Predictors of Seizure Recurrence in Women With Idiopathic Generalized Epilepsy Who Switch From Valproate to Another Medication.

BACKGROUND AND OBJECTIVES: To investigate the predictors of seizure recurrence in women of childbearing age with idiopathic generalized epilepsy (IGE) who switched from valproate (VPA) to alternative antiseizure medications (ASMs) and compare the effectiveness of levetiracetam (LEV) and lamotrigine (LTG) as VPA alternatives after switch. METHODS: This multicenter retrospective study included women of childbearing age diagnosed with IGE from 16 epilepsy centers. Study outcomes included worsening or recurrence of generalized tonic-clonic seizure (GTCS) at 12 months and 24 months after the switch from VPA to an alternative ASM. The comparative effectiveness of LEV and LTG as alternative ASM following VPA discontinuation was assessed through inverse probability treatment-weighted (IPTW) Cox regression analysis. RESULTS: We included 426 women with IGE, with a median (interquartile range) age at VPA switch of 24 (19-30) years and a median VPA dosage of 750 (500-1,000) mg/d. The most common reason for VPA switch was teratogenicity concern in 249 women (58.6%), and the most common ASM used in place of VPA was LEV in 197 (46.2%) cases, followed by LTG in 140 (32.9%). GTCS worsening/recurrence occurred in 105 (24.6%) and 139 (32.6%) women at 12 and 24 months, respectively. Catamenial worsening of seizures, higher VPA dosage during switch, multiple seizure types, and shorter duration of GTCS freedom before switch were independent predictors of GTCS recurrence or worsening at 12 months according to mixed multivariable logistic regression analysis. After internal-external validation through 16 independent cohorts, the model showed an area under the curve of 0.71 (95% CI 0.64-0.77). In the subgroup of 337 women who switched to LEV or LTG, IPTW Cox regression analysis showed that LEV was associated with a reduced risk of GTCS worsening or recurrence compared with LTG (adjusted hazard ratio 0.59, 95% CI 0.40-0.87, p = 0.008) during the 24-month follow-up. DISCUSSION: Our findings can have practical implications for optimizing counselling and treatment choices in women of childbearing age with IGE and may help clinicians in making informed treatment decisions in this special population of patients. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for women with IGE switching from VPA, LEV was associated with a reduced risk of GTCS worsening or recurrence compared with LTG.

Antiseizure medication withdrawal in adult patients with idiopathic generalized epilepsy: Performance of two seizure recurrence prediction models.

PURPOSE: Currently, there is a limited availability of tools to predict seizure recurrence after discontinuation of antiseizure medications (ASMs). This study aimed to establish the seizure recurrence rate following ASM cessation in adult patients with idiopathic generalized epilepsy (IGE) and to assess the predictive performance of the Lamberink and the Stevelink prediction models using real-world data. METHODS: Retrospective longitudinal study in IGE patients who underwent ASM withdrawal in a tertiary epilepsy clinic since June 2011, with the latest follow up in January 2024. The minimum follow-up period was 12 months. Clinical and demographic variables were collected, and the seizure recurrence prediction models proposed by Lamberink and Stevelink were applied and evaluated. RESULTS: Forty-seven patients (mean age 33.15 ± 8 [20-55] years; 72.35 % women) were included. During the follow-up period, seizures recurred in 25 patients (53.2 %). Median time to recurrence was 8 months [IQR 3-13.5 months], and 17 patients (68 %) relapsed within the first year. None of the relapsing patients developed drug-resistant epilepsy. The only significant risk factor associated with recurrence was a seizure-free period of less than 2 years before discontinuing medication (91.7 % vs 40 %, p =.005). The Stevelink prediction model at both 2 (p =.015) and 5 years (p =.020) achieved statistical significance, with an AUC of 0.72 (95 % CI 0.56-0.88), while the Lamberink model showed inadequate prognostic capability. CONCLUSION: In our real-world cohort, a seizure-free period of at least 2 years was the only factor significantly associated with epilepsy remission after ASM withdrawal. Larger studies are needed to accurately predict seizure recurrence in IGE patients.

