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IntroductionNon-Hodgkin's lymphoma (NHL) encompasses a diverse group of lymphoma subtypes with a wide range in disease course. Previous studies show that hypogammaglobulinemia in treatment-naïve patients is associated with poorer survival in high grade B-cell non-Hodgkin's lymphomas, though it is not known how this applies across all B-cell lymphoid malignancies.MethodsWe conducted a retrospective study of immunoglobulin levels and clinical outcomes including survival, hospitalization, and infection rates in patients diagnosed with B-cell non-Hodgkin lymphomas of all grades at our institution.ResultsTwo-hundred twenty-three adults (aged = 18 years) with available pre-treatment IgG levels were selected, with hypogammaglobulinemia defined as IgG< 500 mg/mL. For this analysis, we grouped DLBCL (n=90), Primary CNS (n=5), and Burkitt lymphoma (n=1) together as high-grade, while CLL (n=52), mantle cell (n=20), marginal zone (n=25), follicular (n=21), and Waldenstrom macroglobulinemia (n=5) were low-grade. The incidence of hypogammaglobulinemia in our cohort of both high and low-grade lymphoma patients was 13.5% (n=30). Across all NHL subtypes, individuals with baseline IgG< 500 mg/dL showed an increased rate of hospitalization (4.453, CI: 1.955-10.54, p= 0.0005) and higher mortality (3.325, CI: 1.258, 8.491, p= 0.013), yet no association in number of infections when compared with those with IgG=500 mg/dL. There was a higher hospitalization rate (3.237, CI: 1.77-6.051, p=0.0017) in those with high-grade lymphoma with hypogammaglobulinemia when compared with low-grade. There was no statistically significant difference in individuals who were alive after three years in those with baseline IgG

Introduction/Aims Methods Results Discussion Prospective, randomized, controlled trials of intravenous immunoglobulin (IVIG) maintenance therapy in myasthenia gravis (MG) are lacking. In this trial, we evaluated the safety and efficacy of caprylate/chromatography‐purified IVIG; (IGIV‐C) in patients with generalized MG undergoing standard care.Sixty‐two patients enrolled in this phase 2, multicenter, international, randomized trial (1:1 IGIV‐C [2 g/kg loading dose; 1 g/kg every 3 weeks through week 21] or placebo). Efficacy was assessed by changes in Quantitative MG (QMG) score at week 24 versus baseline (primary endpoint) and percentage of patients with clinical improvement in QMG, MG Composite (MGC), and MG‐Activities of Daily Living (MG‐ADL) scores (secondary endpoints). Safety assessments reported all adverse events (AEs).The change in QMG at 24 weeks was −5.1 for IGIV‐C and −3.1 for placebo (p = .187). Seventy percent of patients in the IGIV‐C group had improvement in MG‐ADL (≥2‐point decrease) versus 40.6% in the placebo group (p = .025). Patients showing clinical improvement in QMG and MGC (≥3‐point decrease) were 70.0% for IGIV‐C versus 59.4% for placebo (p = .442) and 60.0% for IGIV‐C versus 53.1% for placebo (p = .610). IGIV‐C was well tolerated; serious AEs were similar between arms. Three of four MG exacerbations requiring hospitalizations occurred in the IGIV‐C arm with one death.Several efficacy parameters showed numerical results greater than those seen in the placebo group. This was a small study and may have been underpowered to see significant differences. Additional studies may be warranted to fully determine the efficacy of IVIG maintenance therapy in MG. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Hypogammaglobulinemia is a common yet under‐recognized feature of myotonic dystrophy type 1 (DM1). The aims of our study were to determine the frequency of immunoglobulin G (IgG) deficiency in our cohort, to examine the association between immunoglobulin levels and cytosine–thymine–guanine (CTG) repeat length in the DMPK gene, and to assess whether IgG levels are associated with an increased risk of infection in DM1 patients. Methods: We conducted a single‐center, retrospective cross‐sectional study of 65 adult patients with DM1 who presented to the Neuromuscular Clinic at Concord Repatriation General Hospital, Sydney, Australia, between January 2002 and January 2022. We systematically collected and analyzed clinical, laboratory, and genetic data for all patients with available serum electrophoresis and/or IgG level results. Results: Forty‐one percent of DM1 patients had IgG deficiency despite normal lymphocyte counts, IgA, IgM, and albumin levels. There was an association between CTG repeat expansion size and the degree of IgG deficiency (F = 6.3, p =.02). There was no association between IgG deficiency and frequency of infection in this group (p =.428). Discussion: IgG deficiency is a frequent occurrence in DM1 patients and is associated with CTG repeat expansion size. Whether hypogammaglobulinemia is associated with increased infection risk in DM1 is unclear. A prospective multicenter cohort study is needed to evaluate this. [ABSTRACT FROM AUTHOR]

Background and objective: Systemic sclerosis (SSc) is a highly heterogeneous disease whose treatment is based mainly on immunosuppressants, antifibrotics, and vasodilators. Intravenous immunoglobulin (IVIG) have proved effective in other autoimmune diseases. The objective of this study is to evaluate the efficacy and safety of IVIG in SSc. Methods: The systematic review was conducted according to the PRISMA Statement. Medline, Embase and Cochrane Library databases were searched until March 2024. We assessed the quality of included studies using the Cochrane Risk of Bias 2.0 tool (RoB 2) for randomised clinical trials and the Cochrane Risk in non-randomized studies (ROBINS-I) tool for observational studies. Results: From 1242 studies identified, 15 studies were included, of which 14 were observational studies. In total, 361 patients with SSc were included, and 295 received treatment with IVIG. Most of the studies used a dose of 2 g/kg IVIG. Ten studies, including the clinical trial, showed high risk of bias, and five had a critical risk. Skin involvement was assessed using modified Rodnan skin score, in 11 studies and the authors reported cutaneous efficacy in 9 of them. The 6 studies that assessed muscle involvement reported an improvement. Six studies reported data on gastrointestinal efficacy. Other domains such as lung and joint involvement and steroid-sparing effect were evaluated. The most frequent adverse events were mild, including headache, abdominal pain, fever, and skin rash. Conclusion: Treatment with IVIG in SSc patients could be helpful and safe in patients with cutaneous, muscular, or digestive manifestations. [ABSTRACT FROM AUTHOR]

Introduction: Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) is characterized by abrupt onset of obsessive-compulsive disorder or eating restriction along with the abrupt onset of other co-occurring symptoms (tics, behavioral and cognitive regression, etc.). PANS is thought to be a postinfectious immunopsychiatric disorder, although as with most post-infectious disorders, it is challenging to establish a causal relationship with proposed infectious triggers. Intravenous immunoglobulin (IVIG) can modulate inflammation and support the elimination of infection and has been used for treatment of many post-infectious inflammatory disorders and autoimmune conditions. The aim of the study is to explore the pro-inflammatory state in PANS before and after administration of IVIG. Methods: Children with moderate-to-severe PANS received six infusions of IVIG (Octagam 5%, Octapharma) every 3 weeks with post treatment follow-up. Blood samples and psychiatric measures were obtained at Visits 1 (pre-treatment), 7 and 8 (4 and 11 weeks after last infusion, respectively). Myeloid cell activation was assessed via flow cytometry. Results: All ten patients included in the study were male, White, with mean age 12.4 years (range 6–16). Statistically significant improvements following IVIG treatment were demonstrated in all psychometric assessments and parent questionnaires including CY-BOCS (obsessive compulsive scale), YGTSS (tic scale) and a parent PANS rating scale (for all scales p<0.001). The fraction of pro-inflammatory monocytes and dendritic cells decreased from pre-IVIG treatment levels. The proportional reductions were not compensated by increases in total white blood cells; pro-inflammatory monocytes post-IVIG were decreased as a proportion of CD14+ myeloid cells and in absolute number. Conclusions: The results of this study suggest that active PANS is associated with a pro-inflammatory state. This pro-inflammatory profile and psychometric scores improved following IVIG treatment. Future work will aim to further elucidate the roles of innate and adaptive immune responses in PANS and the regulatory mechanism(s) of IVIG in PANS treatment. [ABSTRACT FROM AUTHOR]

