Guillain-barré syndrome (GBS) with antecedent chikungunya infection: a case report and literature review.

Guillain-Barré Syndrome (GBS) is an autoimmune neuropathy. Antecedent infections have been seen to be significant triggering factors for developing GBS. Among them, arboviral infections are rapidly gaining importance as significant triggers, especially in the areas where they are endemic. Chikungunya, an arboviral infection that usually causes a self-limiting acute febrile illness can lead to GBS as one its severe complications. Herein, we describe a case of a 21-year-old female who presented with weakness in all four limbs and paresthesia. Nerve conduction study and cerebrospinal fluid (CSF) analysis showed axonal, demyelinating motor and sensory neuropathy with albuminocytological dissociation indicating Acute Motor and Sensory Axonal Neuropathy (AMSAN) variant of GBS. Serum IgM antibodies against ganglioside GM1 were detected. Anti-Chikungunya IgM antibodies were found in both serum and CSF samples. The patient was initiated with Intravenous Immunoglobulin (IVIG) therapy. In view of hypoxia, she was intubated and was on mechanical ventilation. After 2 weeks of being comatose, the patient gradually improved and was discharged with no sequelae.A literature review on antecedent infections in GBS is presented alongside the case report to better understand the association of GBS with antecedent infections, especially the endemic arboviral infections like Chikungunya, Dengue and Zika. This will help in reinforcing the significance of having robust surveillance and public health control measures for infectious diseases.

A practical guide to the management of immune thrombocytopenia co-existing with acute coronary syndrome.

Introduction: Immune thrombocytopenia (ITP) management with co-existing acute coronary syndrome (ACS) remains challenging as it requires a clinically relevant balance between the risk and outcomes of thrombosis and the risk of bleeding. However, the literature evaluating the treatment approaches in this high-risk population is scarce. Methods and Results: In this review, we aimed to summarize the available literature on the safety of ITP first- and second-line therapies to provide a practical guide on the management of ITP co-existing with ACS. We recommend holding antithrombotic therapy, including antiplatelet agents and anticoagulation, in severe thrombocytopenia with a platelet count < 30 × 109/L and using a single antiplatelet agent when the platelet count falls between 30 and 50 × 109/L. We provide a stepwise approach according to platelet count and response to initial therapy, starting with corticosteroids, with or without intravenous immunoglobulin (IVIG) with a dose limit of 35 g, followed by thrombopoietin receptor agonists (TPO-RAs) to a target platelet count of 200 × 109/L and then rituximab. Conclusion: Our review may serve as a practical guide for clinicians in the management of ITP co-existing with ACS.

Demyelinating neuropathy in patients with hepatitis B virus: A case report.

BACKGROUND: Hepatitis B rarely leads to demyelinating neuropathy, despite peripheral neuropathy being the first symptom of hepatitis B infection. CASE SUMMARY: A 64-year-old man presented with sensorimotor symptoms in multiple peripheral nerves. Serological testing showed that these symptoms were due to hepatitis B. After undergoing treatment involving intravenous immunoglobulin and an antiviral agent, there was a notable improvement in his symptoms. CONCLUSION: Although hepatitis B virus (HBV) infection is known to affect hepatocytes, it is crucial to recognize the range of additional manifestations linked to this infection. The connection between long-term HBV infection and demyelinating neuropathy has seldom been documented; hence, prompt diagnostic and treatment are essential. The patient's positive reaction to immunoglobulin seems to be associated with production of the antigen-antibody immune complex.

Case Series: Efficacy of Polyclonal Intravenous Immunoglobulin for Refractory Clostridioides difficile Infection.