A Supramolecular Assembly of EGCG for Long-Term Treatment of Allergic Rhinitis.

Allergic rhinitis (AR) is a type-I hypersensitivity disease mediated by immunoglobulin E (IgE). Although antihistamines, glucocorticoids, leukotriene receptor antagonists, and other drugs are widely used to treat AR, the various adverse side effects of long-term use of these drugs should not be ignored. Therefore, more effective and safe natural alternative strategies are urgently needed. To this end, this study designed a nanosupramolecular delivery system composed of ß-cyclodextrin supramolecular polymer (PCD), thiolated chitosan (TCS), and natural polyphenol epigallocatechin gallate (EGCG) for intranasal topical continuous treatment of AR. The TCS/PCD@EGCG nanocarriers exhibited an excellent performance in terms of retention and permeability in the nasal mucosa and released the vast majority of EGCG responsively in the nasal microenvironment, thus resulting in the significantly high antibacterial and antioxidant capacities. According to the in vitro model, compared with free EGCG, TCS/PCD@EGCG inhibited mast cell activity and abnormal histamine secretion in a more long-term and sustained manner. According to the in vivo model, whether in the presence of continuous or intermittent administration, TCS/PCD@EGCG substantially inhibited the secretion of allergenic factors and inflammatory factors, mitigated the pathological changes of nasal mucosa, alleviated the symptoms of rhinitis in mice, and produced a satisfactory therapeutic effect on AR. In particular, the therapeutic effect of TCS/PCD@EGCG systems were even superior to that of budesonide during intermittent treatment. Therefore, the TCS/PCD@EGCG nanocarrier is a potential long-lasting antiallergic medicine for the treatment of AR.

Focal electroclinical features in generalized tonic-clonic seizures: Decision flowchart for a diagnostic challenge.

OBJECTIVE: Bilateral tonic-clonic seizures with focal semiology or focal interictal electroencephalography (EEG) can occur in both focal and generalized epilepsy types, leading to diagnostic errors and inappropriate therapy. We investigated the prevalence and prognostic values of focal features in patients with idiopathic generalized epilepsy (IGE), and we propose a decision flowchart to distinguish between focal and generalized epilepsy in patients with bilateral tonic-clonic seizures and focal EEG or semiology. METHODS: We retrospectively analyzed video-EEG recordings of 101 bilateral tonic-clonic seizures from 60 patients (18 with IGE, 42 with focal epilepsy). Diagnosis and therapeutic response were extracted after ≥1-year follow-up. The decision flowchart was based on previous observations and assessed concordance between interictal and ictal EEG. RESULTS: Focal semiology in IGE was observed in 75% of seizures and 77.8% of patients, most often corresponding to forced head version (66.7%). In patients with multiple seizures, direction of head version was consistent across seizures. Focal interictal epileptiform discharges (IEDs) were observed in 61.1% of patients with IGE, whereas focal ictal EEG onset only occurred in 13% of seizures and 16.7% of patients. However, later during the seizures, a reproducible pattern of 7-Hz lateralized ictal rhythm was observed in 56% of seizures, associated with contralateral head version. We did not find correlation between presence of focal features and therapeutic response in IGE patients. Our decision flowchart distinguished between focal and generalized epilepsy in patients with bilateral tonic-clonic seizures and focal features with an accuracy of 96.6%. SIGNIFICANCE: Focal semiology associated with bilateral tonic-clonic seizures and focal IEDs are common features in patients with IGE, but focal ictal EEG onset is rare. None of these focal findings appears to influence therapeutic response. By assessing the concordance between interictal and ictal EEG findings, one can accurately distinguish between focal and generalized epilepsies.

Topiramate ban in women of childbearing potential with idiopathic generalized epilepsy: Does effectiveness offset the teratogenic risks?

