Predicting complications in paediatric ulcerative colitis: A longitudinal multicentre cohort study.

BACKGROUND: To prevent complications of paediatric ulcerative colitis (UC), it is critical to understand their predictors. The Paediatric Inflammatory Bowel Disease Ahead (PIBD Ahead) program identified the relevant outcomes and their potential predictors. However, external validation of these results in larger cohorts is required. AIMS: The aim of this study is to investigate these outcomes and their predictors. METHODS: We included 743 patients aged under 18 years with UC from the multicentre German-Austrian CEDATA-GPGE registry. We performed Cox regressions, Kaplan-Meier estimator, and receiver operating characteristics curve analyses to analyse predictors of poor outcomes. RESULTS: Older age at diagnosis was associated with relapse, hospitalisation, the use of immunomodulators, use of biologics, and therapy escalation. Higher disease activity, as in acute severe colitis in the first 3 months, was significantly associated with further acute severe colitis and the need for biologics. Upper gastrointestinal tract involvement was a risk factor for the need of intravenous corticosteroids and biologics. A faecal calprotectin of >685 µg/g was associated with a higher risk of subsequent acute severe colitis with a sensitivity of 79.0% and a specificity of 59.1%. A lower haematocrit at diagnosis was predictive of the use of biologics. Colectomy was rare. CONCLUSIONS: This study validates predictors of poor outcomes in paediatric patients with UC. Our results might help physicians to anticipate poor outcomes and initiate appropriate treatment strategies at an early stage.

Immunomodulatory effect of bovine lactoferrin during SARS-CoV-2 infection.

Introduction: Lactoferrin (Lf) is an important immunomodulator in infections caused by different agents. During SARS-CoV-2 infection, Lf can hinder or prevent virus access to the intracellular environment. Severe cases of COVID-19 are related to increased production of cytokines, accompanied by a weak type 1 interferon response. Methods: We investigated the influence of bovine Lf (bLf) in the immune response during SARS-CoV-2 infection in vitro and in vivo assays. Results: Our results show a strong binding between bLf and TLR4/NF-κB in silico, as well as an increase in mRNA expression of these genes in peripheral blood mononuclear cells (PBMCs) treated with bLf. Furthermore, the treatment increased TLR4/TLR9 mRNA expression in infected K18-hACE2 mouse blood, indicating an activation of innate response. Our results show that, when bLf was added, a reduction in the NK cell population was found, presenting a similar effect on PD-1 in TCD4+ and TCD8+ cells. In the culture supernatant of PBMCs from healthy participants, bLf decreased IL-6 levels and increased CCL5 in COVID-19 participants. In addition, K18-hACE2 mice infected and treated with bLf presented an increase of serum pro-inflammatory markers (GM-CSF/IL-1ß/IL-2) and upregulated mRNA expression of IL1B and IL6 in the lung tissue. Furthermore, bLf treatment was able to restore FTH1 levels in brain tissue. Discussion: The data indicate that bLf can be part of a therapeutic strategy to promote the immunomodulation effect, leading to homeostasis during COVID-19.

The immunomodulatory effects of vitamins in cancer.

Nutrition may affect animal health due to the strong link between them. Also, diets improve the healing process in various disease states. Cancer is a disease, where the harmful consequences of tumors severely impair the body. The information regarding the evolution of this disease is extrapolated from human to animal because there are few specific studies regarding nutritional needs in animals with cancer. Thus, this paper aims to review the literature regarding the immunomodulatory effects of vitamins in mammal cancer. An adequate understanding of the metabolism and requirements of nutrients for mammals is essential to ensuring their optimal growth, development, and health, regardless of their food sources. According to these: 1) Some species are highly dependent on vitamin D from food, so special attention must be paid to this aspect. Calcitriol/VDR signaling can activate pro-apoptotic proteins and suppress anti-apoptotic ones. 2) Nitric oxide (NO) production is modulated by vitamin E through inhibiting transcription nuclear factor kappa B (NF-κB) activation. 3) Thiamine supplementation could be responsible for the stimulation of tumor cell proliferation, survival, and resistance to chemotherapy. 4) Also, it was found that the treatment with NO-Cbl in dogs is a viable anti-cancer therapy that capitalizes on the tumor-specific properties of the vitamin B12 receptor. Therefore, diets should contain the appropriate class of compounds in adequate proportions. Also, the limitations of this paper are that some vitamins are intensively studied and at the same time regarding others, there is a lack of information, especially in animals. Therefore, some subsections are longer and more heavily debated than others.

