Received Intravenous Immunoglobulin Treatment Research Articles

Exploring the diagnostic value of CLR and CPR in differentiating Kawasaki disease from other infectious diseases based on clinical predictive modeling.

Kawasaki disease (KD) is an important cause of acquired heart disease in children and adolescents worldwide. KD and infectious diseases can be easily confused when the clinical presentation is inadequate or atypical, leading to misdiagnosis or underdiagnosis of KD. In turn, misdiagnosis or underdiagnosis of KD can lead to delayed use of intravenous immunoglobulin (IVIG), increasing the risk of drug resistance and coronary artery lesions (CAL). The purpose of this study was to develop a predictive model for identifying KD and infectious diseases in children in the hope of helping pediatricians develop timely and accurate treatment plans. The data Patients diagnosed with KD from January 2018 to July 2022 in Shenzhen Longgang District Maternity & Child Healthcare Hospital, and children diagnosed with infectious diseases in the same period will be included in this study as controls. We collected demographic information, clinical presentation, and laboratory data on KD before receiving IVIG treatment. All statistical analyses were performed using R-4.2.1 (https://www.rproject.org/). Logistic regression and Least Absolute Shrinkage with Selection Operator (LASSO) regression analyses were used to build predictive models. Calibration curves and C-index were used to validate the accuracy of the prediction models. A total of 1,377 children were enrolled in this study, 187 patients with KD were included in the KD group and 1,190 children with infectious diseases were included in the infected group. We identified 15 variables as independent risk factors for KD by LASSO analysis. Then by logistic regression we identified 7 variables for the construction of nomogram including white blood cell (WBC), Monocyte (MO), erythrocyte sedimentation rate (ESR), alanine transaminase (ALT), albumin (ALB), C-reactive protein to procalcitonin ratio (CPR) and C-reactive protein to lymphocyte ratio (CLR). The calibration curve and C-index of 0.969 (95% confidence interval: 0.960-0.978) validated the model accuracy. Our predictive model can be used to discriminate KD from infectious diseases. Using this predictive model, it may be possible to provide an early determination of the use of IVIG and the application of antibiotics as soon as possible.

Intravenous immunoglobulin for patients with unexplained recurrent implantation failure: a 6-year single center retrospective review of clinical outcomes

The effectiveness of intravenous immunoglobulin (IVIg) for patients with unexplained recurrent implantation failure (uRIF) remains debated. We retrospectively analysed outcomes of uRIF patients treated with IVIg compared to a separate control uRIF cohort within our center (01/2014–12/2021). Primary outcomes included live birth, miscarriage, or transfer failure. We documented IVIg side effects and maternal/fetal outcomes. Logistic regression analysis was used to assess for association of IVIg exposure with outcomes and adjust for confounders. The study included 143 patients, with a 2:1 ratio of controls to patients receiving IVIg treatment. Patient characteristics were similar between groups. There was higher live birth rate (LBR) in patients receiving IVIg (32/49; 65.3%) compared to controls (32/94; 34%); p < 0.001). When stratifying patients into moderate and severe uRIF (respectively 3–4 and ≥\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\ge$$\\end{document} 5 previous good quality blastocyst transfer failures), only patients with severe uRIF benefited from IVIg (LBR (20/29 (69%) versus 5/25 (20%) for controls, p = 0.0004). In the logistic regression analysis, IVIg was associated with higher odds of live birth (OR 3.64; 95% CI 1.78–7.67; p = 0.0004). There were no serious adverse events with IVIg. IVIg can be considered in well selected patients with ≥\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\ge$$\\end{document} 5 previous unexplained, high quality blastocyst transfer failures. A randomized controlled trial is needed to confirm these findings.

Effect of Hetrombopag Combined with Rhtpo in Patients with Severe Immune Thrombocytopenia