Regulatory agencies have recently discouraged the prescription of topiramate (TPM) to women of childbearing potential with epilepsy due to growing evidence of the teratogenic and neurodevelopmental risks associated with its use during pregnancy. It remains, however, unclear whether the use of TPM in this population can be supported to some extent by its high effectiveness. In this multicenter, retrospective, cohort study performed at 22 epilepsy centers, we investigated the comparative effectiveness of TPM and levetiracetam (LEV) given as first-line antiseizure medication in a cohort of women of childbearing potential with idiopathic generalized epilepsy (IGE). A total of 336 participants were included, of whom 24 (7.1%) received TPM and 312 (92.9%) LEV. Women treated with TPM had significantly higher risks of treatment failure and treatment withdrawal and were less likely to achieve seizure freedom at 12 months compared to women treated with LEV. In conclusion, this study highlighted a low tendency among clinicians to use TPM in women of childbearing potential with IGE, anticipating the recently released restrictions on its use. Furthermore, the available data on effectiveness do not appear to support the use of TPM in this population.

The Effect of Immunoglobulin G on the Humoral Immunity in Patients with Tuberculosis/HIV Coinfection.

Previously, an increase in clinical effectiveness of the antituberculosis treatment (ATT) and antiretroviral therapy (ART) in case of additional immunoglobulin G (IgG) administration in patients with multidrug-resistant tuberculosis (MDR-TB)/HIV coinfection was reported. The aim of this study was to investigate the impact of IgG administration in addition to the standard second-line ATT and ART on the humoral immunity status in patients with MDR-TB/HIV coinfection immune deficiency. The study involved 52 patients living with HIV with MDR-TB coinfection and CD4+ lymphocyte cell count below 50 cells/µCL. Patients in the control group and intervention group received the second-line ATT and ART; in addition, patients in the intervention group received IgG intravenously. The humoral immunity status was evaluated by measurement of IgA, IgE, IgG, and IgM in plasma. The standard ATT and ART resulted in a two-step change in humoral immunity: IgM, IgG, IgA, and IgE levels gradually increased to a maximal level at the 5-month mark and started to gradually decrease after the 8-month mark. Addition of IgG to the standard therapy resulted in a steeper decrease in the immunoglobulin level in serum, especially IgG, compared with standard therapy alone, allowing for an earlier initiation of ART in patients in the intervention group.

Screening of Prospective Antiallergic Compound as FcεRI Inhibitors and Its Antiallergic Efficacy Through Immunoinformatics Approaches.

The occurrence of allergy, a type I hypersensitivity reaction, is rising exponentially all over the world. Sometimes, allergy proves to be fatal for atopic patients, due to the occurrence of anaphylaxis. This study is aimed to find an anti-allergic agent that can inhibit the binding of IgE to Human High Affinity IgE Receptor (FCεRI), thereby preventing the degranulation of mast cells. A considerable number of potential anti-allergic compounds were assessed for their inhibitory strength through ADMET studies. AUTODOCK was used for estimating the binding energy between anti-allergic compounds and FCεRI, along with the interacting amino acids. The docked pose showing favorable binding energy was subjected to molecular dynamics simulation study. Marrubiin, a diterpenoid lactone from Lamiaceae, and epicatechin-3-gallate appears to be effective in blocking the Human High Affinity IgE Receptor (FCεRI). This in-silico study proposes the use of marrubiin and epicatechin-3-gallate, in the downregulation of allergic responses. Due to the better inhibition constant, future direction of this study is to analyze the safety and efficacy of marrubiin in anti-allergic activities through in-vivo clinical human trials.

Epilepsy with generalized tonic-clonic seizures alone: Electroclinical features and prognostic patterns.