Background: The incidence of refractory Mycoplasma pneumoniae pneumonia (RMPP) in children is increasing, posing a serious threat to life safety. Intravenous immunoglobulin (IVIG) has demonstrated the ability to modulate the immune system and has shown the potential to treat RMPP. This study evaluated the clinical efficacy and safety of azithromycin combined with IVIG in the treatment of RMPP in children through a meta-analysis. Methods: A comprehensive search was conducted in seven databases including PubMed and Cochrane Library, and the studies on the treatment of RMPP in children with azithromycin combined with IVIG were screened. After data extraction, meta-analysis and sensitivity analysis were performed to assess heterogeneity and stability. Results: Thirteen randomized controlled trials and two cohort studies were included, totaling 1,142 children. The results of meta-analysis showed a higher clinical efficacy rate (RR = 1.18, 95% CI: 1.11–1.25, P < 0.01) and shorter time to defervescence (MD = -2.12, 95% CI: -2.69–-1.55), time to disappearance of pulmonary rales (MD = -2.90, 95% CI: -3.57–-2.23), time to disappearance of cough (MD = -3.59, 95% CI: -4.51–-2.67), and hospital length of stay (MD = -5.72, 95% CI: -8.80–-2.64) in the experimental group receiving azithromycin combined with IVIG treatment compared to the control group treated with azithromycin alone. Additionally, there was no significant publication bias in this meta-analysis. Conclusion: Treatment with azithromycin combined with IVIG is more effective than treatment with azithromycin alone for children with RMPP. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

Background: Pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS) is a controversial diagnosis with limited evidence-based treatment guidelines available, particularly for severe and treatment-resistant cases. Case presentation: : This report describes a 9-year-old male presenting with sudden onset, severe obsessive-compulsive disorder (OCD) symptoms one month following a streptococcus infection. His symptoms included suicidality and recurrent self-injurious behaviors, which led to multiple inpatient hospitalizations. He was diagnosed with PANDAS and was treated with psychotropic medications, antibiotics, immunotherapy, and a tonsillectomy. Over the two years since initial admission, the patient's condition improved, with a decrease in symptom severity and an increase in adaptive functioning, though symptom remission was slow to occur. Conclusions: This paper explores the controversies surrounding the PANDAS diagnosis, reviews potential treatments, and discusses the dilemmas of medical decision-making in the setting of severe treatment-resistant symptoms and limited evidence-based guidelines. We hope that this case report will be valuable to healthcare providers facing similar presentations and inspire further investigation into this complex condition. [ABSTRACT FROM AUTHOR]

Introduction: Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) is characterized by abrupt onset of obsessive-compulsive disorder or eating restriction along with the abrupt onset of other co-occurring symptoms (tics, behavioral and cognitive regression, etc.). PANS is thought to be a postinfectious immunopsychiatric disorder, although as with most post-infectious disorders, it is challenging to establish a causal relationship with proposed infectious triggers. Intravenous immunoglobulin (IVIG) can modulate inflammation and support the elimination of infection and has been used for treatment of many post-infectious inflammatory disorders and autoimmune conditions. The aim of the study is to explore the pro-inflammatory state in PANS before and after administration of IVIG. Methods: Children with moderate-to-severe PANS received six infusions of IVIG (Octagam 5%, Octapharma) every 3 weeks with post treatment follow-up. Blood samples and psychiatric measures were obtained at Visits 1 (pre-treatment), 7 and 8 (4 and 11 weeks after last infusion, respectively). Myeloid cell activation was assessed via flow cytometry. Results: All ten patients included in the study were male, White, with mean age 12.4 years (range 6-16). Statistically significant improvements following IVIG treatment were demonstrated in all psychometric assessments and parent questionnaires including CY-BOCS (obsessive compulsive scale), YGTSS (tic scale) and a parent PANS rating scale (for all scales p<0.001). The fraction of pro-inflammatory monocytes and dendritic cells decreased from pre-IVIG treatment levels. The proportional reductions were not compensated by increases in total white blood cells; pro-inflammatory monocytes post-IVIG were decreased as a proportion of CD14+ myeloid cells and in absolute number. Conclusions: The results of this study suggest that active PANS is associated with a pro-inflammatory state. This pro-inflammatory profile and psychometric scores improved following IVIG treatment. Future work will aim to further elucidate the roles of innate and adaptive immune responses in PANS and the regulatory mechanism(s) of IVIG in PANS treatment. [ABSTRACT FROM AUTHOR]

Summary Intravenous immunoglobulin (IVIg) is the gold standard treatment for severe cases of immune thrombocytopaenia (ITP). However, its cost, limited duration of efficacy and market supply tension have led French guidelines to reserve IVIg for ITP patients with formal contra‐indications to corticosteroids, with French bleeding score (‘Khellaf score’) > 8, and corticosteroid‐resistant patients either with Khellaf score ≤ 8 or in preparation for an invasive procedure or during pregnancy. We studied the prescribing practices of IVIg for ITP in real‐life conditions and assessed their compliance with French guidelines. A monocentric retrospective study was conducted between 2016 and 2020 among 114 patients hospitalized in our unit, for a total of 208 IVIg treatments. In 37% of cases, the Khellaf score was >8, validating IVIg prescription according to French guidelines. In the remaining cases, reasons noted for use of IVIg included corticosteroid resistance (33.7%), preparation for an invasive procedure (8.5%), context of pregnancy (6.6%) and contra‐indication to corticosteroids (3.3%). After analysis, IVIg prescription was considered valid according to current French guidelines in 84.4% of cases. Non‐compliant IVIg prescription was more frequent in younger patients (p = 0.027). Concomitant anti‐coagulation was also noted as an argument for IVIg prescription outside of the current French guidelines. [ABSTRACT FROM AUTHOR]

Background and Objectives: Intravenous immunoglobulins (IVIgs) contain various autoantibodies, including those against glutamic acid decarboxylase (GADAb), a valuable biomarker of type 1 diabetes mellitus. Passive transfer of GADAb from IVIgs to patients poses a risk of misdiagnosis, and information on the specific titres of GADAb and their impact on diagnostic accuracy remains limited. This study aimed to provide further insights into the origin of GADAb detected in patient serum following IVIg infusion. Materials and Methods: GADAb titres in IVIg products from Japan and the United States were measured using enzyme‐linked immunosorbent assay‐based assays. For reliable quantification, GADAb titres in pooled plasma were quantified and compared with those in the IVIg products. The determined titres were used to estimate the likelihood of passively detecting acquired GADAb in individuals receiving IVIgs. Results: GADAbs were prevalent in IVIg products; however, the titres varied significantly among different lots and products. Importantly, IVIg‐derived GADAb was estimated to remain detectable in patient serum for up to 100 days following a dosage of 2000 mg/kg. Conclusion: Clinicians should consider that IVIg preparations may contain GADAb, which can lead to false‐positive results in serological assays. Careful interpretation of the assay results is key to the definitive diagnosis of type 1 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Introduction/Aims Methods Results Discussion Despite treatment, a considerable proportion of patients with Guillain–Barré syndrome (GBS) experience poor recovery, highlighting a therapeutic need. There is a lack of evidence that treatment timing affects recovery. This study aims to investigate the effects of intravenous immunoglobulin (IVIg) timing on disability and speed of recovery in GBS.We performed a retrospective study of 136 IVIg‐treated GBS patients admitted to two Korean centers between 2010 and 2021. We analyzed the effect of time to IVIg on the GBS disability scale (GBS‐DS) and the degree of improvement from nadir (∆GBS‐DS) at 1, 3, 6, and 12 months, as well as the time to regain the ability to walk or run unaided. Time to IVIg was treated either as a continuous variable or categorized into 1‐week intervals to explore critical time windows. Known prognostic factors, the modified Erasmus GBS Outcome Scores on admission and pre‐treatment serum albumin levels were adjusted as covariates.Shorter time to IVIg was independently associated with better GBS‐DS, greater ∆GBS‐DS, and shorter time to walk or run unaided at all time points. The therapeutic effect of IVIg was notably diminished when administered beyond the first 2 weeks of onset.Our study highlights the timing of IVIg as a modifiable prognostic factor in GBS. The earlier IVIg is initiated, the better the outcomes, with the ideal time window being within the first 2 weeks. These findings underscore the importance of prompt diagnosis and early intervention to optimize recovery in GBS patients. [ABSTRACT FROM AUTHOR]