BACKGROUND: Intravenous immunoglobulin (IVIg) for Clostridioides difficile infection (CDI) no longer features in treatment guidelines. However, IVIg is still used by some clinicians for severe or recurrent CDI (rCDI) cases. The main objective of this study was to investigate the efficacy of IVIg and to identify possible predictors of disease resolution post IVIg administration for patients with CDI. METHODS: This retrospective observational cohort study of patients ≥2 years old hospitalised with severe, relapsing, or rCDI treated with IVIg therapy was performed in a large UK tertiary hospital between April 2018 and March 2023. Scanned electronic notes from patient admissions and clinical reporting systems were used to collect relevant data. RESULTS: In total, 20/978 patients diagnosed with CDI over the 5-year study were treated with IVIg. Twelve (60%) had hospital-onset CDI. Eleven of the twenty patients (55%) responded to treatment, with a mean of 8.6 (SD 10.7) days to disease resolution. Sixteen (80%) patients were treated for severe CDI and four (20%) for rCDI (n = 3) and relapsing CDI (n = 1). There were no statistically significant differences in possible independent predictors of disease resolution post IVIg administration between groups. There was an average of 6.2 (4.9) days to IVIg administration after diagnosis with no difference between responders and non-responders (p = 0.88) and no further significant difference in additional indicators. Four (36%) of the responders were immunosuppressed compared to just one (11%) of the non-responders (p = 0.15). Six of the responders (two with recurrent and four with severe CDI) improved rapidly within 2 days, and three of these were immunosuppressed. CONCLUSION: We observed disease resolution post IVIg therapy in over 50% of patients with refractory CDI. Our data also support a potential enhanced effect of IVIg in immunosuppressed individuals. Thus, the role of IVIg for CDI treatment, particularly in the immunosuppressed, warrants future case-control studies coupled to mechanistic investigations to improve care for this ongoing significant healthcare-associated infection.

Corrigendum: Effect of intravenous immunoglobulin therapy on the prognosis of patients with severe fever with thrombocytopenia syndrome and neurological complications.

[This corrects the article DOI: 10.3389/fimmu.2023.1118039.].

Protective effect of breastfeeding on Kawasaki disease: A systemic review and meta-analysis.

BACKGROUND: Previous research has indicated a negative correlation between exclusive breastfeeding and the incidence of Kawasaki disease (KD). However, the validation of this discovery through meta-analytical studies has been lacking. Furthermore, uncertainties persist regarding whether breastfeeding reduces the risk of coronary artery lesions (CAL) or resistance to intravenous immunoglobulin (IVIG). METHODS: A systematic exploration of the MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, and ClinicalTrials.gov databases was conducted to identify longitudinal or randomized controlled trials investigating the efficacy of breastfeeding in preventing KD. The primary focus was on the incidence of KD, with secondary emphasis placed on the incidence of CAL and IVIG resistance. Data were pooled using a frequentist-restricted maximum-likelihood random-effects model. RESULTS: Of the 179 potentially eligible studies identified, five (n = 1,982,634) were included. The analysis revealed a significantly lower risk of KD (expressed as odds ratio, with 95% confidence intervals and p-values) in comparisons between exclusive breastfeeding and formula feeding (0.62, 0.43-0.91, p = 0.014), exclusive breastfeeding/partial breastfeeding and formula feeding (0.66, 0.46- 0.96, p = 0.03), and exclusive breastfeeding and partial breastfeeding/formula feeding (0.81, 0.74- 0.90, p < 0.01). However, no significant difference was observed in the risk of developing KD when comparing partial breastfeeding to formula feeding exclusively. Regarding secondary outcomes, no statistically significant difference was found in the risk of CAL or IVIG resistance across any comparison formats. CONCLUSIONS: Our study suggests that breastfeeding correlated with a reduced risk of KD but not with a reduced risk of CAL or IVIG resistance. These findings advocate for the implementation of breastfeeding policies in clinical practice.

Reliability, validity, and sensitivity of the Japanese version of the University of California Los Angeles scleroderma clinical trial consortium gastrointestinal tract instrument: Application to efficacy assessment of intravenous immunoglobulin administration.