Background: Severe Immune Thrombocytopenia (ITP) is a life-threatening acquired hemorrhagic disease with dramatically decreased platelet number and clinical bleeding symptoms. Some patients with severe ITP did not respond to first-line treatment including steroids and Intravenous Immunoglobulin (IVIG). It was critical for them to use effective treatments to promote platelet and reduce the risk of fatal bleeding. Clinical practice guidelines have recommended the use of thrombopoietin receptor agonist (TPO-RA) as a second-line treatment for ITP. Recombinant human thrombopoietin (rhTPO) and hetrombopag are two distinct TPO-RAs with different mechanisms. As reported, there remains no study assessing the efficacy and safety of hetrombopag combined with rhTPO in the treatment of ITP. Therefore, the present study aimed to investigate the efficacy of hetrombopag plus rhTPO in Chinese patients with severe ITP, focusing on the short rather than the long-term efficacy, such as quickly increasing platelet count and significantly reducing bleeding, which would be more meaningful for severe patients whose platelet count &amp;lt;10 × 10 9/L. Methods: This was a prospective, open-label, single-center study with a planned enrollment of 30 patients. The inclusion criteria were patients ≥ 18 years, diagnosed with primary immune thrombocytopenia, platelet count &amp;lt;10 × 10 9/L, or bleeding score ≥ 5. Patients receiving other ITP drugs as maintenance therapy were eligible if previous glucocorticoid therapy doses were stable, and rituximab was used for at least 2 months and other immunosuppressants were stable for at least 4 weeks. Patients who had received IVIG, avatrombopag, eltrombopag, or romiplostim within 2 weeks prior to enrollment were excluded. Histories of platelet transfusion one week before treatment were excluded. Hetrombopag was given at 5 mg/day for 28 days, while rhTPO was administered at 300 U/kg subcutaneously daily for 14 days. When PLT &amp;gt; 100 × 10 9/L, rhTPO should be discontinued. When PLT &amp;gt; 150 × 10 9/L, the dosage of hetrombopag was reduced to 2.5mg/day, and it would be discontinued if PLT &amp;gt; 250 × 10 9/L. The primary endpoints were proportion of subjects with platelet count ≥30×10 9/L and at least doubled the baseline platelet count within 28 days. Secondary endpoints included bleeding score, incidence of thrombotic events, and adverse events (AEs). Results: As to July 27, 2023, a total of 20 patients were included in this study, with a median age of 36 years and a male proportion of 50%. Among them, 70% (14 cases) were newly diagnosed ITP patients. 50% of patients have received ≥ 1 line of previous treatment, of which 2 patients have received IVIG treatment and both have achieved CR (PLT ≥ 100 × 10 9/L). The baseline median platelet count was 5 × 10 9/L, and 95% (19 cases) of patients had active bleeding with a bleeding score of ≥ 1 point. The median duration for hetrombopag at dose of 5mg is 8.0 days, and rhTPO is 6.5 days. After combined treatment, the median time for platelet counts reached 30, 50, and 100 × 10 9/L was 4.5 days, 6 days, and 7 days, respectively. Among them, the median platelet count reached 103 × 10 9/L after 7 days treatment and 214.5 × 10 9/L after 15 days. Within 15 days of combined treatment, 15% (3 cases) of patients achieved partial platelet reaction (PLT &amp;gt; 50 × 10 9/L, without bleeding), and 85% (17 cases) achieved complete platelet reaction (PLT &amp;gt; 100 × 10 9/L, without bleeding). In terms of safety, two patients experienced liver function abnormalities, both of which were grade 1-2. One was related to treatment drugs, and the other was associated with underlying autoimmune liver disease. No thrombotic events occurred in all patients. Conclusion: This study innovatively explores the efficacy and safety of combination therapy with hetrombopag and rhTPO in the treatment of severe ITP. It is preliminarily confirmed that this combination therapy can effectively and quickly improve the early platelet response of ITP patients, avoid bleeding damage, and is expected to become a new treatment choice for severe ITP patients. We also look forward to the overall efficacy evaluation results of all patients after completing treatment in the future.

Establishment of a risk model for severe adenovirus pneumonia and prospective study of the timing of intravenous immunoglobulin therapy in children

To develop a risk prediction model for severe adenovirus pneumonia (AVP) in children, and to explore the appropriate timing for intravenous immunoglobulin (IVIG) therapy for severe AVP. Medical data of 1 046 children with AVP were retrospectively analyzed, and a risk prediction model for severe AVP was established using multivariate logistic regression. The model was validated with 102 children with AVP. Then, 75 children aged ≤14 years who were considered at risk of developing severe AVP by the model were prospectively enrolled and divided into three groups (A, B and C) in order of visit, with 25 children in each group. Group A received symptomatic supportive therapy only. With the exception of symptomatic supportive therapy, group B received IVIG treatment at a dose of 1g/(kg·d) for 2 consecutive days, before progressing to severe AVP. With the exception of symptomatic supportive therapy, group C received IVIG treatment at a dose of 1 g/(kg·d) for 2 consecutive days after progressing to severe AVP. Efficacy and related laboratory indicators were compared among the three groups after treatment. Age<18.5 months, underlying diseases, fever duration >6.5 days, hemoglobin level <84.5 g/L, alanine transaminase level >113.5 U/L, and co-infection with bacteria were the six variables that entered into the risk prediction model for severe AVP. The model had an area under the receiver operating characteristic curve of 0.862, sensitivity of 0.878, and specificity of 0.848. The Hosmer-Lemeshow test showed good consistency between the predicted values and the actual observations (P>0.05). After treatment, group B had the shortest fever duration and hospital stay, the lowest hospitalization costs, the highest effective rate of treatment, the lowest incidence of complications, the lowest white blood cell count and interleukin (IL)-1, IL-2, IL-6, IL-8, IL-10 levels, and the highest level of tumor necrosis factor alpha (P<0.05). The risk model for severe AVP established in this study has good value in predicting the development of severe AVP. IVIG therapy before progression to severe AVP is more effective in treating AVP in children.