Combination of low-dose, long-term immunoglobulin and mirtazapine is effective in progressive multifocal leukoencephalopathy caused by JC virus infection.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is an often fatal disease of the central nervous system caused by opportunistic infection of John Cunningham Polyomavirus (JCV). There's still no antiviral therapeutic strategy which was generally recognized as effective. The prognosis may differ in patients with different pathological mechanisms and treatments. We aim to report the effectiveness of combined treatment of low-dose, long-term immunoglobulin and mirtazapine in a pathologically proved PML case. CASE PRESENTATION: A patient presented with progressive acalculia, right-left confusion and visual neglection was recorded. She received 10-year immunosuppressive therapy for dermatomyositis. White matter lesions located in bilateral parietal lobe and callosum area symmetrically in MR scanning. JC virus analysis and brain biopsy in left parietal lobe were performed. The number of JCV copies was 2595 in CSF and 282,809 in brain specimen. Abundant foamy macrophages and the lymphatic cells were obvious in immunohistochemistry staining. Few SV-40 positive JC infected cell and more CD4 + and CD68 + cells were predominant. Immunosuppressive drugs were terminated after being diagnosed as PML for positive JCV and pathological characteristics. In addition, immunoglobulin (5 g/day) and mirtazapine (45 mg/day) were used. JC virus in CSF decreased to 0 after treatment for 4 months and was still negative in June 2023. The clinical symptoms improved, and white matter lesions recovered significantly. CONCLUSIONS: We demonstrated that the combination treatment of IVIG and mirtazapine was effective in PML. Low-dose, long-term immunoglobulin might regulate the immune status in our case with controlled inflammatory reaction instead of destructive virus spreading. The therapy may be a prospective option for PML.

Toll-like receptors ligand immunomodulators for the treatment congenital diaphragmatic hernia.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a rare disease that affects the development of the diaphragm, leading to abnormal lung development. Unfortunately, there is no established therapy for CDH. Retinoic acid pathways are implicated in the ethology of CDH and macrophages are known to play a role in repairing organ damage. METHODS: We have analyzed the effect of several Toll like receptor (TLR) ligands in the nitrofen-induced CDH model in pregnant rats widely used to study this disease and in the G2-GATA4Cre;Wt1fl/fl CDH genetic mice model. Morphometric and histological studies were carried out. Immune cell infiltration was assayed by immunochemistry and immunofluorescence and retinoic pathway gene expression analyzed in vivo and in vitro in macrophages. RESULTS: We found that administering a single dose of atypical TLR2/4 ligands (CS1 or CS2), 3 days after nitrofen, cured diaphragmatic hernia in 73% of the fetuses and repaired the lesion with complete diaphragm closure being on the other hand nontoxic for the mothers or pups. Moreover, these immunomodulators also improved pulmonary hypoplasia and alveolar maturation and vessel hypertrophy, enhancing pulmonary maturity of fetuses. We also found that CS1 treatment rescued the CDH phenotype in the G2-GATA4Cre;Wt1fl/fl CDH genetic mice model. Only 1 out of 11 mutant embryos showed CDH after CS1 administration, whereas CDH prevalence was 70% in untreated mutant embryos. Mechanistically, CS1 stimulated the infiltration of repairing M2 macrophages (CD206+ and Arg1+) into the damaged diaphragm and reduced T cell infiltration. Additionally, those TLR ligands induced retinol pathway genes, including RBP1, RALDH2, RARα, and RARß, in the affected lungs and the diaphragm and in macrophages in vitro. CONCLUSIONS: Our research has shown that TLR ligand immunomodulators that influence anti-inflammatory macrophage activation can be effective in treating CDH, being nontoxic for the mothers or pups suggesting that those TLR ligands are a promising solution for CDH leading to orphan drug designation for CS1. The immune system of the fetus would be responsible for repairing the damage and closure of the hernia in the diaphragm and enhanced proper lung development after CS1 treatment.