Summary Antibodies provide an essential layer of protection from infection and reinfection with microbial pathogens. An impaired ability to produce antibodies results in immunodeficiency and necessitates the constant substitution with pooled serum antibodies from healthy donors. Among the five antibody isotypes in humans and mice, immunoglobulin G (IgG) antibodies are the most potent anti‐microbial antibody isotype due to their long half‐life, their ability to penetrate almost all tissues and due to their ability to trigger a wide variety of effector functions. Of note, individuals suffering from IgG deficiency frequently produce self‐reactive antibodies, suggesting that a normal serum IgG level also may contribute to maintaining self‐tolerance. Indeed, the substitution of immunodeficient patients with pooled serum IgG fractions from healthy donors, also referred to as intravenous immunoglobulin G (IVIg) therapy, not only protects the patient from infection but also diminishes autoantibody induced pathology, providing more direct evidence that IgG antibodies play an active role in maintaining tolerance during the steady state and during resolution of inflammation. The aim of this review is to discuss different conceptual models that may explain how serum IgG or IVIg can contribute to maintaining a balanced immune response. We will focus on pathways depending on the IgG fragment crystallizable (Fc) as pre‐clinical data in various mouse model systems as well as human clinical data have demonstrated that the IgG Fc‐domain recapitulates the ability of intact IVIg with respect to its ability to trigger resolution of inflammation. We will further discuss how the findings already have or are in the process of being translated to novel therapeutic approaches to substitute IVIg in treating autoimmune inflammation. [ABSTRACT FROM AUTHOR]

Introduction/Aims Methods Results Discussion Randomized controlled trials show that repeat intravenous immunoglobulin (IVIG) dosing and plasma exchange (PLEX) followed by IVIG (combination therapy) have no additional therapeutic benefit in Guillain‐Barre Syndrome (GBS) non‐responders. Furthermore, the delineation between GBS and Acute Onset CIDP (A‐CIDP) can be particularly challenging and carries therapeutic implications. We aimed to evaluate the presence of repeat IVIG, combination therapy, and diagnostic reclassification from GBS to CIDP.We performed a retrospective study of a large healthcare database for patients with GBS in the US from 2001 to 2018. We identified individuals initially diagnosed with GBS and later re‐classified as CIDP. Multivariable logistic regression models were developed to determine associations between patient factors and repeat IVIG dosing, combination therapy, and diagnostic re‐classification from GBS to CIDP.We identified 2325 patients with GBS. A total of 39.7% received repeat IVIG and 6.1% received combination therapy. The proportion of individuals initially diagnosed with GBS and then re‐classified as CIDP was 32.0%. Repeat IVIG, combination therapy, and diagnostic reclassification remained stable over time. Female sex (OR 0.79, 95% CI 0.65–0.96) and medium‐high net worth (OR 0.64, 95% CI 0.45–0.90) associated with repeat IVIG therapy, while Asian ethnicity associated with diagnostic re‐classification from GBS to CIDP (OR 1.77, 95% CI 1.09–2.86).Repeat IVIG dosing was quite common in GBS before newer trials suggesting harm in non‐responders, and IVIG/PLEX combination therapy continues to persist despite strong evidence against use in non‐responders. Further, nearly one in three patients initially diagnosed with GBS is subsequently diagnosed with CIDP, but the reasons are unclear. [ABSTRACT FROM AUTHOR]

Background: This study aimed to clarify serum salicylic acid (SA) levels in patients with Kawasaki disease (KD) after the administration of moderate-dose acetylsalicylic acid (ASA) and their relationship with the therapeutic effect. Methods: We retrospectively analyzed the clinical data of 142 children with KD. We measured serum SA trough levels during the acute and recovery periods and determined their relationship with clinical and laboratory parameters. Results: The median age of patients was 2.4 years. Thirty-one patients had incomplete KD, 29 were intravenous immunoglobulin (IVIG) non-responders, and one patient had coronary artery lesions. The median ASA dose was 49.7 mg/kg/day. The median serum SA level was 22 µg/mL in the acute period and 15 µg/mL in the recovery period, with 45 (33%) in the acute period and 60 (44%) in the recovery period below the limit of measurement (< 10 µg/mL). Serum SA levels during the recovery period were significantly lower in patients who received steroids. There were no significant differences in IVIG responsiveness based on serum SA levels. Conclusions: Serum SA trough levels in KD patients treated with moderate-dose ASA were highly variable and did not reach sufficient levels. Serum SA levels were not associated with IVIG responsiveness. [ABSTRACT FROM AUTHOR]

Neonatal sepsis, a bloodstream infection in the first 28 days of life, is a leading cause of morbidity and mortality among infants in both developing and developed countries. Additionally, sepsis is distinguished in neonates by unique pathophysiological and presentational factors relating to its development in immature neonatal immune systems. This review focuses on the current understanding of the mechanics and implications of neonatal sepsis, providing a comprehensive overview of the epidemiology, aetiology, pathophysiology, major risk factors, signs and symptoms and recent consensus on the diagnosis and management of both early-onset and late-onset neonatal sepsis. It also includes a discussion on novel biomarkers and upcoming treatment strategies for the condition as well as the potential of COVID-19 infection to progress to sepsis in infants. [ABSTRACT FROM AUTHOR]

Background: Multisystem inflammatory syndrome in children (MIS-C) is one of the complications of SARS-CoV-2 infection. This study aims to evaluate the clinical and laboratory characteristics, as well as treatment results, of MIS-C patients who received intravenous immunoglobulin (IVIG) monotherapy. Methods: This retrospective study included patients diagnosed with MIS-C. Demographic data, organ involvements at the admission, laboratory evaluations for diagnosis, treatment, and follow-up were recorded. We evaluated outcomes by the length of the intensive care unit stay, the total hospitalization period, complications, and mortality. Results: A total of 95 patients diagnosed with MIS-C were evaluated. The mean age was 118.8 (± 52.5) months. 76.8% of the patients had four or more organ systems involved. Seventy-nine patients (83%) were hospitalized in the pediatric intensive care unit (PICU) for a mean of 4.59 days. Seventy-seven (81%) patients received IVIG. A second dose of IVIG was administered to 66.3% of patients. All patients received vitamin D and C supplementation. Six patients who had cardiac involvement or cerebral infarction were treated with plasmapheresis. No patients received steroids. There was no mortality at the end of the follow-up. Conclusions: Favorable outcomes may be obtained with IVIG monotherapy in MIS-C patients. More clinical trials are needed to establish the role of supportive treatments like vitamin D and C in MIS-C management. [ABSTRACT FROM AUTHOR]