This study aimed to develop and assess the reliability, validity, and sensitivity of the Japanese version of the University of California Los Angeles Scleroderma Clinical Trial Consortium gastrointestinal tract (GIT) Instrument 2.0 (the GIT score), as an evaluation tool for GIT symptoms in systemic sclerosis (SSc). The Japanese version of the GIT score was constructed using the forward-backward method. The reliability and validity of this instrument were evaluated in a cohort of 38 SSc patients. Correlation analysis was conducted to assess the relationship between the GIT score and existing patient-reported outcome measures. Additionally, the sensitivity of the GIT score was examined by comparing GIT scores before and after intravenous immunoglobulin (IVIG) administration in 10 SSc-myositis overlap patients, as IVIG has recently demonstrated effectiveness in alleviating GIT symptoms of SSc. As a result, the Japanese version of the GIT score exhibited internal consistency and a significant association with the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease. Furthermore, the total GIT score, as well as the reflux and distention/bloating subscales, displayed moderate correlations with the EuroQol 5 dimensions (EQ-5D) pain/discomfort subscale and the Short Form-36 body pain subscale. Notably, following IVIG treatment, there was a statistically significant reduction in the total GIT score and multiple subscales. We first validated the Japanese version of the GIT score in Japanese SSc patients in real-world clinical settings. This instrument holds promise for application in future clinical trials involving this patient population.

A Rare Case of Overlapping Durvalumab-induced Myositis, Takotsubo-like Morphological Changes Caused by Myocarditis, and Myasthenia Gravis.

Immune checkpoint inhibitors can cause a range of immune-related adverse events, including myositis, Takotsubo cardiomyopathy, and myasthenia gravis. We herein report a rare case of a 78-year-old man with concurrent durvalumab-induced myositis, Takotsubo-like morphological changes caused by myocarditis, and myasthenia gravis. The patient initially required invasive ventilation and exhibited symptoms of myasthenia gravis after treatment with high-dose steroids. However, he subsequently achieved successful recovery after the administration of intravenous immunoglobulin, plasmapheresis, and high-dose steroids. We advocate vigilant neurological monitoring of patients with immune checkpoint inhibitor-induced myositis, including the assessment of ptosis and other relevant signs, so that prompt treatment can be initiated at the time of emergence or progression of immune checkpoint inhibitor-induced myasthenia gravis.

Intravenous immunoglobulin alleviates Japanese encephalitis virus-induced peripheral neuropathy by inhibiting the ASM/ceramide pathway.

Japanese encephalitis virus (JEV) infection is considered a global public health emergency. Severe peripheral neuropathy caused by JEV infection has increased disability and mortality rates in recent years. Because there are very few therapeutic options for JEV infection, prompt investigations of the ability of clinically safe, efficacious and globally available drugs to inhibit JEV infection and ameliorate peripheral neuropathy are urgently needed. In this study, we found that high doses of intravenous immunoglobulin, a function inhibitor of acid sphingomyelinase (FIASMA), inhibited acid sphingomyelinase (ASM) and ceramide activity in the serum and sciatic nerve of JEV-infected rats, reduced disease severity, reversed electrophysiological and histological abnormalities, significantly reduced circulating proinflammatory cytokine levels, inhibited Th1 and Th17 cell proliferation, and suppressed the infiltration of inflammatory CD4 + cells into the sciatic nerve. It also maintained the peripheral nerve-blood barrier without causing severe clinical side effects. In terms of the potential mechanisms, ASM was found to participate in immune cell differentiation and to activate immune cells, thereby exerting proinflammatory effects. Therefore, immunoglobulin is a FIASMA that reduces abnormal immune responses and thus targets the ASM/ceramide system to treat peripheral neuropathy caused by JEV infection.

C-reactive protein to albumin ratio as a prognostic tool for predicting intravenous immunoglobulin resistance in children with kawasaki disease: a systematic review of cohort studies.