Rituximab induced cerebral venous sinus thrombosis in a patient with anti-N-methyl-D-aspartate receptor-antibody encephalitis: a case report and review of literature.

BACKGROUND: Cerebral venous sinus thrombosis has not been reported in anti-N-methyl-D-aspartate receptor-antibody encephalitis in the absence of an underlying thrombotic state while rituximab induced cerebral venous sinus thrombosis is rarely reported. We report a patient with anti-N-methyl-D-aspartate receptor-antibody encephalitis without a prothrombotic state who developed cerebral venous sinus thrombosis following rituximab treatment. CASE PRESENTATION: A 15-year-old Sri Lankan girl who had been in remission following an episode of anti-N-methyl-D-aspartate receptor-antibody encephalitis 2 years ago, presented with a relapse of anti-N-methyl-D-aspartate receptor-antibody encephalitis characterized by recurrent seizures, mutism, and cognitive abnormalities. Since response was inadequate to first-line immunotherapy, she was administered four doses of rituximab at weekly intervals. Two days after the fourth dose, she developed increasing headaches, and her cranial magnetic resonance venogram confirmed the development of cerebral venous sinus thrombosis. Screening for prothrombotic states were negative. She made an unremarkable recovery following anticoagulation. CONCLUSION: This case highlights the occurrence of the rare but serious complication of cerebral venous sinus thrombosis following rituximab in the context of anti-N-methyl-D-aspartate receptor-antibody encephalitis and informs the clinician to be wary of new onset headache in patients with anti-N-methyl-D-aspartate receptor-antibody encephalitis treated with immunotherapy.

Brain volume loss in relapsing multiple sclerosis: indirect treatment comparisons of available disease-modifying therapies.

BACKGROUND: Brain volume loss (BVL) has been identified as a predictor of disability progression in relapsing multiple sclerosis (RMS). As many available disease-modifying treatments (DMTs) have shown an effect on slowing BVL, this is becoming an emerging clinical endpoint in RMS clinical trials. METHODS: In this study, a systematic literature review was conducted to identify BVL results from randomized controlled trials of DMTs in RMS. Indirect treatment comparisons (ITCs) were conducted to estimate the relative efficacy of DMTs on BVL using two approaches: a model-based meta-analysis (MBMA) with adjustment for measurement timepoint and DMT dosage, and a network meta-analysis (NMA). RESULTS: In the MBMA, DMTs associated with significantly reduced BVL versus placebo at two years included fingolimod (mean difference [MD] = 0.25; 95% confidence interval [CI] = 0.15 - 0.36), ozanimod (MD = 0.26; 95% CI = 0.12 - 0.41), teriflunomide (MD = 0.38; 95% CI = 0.20 - 0.55), alemtuzumab (MD = 0.38; 95% CI = 0.10 - 0.67) and ponesimod (MD = 0.71; 95% CI = 0.48 - 0.95), whereas interferons and natalizumab performed the most poorly. The results of NMA analysis were generally comparable with those of the MBMA. CONCLUSIONS: Limitations of these analyses included the potential for confounding due to pseudoatrophy, and a lack of long-term clinical data for BVL. Our findings suggest that important differences in BVL may exist between DMTs. Continued investigation of BVL in studies of RMS is important to complement traditional disability endpoints, and to foster a better understanding of the mechanisms by which DMTs can slow BVL.