Background: Transient positivity for hepatitis B core antibody (Anti‐HBc) following intravenous immunoglobulin (IVIG) and subcutaneous immunoglobulin exposure is a well‐described phenomenon. The aim of this study was to retrospectively review Hepatitis B viral screening practices in IVIG recipients in a hematology specific cohort at a single center. Methods: Electronic databases were analyzed to identify all hematology patients who received IVIG from September 2022 to March 2022 at a single Irish center (n = 43). The proportion of patients that had a baseline anti‐HBc tested prior to IVIG receipt was assessed as well as the proportion of patients that developed a transiently positive anti‐HBc following IVIG exposure. Data were also collected relating to signal cut‐off ratios in patients with detectable anti‐HBc post‐IVIG. Results: 58.1% of patients had at least one serological hepatitis B viral test sent prior to IVIG exposure. Anti‐HBc was the least common serological investigation performed prior to IVIG exposure (21% of recipients). A positive or equivocal "low level antibody" was identified in 15% of recipients and this was proven to be transient in all cases. Conclusion: The minority of hematology patients had a baseline anti‐HBc assessed prior to IVIG exposure. All patients in this study had the potential to require further immunosuppressive therapies, which could be limited by a misleading anti‐HBc result. We therefore advocate for baseline anti‐HBc testing to be performed prior to IVIG exposure in hematology patients and for cautious interpretation of anti‐HBc results taking into account signal cut‐off ratios post‐IVIG exposure. [ABSTRACT FROM AUTHOR]

Approximately 10–20 % of individuals develop a recrudescent or persistent fever after intravenous immunoglobulin (IVIG) infusion for the initial treatment of Kawasaki disease. The aim of this study was to evaluate the efficacy and safety of the initial IVIG treatment of Kawasaki disease based on duration of infusion. This retrospective, single-center study included 53 patients with Kawasaki disease who were initially treated with 2 g/kg of IVIG by means of a single infusion from June 2018 to August 2019. We classified patients into two groups based on the duration of the infusion: the 12-h group and the 24-h group. We compared the treatment response of the primary IVIG and its adverse events using the Mann-Whitney U test and Fisher's exact or Chi-square tests. There were no significant differences in the response to initial IVIG treatment between the two groups. The duration from treatment onset to defervescence was shorter in the 12-h group than the 24-h group (7 h vs. 12 h, respectively, p = 0.07); however, this was not significant. There were no significant between-group differences regarding adverse events. We concluded that the initial 12-h IVIG treatment was comparable to the 24-h treatment in terms of efficacy and safety. This will enable physicians to feel confident about pursuing a shorter course of treatment with similar results as conventional treatment and decide on administering additional therapy to their patients. [ABSTRACT FROM AUTHOR]

Mohamed Farah Osman Hidig,1 Mohamed Sheikh Hassan,1,2 Abdiwahid Ahmed Ibrahim,1 Bakar Ali Adam,1 Nor Osman Sidow,1 Said Abdi Mohamed1 1Department of Neurology, Mogadishu Somalia Turkish Training and Research Hospital, Mogadishu, Somalia; 2Faculty of Medicine and Surgery, Mogadishu University, Mogadishu, SomoliaCorrespondence: Mohamed Farah Osman Hidig, Department of Neurology, Mogadishu Somalia Turkish Training and Research Hospital, Mogadishu, Somalia, Email mfhidig@gmail.comAbstract: Emerging symmetrical limb weakness, altered sensory perception, and absent or reduced deep tendon reflexes are the hallmarks of Guillain-Barre syndrome (GBS). There are numerous studies that indicate up to two-thirds of patients with GBS may also have autonomic dysfunction. One uncommon presenting characteristic of GBS before motor weakness is evident is paralytic ileus, a sign of gastrointestinal dysautonomia. Here we describe the case of a 55-year-old man who was brought to the emergency room of our hospital with paralytic ileus, a less common symptom of early-stage GBS. The patient was initially treated with prokinetic drugs and total parenteral nutrition with no clinical improvement. The patient quickly developed ascending lower limb weakness that progressed to quadriplegia, which ultimately affected respiratory muscles, leading to respiratory failure requiring mechanical ventilation and intensive care unit hospitalization. A nerve conduction study showed demyelinating sensorimotor polyneuropathy. Analysis of cerebrospinal fluid revealed albumin-cytological dissociation. The patient was treated with intravenous immunoglobulin (IVIG) and other supportive treatments. Even though the patient’s enteral feeding support was uncomfortable due to a profound infection complicating lack of stomach emptying during the hospital stay, the patient passed away two months after being admitted. Lack of awareness about GBS gastrointestinal dysautonomia may cause delays in treatment initiation, and as a result, GBS may lead to life-threatening events. Reducing mortality and morbidity from GBS requires prompt diagnosis and treatment. This case reminds us that GBS may present as gastrointestinal dysautonomia.Keywords: Gullian-Barre syndrome, paralytic ileus, quadraparesis, intravenous immunoglobulin

Abstract Background Pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS) is a controversial diagnosis with limited evidence-based treatment guidelines available, particularly for severe and treatment-resistant cases. Case presentation : This report describes a 9-year-old male presenting with sudden onset, severe obsessive-compulsive disorder (OCD) symptoms one month following a streptococcus infection. His symptoms included suicidality and recurrent self-injurious behaviors, which led to multiple inpatient hospitalizations. He was diagnosed with PANDAS and was treated with psychotropic medications, antibiotics, immunotherapy, and a tonsillectomy. Over the two years since initial admission, the patient’s condition improved, with a decrease in symptom severity and an increase in adaptive functioning, though symptom remission was slow to occur. Conclusions This paper explores the controversies surrounding the PANDAS diagnosis, reviews potential treatments, and discusses the dilemmas of medical decision-making in the setting of severe treatment-resistant symptoms and limited evidence-based guidelines. We hope that this case report will be valuable to healthcare providers facing similar presentations and inspire further investigation into this complex condition.

Abstract Background The incidence of refractory Mycoplasma pneumoniae pneumonia (RMPP) in children is increasing, posing a serious threat to life safety. Intravenous immunoglobulin (IVIG) has demonstrated the ability to modulate the immune system and has shown the potential to treat RMPP. This study evaluated the clinical efficacy and safety of azithromycin combined with IVIG in the treatment of RMPP in children through a meta-analysis. Methods A comprehensive search was conducted in seven databases including PubMed and Cochrane Library, and the studies on the treatment of RMPP in children with azithromycin combined with IVIG were screened. After data extraction, meta-analysis and sensitivity analysis were performed to assess heterogeneity and stability. Results Thirteen randomized controlled trials and two cohort studies were included, totaling 1,142 children. The results of meta-analysis showed a higher clinical efficacy rate (RR = 1.18, 95% CI: 1.11–1.25, P

Abstract Background Multisystem inflammatory syndrome in children (MIS-C) is one of the complications of SARS-CoV-2 infection. This study aims to evaluate the clinical and laboratory characteristics, as well as treatment results, of MIS-C patients who received intravenous immunoglobulin (IVIG) monotherapy. Methods This retrospective study included patients diagnosed with MIS-C. Demographic data, organ involvements at the admission, laboratory evaluations for diagnosis, treatment, and follow-up were recorded. We evaluated outcomes by the length of the intensive care unit stay, the total hospitalization period, complications, and mortality. Results A total of 95 patients diagnosed with MIS-C were evaluated. The mean age was 118.8 (± 52.5) months. 76.8% of the patients had four or more organ systems involved. Seventy-nine patients (83%) were hospitalized in the pediatric intensive care unit (PICU) for a mean of 4.59 days. Seventy-seven (81%) patients received IVIG. A second dose of IVIG was administered to 66.3% of patients. All patients received vitamin D and C supplementation. Six patients who had cardiac involvement or cerebral infarction were treated with plasmapheresis. No patients received steroids. There was no mortality at the end of the follow-up. Conclusions Favorable outcomes may be obtained with IVIG monotherapy in MIS-C patients. More clinical trials are needed to establish the role of supportive treatments like vitamin D and C in MIS-C management.

