0 mm (1.5-3.5 mm, 2.1 ± 0.6 mm). The device was successfully implanted in 23 patients (95.8%), and one patient failed to be closed because of the underestimation of defect size due to preoperative aortic valve prolapse, with 16 patients by the antegrade approach and eight patients by retrograde approach. The diameters of the device used were 3/4, 4/4, and 5/4 mm. The median operative time was 40.0 min (20.0-75.0 min, 41.7 ± 13.7 min), and the median fluoroscopic time was 5.0 min (3.0-25.0 min, 6.8 ± 5.0 min). With a follow-up duration of 1+ to 45+ months, only 1 patient presented with new-onset mild aortic regurgitation (AR). Conclusion: Transfemoral closure of small dcVSD with ADO-II is technically feasible and safe in the selected children. However, the development or worsening of AR requires long-term follow-up.

Clinical characteristics of Kawasaki disease in adolescents.

OBJECTIVE: Studies focusing on Kawasaki disease (KD) in adolescents are lacking in Southwest China. We systematically summarized the clinical characteristics of KD in adolescents to improve pediatricians' recognition of this condition. METHODS: The clinical data of patients with adolescent-onset KD in our center were retrospectively analyzed. The patients were divided into Group A (n = 7), whose first hospitalization was at our hospital, and Group B (n = 10), who were transferred from their local hospital or community health center. RESULTS: Seventeen patients with adolescent-onset KD were identified (constituent ratio of 0.8%). Seven patients had an intermittent fever for >10 days. The incidence of incomplete KD was 52.9%. These patients had a high incidence of other atypical clinical manifestations. Fifteen patients were initially misdiagnosed with other infectious diseases. Although the incidence of typical KD was higher in Group B, the overall misdiagnosis rate at the initial stages was higher and the average fever duration on arrival and before IVIG administration were much longer in Group B than A. CONCLUSIONS: KD in adolescents was frequently misdiagnosed, which might be associated with its atypical, diverse clinical features and pediatricians' poor recognition. Pediatricians must be aware of the possibility of KD in adolescents.

Predictive Value of the Systemic Immune-Inflammation Index for Intravenous Immunoglobulin Resistance and Cardiovascular Complications in Kawasaki Disease.

Background: The prediction of intravenous immunoglobulin (IVIG) resistance and cardiovascular complications are critically clinical issues in Kawasaki disease (KD). This prospective study firstly aimed to determine the predictive ability of the systemic immune inflammation index (SII) for IVIG resistance and cardiovascular complications and compare the prognostic accuracy of SII with that of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR). Methods: Patients with KD were divided into different groups according to the presence of IVIG resistance or cardiovascular complications (coronary artery lesions, valve regurgitation, myocarditis, pericardial effusion, and Kawasaki disease shock syndrome [KDSS]). The clinical and laboratory parameters were compared. Further analysis stratified by platelet level was performed. Multivariate logistic regression analysis was used to identify predictors for IVIG resistance and cardiovascular complications. The receiver operating characteristic (ROC) curve was applied to assess and compare the ability of SII, NLR, and PLR for predicting IVIG resistance and cardiovascular complications. Results: SII was significantly higher in KD patients with IVIG-resistance, myocarditis, valve regurgitation, and KDSS. It was identified as an independent risk factor for IVIG resistance, myocarditis, and valve regurgitation. For KD patients with thrombocytopenia, there were no significant differences in SII between KD patients with IVIG resistance/cardiovascular complications and those without. The best cutoff values of SII for IVIG resistance, myocarditis, valve regurgitation, and KDSS prediction in the whole cohort were 1331.4 × 109, 1368.6 × 109, 1002.4 × 109, and 1485.4 × 109, with a corresponding sensitivity of 0.525, 0.614, 0.754, and 0.670, a specificity of 0.711, 0.723, 0.584, and 0.730, respectively. The predictive value of SII for both IVIG resistance and cardiovascular complications were not superior to that of NLR. Conclusion: Although the parameter of SII may predict IVIG resistance, myocarditis, valve regurgitation, and KDSS in KD as a single parameter, its predictive ability was not good enough and not superior to NLR. SII might not be applicable in patients with KD having thrombocytopenia.

Predictive value of Albumin-Bilirubin grade for intravenous immunoglobulin resistance in a large cohort of patients with Kawasaki disease: a prospective study.