Steroids and Immunomodulatory Therapies for Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) is characterized by a dysregulated immune response to infection or injury. This framework has driven long-standing interest in immunomodulatory therapies as treatments for ARDS. In this narrative review, we first define what constitutes a dysregulated immune response in ARDS. In this context, we describe the rationale and available evidence for immunomodulatory therapies studied in randomized controlled trials of ARDS patients to date. Finally, we address factors that have contributed to the failure to develop therapies in the past and highlight current and future developments designed to address them.

Efficacy of azithromycin combined with intravenous immunoglobulin in the treatment of refractory mycoplasma pneumoniae pneumonia in children: a meta-analysis.

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.

Small molecule innate immune modulators in cancer therapy.

Immunotherapy has proved to be a breakthrough in cancer treatment. So far, a bulk of the approved/late-stage cancer immunotherapy are antibody-based. Although these antibody-based drugs have demonstrated great promise, a majority of them are limited due to their access to extracellular targets, lack of oral bioavailability, tumor microenvironment penetration, induction of antibody dependent cytotoxicity etc. In recent times, there has been an increased research focus on the development of small molecule immunomodulators since they have the potential to overcome the aforementioned limitations posed by antibodies. Furthermore, while most biologics based therapeutics that are in clinical use are limited to modulating the adaptive immune system, very few clinically approved therapeutic modalities exist that modulate the innate immune system. The innate immune system, which is the body's first line of defense, has the ability to turn cold tumors hot and synergize strongly with existing adaptive immune modulators. In preclinical studies, small molecule innate immune modulators have demonstrated synergistic efficacy as combination modalities with current standard-of-care immune checkpoint antibodies. In this review, we highlight the recent advances made by small molecule innate immunomodulators in cancer immunotherapy.

Anti-CD20 Therapies in Drug-Naive Patients With Primary Progressive Multiple Sclerosis: A Multicenter Real-Life Study.

BACKGROUND AND OBJECTIVES: Although rituximab failed to demonstrate a significant effect on disability progression in primary progressive multiple sclerosis (PPMS), ocrelizumab succeeded. Our main objective was to analyze confirmed disability progression (CDP) in a cohort of patients with PPMS treated with anti-CD20 therapies compared with a weighted untreated control cohort. METHODS: This was a retrospective study using data from the French MS registry (Observatoire Français de la Sclérose En Plaques). We included patients with PPMS treated or never treated with anti-CD20 therapies from 2016 to 2021, with an Expanded Disability Status Scale score of ≤6.5 at baseline. The primary outcome was time to first CDP. The secondary outcomes were time to first relapse, MRI activity at 2 years, identification of risk factors associated with CDP, and serious infection incidence rates (IIRs). Each outcome was studied using an inverse probability of treatment weighting method. The outcomes were modeled using a weighted proportional Cox model for the time-to-event outcomes and by a logistic regression regarding the MRI activity. RESULTS: A total of 1,184 patients (426 treated and 758 untreated) fulfilled the inclusion criteria. Median age (Q1-Q3) was 56 years (49.3-63.8), and 52.7% were female. Among treated patients, 295 received rituximab, whereas 131 received ocrelizumab. At baseline, anti-CD20-treated patients were younger (median 51.9 vs 58.6 years, Cohen d = 0.683) and had more active disease (54.5 vs 27.8%, Cohen d = 0.562). 91.6% were drug-naive at inclusion. In time to first CDP analysis, no statistical significance was observed (hazard ratio [HR], 1.13; 95% CI 0.93-1.36, p = 0.2113). In time to first relapse analysis, a nonsignificant trend toward fewer patients relapsing in the treated group was observed (HR 0.83; 95% CI 0.48-1.28, p = 0.0809). For MRI activity, no significant difference was found between the 2 groups. Risk factors associated with CDP in the treated group were male sex and MS duration. IIR was 6.67 (95% CI 3.12-14.25) per 100 person-years in the treated group vs 2.67 (95% CI 0.80-8.86) in the untreated group. DISCUSSION: Time to first CDP was not different between anti-CD20 treated and untreated patients with PPMS. Although our study is retrospective and mainly included patients treated by rituximab, our results indicate that there should be a constant evaluation of all available data to ascertain the best risk/benefit ratio for patients with PPMS. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that anti-CD20 therapy of previously untreated patients with PPMS was not superior to no therapy in delaying time to first CDP.