Abstract Background This study aimed to clarify serum salicylic acid (SA) levels in patients with Kawasaki disease (KD) after the administration of moderate-dose acetylsalicylic acid (ASA) and their relationship with the therapeutic effect. Methods We retrospectively analyzed the clinical data of 142 children with KD. We measured serum SA trough levels during the acute and recovery periods and determined their relationship with clinical and laboratory parameters. Results The median age of patients was 2.4 years. Thirty-one patients had incomplete KD, 29 were intravenous immunoglobulin (IVIG) non-responders, and one patient had coronary artery lesions. The median ASA dose was 49.7 mg/kg/day. The median serum SA level was 22 µg/mL in the acute period and 15 µg/mL in the recovery period, with 45 (33%) in the acute period and 60 (44%) in the recovery period below the limit of measurement (

Abstract Background This study aimed to evaluate the effectiveness of Egami, Kobayashi and Sano scores in predicting intravenous immunoglobulin (IVIG) resistance in infant Kawasaki disease (KD), considering its unique clinical presentation. Methods We retrospectively analysed 143 infants aged

Background: Approximately 10–20 % of individuals develop a recrudescent or persistent fever after intravenous immunoglobulin (IVIG) infusion for the initial treatment of Kawasaki disease. The aim of this study was to evaluate the efficacy and safety of the initial IVIG treatment of Kawasaki disease based on duration of infusion. Methods: This retrospective, single-center study included 53 patients with Kawasaki disease who were initially treated with 2 g/kg of IVIG by means of a single infusion from June 2018 to August 2019. We classified patients into two groups based on the duration of the infusion: the 12-h group and the 24-h group. We compared the treatment response of the primary IVIG and its adverse events using the Mann-Whitney U test and Fisher's exact or Chi-square tests. Results: There were no significant differences in the response to initial IVIG treatment between the two groups. The duration from treatment onset to defervescence was shorter in the 12-h group than the 24-h group (7 h vs. 12 h, respectively, p = 0.07); however, this was not significant. There were no significant between-group differences regarding adverse events. Conclusion: We concluded that the initial 12-h IVIG treatment was comparable to the 24-h treatment in terms of efficacy and safety. This will enable physicians to feel confident about pursuing a shorter course of treatment with similar results as conventional treatment and decide on administering additional therapy to their patients.

Antibodies to Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) have been reported in pooled healthy donor plasma and intravenous immunoglobulin products (IVIG). It is not known whether administration of IVIG increases circulating anti-SARS-CoV-2 antibodies (COVID ab) in IVIG recipients. COVID ab against the receptor binding domain of the spike protein were analyzed using a chemiluminescent microparticle immunoassay in patients with idiopathic inflammatory myopathies (IIM) both receiving and not receiving IVIG (IVIG and non-IVIG group, respectively). No significant differences in COVID ab levels were noted between IVIG and non-IVIG groups (417 [67-1342] AU/mL in IVIG vs 5086 [43-40,442] AU/mL in non-IVIG, p = 0.11). In linear regression models including all post-vaccination patient samples, higher number of vaccine doses was strongly associated with higher COVID ab levels (2.85 [1.21, 4.48] log AU/mL, regression coefficient [Formula: see text] [95% CI], p = 0.001), while use of RTX was associated with lower ab levels (2.73 [- 4.53, - 0.93] log AU/mL, [Formula: see text][95%CI], p = 0.004). In the IVIG group, higher total monthly doses of IVIG were associated with slightly higher COVID ab levels (0.02 [0.002-0.05] log AU/mL, p = 0.04). While patients on IVIG did not have higher COVID ab levels compared to the non-IVIG group, higher monthly doses of IVIG were associated with higher circulating levels of COVID ab in patients receiving IVIG, particularly in patients concomitantly receiving RTX. Our findings suggest that IIM patients, especially those at increased risk of COVID infection and worse COVID outcomes due to RTX therapy may have protective benefits when on concurrent IVIG treatment.

Background: Therapeutic plasma exchange (TPE) is a highly effective rescue treatment for patients with acute exacerbation of neuroimmunological disease that removes circulating autoantibodies and inflammatory components from the bloodstream. The aims of this study are to explore the safety and the effectiveness of TPE in patients with autoimmune neurological disorders. Methods: We retrospectively evaluated the frequency of adverse events (AEs) and the effectiveness of TPE using the modified Ranking Scale (mRS) in patients with acute neurological flares who underwent TPE at the University Hospital of Palermo. Results: Of 59 patients, the majority underwent TPE due to multiple sclerosis (MS) relapse. In 23.7% of cases, TPE was performed before obtaining a definite diagnosis due to the severity of the clinical presentation. After TPE, the mRS score was globally reduced (p < 0.0001), and this effect was marked in patients with MS, Guillain–Barré syndrome, and myasthenia gravis crisis but not in those with paraneoplastic syndromes. Circulating pathogenetic antibodies, younger age, and the early use of TPE were factors strongly associated with TPE effectiveness. The overall safety profile of TPE was satisfactory with an AE frequency of 15%. Conclusions: These results highlight the early use of TPE in patients with circulating pathogenetic antibodies as well as its favorable safety profile.

The use of posttransplant cyclophosphamide has revolutionized the field of haploidentical hematopoietic stem cell transplant. The impact has been especially enhanced in low- and middle-income countries. Unrelated donor pool in developing nations is often limited due to the lack of large unrelated donor registries. Donor-specific antibodies (DSAs) are preformed immunoglobulin G anti-human leukocyte antigen (HLA) antibodies against HLA antigens that are not shared with the donor. We present successful desensitization in a 13-year-old patient with class III β-thalassemia with very high MFI DSAs with flow crossmatch positivity, persisting after pretransplant immunosuppression.

Abstract Background Kawasaki disease (KD) is an acute systemic immune vasculitis affecting multiple organs and systems in children, and is prevalent in children under 5 years of age. Muscular weakness is a rare manifestation of KD, and only 11 pediatric patients with KD combined with muscular weakness have been reported, of which evidence of myositis was found in 2/3 of the patients, and 1/3 could not be explained by myositis, the mechanism of which is still unclear. Cases of KD combined with bladder retention are even more rare, and there has been only 1 case report of KD combined with bladder retention in a child with no previous underlying disease. Case presentation We report a 22-month-old Asian child with incomplete Kawasaki disease (IKD) who initially presented with fever and progressive muscular weakness in the lower extremities, followed by the bladder and bowel retention abnormalities and rapid onset of heart failure, respiratory failure and shock. The child developed coronary artery ectasia (CAA) without the main clinical features of KD such as rash, conjunctival congestion, desquamation of the extremity endings, orofacial changes and enlarged lymph nodes in the neck. Creatine kinase and electromyography were normal. Temperature gradually normalized and muscle strength recovered slightly after intravenous immunoglobulin. The child could be helped to walk after 1 week of aspirin combined with steroid therapy. Conclusions We present the case of a 22-month-old child with IKD. The child began with progressive muscular weakness in the extremities, followed by the bladder and bowel retention abnormalities, and rapidly developed heart failure, respiratory failure, and shock. Despite early failure to detect the disease, the child recovered rapidly and had a favorable prognosis. KD comorbidities with muscular weakness as the main manifestation are uncommon. This is the first case report of IKD combined with both muscular weakness and bladder and bowel retention, which may provide clinicians with diagnostic and therapeutic ideas, as well as a basis for future exploration of the mechanisms of KD combined with muscular weakness or bladder and bowel retention abnormalities.