BACKGROUND: Intravenous immunoglobulin (IVIG) resistance prediction is one of the primary clinical issues and study hotspots in KD. This study aimed to prospectively investigate the value of albumin-bilirubin grade (ALBI) in predicting IVIG resistance in KD and to assess whether ALBI has more predictive value or accuracy than either ALB or TBil alone in predicting IVIG resistance. METHODS: A total of 823 patients with KD were prospectively enrolled. The clinical and laboratory data were compared between the IVIG-response group (n = 708) and the IVIG-resistance group (n = 115). Multivariate logistic regression analysis was performed to identify the independent risk factors for IVIG resistance. Receiver operating characteristic (ROC) curves analysis was applied to assess the validity of ALBI, ALB, and TBil in predicting IVIG resistance. RESULTS: ALBI was significantly higher in patients with IVIG resistance and was identified as an independent risk factor for IVIG resistance in KD. The parameter of ALBI ≥ - 2.57 (AUC: 0.705, 95 %CI: 0.672-0.736), ALB ≤ 33.0 g/L (AUC: 0.659, 95 %CI: 0.626-0.692), and TBil ≥ 16.0µmol/L (AUC: 0.626, 95 %CI: 0.592-0.659), produced a sensitivity, specificity, PPV, and NPV of 0.617, 0.657, 0.226 and 0.914; 0.374, 0.850, 0.289 and 0.893; 0.269, 0.941, 0.425 and 0.888, respectively. CONCLUSIONS: A higher ALBI was an independent risk factor for IVIG resistance in KD. It yielded better predictive ability than ALB and TBil alone for initial IVIG resistance.

Case Report: Prenatal Diagnosis and Treatment of Fetal Autoimmune-Associated First-Degree Atrioventricular Block: First Report From China.

Background: The rapid progression from fetal first-degree atrioventricular block (AVB) to third-degree AVB had been reported. However, how to define fetal first-degree AVB with proper technique and the necessity of the treatment in utero for fetal autoimmune-associated first-degree AVB are still controversial. Purpose: To explore the diagnosis and the effect of treatment for fetal first-degree AVB. Cases Presentation: Four pregnant women with positive autoantibodies anti-SSA/Ro were admitted into our hospital with complaints of rapid prolonged atrioventricular (AV) intervals of their fetuses. Fetal AV intervals were re-measured by tissue Doppler imaging (TDI) from the onset of atrial contraction to ventricular systole (Aa-Sa), which were 170 ms (case 1-twin A), 160 ms (case 1-twin B), 163 ms (case 2) and 172 ms (case 3) and 170 ms (case 4), respectively. The histories of medication usage or infection during gestation were denied. Amniotic fluid genetic screenings and virological tests were negative in all cases. No structural cardiac disorders were found and the cardiovascular profile scores were 10 for each fetus. Oral dexamethasone (initial dose of 4.5 mg daily) and hydroxychloroquine (200 mg bid) plus weekly follow-up surveillance were suggested. The dosage of dexamethasone was adjusted according to the changes of the AV intervals and fetal development of biparietal diameters (BPD) and femur lengths (FL). All fetal AV intervals were controlled well. Maternal and fetal adverse effects were noted as diabetes in 1 mother and growth retardation in all fetuses. All fetuses were delivered via cesarean section at 35+4, 37, 38, and 37+1 gestational weeks, with 10 scores of Apgar score. Postnatally, positive anti-SSA/Ro was found in all neonates. However, there were no clinical or laboratory evidence of neonatal lupus syndrome. No abnormal signs were found on postnatal electrocardiogram and echocardiography for all neonates. With a follow-up of 8-53 months, there was no progression of disease and all infants demonstrated normal physical, mental, and motor development. Conclusion: Prenatal treatment for fetal autoimmune-associated first-degree AVB could be an alternative. Strict surveillance and timely adjustment of the treatment according to the conditions of the mother and the fetus are indicated. Further studies are necessary to prove our concept.

Case Report: Hypothyroidism Misdiagnosed as Fulminant Myocarditis in a Child.

Background: Hypothyroidism can lead to bradycardia, reduced cardiac output, cardiac enlargement, and abnormal electrocardiogram. However, hemodynamic instability and malignant arrhythmias due to hypothyroidism is rarely reported in children. Patient Findings: We report the case of a child with third-degree atrioventricular block, cardiogenic shock, and Adams Stokes Syndrome, who was initially misdiagnosed with fulminant myocarditis and was later found to have hypothyroidism during treatment. Summary: The child's condition did not improve after the administration of gamma globulin, methylprednisolone, and isoproterenol. Even after the placement of temporary pacemakers, the therapeutic effect was still not ideal. Upon reviewing the medical history, the child's condition improved rapidly after levothyroxine supplementation. Conclusions: Hypothyroidism is a common disease, but secondary severe cardiovascular lesions are particularly rare in children. Therefore, the delay in diagnosis can lead to serious cardiovascular manifestations. When pediatric patients develop severe AVB and bradycardia, hypothyroidism should be considered as a possible cause.