OBJECTIVE: Epilepsy with generalized tonic-clonic seizures alone (GTCA) is a common but poorly characterized idiopathic generalized epilepsy (IGE) syndrome. Hence, we investigated electroclinical features, seizure outcome, and antiseizure medication (ASM) withdrawal in a large cohort of GTCA patients. METHODS: In this multicenter retrospective study, GTCA patients defined according to the diagnostic criteria of the International League Against Epilepsy (2022) were included. We investigated prognostic patterns, drug resistance at the last visit, and ASM withdrawal, along with their prognostic factors. RESULTS: We included 247 patients with a median (interquartile range [IQR]) age at onset of 17 years (13-22) and a median follow-up duration of 10 years (IQR = 5-20). Drug resistance at the last visit was observed in 40 (16.3%) patients, whereas the median latency to achieve 2-year remission was 24 months (IQR = 24-46.5) with a median number of 1 (IQR = 1-2) ASM. During the long-term follow-up (i.e., 202 patients followed ≥5-years after the first ASM trial), 69 (34.3%) patients displayed an early remission pattern and 36 (17.9%) patients displayed a late remission pattern, whereas 16 (8%) and 73 (36.3%) individuals had no-remission and relapsing-remitting patterns, respectively. Catamenial seizures and morning predominance of generalized tonic-clonic seizures (GTCS) independently predicted drug resistance at the last visit according to multivariable logistic regression. Treatment withdrawal was attempted in 63 (25.5%) patients, with 59 (93.7%) of them having at least a 12-month follow-up after ASM discontinuation. At the last visit, 49 (83%) of those patients had experienced GTCS recurrence. A longer duration of seizure freedom was the only factor predicting a higher chance of successful ASM withdrawal according to multivariable Cox regression. SIGNIFICANCE: GTCA could be considered a relatively easily manageable IGE syndrome, with a low rate of drug resistance and a high prevalence of early response to treatment. Nevertheless, a considerable proportion of patients experience relapsing patterns of seizure control, highlighting the need for appropriate counseling and lifestyle recommendations.

Exploration of efficacy and mechanism of 0.05% cyclosporine eye drops (II) monotherapy in allergic conjunctivitis-associated dry eye.

PURPOSE: To explore the efficacy and relevant mechanism of 0.05% cyclosporine A (CsA) eye drops (II) monotherapy in patients with allergic conjunctivitis-associated dry eye (ACDE). METHODS: Prospective, randomized, controlled study. Fifty-three patients with mild-to-moderate ACDE were randomly assigned to two groups. The CsA group received 0.05% CsA eye drops (II) monotherapy four times daily. The control group received 0.1% olopatadine twice daily combined with 0.1% preservative-free artificial tears four times daily. Clinical symptoms and signs, tear total IgE, and lymphotoxin-α (LT-α) concentrations were assessed at pre- and post-treatment days 7, 30, and 60. And we further measured six tear cytokines levels using a microsphere-based immunoassay. RESULTS: The CsA group showed significant improvement in symptoms (Ocular Surface Disease Index and itching scores) and signs (conjunctival hyperaemia, conjunctival oedema, conjunctival papillae, tear break-up time (TBUT), corneal fluorescein staining, and goblet cell density) at each follow-up period compared to pre-treatment (all P < 0.050). And its improvement in itching scores (P7th < 0.001, P30th = 0.039, and P60th = 0.031) and TBUT (P7th = 0.009, P30th = 0.003, and P60th = 0.005) was more significant than the control group at all follow-up periods. The tear total IgE, interleukin (IL)-5, IL-6, periostin, eotaxin-3, and MMP-9 levels significantly decreased in the CsA group at day 60 after treatment (all P < 0.050). And the changed values in tear total IgE were positively correlated with the change in itching scores. CONCLUSIONS: 0.05% CsA eye drops (II) monotherapy can rapidly improve the symptoms and signs, especially in ocular itching and TBUT, in patients with ACDE. And its efficacy is superior to 0.1% olopatadine combined with artificial tears. Moreover, CsA downregulates the expression levels of tear inflammatory cytokines, including tear total IgE, IL-5, IL-6, periostin, eotaxin-3, and MMP-9. Among that, the reduction in tear total IgE levels may reflect the improvement of ocular itching.

Feast for thought: A comprehensive review of food allergy 2021-2023.