Objective: To assess the effect of intravenous immunoglobulin (IVIG) therapy on unexplained recurrent spontaneous abortion (URSA). Methods: We retrieved all randomized controlled trials (RCTs) related to the effect of IVIG therapy on URSA in the following databases: PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials before April 30, 2023, according to the PRISMA statement. The therapeutic effect of IVIG was measured by live birth rates. Quality assessment was conducted independently by two reviewers, based on the Newcastle-Ottawa scale. For the meta-analysis, we used odds ratios (random effects model and fixed effects model). The between-study heterogeneity was assessed by the Q test. Publication bias was assessed by funnel plots. Results: A total of 12 studies with 751 participants were included in this metaanalysis. There was no statistical significance [OR = 1.07, 95%CI (0.65, 1.75), P=0.80] between the IVIG group and the non-IVIG group, including low molecular weight heparin (LMWH) plus low-dose aspirin (LDA), intralipid, multivitamins, albumin, and normal saline. A subgroup analysis was conducted according to the different treatment regimens of the non-IVIG group. Compared to the placebo group, including multivitamins, albumin, and saline, the live birth rate of the IVIG group is superior, but there was no statistical significance [OR =1.43, 95%CI (0.99, 2.07), P=0.05]. Another subgroup analysis was performed according to URSA with positive for antiphospholipid antibodies (aPLs). Results showed the live birth rate of IVIG on URSA with positive for aPLs is inferior to that of LMWH plus LDA [OR = 0.25, 95%CI (0.11, 0.55), P=0.0007]. Conclusions: IVIG didn't increase the live birth rate of URSA compared to placebo. Conversely, compared with the IVIG, the LMWH plus LDA treatment schedule can increase the live birth rate of URSA with positive for aPLs. [ABSTRACT FROM AUTHOR]

Coagulation disorders are common in Kawasaki disease (KD). The main objectives of the present study were to probe the associations of coagulation profiles with clinical classification, IVIG responsiveness, coronary artery abnormalities (CAAs) in the acute episode of KD. A total of 313 KD children were recruited and divided into six subgroups, including complete KD (n = 217), incomplete KD (n = 96), IVIG-responsive KD (n = 293), IVIG-nonresponsive KD (n = 20), coronary artery noninvolvement KD (n = 284) and coronary artery involvement KD (n = 29). Blood samples were collected within 24-h pre-IVIG therapy and 48-h post-IVIG therapy. Coagulation profiles, conventional inflammatory mediators and blood cell counts were detected. Echocardiography was performed during the period from 2- to 14-day post-IVIG infusion. In addition, 315 sex- and age-matched healthy children were enrolled as the controls. (1) Before IVIG therapy, coagulation disorders were more prone to appear in KD patients than in healthy controls, and could be overcome by IVIG therapy. FIB and DD significantly increased in the acute phase of KD, whereas reduced to normal levels after IVIG therapy. (2) PT and APTT were significantly longer in patients with complete KD when compared with their incomplete counterparts after IVIG therapy. (3) The larger δDD, δFDP and the smaller δPT, δINR predicted IVIG nonresponsiveness. (4) The higher δDD and δFDP correlated with a higher risk for CAAs (DD: r = −0.72, FDP: r = −0.54). Coagulation disorders are correlated with complete phenotype, IVIG nonresponsiveness and CAA occurrence in the acute episode of KD, and can be rectified by synergistic effects of IVIG and aspirin. [ABSTRACT FROM AUTHOR]

Background: Guillain-Barre' syndrome (GBS) is a polyradiculoneuropathy mediated by the immune system and is the primary reason for acute flaccid paralysis. Intravenous immunoglobulin (IVIg) is a recognized immunotherapeutic drug that can accelerate recovery from GBS. Limited literature exists concerning cerebral infarction complications with IVIg following its use in the treatment of GBS. Case presentation: A patient was diagnosed with the acute inflammatory demyelinating polyradiculoneuropathy subtype of GBS, while another patient was diagnosed with the acute bulbar palsy variant of GBS 2 years prior and experienced a relapse of GBS. Both patients received immunoglobulin therapy, during which multiple acute cerebral infarctions were detected using magnetic resonance imaging. Both patients had a history of coronary artery atherosclerotic heart disease and vertebral artery stenosis, and D-dimer and fibrinogen degradation products were significantly elevated after immunoglobulin therapy. Conclusions: The risk of cerebral infarction associated with IVIg is generally low in patients with different GBS variants. Nevertheless, the occurrence of cerebral infarction associated with IVIg might not be insignificant in older patients with vascular risk factors and should be carefully monitored. [ABSTRACT FROM AUTHOR]

Herpes simplex virus-2 encephalitis (HSV2E) in immunocompetent adults is exceptionally rare, and the subsequent onset of autoimmune encephalitis after HSV2E is even less common. This report presents the inaugural Chinese case of anti-N-methyl-d-aspartate receptor encephalitis (NMDARE) induced by HSV2E, confirmed via metagenomic next-generation sequencing (mNGS). The patient demonstrated a favorable response to intravenous immunoglobulin (IVIG) monotherapy. This case emphasizes the importance of considering autoimmune encephalitis in patients exhibiting new or recurrent neurological symptoms after HSV2E recovery. Comprehensive mNGS and neuronal antibody testing are essential for timely diagnosis. Moreover, IVIG monotherapy can serve as an effective treatment for NMDARE induced by HSV2, providing a viable alternative, particularly when steroid therapy is contraindicated. [ABSTRACT FROM AUTHOR]

Background: Therapeutic plasma exchange (TPE) is a highly effective rescue treatment for patients with acute exacerbation of neuroimmunological disease that removes circulating autoantibodies and inflammatory components from the bloodstream. The aims of this study are to explore the safety and the effectiveness of TPE in patients with autoimmune neurological disorders. Methods: We retrospectively evaluated the frequency of adverse events (AEs) and the effectiveness of TPE using the modified Ranking Scale (mRS) in patients with acute neurological flares who underwent TPE at the University Hospital of Palermo. Results: Of 59 patients, the majority underwent TPE due to multiple sclerosis (MS) relapse. In 23.7% of cases, TPE was performed before obtaining a definite diagnosis due to the severity of the clinical presentation. After TPE, the mRS score was globally reduced (p < 0.0001), and this effect was marked in patients with MS, Guillain–Barré syndrome, and myasthenia gravis crisis but not in those with paraneoplastic syndromes. Circulating pathogenetic antibodies, younger age, and the early use of TPE were factors strongly associated with TPE effectiveness. The overall safety profile of TPE was satisfactory with an AE frequency of 15%. Conclusions: These results highlight the early use of TPE in patients with circulating pathogenetic antibodies as well as its favorable safety profile. [ABSTRACT FROM AUTHOR]