Neonatal pemphigus vulgaris.

A neonate presented to a tertiary clinic with blisters and erosions over his trunk and extremities. The mother had multiple erosions with crusts affecting the scalp, oral cavity and trunk present since the first trimester and worse since delivery. Skin biopsy for histopathology and direct immunofluorescence confirmed pemphigus vulgaris (PV) in the mother. Indirect immunofluorescence assays for serum antibodies against desmogleins 1 and 3 were positive in both mother and baby confirming a diagnosis of neonatal PV. The baby's lesions healed spontaneously within 2 weeks, and the mother was clear at 2 months following treatment with rituximab.

Frequency of pharmacogenomic variants affecting safety and efficacy of immunomodulators and biologics in a South Asian population from Sri Lanka.

BACKGROUND: Immunomodulators are important for management of autoimmune diseases and hematological malignancies. Significant inter-individual variation in drug response/reactions exists due to genetic polymorphisms. We describe frequency of identified genetic polymorphisms among Sri Lankans. METHODS: Sri Lankan data were obtained from an anonymized database of 670 participants. Data on variants and global distribution of Minor Allele frequency (MAF) of other populations (South Asian, Ashkenazi-Jewish, East-Asian, European-Finnish, European-non-Finnish, Latino-American, African/African-American) were obtained from pharmGKB online database. RESULTS: SLC19A1 (rs1051266) variant had a MAF (95% CI) of 63.3% (60.7-65.9). Other common variants included FCGR3A (rs396991), MTHFR (rs1801133), ITPA (rs1127354), CYP2C9*3 (rs1057910) and NUD15*3 (rs116855232), with MAFs of 35.3% (32.7-37.9), 12.2% (10.4-13.9), 10.9% (9.2-12.6), 9.8% (8.2-11.4), 8.3% (6.8-9.8) respectively. Less commonly present variants included CYP2C9*2 (rs1799853) (2.5%[1.7-3.4]), TPMT*3C (rs1142345) (1.9%[1.1-2.6]), TPMT*3B (rs1800460) (0.2%[0-0.5]), CYP3A5*6 (rs10264272) (0.2%[0-0.4]) and CYP3A4*18 (rs28371759) (0.1%[0-0.2]). The SLC19A1 (rs1051266), NUD15*3 (rs116855232), CYP2C9*3 (rs1057910), FCGR3A (rs396991), and ITPA (rs1127354) showed significantly higher frequencies in Sri Lankans compared to many other populations, exceptions include FCGR3A in Ashkenazi-Jewish and ITPA in East-Asians. Conversely, MTHFR (rs1801133), TPMT*3B (rs1800460), and CYP2C9*2 (rs1799853) were significantly less prevalent among Sri Lankans than in  many other populations. Sri Lankans exhibited lower prevalence of TPMT*3C (rs1142345) compared to European-non-Finnish, Latino-Americans, and African/African-Americans; CYP3A4*18 (rs28371759) compared to East-Asians; and CYP3A5*6 (rs10264272) compared to African/African-Americans and Latino-Americans. CONCLUSION: Sri Lankans exhibit higher frequencies in variants reducing methotrexate efficacy (SLC19A1), increasing azathioprine myelotoxicity (NUDT15), and lower frequencies in variants linked to increased azathioprine toxicity (TPMT*3B, TPMT*3C), reduced tacrolimus efficacy (CYP3A4*18), and methotrexate toxicity risk (MTHFR). Beneficial variants enhancing rituximab efficacy (FCGR3A) are more prevalent, while those reducing tacrolimus dosage (CYP3A5*6) are less common. This highlights need for targeted medication strategies to improve treatment outcomes.

Immunomodulatory metal-based biomaterials for cancer immunotherapy.