A review of the latest publications in food allergy over the past couple of years confirmed that food allergy is a major public health concern, affecting about 8% of children and 10% of adults in developed countries. The prevalence of food allergy varies around the world, with the increase being driven mainly by environmental factors, possibly together with genetic susceptibility to environmental changes. A precise diagnosis of food allergy is extremely important. Both new tests (eg, the basophil activation test) and improved optimization of information provided by existing tests (eg, the skin prick test and measurement of specific IgE level) can contribute to improving the accuracy and patients' comfort of food allergy diagnosis. Understanding the underlying immune mechanisms is fundamental to designing allergen-specific treatments that can be safe and effective in the long term. New discoveries of the immune response to food allergens, including T-cell and B-cell responses, have emerged. Novel therapeutic approaches are being trialed at various stages of development as attempts to allow for more active intervention to treat food allergy. Prevention is key to reducing the increase in prevalence. Early introduction of allergenic foods seems to be the most effective intervention, but others are being studied, and will, it is hoped, lead to modification of the epidemiologic trajectory of food allergy over time.

Levetiracetam vs Lamotrigine as First-Line Antiseizure Medication in Female Patients With Idiopathic Generalized Epilepsy.

Importance: After the recent limitations to prescribing valproate, many studies have highlighted the challenging management of female patients of reproductive age with idiopathic generalized epilepsy (IGE). However, no study, to the authors' knowledge, has addressed the comparative effectiveness of alternative antiseizure medications (ASMs) in these patients. Objective: To compare the effectiveness and safety of levetiracetam and lamotrigine as initial monotherapy in female patients of childbearing age with IGE. Design, Setting, and Participants: This was a multicenter, retrospective, comparative effectiveness cohort study analyzing data from patients followed up from 1994 to 2022. Patients were recruited from 22 primary, secondary, and tertiary adult and child epilepsy centers from 4 countries. Eligible patients were female individuals of childbearing age, diagnosed with IGE according to International League Against Epilepsy (2022) criteria and who initiated levetiracetam or lamotrigine as initial monotherapy. Patients were excluded due to insufficient follow-up after ASM prescription. Exposures: Levetiracetam or lamotrigine as initial monotherapy. Main Outcomes and Measures: Inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazards regression was performed to compare treatment failure (TF) among patients who received levetiracetam or lamotrigine as initial monotherapy. Results: A total of 543 patients were included in the study, with a median (IQR) age at ASM prescription of 17 (15-21) years and a median (IQR) follow-up of 60 (24-108) months. Of the study population, 312 patients (57.5%) were prescribed levetiracetam, and 231 (42.5%) were prescribed lamotrigine. An IPTW-adjusted Cox model showed that levetiracetam was associated with a reduced risk of treatment failure after adjustment for all baseline variables (IPTW-adjusted hazard ratio [HR], 0.77; 95% CI, 0.59-0.99; P = .04). However, after stratification according to different IGE syndromes, the higher effectiveness of levetiracetam was confirmed only in patients with juvenile myoclonic epilepsy (JME; IPTW-adjusted HR, 0.47; 95% CI, 0.32-0.68; P < .001), whereas no significant differences were found in other syndromes. Patients treated with levetiracetam experienced adverse effects more frequently compared with those treated with lamotrigine (88 of 312 [28.2%] vs 42 of 231 [18.1%]), whereas the 2 ASMs had similar retention rates during follow-up (IPTW-adjusted HR, 0.91; 95% CI, 0.65-1.23; P = .60). Conclusions and Relevance: Results of this comparative effectiveness research study suggest the use of levetiracetam as initial alternative monotherapy in female patients with JME. Further studies are needed to identify the most effective ASM alternative in other IGE syndromes.

Drug-resistant idiopathic generalized epilepsy: A meta-analysis of prevalence and risk factors.