Hepatic arterial infusion chemotherapy in conjunction with the combination therapy of atezolizumab (T) and bevacizumab (A) is widely used in hepatocellular carcinoma. Some adverse events such as hypertension, weakness and elevated transaminase levels occurred during treatment, while there is currently no reported case about thrombocytopenia with concomitant HLA antibody‐positive PTR. We summarize the critical care nursing experience of a patient with PTR because of HLA antibody positivity during hepatic arterial infusion chemotherapy in conjunction with atezolizumab plus bevacizumab (T + A) regimen. This paper explains the nursing measures for patients with severe thrombocytopenia and proposes nursing measures for situations where conventional treatments are ineffective. Key nursing points include the administration of intravenous immunoglobulin (IVIG) and HLA‐compatible platelets, prevention of complications, psychological care, oral care, and skin management. Through systematic treatment and targeted nursing care, the patient's platelet count rebounded after 9 days, leading to a successful recovery and discharge. Subsequent follow‐up assessments revealed the patient's sustained well‐being. Thrombocytopenia is a potential adverse reaction during the treatment of liver cancer. When platelet transfusion is ineffective, vigilance is necessary for the possibility of HLA positivity, and prompt symptomatic management is warranted. [ABSTRACT FROM AUTHOR]

This study aimed to describe the characteristics of multisystemic inflammatory syndrome associated with COVID-19 (MIS-C) in the first three years of the pandemic in children in a pediatric hospital in Peru. We conducted an observational, descriptive study with data from 73 patients and described the clinical and laboratory characteristics, treatment and complications according to the wave of the pandemic and whether they had shock. The median age was 6 years, gastrointestinal and mucocutaneous manifestations were frequent in the three waves. Kawasaki disease-like phenotype was present in 34 (46.6%) patients and 21 (28.8%) patients developed shock. The most commonly used treatment was immunoglobulin (95.9%), followed by acetylsalicylic acid (94.5%) and corticosteroid (86.3%). Five (7%) patients had coronary aneurysm and 17 (23.3%) were admitted to the intensive care unit (ICU). Patients with shock had greater laboratorial alteration and need for mechanical ventilation. In conclusion, MIS-C has decreased in the first three years of the pandemic, possibly due to COVID-19 vaccination in children. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Epidermolysis bullosa acquisita (EBA) is a rare dermatosis of the mucous membrane and/or skin. Employing biologic treatment modalities, specifically rituximab (RTX), have become pivotal measure in treating patients with blistering diseases. This study aims to summarize the current evidence on the safety and efficacy of RTX in EBA. METHODS: An extensive search was performed in MEDLINE/PubMed, Embase, Scopus, and Web of Science databases until the end of August 19th, 2023. Two independent reviewers screened the papers, and collected data. Two hundred thirty-three studies were screened using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. RESULTS: Thirty-one studies were enrolled. The most common reason of RTX administration in patients with EBA was recalcitrant diseases. Clinical response and disease remission was recorded as 92.7 percent (63 patients) and 73.8 percent (45 patients) of the patients, respectively. A relapse rate of 39.5 percent (15 patients) in the mean follow-up of 23.0 months was reported in the studies. Of the patients, 28.2 percent (11 patients) experienced RTX-related side events, mostly mild and transient infusion reactions. CONCLUSION: The results of this systematic review demonstrated that RTX is safe and effective in patients with EBA. This biological treatment modality can be routinely used in managing EBA. [ABSTRACT FROM AUTHOR]

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Background: Kawasaki disease (KD) is an acute systemic immune vasculitis affecting multiple organs and systems in children, and is prevalent in children under 5 years of age. Muscular weakness is a rare manifestation of KD, and only 11 pediatric patients with KD combined with muscular weakness have been reported, of which evidence of myositis was found in 2/3 of the patients, and 1/3 could not be explained by myositis, the mechanism of which is still unclear. Cases of KD combined with bladder retention are even more rare, and there has been only 1 case report of KD combined with bladder retention in a child with no previous underlying disease. Case presentation: We report a 22-month-old Asian child with incomplete Kawasaki disease (IKD) who initially presented with fever and progressive muscular weakness in the lower extremities, followed by the bladder and bowel retention abnormalities and rapid onset of heart failure, respiratory failure and shock. The child developed coronary artery ectasia (CAA) without the main clinical features of KD such as rash, conjunctival congestion, desquamation of the extremity endings, orofacial changes and enlarged lymph nodes in the neck. Creatine kinase and electromyography were normal. Temperature gradually normalized and muscle strength recovered slightly after intravenous immunoglobulin. The child could be helped to walk after 1 week of aspirin combined with steroid therapy. Conclusions: We present the case of a 22-month-old child with IKD. The child began with progressive muscular weakness in the extremities, followed by the bladder and bowel retention abnormalities, and rapidly developed heart failure, respiratory failure, and shock. Despite early failure to detect the disease, the child recovered rapidly and had a favorable prognosis. KD comorbidities with muscular weakness as the main manifestation are uncommon. This is the first case report of IKD combined with both muscular weakness and bladder and bowel retention, which may provide clinicians with diagnostic and therapeutic ideas, as well as a basis for future exploration of the mechanisms of KD combined with muscular weakness or bladder and bowel retention abnormalities. [ABSTRACT FROM AUTHOR]

We analyzed the relationship between recovery from coronary artery aneurysms (CAAs) and concurrent infections in patients with Kawasaki disease (KD). The estimated median time of aneurysm persistence between patients with and without infections was compared using Kaplan-Meier survival analyses. Risk factors associated with persistent CAAs at 2 years were identified using multivariable analyses. Co-infection was confirmed in 20.5% (106/518) of patients diagnosed with KD. No significant differences regarding treatment or coronary artery outcome were identified between patients with and without infections. The estimated median time of aneurysm persistence was higher in the co-infected group (9 vs. 6 months). A maximum Z -score ≥ 4.00 at 1 month had 78% sensitivity and 83% specificity in predicting CAAs without recovery within 1 year of onset, whereas the predictability was higher within 2 years of onset, with a Z -score ≥ 4.88 (sensitivity, 92%; specificity, 91%). Concomitant infections did not affect the response to treatment or coronary artery outcomes in patients with KD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To explore the appropriate time of intravenous immunoglobulin (IVIG) in standard initial treatment of Kawasaki disease in children. Methods: To consult the data of children with Kawasaki disease admitted to Department of Pediatrics, Sanming First Hospital Affiliated to Fujian Medical University from January 2016 to March 2021. A total of 163 eligible cases were retrieved during the study period, of which 53 cases in early group were treated with initial IVIG 1~4 days after onset; initial IVIG treatment time was 5~7 days after onset in medium-term group, with a total of 54 cases; initial IVIG treatment time was 8~10 days after onset in late group, with a total of 56 cases. Immune function, biological markers, echocardiography, initial IVIG non-response, hospitalization days and main clinical manifestations after treatment were compared. Results: After treatment, levels of lymphocyte subsets in three groups were improved, among which the levels of CD4+T, CD4+T/CD8+T and CD19+T were decreased, while levels of CD3+T, CD8+T and NK were increased. Levels of biological markers were lower than those before treatment; there were significant differences in levels of lymphocyte subsets, biological markers, incidence of IVIG inactive Kawasaki disease, incidence of coronary artery lesion and coronary aneurysm among the three groups after treatment (P<0.05). The differences between the early group and the mediumterm group and the late group were statistically significant (P<0.05). There was no significant difference between the medium-term group and the late group( P>0.05); and the early group had the best major clinical manifestations and the shortest hospital stay. Conclusion: In standard initial treatment of Kawasaki disease in children, the use of IVIG within 5 days after onset of immune function recovery is the best, reduce level of inflammation and protein markers is the best, but also can quickly improve clinical symptoms, shorten the length of hospital stay, and has the lowest incidence of IVIG no-response to Kawasaki disease, minimal coronary artery disease and coronary aneurysm complications, may be suitable for use. [ABSTRACT FROM AUTHOR]