Predictive Value of Serum Lipid for Intravenous Immunoglobulin Resistance and Coronary Artery Lesion in Kawasaki Disease.

CONTEXT: Intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) prediction are pivotal topic of interests in Kawasaki disease (KD). However, data on the predictive value of lipid profile for both IVIG resistance and CALs are limited. PURPOSE: To investigate the predictive validity of lipid profile for IVIG resistance and CALs in KD. DESIGN: Prospective cohort study. SETTING: West China Second University Hospital. PATIENTS: 363 KD patients were divided into the initial IVIG-resistant group and initial IVIG-responsive group; repeated IVIG-resistant group and repeated IVIG-responsive group; CAL+ group and CAL- group. MAIN OUTCOME MEASURES: Validity of lipid profile in predicting IVIG resistance and CALs. RESULTS: Triglycerides were significantly higher whereas total cholesterol (TC), high-densisty lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein A (Apo A) were significantly lower in initial IVIG-resistant subjects, with cut-off values of 1.625 mmol/L, 3.255 mmol/L, 0.475 mmol/L, 1.965 mmol/L, and 0.665 g/L, yielding sensitivities of 52%, 70%, 52%, 61%, and 50% and specificities of 68%, 53%, 78%, 71%, and 81%, respectively. TC, LDL-C, and Apo A levels were significantly lower in repeated IVIG-resistant subjects, with cut-off values of 3.20 mmol/L, 1.78 mmol/L, and 0.605 g/L, producing sensitivities of 91%, 70%, and 57% and specificities of 55%, 67%, and 70%, respectively. Apo A level was significantly lower in the CAL+ group, with cut-off value of 0.805 g/L, yielding sensitivity of 66% and specificity of 54%. CONCLUSIONS: Lipid profiles were significantly dysregulated in KD patients suffering IVIG resistance and CALs. Some of them, such as LDL-C and Apo A, could serve as complementary laboratory markers for predicting both IVIG resistance and CALs.

Predictive value of coagulation profiles for both initial and repeated immunoglobulin resistance in Kawasaki disease: A prospective cohort study.

BACKGROUND: Intravenous immunoglobulin (IVIG) resistance prediction remains substantial in Kawasaki disease (KD), with limited data on the predictive value of coagulation profile for IVIG resistance, particularly for repeated IVIG resistance. Therefore, the aim of our study was to testify the predictive validity of coagulation profile for both initial IVIG resistance and repeated IVIG resistance in KD. METHODS: A total of 385 KD patients were prospectively recruited between April 2015 and May 2019. Coagulation and other profiles were evaluated between the IVIG-responsive and IVIG-resistant groups. Multivariate logistic regression analysis was applied to determine the association between coagulation profiles and IVIG resistance. ROC curves analysis was further performed to assess the validity of coagulation profiles in predicting both initial IVIG resistance and repeated IVIG resistance. RESULTS: Prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), fibrinogen degradation products (FDPs), and D-dimer were significantly increased in the initial IVIG-resistant group with antithrombin III (ATIII) and thrombin time (TT) significantly reduced. Meanwhile, ATIII was declined markedly in repeated IVIG-resistant patients. Multivariate logistic regression analysis showed that PT, APTT, D-dimer, and ATIII were independent risk factors for predicting initial IVIG resistance and ATIII for predicting repeated IVIG-resistant patients with KD. PT, APTT, D-dimer, and ATIII cutoff values of 13.95 s, 41.15 s, 1.48 mg/L, and 89.5% yielded sensitivities of 73%, 32%, 71%, and 81%, and specificities of 55%, 88%, 62%, and 51% for predicting initial IVIG resistance, respectively. The cutoff value of ATIII for predicting repeated IVIG resistance was 68.5%, with sensitivity of 71% and specificity of 55%. CONCLUSIONS: KD patients who have hypercoagulation during the acute phase might be at higher risk of developing IVIG resistance.

Predictive value of C-reactive protein to albumin ratio as a biomarker for initial and repeated intravenous immunoglobulin resistance in a large cohort of Kawasaki disease patients: a prospective cohort study.