Mortality in Mechanically Ventilated Myasthenia Gravis Adult Patients: Comparing Intravenous Immunoglobulin vs Steroids (P1-5.010)

<h3>Objective:</h3> To investigate whether there is a significant difference in mortality in adult patients with severe myasthenia gravis, determined by use of a mechanical ventilator, between intravenous immunoglobulin (IVIg) and steroids. <h3>Background:</h3> Steroids and IVIg are both used in the treatment of patients with severe myasthenia gravis. <h3>Design/Methods:</h3> The New York State Planning and Research Cooperation (SPARCS) database was utilized to collect all adult patients with myasthenia gravis (MG) who were mechanically ventilated. Patient’s age was restricted to 18 or older. Patients taking both IVIg and Steroids were excluded from analysis. <h3>Results:</h3> 1,730 patients with MG on mechanical ventilators were collected for analysis. 595 patients died. 63 patients received steroid treatment and 19 of these patients died (30.1%). 154 myasthenia gravis patients received IVIg treatment and 30 of them died (19.4%). There was no significant difference in average age between the two groups (77.13±14.54 vs 72.58±10.34; p=0.241) or gender (p=0.136). There was no significant difference in proportion who received IVIg versus steroid (p=0.116). Multivariate regression analysis performed on all patients demonstrated that the likelihood of death is not significantly different between the use of steroids compared to patients not treated with steroids or IVIg (OR: 1.023; 95% CL: 0.578–1.812; p=0.937). However, the likelihood of death was significantly reduced in the group treated with IVIg compared to the patients who did not receive IVIg or steroids (OR: 0.510; 95% CL: 0.332–0.782; p=0.002). <h3>Conclusions:</h3> IVIg was associated with a decreased likelihood of mortality in patients with severe myasthenia gravis when compared to steroids. Limitations of this analysis include differential treatment algorithms for IVIg and steroids, and different situations for their use. Work is ongoing to calculate the likelihood confounding for comorbid conditions, with subgroup analysis and increasing length of time for study period. <b>Disclosure:</b> Mr. Mandava has nothing to disclose. Mr. Jaffry has nothing to disclose. Mr. Jaffry has nothing to disclose. Miss Shaikh has nothing to disclose. Mr. Trivedi has nothing to disclose. Mr. Ors has nothing to disclose. Ms. Faiz has nothing to disclose. Mr. Mohammed Ali has nothing to disclose. Mr. Mostafa has nothing to disclose. Dr. Khan has nothing to disclose. Dr. Souayah has received publishing royalties from a publication relating to health care.

Factors Affecting Mortality in Covid-19 Patients Treated with Intravenous Immunoglobulin

Background: Intravenous immunoglobulin (IVIG), used as an option in the treatment of severe Coronavirus disease 2019 (COVID-19), has been shown to have effects on the suppression of the hyperinflammatory state through immunomodulatory actions. The aim of our study was to evaluate the factors associated with mortality in patients treated with IVIG for COVID-19. Methods: Patients diagnosed with COVID-19 and receiving IVIG therapy in addition to standard care therapy were included in the study. Results: A total of 46 patients who received IVIG treatment were included in the study. The mortality rate was higher in patients aged over 52 years (p:&lt;0.001). The mortality rate was found to be higher in patients with an interval of more than 7 days between hospitalization and the start of IVIG treatment (p:0.009). Patients with a higher Charlson Comorbidity Index (CCI) score had a more mortal course (p&lt;0.001). Mortality rate was higher in patients with high immunoglobulin A (Ig A) levels before IVIG treatment (p:0.004). Survival rate was lower in patients with high neutrophil lymphocyte ratio (NLR), urea and prothrombin time (PT)and low albumin and lymphocyte counts. Conclusions: A high Charlson Comorbidity Index score and high immunoglobulin A level are poor prognostic in COVID 19 patients treated with IVIG. Studying mortality risk factors is valuable in predicting response to IVIG therapy and may help in early identification of patients with poor prognosis and re-evaluate of treatment strategy.

Investigation of cardiac adverse effects in COVID-19 ARDS patients treated with intravenous immunoglobulin.