BACKGROUND: Intravenous immunoglobulin (IVIG) is the primary treatment for Kawasaki disease (KD). However, 10-20% of KD patients show no response to IVIG treatment, making the early prediction of IVIG resistance a key focus of KD research. Our aim is to explore the application of the C-reactive protein to albumin ratio (CAR) for predicting IVIG resistance in children with KD through meta-analysis. METHODS: Cochrane Library, PubMed, MEDLINE, EMbase, CNKI, WanFang, the Chinese Biomedical Database, and CQVIP were searched up to November 2023 for cohort studies on predicting IVIG-resistant KD using the CAR. Articles were selected based on pre-established inclusion and exclusion criteria after extracting literature data and assessing them using the QUADAS-2.0 tool for evaluating the accuracy of diagnostic tests. Stata 15.0 software was used for meta-analysis. RESULTS: Four Chinese and English literature reports were included in this meta-analysis. The results revealed the presence of a threshold effect and high heterogeneity among the included studies. The combined sensitivity for CAR predicting IVIG-resistant KD was calculated as 0.65 (95% CI 0.58-0.72), specificity as 0.71 (95% CI 0.57-0.81), and the area under the curve (AUC) as 0.70 (95% CI 0.66-0.74) using the random-effects model. The combined positive likelihood ratio was 2.22 (95% CI 1.35-3.65), the combined negative likelihood ratio was 0.49 (95% CI 0.35-0.69), and the diagnostic odds ratio was 5 (95% CI 2-10). CONCLUSION: CAR is an auxiliary predictive indicator with moderate diagnostic value that provides guidance in the early treatment of the disease, demonstrating a certain predictive value that warrants further investigation. However, CAR cannot yet be considered as a definitive diagnostic or exclusionary marker for IVIG-resistant KD. Therefore, multi-center, large sample, and high-quality long-term follow-up trials are warranted to confirm the current findings.

High-Dose Immunoglobulin Therapy for Multiple Thromboembolism in Persisting Heparin-Induced Thrombocytopenia.

This report presents a case of an 81-year-old male with acute respiratory distress syndrome secondary to aspiration pneumonia who developed heparin-induced thrombocytopenia (HIT). His platelet count remained persistently low despite discontinuing unfractionated heparin and initiating intravenous argatroban. Multiple thromboembolisms, including a new aortic mural thrombus in the descending aorta, were observed on contrast-enhanced computed tomography (CT), resulting in a diagnosis of autoimmune HIT (aHIT). Subsequent high-dose intravenous immunoglobulin (IVIG) therapy substantially improved the platelet count and resolved thromboembolisms. This case is notable owing to the improvement of aHIT complicated by multiple thromboembolisms, including an aortic mural thrombus, following high-dose IVIG therapy. In recent years, a growing number of reports have documented the effectiveness of high-dose IVIG therapy for aHIT. However, reports on whether high-dose IVIG therapy could improve an aortic mural thrombus complicating aHIT are lacking. The successful use of high-dose IVIG therapy in the current case highlights its potential efficacy in treating aHIT complicated by multiple thromboembolisms. Further studies are required to clarify the role of IVIG in the management of aHIT with thromboembolism.

Intravenous immunoglobulin therapy for COVID-19 in immunocompromised patients: a retrospective cohort study.

OBJECTIVES: To investigate the effectiveness of intravenous immunoglobulin (IVIG) as treatment for COVID-19 in immunocompromised patients. METHODS: This retrospective study investigated outcomes for immunocompromised, vaccine non-responsive, patients that between September 2022 and April 2023 received IVIG as treatment for COVID-19 in the region of Västerbotten, Sweden. We analyzed clinical data, viral load, and anti-SARS-CoV-2 IgG binding and neutralization levels of patient serum samples and IVIG production batches. Primary and secondary outcomes were clinical cure and viral clearance, respectively. RESULTS: Sixteen patients were analyzed. After a median COVID-19 duration of four weeks, a median 60g IVIG infusion increased SARS-CoV-2 binding and neutralizing antibody levels, with broad in vitro activity against tested variants. The treatment resulted in abrogation of viremia in all patients and general improvement in 15 survivors that all met the primary endpoint. Thirteen patients met the secondary endpoint at follow-up after a median of four months. Two subjects with persistent SARS-CoV-2 carriage relapsed but were successfully retreated with IVIG. CONCLUSIONS: Antibodies in IVIG efficiently neutralized several SARS-CoV-2 variants. Treatment with IVIG was associated with clinical cure and viral clearance in immunocompromised patients. Our data suggests that IVIG could be a novel treatment alternative for COVID-19 for this patient category.

Immunoglobulin replacement therapies in inborn errors of immunity: a review.