BACKGROUND: Intravenous immunoglobulin (IVIG) resistance prediction is one pivotal topic of interests in Kawasaki disease (KD). This study aimed to prospectively investigated the value of C-reactive protein-to-albumin (CAR) in predicting both initial and repeated IVIG resistance in patients with KD, and to test the hypothesis that CAR was more valuable or accurate than either C-reactive protein (CRP) or albumin (ALB) alone in IVIG resistance prediction. METHOD: A prospective cohort study involving 550 patients with KD was conducted. The clinical and laboratory data were compared between IVIG-response group and IVIG-resistance group. Multivariate logistic regression analysis was performed to identify the independent risk factors of initial/repeated IVIG resistance. Receiver operating characteristic (ROC) curves analysis was applied to assess the validity of CAR, CRP and ALB in predicting both initial and repeated IVIG resistance. RESULTS: CAR was significantly higher in IVIG non-responders and was identified as independent risk factor for both initial and repeated IVIG resistance in KD. The best cut-off value of CAR for initial and repeated IVIG resistance prediction was 2.07 and 3.34, with a corresponding sensitivity of 0.610 and 0.548, a specificity of 0.552 and 0.813, respectively. The value of CAR was not better than either CRP or ALB alone for both initial and repeated IVIG resistance prediction. CONCLUSION: A higher CAR was an independent risk factor for both initial and repeated IVIG resistance. However, similar with that of CRP or ALB, the predictive value of CAR was not good enough for both initial and repeated IVIG resistance prediction in KD.

Grisel's syndrome in Kawasaki disease.

BACKGROUND: Approximately 50-70% of patients with Kawasaki disease (KD) could present with cervical lymphadenopathy associated with deep neck inflammation, which may result in Grisel's syndrome (GS). Given the possibility of neurological impairment owing to GS, it is important to understand the disease profile in KD. Therefore, we carried out this study to investigate this possible complication of KD, with the aim of improving pediatricians' recognition and awareness. METHODS: Patients with KD complicated by GS in our hospital were retrospectively recruited for our study. The profiles of patients with GS (n = 10) were compared to those patients without GS (n = 1254). All the available literature describing these complications of KD was reviewed. RESULTS: The incidence of GS in KD was 0.6% in our population. Compared to patients without GS, KD patients with GS were older, presented with a significantly lower male:female ratio, and a higher incidence of cervical lymphadenopathy, a higher level of neutrophil count, and erythrocyte sedimentation rate. Ten articles reporting 14 KD patients with GS were reviewed. Of the total 24 patients, GS affected 7 males and 17 females, aged from 3.5 to 9 years old. Encouragingly, no delayed diagnosis and treatment of KD was found, and all patients received conservative therapy for GS, without intravenous immunoglobulin resistance, coronary artery lesions, and neurological impairment. CONCLUSIONS: GS is a rare complication of KD with an incidence of 0.6%, predominantly affecting older, female children. The overall outcome of this disorder in KD was satisfactory with conservative therapy. Pediatricians, especially pediatric surgeons, should recognize and be aware of this possible complication of KD to avoid misdiagnosis and overtreatment.

Neurological involvement in Kawasaki disease: a retrospective study.

BACKGROUND: Kawasaki disease (KD) is an acute, self-limiting systemic vasculitis that predominately affects children. Neurological involvement is a known complication of KD, however, its association with KD severity remains elusive. We aimed to systematically describe the general manifestations of neurological involvement in KD, determine whether neurological involvement is a marker of disease severity in patients with KD, and assess the relationship of such involvement with intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs). METHODS: We retrospectively reviewed data from 1582 patients with KD between January 2013 and December 2017. Profiles of patients with neurological symptoms (group A, n = 80) were compared to those of gender- and admission date-matched patients without neurological involvement (group B, n = 512). Multivariate logistic regression analyses were performed to determine whether neurological involvement was significantly associated with IVIG resistance. RESULTS: Neurological involvement was observed in 5.1% (80/1582) of patients with KD. The neurological manifestations were diffuse, presenting as headache (13/80, 16.3%), convulsions (14/80, 17.5%), somnolence (40/80, 50.1%), extreme irritability (21/80, 26.3%), signs of meningeal irritation (15/80, 18.8%), bulging fontanelles (7/80, 8.8%), and facial palsy (1/80, 1.3%). Neurological symptoms represented the initial and/or predominant manifestation in 47.5% (38/80) of patients with KD. The incidence of IVIG resistance and levels of inflammatory markers were higher in group A than in group B. However, neurological involvement was not an independent risk factor for IVIG resistance or CALs. CONCLUSION: Rates of neurological involvement were relatively low in patients with KD. Neurological involvement was associated with an increased risk of IVIG resistance and severe inflammatory burden. Our results highlight the need for pediatricians to recognize KD with neurological involvement and the importance of standard IVIG therapy. TRIAL REGISTRATION: Retrospectively registered.