The popularity of intravenous immunoglobulin (IVIG) therapy in Acute Respiratory Distress Syndrome (CARDS) secondary to COVID-19 infection is increasing day by day. In this study, we aimed to retrospectively evaluate the possible cardiac effects in our CARDS patients treated with IVIG. Demographic and clinical characteristics, mortality, sequential electrocardiography (ECG), echocardiography, cardiac markers, and other laboratory parameters of CARDS patients who received IVIG treatment were recorded. The mean age of the patients was 68.7±13.6%, and 70.5% were female. The mean number of days of hospitalization in the intensive care unit was 18.2±9.7, and the mortality rate was recorded as 35.2%. No pathological rhythm or ischemic change was observed in sequential ECG follow-ups. However, in consecutive ECO follow-ups, the sPAP values at the treatment end were numerically lower, although not statistically significant. Our study suggests that IVIG therapy may be used safely in COVID-19 patients with cardiovascular side effects. However, due to the high risk of coagulopathy in these patients, the use of IVIG therapy in COVID-19 infection should be monitored with close monitoring, as it may increase the potential for cardiovascular risk. Furthermore, monitoring cardiac parameters are also essential as it may predict high cardiovascular risk in patients. For this reason, patients need lower infusion rates, steroid combination, adequate hydration, and effective anticoagulation therapy to avoid these side effects.

Disease profile of Guillain-Barré syndrome among Indian patients receiving intravenous immunoglobulin: a real-world observational study

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Objectives of the study were to evaluate the real-world usage pattern of intravenous immunoglobulin (IVIg) for the treatment of patients with Guillain‐Barré syndrome (GBS), and to understand the disease characteristics and demographic patterns of these patients.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; This real-world, retrospective, analysis included data of patients with GBS who received IVIg treatment at various centers across India. The study data was collected between April 2021 and March 2022. &lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; A total of 3064 patients with GBS who received IVIg treatment were included. The mean (SD) age of the patients was 48.97 (14.97) years, and majority of the patients were men (68.8%). Acute inflammatory demyelinating polyneuropathy (AIDP) was the most common subtype of GBS (60.5%), followed by acute motor axonal neuropathy (AMAN; 11.6%), and acute motor sensory axonal neuropathy (AMSAN; 3%). The majority (&amp;gt;94%) of patients received IVIg therapy as first-line treatment. A large proportion of the patients (n=2402, 78.4%) were given the standard dose of 2 g/kg bodyweight (given over 5 days) and 97.1% (n=2974) of the total study population received IVIg regimen over the standard protocol of 5 days.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; In the clinical spectrum of GBS, AIDP was the most common subtype. IVIg was used at generally recommended dose and duration in patients with GBS.&lt;/p&gt;

İntravenöz İmmünoglobulin Replasmanı Öncesi Yüksek Üre Değerleri COVID-19’a Bağlı Mortalite için Bir Risk Faktörü müdür?

Aim: This study aimed to examine the data of the coronavirus disease 2019 (COVID-19) patients treated with intravenous immunoglobulin (IVIG) treatment and to investigate the effects of the patients' clinical, laboratory, and treatment characteristics and risk factors for mortality. Material and Methods: The study evaluated 81 adult COVID-19 patients who were hospitalized for the treatment of COVID-19 between April 2020 and September 2020 and were followed up, treated, and consulted in the immunology clinic for IVIG treatment, in a retrospective manner. Results: The univariate analyses revealed that the duration of hospitalization in service, being intubated, duration of IVIG treatment, and the urea value before IVIG treatment were related to mortality in COVID-19 patients treated with IVIG treatment. As a result of multivariate analysis, being intubated and urea value before IVIG treatment were found to be independent risk factors for mortality (p=0.001 and p=0.009, respectively). It was found that for the 60 mg/dL level of urea value before IVIG treatment to predict mortality, the sensitivity was 46.2%, and the specificity was 35.5%. The area under the curve was found as 0.647; 95% confidence interval 0.518-0.776 (p=0.029). Conclusion: The study found that urea values before IVIG treatment were a risk factor for mortality in patients who received IVIG treatment for COVID-19. This is important as it indicates that urea values should be closely monitored in patients given IVIG treatment for COVID-19. It also suggests that when resources are limited and risk stratification is required in COVID-19 patients, urea values can be helpful.