Cancer immunotherapy, as an emerging cancer treatment approach, harnesses the patient's own immune system to effectively prevent tumor recurrence or metastasis. However, its clinical application has been significantly hindered by relatively low immune response rates. In recent years, metal-based biomaterials have been extensively studied as effective immunomodulators and potential tools for enhancing anti-tumor immune responses, enabling the reversal of immune suppression without inducing toxic side effects. This review introduces the classification of bioactive metal elements and summarizes their immune regulatory mechanisms. In addition, we discuss the immunomodulatory roles of biomaterials constructed from various metals, including aluminum, manganese, gold, calcium, zinc, iron, magnesium, and copper. More importantly, a systematic overview of their applications in enhancing immunotherapy is provided. Finally, the prospects and challenges of metal-based biomaterials with immunomodulatory functions in cancer immunotherapy are outlined.

Evaluating the performance of egami, kobayashi and sano scores in predicting IVIG resistance in infant kawasaki disease.

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 < 12 months and diagnosed with KD at a single centre from 2019 to 2023. Patients were divided into IVIG-resistant and IVIG-responsive groups. Demographic, clinical and laboratory data were compared between the groups. The diagnostic performance of Egami, Kobayashi and Sano scores in predicting IVIG resistance was evaluated using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the receiver operating characteristic curve (AUC). Additionally, we developed a new scoring system based on significant predictors identified in our cohort. RESULTS: Among 143 infants, 45 (31.5%) showed IVIG resistance. The IVIG-resistant group had a significantly higher rate of coronary artery lesions (15.6% vs. 5.1%, p = 0.036). Incomplete KD was observed in 61.5% of cases. Egami, Kobayashi and Sano scores exhibited low sensitivity (35.6%, 55.6% and 20%, respectively) and moderate specificity (77.6%, 63.3% and 95.9%, respectively) in predicting IVIG resistance. The AUC ranged from 0.583 to 0.674, indicating poor to fair discriminative ability. Our newly developed scoring system, based on total bilirubin and albumin levels, showed similar performance (AUC 0.633) to existing scores. CONCLUSIONS: Existing Japanese risk scoring systems and our newly developed score showed limited effectiveness in predicting IVIG resistance in infant KD. The high proportion of incomplete presentation and IVIG resistance in infants highlights the need for age-specific risk assessment and management. Further research is necessary to develop more sophisticated, dedicated prediction model for IVIG resistance in infants with KD.

S3 guideline: Diagnosis and treatment of epidermal necrolysis (Stevens-Johnson syndrome and toxic epidermal necrolysis) - Part 1: Diagnosis, initial management, and immunomodulating systemic therapy.

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are rare, predominantly drug-induced, acute, life-threatening diseases of skin and mucosae. SJS and TEN are nowadays considered variants of one disease entity with varying degrees of severity called epidermal necrolysis (EN). EN is associated with high morbidity and mortality and constitutes a major disease burden for affected patients. The guideline "Diagnosis and treatment of epidermal necrolysis (Stevens-Johnson syndrome and toxic epidermal necrolysis)" was developed under systematic consideration of existing scientific literature and in a formal consensus process according to regulations issued by the Association of Scientific Medical Societies in Germany (AWMF) to establish an evidence-based framework to support clinical decision-making. The interdisciplinary guideline commission consisted of representatives from various specialist societies and patient representatives. The guideline is aimed at specialists in the fields of dermatology, ophthalmology, plastic surgery, intensive care, and pediatrics in hospitals and offices, as well as other medical speciallved in the diagnosis and treatment of EN. The guideline is also aimed at patients, their relatives, insurance funds, and policymakers. This first part focuses on the diagnostic aspects, the initial management as well as the immunomodulating systemic therapy.

Advances in macrophage-derived exosomes as immunomodulators in disease progression and therapy.