Neurodegeneration, known as the progressive loss of neurons in terms of their structure and function, is the principal pathophysiological change found in the majority of brain-related disorders. Ageing has been considered the most well-established risk factor in most common neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease (AD). There is currently no effective treatment or cure for these diseases; the approved therapeutic options to date are only for palliative care. Ageing and neurodegenerative diseases are closely intertwined; reversing the aspects of brain ageing could theoretically mitigate age-related neurodegeneration. Ever since the regenerative properties of young blood on aged tissues came to light, substantial efforts have been focused on identifying and characterizing the circulating factors in the young and old systemic milieu that may attenuate or accentuate brain ageing and neurodegeneration. Later studies discovered the superiority of old plasma dilution in tissue rejuvenation, which is achieved through a molecular reset of the systemic proteome. These findings supported the use of therapeutic blood exchange for the treatment of degenerative diseases in older individuals. The first objective of this article is to explore the rejuvenating properties of blood-based therapies in the ageing brains and their therapeutic effects on AD. Then, we also look into the clinical applications, various limitations, and challenges associated with blood-based therapies for AD patients. [ABSTRACT FROM AUTHOR]

Immunocompromised individuals are at significantly elevated risk for severe courses of coronavirus disease 2019 (COVID‐19). In addition to vaccination, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) neutralizing antibodies (nAbs) have been applied throughout the pandemic, with time of treatment onset and potency against the currently prevailing virus variant identified as relevant factors for medical benefit. Using data from the European Society for Immunodeficiencies (ESID) registry, the present study evaluated COVID‐19 cases in three groups of patients with inborn errors of immunity (IEI; 981 agammaglobulinemia patients on immunoglobulin replacement therapy (IGRT); 8960 non‐agammaglobulinemia patients on IGRT; 14 428 patients without IGRT), and the neutralizing capacity of 1100 immunoglobulin lots against SARS‐CoV‐2 ("Wuhan" and Omicron strains), throughout 3 years. From the first (2020/2021) to the second (2021/2022) cold season, i.e., during the virus drift to the more contagious Omicron variants, an increase in case numbers was recorded that was comparable (~2‐ to 3‐fold) for all three study groups. During the same period, immunoglobulin lots showed a profound nAb increase against the archetypal SARS‐CoV‐2 strain, yet only low levels of Omicron nAbs. Notably, shortly before the third (2022/2023) cold season, Omicron‐neutralizing capacity of released immunoglobulin lots had plateaued at high levels. From the second to the third cold season, COVID‐19 cases dropped markedly. While a ~6‐fold case reduction was recorded for the groups of non‐agammaglobulinemia patients on IGRT and IEI patients not receiving IGRT, the decline was ~30‐fold for the group of agammaglobulinemia patients on IGRT. These findings suggest a substantial COVID‐19‐protective effect of IGRT, at least for distinct groups of antibody‐deficient patients. [ABSTRACT FROM AUTHOR]

Anti‐PP1PK alloimmunization is rare given ubiquitous P1PK expression. Prevention of recurrent miscarriages and hemolytic disease of the fetus and newborn (HDFN) in pregnant individuals with anti‐PP1PK antibodies has relied upon individual reports. Here, we demonstrate the successful management of maternal anti‐PP1PK alloimmunization in a 23‐year‐old, G2P0010, with therapeutic plasma exchange (TPE), intravenous immunoglobulin (IVIG), and monitoring of anti‐PP1Pk titers. Twice‐weekly TPE (1.5 plasma volume [PV], 5% albumin replacement) with weekly titers and IVIG (1 g/kg) was initiated at 9 weeks of gestation (WG). The threshold titer was ≥16. Weekly middle cerebral artery‐peak systolic velocities (MCA‐PSV) for fetal anemia monitoring was initiated at 16 WG. PVs were adjusted throughout pregnancy based on treatment schedule, titers, and available albumin. Antigen‐negative, ABO‐compatible RBCs were obtained through the rare donor program and directed donation. An autologous blood autotransfusion system was reserved for delivery. Titers decreased from 128 to 8 by 10 WG. MCA‐PSV remained stable. At 24 WG, TPE decreased to once weekly. After titers increased to 32, twice‐weekly TPE resumed at 27 WG. Induction of labor was scheduled at 38 WG. Vaginal delivery of a 2950 g neonate (APGAR score: 9, 9) occurred without complication (Cord blood: 1+ IgG DAT; Anti‐PP1Pk eluted). Newborn hemoglobin and bilirubin were unremarkable. Discharge occurred postpartum day 2. Anti‐PP1Pk alloimmunization is rare but associated with recurrent miscarriages and HDFN. With multidisciplinary care, a successful pregnancy is possible with IVIG and TPE adjusted to PV and titers. We also propose a patient registry and comprehensive management plan. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

IntroductionIntravenous immunoglobulin (IVIG) is the only approved treatment for multifocal motor neuropathy (MMN), a rare, chronic, immune-mediated demyelinating neuropathy. There is a significant gap in understanding of the role of serum immunoglobulin G (IgG) levels in the efficacy of IVIG in affected patients. We aimed to characterize the interplay between dose and exposure of IVIG and the effects of patient factors on individual variabilities.MethodsSerum IgG trough concentration data from a phase 3, randomized, double-blind, placebo-controlled, crossover trial of IVIG 10% in 44 patients with MMN (NCT00666263) were analyzed using fit-for-purpose population PK modeling. Patient factors were tested as covariates, and IgG PK profiles following various dosing regimens were simulated.ResultsSerum IgG levels, with significant inter-patient variability, correlated with dose and treatment interruptions at the individual patient level. Simulated data for various dosing regimens (0.4–2 g/kg once every 1–4 weeks [Q1–4W]) revealed that more frequent dosing provided more stable IgG levels than less frequent dosing, and dose splitting over multiple days had no significant effects on PK.DiscussionIn patients with MMN, stable dosing and consistent serum IgG levels are crucial to avoid negative responses owing to treatment interruptions. Dosing intervals more frequent than Q4W may alleviate periodic symptom deterioration. Dose splitting potentially offers flexibility for patients requiring large volumes of IVIG without negatively affecting serum IgG PK, while maintaining treatment efficacy. Variability in serum IgG levels between patients suggests that individualizing IVIG treatment regimens and target IgG levels may play a key role in managing MMN.

Guillain-Barré syndrome represents a heterogeneous group of immune-mediated peripheral neuropathies that are characterized by various clinical manifestations. Reporting this clinical case emphasizes the rarity of Guillain-Barré syndrome, the diagnostic challenges faced by healthcare providers, and the risk of delayed diagnosis for both the mother and fetus. A 34-year-old pregnant woman at 33 weeks of gestation presented to the inpatient ward complaining of paresthesia in the lower and upper limbs, muscle pain, balance disturbances, moderate headache, nausea and vertigo, general weakness, and pronounced fatigue. The patient had experienced an acute viral respiratory infection 4 weeks before presenting to the hospital. The patient was admitted to the intensive care unit with a preliminary diagnosis of acute viral respiratory infection and nasopharyngitis. The patient's condition worsened dynamically, manifesting bulbar syndrome (swallowing problems), paresthesia of the anterior abdominal wall, reduced perception of fetal movements, numbness of the tongue, and low fever (37.2°C). A diagnosis of acute inflammatory demyelinating polyradiculopathy (Guillain-Barré syndrome) was established. Despite treatment, the neurologic symptoms worsened. The paravertebral radicular type pains were difficult to manage with administered analgesic therapy, and there was a progression of the bulbar syndrome. Treatment with intravenous immunoglobulin was initiated. Consequently, it was recommended by the multidisciplinary council to perform an emergency cesarean delivery, in the interest of the mother and fetus. Guillain-Barré syndrome is a rare condition that occurs during pregnancy and requires thorough evaluation, prompt multidisciplinary assessment, and individualized management of delivery to improve maternal and fetal prognosis.