Paediatric Acute-onset Neuropsychiatric Syndrome (PANS) and intravenous immunoglobulin (IVIG): comprehensive open-label trial in ten children

BackgroundTreatment with intravenous immunoglobulin (IVIG) in children with Paediatric Acute-onset Neuropsychiatric Syndrome (PANS) has for many years been used on clinical indications, but the research evidence for its efficacy is insufficient.MethodsOpen-label prospective in-depth trial including ten children (median age 10.3 years) with PANS, who received IVIG treatment 2 g/kg monthly for three months. Primary outcomes were changes in symptom severity and impairment from baseline to first and second follow-up visits one month after first and one month after third treatment, using three investigator-rated scales: Paediatric Acute Neuropsychiatric Symptom (PANS) scale, Clinical Global Impression – Severity and Improvement (CGI-S and CGI-I) scales. Secondary outcomes reported here were changes in Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS) scores, and side effects.ResultsAll ten children received three treatments at one-month intervals according to study plan. From baseline to second follow-up marked reductions were seen in mean total PANS scale scores (p = .005), and CGI-S scores (p = .004). CGI-I ratings showed much to very much global improvement (mean CGI-I 1.8). Nine children had clinical response defined as > 30% reduction in PANS Scale scores. Improvements were also noted for CY-BOCS scores (p = .005), and in school attendance. Three children suffered moderate to severe temporary side effects after the first treatment, and the remaining seven had mild to moderate side effects. Side effects were much less severe after second and third treatments.ConclusionsConsiderable and pervasive improvements in symptoms and clinical impairments were seen in these ten children after three monthly IVIG treatments. Moderate to severe transient side effects occurred in three cases.Trial registrationEudraCT no. 2019–004758-27, Clinicaltrials.gov no. NCT04609761, 05/10/2020.

Intravenous Immunoglobulin in the Management of Severe Early Onset Red Blood Cell Alloimmunization

OBJECTIVE: We report the outcome of pregnancies treated with intravenous immunoglobulin (IVIG) for severe red blood cell alloimmunization, evaluating whether IVIG defers the development of severe fetal anaemia and its consequences.BACKGROUND: Although fetal anemia can be treated very successfully with intrauterine transfusion (IUT), procedures before 20 weeks' gestation can be very challenging technically and may be hemodynamically stressful to an extremely premature and already compromised fetus. The procedure-related fetal loss rate is approximately 5.6% for IUTs performed < 20 weeks' gestation, compared to 1.6% overall. IVIG may prevent hemolysis and could therefore be a noninvasive alternative for early transfusions.STUDY DESIGN: We included consecutive pregnancies over a nineteen year period in the Fetal Medicine Unit, Mount Sinai Hospital, University of Toronto, Canada, of alloimmunized women with a history of severe early onset haemolytic disease who received IVIG until intrauterine transfusion could safely be performed. Previous untreated pregnancies were used as controls. IVIG therapy was commenced between 11 and 14 weeks' gestation. Our usual protocol was IVIG 2 g/kg per week every 3 weeks, until the first IUT could be performed. Each 2g/kg dose was administered over 2 days, 1g/kg per day, to reduce the chance of severe headaches. In three pregnancies, IVIG 1g/kg was given weekly. We compared the clinical outcomes (gestation at first IUT, fetal Hb at first FBS, gestation at delivery, perinatal survival) between previous pregnancies without IVIG and the subsequent pregnancy treated with IVIG. In comparing fetal Hb's between two pregnancies, a linear relationship between fetal Hb and gestation was used to correct for variable gestations. The fetal Hb was converted to a standardized fetal Hb value (multiples of the standard deviation [SD]). Statistical analysis was performed on ‘Statistical Package for Social Science Version 16.0‘ (SPSS Inc, Chicago, Illinois).RESULTS: Seventeen women referred to our unit for a previous pregnancy loss secondary to severe RBC alloimmunization received IVIG treatment in 20 subsequent pregnancies; all eventually requiring intrauterine transfusion. For previous early losses despite transfusion, immunoglobulin was associated with a relative increase in fetal hemoglobin between treated and untreated pregnancies of 32.6 g/L (95%CI 15.2-50.0, P=0.003) and improved perinatal survival (8/8 vs 0/6, P=0.001). For previous losses <20 weeks, it enabled first transfusion deferral in subsequent pregnancies to at least 19.9 (mean 23.2) weeks. Of the 17 live-born babies from IVIG-treated pregnancies, three (18%) required an exchange transfusion, eight (47%) a simple “top-up” transfusion, and six (35%) phototherapy.CONCLUSION: Our results show that, among severely sensitized cases with previous early fetal loss despite IUT, use of IVIG in subsequent pregnancies is associated with a significantly higher fetal Hb before first IUT, deferral of first IUT, delivery at a later gestation and increased perinatal survival. The timing of the first FBS/IUT was delayed by 3 weeks in pregnancies treated with IVIG compared to a previous untreated pregnancy. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Increased Expression of Pyroptosis in Leukocytes of Patients with Kawasaki Disease.