Most somatic cells secrete vesicles called exosomes, which contain a variety of biomolecules. Recent research indicates that macrophage-derived exosomes are strongly correlated with tumors, infectious diseases, chronic inflammation, and tissue fibrosis. Therefore, the purpose of this review is to delve into the mechanisms of pathological states and how macrophage-derived exosomes react to them. We also discuss the biological effects of exosomes and how they affect disease. In addition, we have examined the possible uses of exosomes in illness treatment, highlighting both the benefits and drawbacks of these applications.

Assessing hepatitis B virus serologies when transitioning patients from intravenous immune globulin therapy to rituximab for the treatment of autoimmune neuromuscular diseases.

INTRODUCTION/AIMS: Intravenous immune globulin (IVIG) has been used as early treatment for autoimmune neuromuscular diseases, but due to cost and frequency, may be switched to rituximab. Rituximab and other B-cell-depleting medications require screening of hepatitis B virus (HBV) serologies given the risk of HBV reactivation (HBVr). We aimed to describe the incidence and characteristics of passively transferred antiviral serologies from IVIG and how to differentiate between passive antibody transfer and resolved HBV infection. METHODS: This was a single-center descriptive study of neurology patients prescribed rituximab and IVIG. Retrospective medical record reviews were performed and patient-specific variables were collected. RESULTS: Twelve patients had reactive anti-HBc results after starting IVIG, but only 9 were confirmed to have reactive anti-HBc from passive transfer. Whether reactive anti-HBc in the remaining three patients was from passive IVIG transfer could not be confirmed. Five patients with reactive anti-HBc results during rituximab screening did not have pre-IVIG anti-HBc results for comparison and were started on antiviral prophylaxis. Reactive anti-HBc serologies changed to nonreactive after IVIG discontinuation 44-321 days after the last IVIG infusion. DISCUSSION: This study confirms IVIG can passively transfer anti-HBc serologies in a neurologic cohort. Ideally, HBV serologies would be checked before starting IVIG to help later determine if passive transfer occurred. With the increasing use of B-cell-depleting medications for neuromuscular conditions, it is important for providers to be knowledgeable on the interpretation of HBV serologies for patients on IVIG and to ensure implementation of an HBVr prophylaxis management strategy for patients when appropriate.

The efficacy of rituximab in the treatment of IgA vasculitis nephritis.

The utility of Rituximab (RTX) for IgA vasculitis nephritis (IgAVN) is not well established. Up to now, we analysed the largest samples of IgAVN patients treated by RTX with a total of 41 retrieved subjects up to December 29, 2023 in the present systematic review. We assessed the clinical profiles, efficacy, and safety of RTX treatments. The present review showed that the renal function tended to be stabilized (P = 1.000) and urinalysis tended to normalize after RTX treatment with no serious adverse events reported. Moreover, 40% (16/40) of patients was freed use of glucocorticoid after RTX administration (P < 0.001). The remission rate was 92.7% (38/41) and complete remission rate was 46.3% (19/41) in IgAVN patients. Interestingly, 76.9% (10/13) of IgAVN child patients achieved complete remission when compared with 32.1% (9/28) of adult patients (P = 0.017). In summary, our results support the benefit of RTX therapy in IgAVN patients, especially children subjects.

Kawasaki Disease Presenting with Fever and Jaundice: Case Report.

Kawasaki disease (KD), which is also known as cutaneous mucosal lymph node syndrome, is an acute, self-limiting, necrotizing vasculitis with unclear cause that primarily affects small- and medium-sized blood vessels and most commonly affects children aged 6 months to 5 years. Currently, diagnosis is based primarily on typical clinical symptoms. Approximately 15%-20% of patients are highly suspected of having KD; however, they do not match the diagnostic criteria for typical KD, which is referred to as incomplete Kawasaki disease (IKD), and this has become a major challenge in the diagnosis and treatment of KD. We describe a case of a 7-year-old boy who had a fever and jaundice as his initial symptoms. After a series of clinical laboratory and imaging examinations and marked improvement of symptoms after treatment with intravenous immunoglobulin (IVIG), IKD was considered as the diagnosis. When children present with jaundice and fever, physicians should consider KD as a possible diagnosis to ensure early detection and treatment of the disease.