Immunoglobulins (Ig) were used as a therapeutic modality for the first time in a patient with X-linked agammaglobulinemia in 1952 by Colonel Ogden Bruton, decades before the molecular mechanisms causing the disease were unraveled. In many autoimmune and inflammatory illnesses, human immunoglobulin has been employed as a significant immunomodulatory and immunosuppressive drug. In patients with inborn errors of immunity (IEI), immunoglobulin remains a cornerstone of management. IEIs are notable causes of recurrent infections and autoimmunity due to inheritable single-gene defects in genes encoding for different components of the immune system. As there is decreased immunoglobulin production in IEIs with antibody defects, immunoglobulin replacement is the mainstay of therapy in these disorders. Although serum immunoglobulin levels may not be low in combined immune defects, immunoglobulin replacement is still necessary in these disorders due to a deficiency of functional antibodies and qualitative defects of immunoglobulins. Commercial immunoglobulin preparations are generated from plasma donated by thousands of donors. Immunoglobulin preparations are usually available in two forms: intravenous and subcutaneous immunoglobulins. In the developed world, both intravenous immunoglobulin (IVIg) and subcutaneous immunoglobulin (SCIg) are available, and SCIg is preferred over IVIg for replacement therapy in patients with IEIs. In developing countries, IVIg remains the mainstay of replacement therapy. The rate of adverse events has significantly reduced over the last few years due to advancements in the production process. In this review article, we discuss different aspects of the use of Ig (indications, dosing, mechanism of action, route, adverse effects) in patients with IEIs.

Neurological Spectrum of Epstein-Barr Virus Infection: A Rare Clinical Case.

The Epstein-Barr virus (EBV) is a DNA virus that has been infecting humans since ancient times, capable of causing a wide range of pathologies and affecting approximately 90% of the population. A 61-year-old male with no significant medical history presented with a 5-day history of imbalance and difficulty walking. Neurological examination revealed specific findings, including absent reflexes, bilateral asynergy, and gait abnormalities. Contrasting with Guillain-Barré Syndrome, lumbar puncture suggested a central nervous system infection. Serological testing confirmed Epstein-Barr virus (EBV) positivity, and intravenous immunoglobulin led to significant improvement. Electromyogram results suggested inflammatory/ipnfectious polyradiculopathy. Repeat EBV serology, showing strongly positive IgG and negative IgM, confirmed the diagnosis of Polyradiculoneuropathy secondary to EBV. This case underscores the rare neurological complications of EBV and the importance of considering viral infections in such presentations.

A rare case of chikungunya encephalitis and its management: A case report and literature review.

Key Clinical Message: Chikungunya encephalitis, though rare, warrants clinical attention due to its severe complications. Early identification and appropriate management are crucial for improved outcomes in patients with this rare manifestation of chikungunya virus (CHIKV) infection. Abstract: CHIKV infection is commonly associated with fever and joint pains, but neurological complications such as encephalitis are rare. Here, we present a unique case of confirmed chikungunya encephalitis in a 12-year-old male exhibiting atypical neurological symptoms. The diagnostic journey involved comprehensive neuroimaging and serological investigations, revealing intriguing findings on magnetic resonance imaging and positive CHIKV RNA in serum and cerebrospinal fluid. We discuss the clinical presentation, radiological characteristics, and management strategies, emphasizing the importance of recognizing this uncommon neurological manifestation of CHIKV infection.