BACKGROUND: Idiopathic generalized epilepsy (IGE) is a common epilepsy syndrome with early age onset and generally good seizure outcomes. This study aims to determine the incidence and predictive risk factors for drug-resistant IGE. METHODS: We systematically searched three databases (PubMed, Embase, and Cochrane Library) in November 2022 and included 12 eligible studies which reported long-term outcomes (mean = 14.05) after antiseizure medications (ASMs) from 2001 to 2020. We defined drug resistance as the persistence of any seizure despite ASMs treatment (whether as monotherapies or in combination) given the criteria of drug resistance varied in original studies. A random-effects model was used to evaluate the prevalence of refractory IGE. Studies reporting potential poor prognostic factors were included for subsequent subgroup meta-analysis. RESULTS: The pooled prevalence of drug resistance in IGE cohorts was 27% (95% CI: 0.19-0.36). Subgroup analysis of the risk factors revealed that the psychiatric comorbidities (odds ratio (OR): 4.87, 95% confidence interval (CI): 2.97-7.98), combined three seizure types (absences, myoclonic jerks, and generalized tonic-clonic seizures) (OR: 5.37, 95% CI: 3.16-9.13), the presence of absence seizure (OR: 4.38, 95% CI: 2.64-7.28), generalized polyspike trains (GPT) (OR: 4.83, 95% CI: 2.42-9.64), sex/catamenial epilepsy (OR: 3.25, 95% CI: 1.97-5.37), and status epilepticus (OR: 5.94, 95% CI: 2.23-15.85) increased the risk of poor prognosis. Other factors, including age onset, family history, and side effects of ASMs, were insignificantly associated with a higher incidence of refractory IGE. CONCLUSION: Drug resistance is a severe complication of IGE. Further standardized research about clinical and electroencephalography factors is warranted.

Outpatient visit behavior in patients with epilepsy: Generalized Epilepsy is more frequently non-attendance than Focal Epilepsy.

BACKGROUND: Patients with epilepsy (PWE), especially those with Idiopathic Epilepsy (GE), are at a high risk of disadvantage caused by non-adherence. It has been suggested that medical visit behavior may be a surrogate indicator of medication adherence. We hypothesized that patients with IGE would adhere poorly to visits. METHODS: This was a retrospective study of PWE who visited the Department of Psychiatry and Neurology at Hokkaido University Hospital between January 2017 and December 2019. Demographic and clinical information on PWE were extracted from medical records and visit data from the medical information system. Non-attendance of outpatient appointments was defined as "not showing up for the day of an appointment without prior notice." Mixed-effects logistic regression analysis was conducted with non-attendance as the objective variable. RESULTS: Of the 9151 total appointments, 413 were non-attendances, with an overall non-attendance rate of 4.5%. IGE was a more frequent non-attendance than Focal Epilepsy (FE) (odds ratio (OR) 1.94; 95% confidence interval (CI) 1.17-3.21; p = 0.010). History of public assistance receipt was associated with higher non-attendance (OR 2.04; 95% CI 1.22-3.43; p = 0.007), while higher education (OR 0.64; 95% CI 0.43-0.93; p = 0.021) and farther distance to a hospital (OR 0.33; 95% CI 0.13-0.88; p = 0.022), and higher frequency of visits (OR 0.18; 95% CI 0.04-0.86; p = 0.031) were associated with fewer non-attendances. In a subgroup analysis of patients with GE, women were associated with fewer non-attendance (OR 0.31; 95% CI 0.14-0.72; p = 0.006). CONCLUSIONS: GE was more frequent in the non-attendance group than in the FE group. Among patients with GE, females were found to have non-attendance less frequently; however, there was no clear difference in the odds of non-attendance between Juvenile Myoclonic Epilepsy (JME) and IGE other than JME.

Typical absence seizures in children: Review with focus on EEG predictors of treatment response and outcome.

Typical absence seizures (TAS) occur in idiopathic generalized epilepsy (IGE) syndromes and are a common presentation to paediatric neurologists. Considerable overlap in clinical features of IGE syndromes comprising TAS often complicates prognostication. Clinical and EEG diagnostic features in TAS are well known. However, knowledge of prognostic features for each syndrome, whether clinical or EEG-related, is less clear. Perpetuated impressions in clinical practice regarding the role of EEG when used for prognostication in TAS are known. Assumed prognostic features, particularly those relating to EEG have been rarely studied systematically. Despite rapid expansion in epilepsy genetics, the complex and presumed polygenic inheritance of IGE, means that clinical and EEG features are likely to remain the main guide to management and prognostication of TAS for the foreseeable future. We comprehensively reviewed available literature and hereby summarize current knowledge of clinical and EEG characteristics (ictal and interictal) in children with TAS. The literature focuses predominantly on ictal EEG. Where studied, interictal findings reported relate to focal discharges, polyspike discharges, and occipital intermittent rhythmic delta activity, with generalized interictal discharges not thoroughly studied. Furthermore, reported prognostic implications of EEG findings are often conflicting. Limitations of available literature include inconsistent clinical syndrome and EEG finding definitions, and variable EEG analysis methods, particularly lack of raw EEG data analysis. These conflicting findings coupled with varying study methodologies cause lack of clear information or evidence on features which may influence treatment response, outcome, or natural history of TAS.