Background: Kawasaki disease (KD) is a form of febrile vasculitis that primarily occurs in children. It can cause inflammation of the coronary arteries, which leads to aneurysms. The pathogenesis of coronary arteries may be associated with apoptosis or pyroptosis mediated by caspases activity, but this idea has not been discussed much in KD. Materials and Methods: We enrolled 236 participants in this study. In the Affymetrix GeneChip® Human Transcriptome Array 2.0 study, there were 18 KD patients analyzed prior to receiving intravenous immunoglobulin (IVIG) treatment, at least 3 weeks after IVIG treatment, and 36 non-KD control subjects. We also recruited 24 KD patients prior to receiving IVIG treatment, at least 3 weeks after IVIG treatment, and 24 non-KD control subjects for Illumina HumanMethylation450 BeadChip study. A separate cohort of 134 subjects was analyzed to validate real-time quantitative PCR. Results: The mRNA levels of caspase-1, -3, -4, and -5 were significantly increased in KD patients compared with control subjects (p < 0.05). After administration of IVIG, the expression of these genes decreased considerably. Of particular note, the methylation status of the CpG sites of the caspase-4 and -5 genes demonstrated significant opposite tendencies between the KD patients and controls. Furthermore, compared with patients who responded to IVIG, refractory KD patients had a lower expression of the caspase-3 gene prior to IVIG treatment. Conclusion: Our study is the first to report the upregulation of pyroptotic caspase-1, -4, and -5 in peripheral leukocytes of KD patients. Moreover, the expression of caspase-3 may be associated with IVIG resistance in KD.

The Most Common Clinical Features of Kawasaki Disease Patients in King Abdulaziz Medical City.

BackgroundKawasaki disease (KD) is an acute idiopathic vasculitis affecting the small and medium-sized arteries especially coronary artery (CA). it occurs in childhood mostly below five years of age.ObjectiveThis study aims to identify the most common clinical features among KD patients in King Abdulaziz Medical City in Jeddah, Saudi Arabia from 1/1/1982 to 31/12/2018.MethodsA case series study was conducted in all KD patients that were admitted to the King Abdulaziz Medical City from 1/1/1982 to 31/12/2018 except those who were diagnosed in other hospitals or whose diagnosis has later changed. The identification of patient was done by using the International Classification of Diseases (ICD) coding for KD (ICD9 446.1). Our data consisted of the patient’s file number, age at presentation, gender, whether the patients received IVIG treatment or not, number of days of fever before starting IVIG treatment, response to IVIG treatment, season in which the symptoms started and clinical features based on body’s system. ResultThe study included 18 patients, 11 males showed that (55.6%) of patients met the criteria of typical KD and most of them were less than five years old. In addition, most patients were reported to have polymorphous rash, cough, irritability, vomiting, and a murmur. All patients who received intravenous immunoglobulin (IVIG) treatment which demonstrated an improvement even though those who started the treatment after 10 days of fever.ConclusionIn typical KD patients, the distribution of the clinical features was almost identical. However, there were some variations in them among atypical KD patients. Moreover, Evan though KD in our region is not common as in Japan, the incidence of giant aneurism was higher. In addition to that, this study and other study conducted in Saudi Arabia found that screened patients reported tachycardia more than patients in Japan.RecommendationAs KD is still idiopathic, we recommend more details to be collected from the patients, especially consanguinity as it is common in Saudi Arabia

Anxiety among the parents of pediatric patients receiving IVIG therapy during the Covid-19 pandemic.

Symptomatic COVID-19 cases in children occur mostly in those with primary immunodeficiency (PID), chronic lung diseases, and heart disease. Guidelines recommend that patients with PID continue to use their regular medication during the pandemic. This study aimed to evaluate anxiety related to COVID-19 in the parents of patients receiving intravenous immunoglobulin (IVIG) treatment in our hospital and to evaluate the effect of their anxiety on the continuity of treatment. The parents of the patients who underwent IVIG therapy in our clinic during the pandemic (between May 15, 2020 and July 1, 2020) were included in our study. Twenty-seven patients with PID whose IVIG therapy was initiated before the pandemic and 29 non- PID control subjects were included in the study. All patients received IVIG treatment in our clinic continued treatment during the pandemic at the same dose intervals. Parents in the IVIG group had significantly higher state (p=0.003) and trait (p=0.003) anxiety scores compared to control parents. IVIG group showed statistically significant higher scores in Beck depression inventory, than the control group (p=0.002). The parents of PID patients who needed to come to the hospital for IVIG therapy had higher anxiety levels than the parents of similar aged children who presented to our clinic for different complaints between the same dates. Despite their concerns, the parents of all patients under IVIG therapy maintained treatment continuity at the recommended treatment intervals. None of our immunodeficient patients who presented for treatment during the pandemic contracted COVID-19 infection during our study.