Treatment of multisystem inflammatory syndrome in children.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), a relatively uncommon but severe pediatric complication, is associated with coronavirus disease 2019 (COVID-19). A variety of treatment approaches, including intravenous immunoglobulins (IVIGs), glucocorticoids (GCs) and biologic agents, such as anakinra and infliximab, have been described for the management of COVID-19-related MIS-C. Anticoagulant therapy is also important. However, a well-developed treatment system has not been established, and many issues remain controversial. Several recently published articles related to the treatment of MIS-C have been released. Hence, in this review, we identified relevant articles published recently and summarized the treatment of MIS-C more comprehensively and systematically. DATA SOURCES: We reviewed the literature on the treatment of MIS-C through 20 September 2023. The PubMed/Medline, Web of Science, EMBASE, and Cochrane Library databases were searched with the combination of the terms "multisystem inflammatory syndrome", "MIS-C", "PIMS-TS", "therapy", "treatment", "drug", "IVIG", "GCs", "intravenous immunoglobulin", "corticosteroids", "biological agent", and "aspirin". RESULTS: The severity of MIS-C varies, and different treatment schemes should be used according to the specific condition. Ongoing research and data collection are vital to better understand the pathophysiology and optimal management of MIS-C. CONCLUSIONS: MIS-C is a disease involving multiple systems and has great heterogeneity. With the accumulation of additional experience, we have garnered fresh insights into its treatment strategies. However, there remains a critical need for greater standardization in treatment protocols, alongside the pressing necessity for more robust and meticulously conducted studies to deepen our understanding of these protocols. Supplementary file1 (MP4 208044 kb).

Case report: Successful treatment of an anti-D2R and DPPX antibody-associated autoimmune encephalitis patient with high-dose methylprednisolone and intravenous immunoglobulin.

Background: Autoimmune encephalitis is a neurological condition caused by abnormal immune responses, manifesting as cognitive impairments, behavioral abnormalities, and seizures. Its diagnosis depends on the detecting neuronal surface antibodies in serum or cerebrospinal fluid. Despite recent advances in understanding, clinical recognition remains challenging, especially with rare antibodies such as anti-dopamine D2 receptor (D2R) and anti-dipeptidyl-peptidase-like protein 6 (DPPX) antibodies. Delayed diagnosis can lead to severe complications. This case presentation emphasizes the diagnostic intricacies and effective treatment of the anti-D2R and DPPX antibody-associated autoimmune encephalitis. Case description: The patient presented with a 3-day history of fatigue and limb soreness followed by a 3-h episode of confusion and limb convulsions. Upon admission to our facility, the initial diagnosis included status epilepticus, aspiration pneumonia, metabolic acidosis, respiratory alkalosis, and suspected encephalitis. Despite receiving antiepileptic, anti-infection, and antivirus therapy, the patient's condition deteriorated. Both computed tomography (CT) scan and magnetic resonance imaging (MRI) of the brain showed no significant abnormalities. No pathogen was identified in the cerebrospinal fluid (CSF). However, further CSF and serum examination revealed positive results of anti-D2R and anti-DPPX antibodies, confirming a diagnosis of anti-D2R and DPPX antibody-associated autoimmune encephalitis. The patient underwent a comprehensive treatment regimen, including high-dose methylprednisolone pulse therapy combined with intravenous immunoglobulin (IVIG), antiviral and anti-infection treatments, and antiepileptic medications. Significant clinical improvement was observed, and by the 18th day of admission, the patient was stable and coherent. Conclusions: The current patient represents the first reported case of double-positive autoimmune encephalitis for anti-D2R and DPPX antibodies, with epilepsy as a prominent feature. High-dose methylprednisolone pulse therapy combined with IVIG has shown significant safety and efficacy in treating anti-D2R and DPPX antibody-positive autoimmune encephalitis-associated epilepsy.

Intravenous immunoglobulin protects the integrity of the intestinal epithelial barrier and inhibits ferroptosis induced by radiation exposure by activating the mTOR pathway.