Safety and Tolerability of Omalizumab in Children with Allergic (IgE-Mediated) Asthma: A Systematic Review and Meta-Analysis.

BACKGROUND: Omalizumab is a recombinant humanized monoclonal antibody against immunoglobulin E., which can specifically bind to IgE in blood and inhibit the release of inflammatory mediators to improve the symptoms of IgE-mediated asthma effectively. This meta-analysis was used to retrieve the studies in recent years to provide a clinical reference for the omalizumab in treating allergic asthma (AA). METHODS: The databases Ovid, Embase, Pubmed, the Cochrane Library of clinical trials, CNKI (China National Knowledge Infrastructure) (China), and Wangfang Data (China) were searched for all studies on omalizumab involvement in treating allergic childhood asthma up to January 2022. Effectiveness, rate of exacerbation within 24 weeks (and 52 weeks), and the incidence of adverse reactions and serious adverse reactions were used as the primary data analysis indicators. RESULTS: Seven eligible pieces of literature were included. Meta-analysis indicated that omalizumab could significantly improve the treatment efficacy in children with asthma [RR (Risk Ratio) = 1.24, 95% CI (Confidential Interval) (1.09, 1.41), Z = 3.30, p = 0.001], reduced the incidence of significant clinical exacerbation in children with asthma within 24 weeks [RR = 0.55, 95% CI (0.35, 0.85), Z = -2.67, p = 0.001], reduced the incidence of significant clinical exacerbation in children with asthma within 52 weeks [RR = 0.52, 95% CI (0.39, 0.71), Z = -4.2, p < 0.0001], and the incidence of total serious adverse reactions was not statistically different from placebo [RR = 1.00, 95% CI (0.98, 1.03), Z = 0.71, p = 0.479], the incidence of serious adverse reactions was significantly decreased [RR = 0.53, 95% CI (0.36, 0.77), Z = -3.35, p = 0.001]. CONCLUSIONS: In treating IgE (immunoglobulin E)-mediated asthma in children, adding oral (or subcutaneous) omalizumab to a glucocorticoid regimen can enhance the effectiveness of treatment, reduce the probability of significant exacerbation during treatment, and reduce the incidence of serious adverse reactions.

[Clinical features of IgG4-related lung disease].

Objective: To explore the clinical features of IgG4-related lung disease. Methods: The clinical data of 60 patients diagnosed with IgG4-related lung disease in Peking University People's Hospital from February 2012 to May 2021 were retrospectively collected. Analysis was made to explore the features of clinical manifestation, laboratory, imaging, prognosis and other characteristics of the disease. Results: A total of 60 patients were included, with 40 males, age of (58.2±12.9) years, an age of onset of (57.1±13.2) years, and 31.7% (19 cases) of the patients had a history of allergic disease. 36.7% (22 cases) of the patients had respiratory symptoms during the disease. 94.6% (53/56) of patients had serum IgG4>1.35 g/L, 24.1% (14/58) of patients had increased eosinophils, 79.2% (38/48) of patients had increased IgE level, and 53.7% (29/54) of patients had decreased C3 or C4. Common imaging findings included nodular changes (38 cases, 63.3%), mediastinal and/or hilar lymphadenopathy (34 cases, 56.7%), and ground glass opacities (31 cases, 51.7%). Fifty-three cases (88.3%) showed two or more imaging changes. The pathological examination of the patient was mainly characterized by lymphoplasmacytic infiltration and fibrosis, with only one case of phlebitis obliterans. Compared with the asymptomatic group (38 cases), patients with respiratory symptoms (22 cases) showed higher level of serum total IgG and eosinophils (43.2 vs 17.8 g/L, 0.30×109/L vs 0.14×109/L, P<0.05), lower proportion of allergic diseases, and higher proportion of consolidation shadows on chest CT (P<0.05). There were no significant differences in serum IgG4, IgE, complement levels, and imaging outcomes after treatment between the two groups (P>0.05). Conclusions: The clinical manifestations of IgG4-related lung disease are atypical, and asymptomatic patients account for a high proportion. The imaging of the disease is highly heterogeneous, and patients are prone to show coexisted multiple imaging changes. The main clinical features and imaging outcomes of patients with and without respiratory symptoms are not significantly different.