4311Decreased CD177 expression and its association with intravenous immunoglobulin resistance in Kawasaki disease

Abstract Kawasaki disease (KD) is the most common acute coronary vasculitis disease occurring in children. Its occurrence has been attributed to the combined effects of infection, genetics, and immunity. While the etiopathogenesis of KD remains unknown, we have performed a survey of global genetic DNA methylation status and transcripts expression in KD patients to address how they contribute to the pathogenesis of KD. Methods We recruited 148 participants for this study. The chip studies consisted of 18 KD patients that were analyzed prior to administering intravenous immunoglobulin (IVIG) treatment and at least 3 weeks afterward, as well as 36 non-KD control subjects. We performed a separate cohort of 94 subjects to validate real-time quantitative PCR. Results According to the microarray study, CD177, a neutrophil surface molecule, appeared to be most significantly upregulated in KD patients compared to controls with epigenetic hypomethylation. After patients received IVIG treatment, CD177 mRNA levels decreased significantly. PCR validation indicated that the expression of CD177 is consistent with the Transcriptome Array 2.0 results. Furthermore, the area under the curve values of CD177 between KD patients and controls is 0.937. We also observed significantly higher CD177 levels in typical KD than incomplete presentation, which was associated with IVIG resistance in KD patients. Conclusion The present study is the first to highlight the epigenetic hypomethylation of an increased CD177 transcript during the acute stage of KD. Furthermore, the higher expression of CD177 in a typical presentation of KD patients and was related to IVIG resistance.

Factors associated with headache in intravenous immunoglobulin treatment for neurological diseases.

To identify possible risk factors influencing the incidence of intravenous immunoglobulin (IVIg) treatment-related cephalalgia in neurological diseases. Retrospective chart review of neurological patients receiving IVIg treatment between July 13, 2017, and August 14, 2017. Patients with MS receiving natalizumab in the same setting were observed as a reference group. Patients with headache after IVIg infusion (n=22 infusions) showed a reduced heart rate (by 6.0±8.5 beats per minute [bpm]), but no significant difference in blood pressure. Patients without headache after IVIg infusion (n=69 infusions) showed a higher systolic blood pressure increase and a stronger reduction in the heart rate (by 5.7±8.6bpm), compared to patients with headache after IVIg infusion. The infusion rate was significantly slower and age significantly lower in patients developing headache after IVIg infusion. Body temperature was unchanged in both groups. Binary logistic regression analysis revealed that blood pressure at baseline and age significantly influence the occurrence of cephalalgia. In reference, patients receiving natalizumab (ie, shorter infusions/smaller infusion volume), systolic blood pressure, and heart rate decreased, while body temperature increased. Here, one patient developed headache. Intravenous immunoglobulin-associated headache is not associated with an increased blood pressure after infusion but with a reduced heart rate, a slower infusion rate, female sex and seems to be influenced by baseline systolic blood pressure and age. A reaction to immunoglobulin aggregates, stabilizers, or vasoactive mediators are possible explanations. The absence of an association with body temperature does not suggest a systemic immune response as a cause for headache.

Increase expression of CD177 in Kawasaki disease

BackgroundKawasaki disease (KD) is the most common acute coronary vasculitis disease to occur in children. Its incidence has been attributed to the combined effects of infection, genetics, and immunity. Although the etiopathogenesis of KD remains unknown, we have performed a survey of global genetic DNA methylation status and transcripts expression in KD patients in order to determine their contribution to the pathogenesis of KD.MethodsWe recruited 148 participants for this case-control study. The chip studies consisted of 18 KD patients that were analyzed both before undergoing intravenous immunoglobulin (IVIG) treatment and at least 3 weeks afterward, as well as 36 non-KD control subjects, using Illumina HumanMethylation450 BeadChip and Affymetrix GeneChip® Human Transcriptome Array 2.0. We then carried out real-time quantitative PCR on a separate cohort of 94 subjects for validation.ResultsAccording to our microarray study, CD177, a neutrophil surface molecule, appeared to be significantly upregulated in KD patients when compared to controls with epigenetic hypomethylation. After patients received IVIG treatment, CD177 mRNA levels decreased significantly. PCR validation indicated that the CD177 expression is consistent with the Transcriptome Array 2.0 results. Furthermore, the area under the curve values of CD177 between KD patients and controls is 0.937. We also observed significantly higher CD177 levels in typical KD than in incomplete presentation or KD with IVIG resistance.ConclusionIn this study, we have demonstrated the epigenetic hypomethylation and increased expression of CD177 during the acute stage of KD. Furthermore, a higher expression of CD177 in KD patients with typical presentation was associated with IVIG resistance.