Radiation exposure often leads to serious health problems in humans. The intestinal epithelium is sensitive to radiation damage, and radiation causes destruction of the intestinal epithelial barrier, which leads to radiation enteritis (RE), the loss of fluids, and the translocation of intestinal bacteria and toxins; radiation can even threaten survival. In this study, we aimed to explore the influence of IVIg on the integrity of the intestinal epithelial barrier after RE. Using a RE mouse model, we investigated the protective effects of intravenous immunoglobulin (IVIg) on the epithelial junctions of RE mice and validated these findings with intestinal organoids cultured in vitro. In addition, transmission electron microscopy (TEM), western blotting (WB) and immunostaining were used to further investigate changes in intestinal epithelial ferroptosis and related signaling pathways. When RE occurs, the intestinal epithelial barrier is severely damaged. IVIg treatment significantly ameliorated this damage to epithelial tight junctions both in vivo and in vitro. Notably, IVIg alleviated RE by inhibiting intestinal epithelial ferroptosis in RE mice. Mechanistically, IVIg promoted activation of the mTOR pathway and inhibited ferroptosis in the intestinal epithelium of mice. Rapamycin, which is a potent inhibitor of the mTOR protein, significantly abolished the protective effect of IVIg against radiation-induced damage to intestinal epithelial tight junctions. Overall, IVIg can prevent RE-induced damage to the intestinal epithelial barrier and inhibit ferroptosis by activating the mTOR pathway; this study provides a new treatment strategy for patients with RE caused by radiotherapy or accidental nuclear exposure.

Combination of S100A12/TLR2 signaling molecules and clinical indicators in a new predictive model for IVIG-resistant Kawasaki disease.

Although intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) presents with persistent inflammatory stimulation of the blood vessels and an increased risk of coronary artery dilatation. However, the pathogenesis of this disease is unclear, with no established biomarkers to predict its occurrence. This study intends to explore the utility of S100A12/TLR2-related signaling molecules and clinical indicators in the predictive modeling of IVIG-resistant KD. The subjects were classified according to IVIG treatment response: 206 patients in an IVIG-sensitive KD group and 49 in an IVIG-resistant KD group. Real-time PCR was used to measure the expression of S100A12, TLR2, MYD88, and NF-κB in peripheral blood mononuclear cells of patients, while collecting demographic characteristics, clinical manifestations, and laboratory test results of KD children. Multi-factor binary logistic regression analysis identified procalcitonin (PCT) level (≥ 0.845 ng/mL), Na level (≤ 136.55 mmol/L), and the relative expression level of S100A12 (≥ 10.224) as independent risk factors for IVIG-resistant KD and developed a new scoring model with good predictive ability to predict the occurrence of IVIG-resistant KD.

Efficacy and safety of intravenous immunoglobulin retreatment amongst Guillain-Barré syndrome patients who poorly responded to initial IVIG cycle: a systematic review.

INTRODUCTION: Small cross-sectional studies and case reports observed improvement after administration of second IVIG dose (SID) amongst Guillain-Barré Syndrome (GBS) patients not responsive to initial IVIG cycle. Nevertheless, recent clinical trial and larger observational studies did not find any positive effects of SID. Instead, an increased risk of thromboembolism and mortality was noted. The conclusions of these studies however were not robust as confounding and selection bias were present. METHODOLOGY: Two neurologists conducted the search process (KBA and MBP) using the following terms in Medline: [(" Guillain-Barré Syndrome"[MeSH Terms] or GBS or Acute Motor Axonal Neuropathy or Acute Motor Axonal Neuropathy or Acute Inflammatory Demyelinating Polyneuropathy) AND (Poorly Responsive or Poor Prognosis or Progressive)] AND [("Intravenous Immunoglobulin"[MeSH Terms] or IVIG or IGIV) AND (second dose or retreatment or SID)]. RESULTS: Only 7 articles were included in this review. In terms of primary outcomes, although the cross-sectional study found improvement in GBS DS score at 4 weeks (Median GBS DS: 3 vs 5, p = 0.033) and the 2 case series observed improvement after SID, no significant differences between the control and intervention groups were found in the cohort [Early SIV OR: 0.7 (95% CI 0.16-3.04), Late SIV OR: 0.66 (CI: 0.18-2.5)] and clinical trial studies (Adjusted OR: 1.4 (95% CI:0.6-3.3, p = 0.45). Moreover, 4 patients who died in the clinical trial were from the intervention group. CONCLUSION: Based on studies with research designs of higher quality, SID is not effective in the management of GBS patients who poorly responded to initial IVIG. Nevertheless, an adequately powered, randomized, double-blinded, placebo-controlled clinical trial, using GBS-DS of 3 and above after first IVIG dose should be done to effectively establish the efficacy and safety of SID as intervention for this cohort of patients.