Decreased Steroid Hormone Receptor NR4A2 Expression in Kawasaki Disease Before IVIG Treatment.

Kawasaki disease (KD) is anacute febrile coronary vasculitis disease in children. In general, this disease can be treated with a single dose of 2 g/kg intravenous immunoglobulin (IVIG). However, the best timing for administering steroid treatment in acute-stage KD is still under debate. In this study, we recruited 174 participants to survey the transcript levels of steroid hormone receptors in KD patients. The chip studies consisted of 18 KD patients that were analyzed before IVIG treatment and at least 3 weeks after IVIG administration, as well as 36 control subjects, using GeneChip® HTA 2.0. Another cohort consisting of 120 subjects was analyzed to validate qRT-PCR. Our microarray study demonstrated significant downregulated expressions of the mRNA levels of NR1A2, RORA, NR4A1-3, THRA, and PPARD in KD patients in comparision to the controls. However, these genes increased considerably in KD patients after IVIG administration. After PCR validation, our data only revealed decreased NR4A2 mRNA expression in the KD patients compared to those of the controls, which increased after they received IVIG treatment. Our study is the first to report the potential effective utilization of steroid treatment in KD. Prior to IVIG treatment, decreased steroid receptors allowed for the reduced treatment role of steroids. However, after IVIG treatment, increased steroid receptors indicate that steroids are effective as a supplementary treatment for KD.

HAMP promoter hypomethylation and increased hepcidin levels as biomarkers for Kawasaki disease

Kawasaki disease (KD) is the most common coronary vasculitis to appear in children with anemia and has been associated with elevated plasma hepcidin levels. We recruited a total of 241 cases, including 18 KD patients, who were tested both prior to receiving intravenous immunoglobulin (IVIG) and at least 3 weeks after IVIG treatment, and 18 febrile controls, who were observed in the Illumina HumanMethylation450 BeadChip study for their CpG markers. The remaining cases consisted of another 92 KD patients and 113 controls that were used for validation by pyrosequencing. We performed a genetic functional study using Luciferase assays. A support vector machine (SVM) classification model was adopted to identify KD patients and control subjects. In this study, KD patients clearly demonstrated a significantly epigenetic hypomethylation of HAMP promoter compared to controls. After receiving IVIG treatment, the hypomethylation status in KD patients was restored, and we observed a significant opposite tendency between the DNA methylation of target CpG sites (cg23677000 and cg04085447) and the hepcidin level. Furthermore, reporter gene assays were used to detect target CpG sites, the methylation of which displayed decreased levels of HAMP gene expression. Of particular note, we developed a SVM classification model with a 90.9% sensitivity, a 91.9% specificity, and 0.94 auROC in the training set. An independent blind cohort also had good performance (96.1% sensitivity and 89.7% specificity). In this study, we demonstrate HAMP promoter hypomethylation, which upregulates hepcidin expression in KD patients. Furthermore, the reliability and robustness of our SVM classification model can accurately serve as KD biomarkers.

Intravenous Immunoglobulin Treatment for Recurrent Optic Neuritis.

Recurrent optic neuritis neuritis (rON) is an autoimmune inflammatory condition of unknown cause. Intravenous immunoglobulin (IVIg) treatment is used for many autoimmune disorders; however we do not have any information about its effect in rON, other than case reports. We aimed to evaluate our patients with rON who were treated with IVIg. Data from all our patients with rON with or without anti aquaporin4 (AQP4) seropositivity, seen between April 2011 and October 2015, who received IVIg treatment were retrospectively evaluated. Nine patients (all female) with rON had received IVIg. These patients were aged between 34 and 65 years, and had started receiving monthly IVIg from 6 to 58 months after onset of disease. In three out of nine rON patients serum AQP4 antibody were positive. Under current treatments the patients had continued to have attacks, therefore monthly IVIg was given in addition to the existing immunosuppressant drug. The follow up duration was between 6 to 31 months. Three patients, each suffered one relapse under IVIg treatment. Mean number of relapses in the year prior to treatment was 1.4±0.72, whereas it was 0.3±0.5 during the year after IVIg therapy. During follow-up with IVIg administration only one patient had fever and no other adverse events were reported. Monthly IVIg is well-tolerated and safe and it seems to be effective in rON as an add on treatment. However, since our study is a retrospective case series, future randomized controlled trials with IVIg are needed.