Association of subclass distribution of insulin antibody with glucose control in insulin-treated type 2 diabetes mellitus: a retrospective observational study.

Objective: To examine the distribution and effects of the subclass of insulin antibodies on glucose control and side events in patients with type 2 diabetes treated with premixed insulin analog. Methods: A total of 516 patients treated with premixed insulin analog were sequentially enrolled from the First Affiliated Hospital of Nanjing Medical University from June 2016 to August 2020. Subclass-specific insulin antibodies (IAs) (IgG1-4, IgA, IgD, IgE, and IgM) were detected in IA-positive patients by electrochemiluminescence. We analyzed glucose control, serum insulin, and insulin-related events between IA-positive and IA-negative groups, as well as among patients with different IA subclasses. Results: Overall, 98 of 516 subjects (19.0%) were positive for total IAs after premixed insulin analog therapy; of these participants, 92 had subclass IAs, and IgG-IA was the predominant subclass, followed by IgE-IA. IAs were associated with serum total insulin increase and local injection-site reactions but not glycemic control and hypoglycemia. In the subgroup analysis in patients with IA-positive, the IgE-IA and IA subclass numbers were more associated with increased serum total insulin levels. Additionally, IgE-IA might be correlated more strongly with local responses and weakly with hypoglycemia, while IgM-IA might be correlated more strongly with hypoglycemia. Conclusion: We concluded that IAs or IA subclasses might be associated with unfavorable events in patients receiving premixed insulin analog therapy, which can be used as an adjunctive monitoring indicator in clinical insulin trials.

Assessment of dupilumab in children with moderate-to-severe type 2 asthma with or without evidence of allergic asthma.

BACKGROUND: Cytokines, such as interleukins (IL)-4/5/13, play a key role in multiple type 2 inflammatory diseases, including allergic asthma. Dupilumab, a human monoclonal antibody, blocks the shared receptor component for IL-4/IL-13, inhibiting signaling. In this post hoc analysis of VOYAGE (NCT02948959), dupilumab efficacy was evaluated in patients aged 6-11 years with type 2 asthma with or without evidence of allergic asthma (baseline serum total IgE ≥30 IU/mL and ≥1 perennial aeroallergen-specific IgE ≥0.35kU/L). METHODS: Annualized severe exacerbation rates (AER) and changes in pre-bronchodilator (Pre-BD) forced expiratory volume in one second (FEV1 ), percent-predicted pre-BD FEV1 (ppFEV1 ), and Asthma Control Score (ACQ)-7 were assessed during the treatment period. RESULTS: 350 children (261 with and 89 without evidence of allergic asthma) were included. Dupilumab versus placebo significantly reduced AER in patients with (0.24 vs. 0.62, relative risk reduction [RRR]: 62% [95% CI, 39-76], P < .0001) and without (0.39 vs. 0.80, RRR: 51% [95% CI, 0-76], P < .05) evidence of allergic asthma. Significant improvements in ppFEV1 , pre-bronchodilator FEV1 , and ACQ-7 scores were observed in dupilumab versus placebo throughout the treatment period in patients with evidence of allergic asthma. In patients without evidence of allergic asthma, numerical improvements in pre-bronchodilator FEV1 and asthma control were observed by Week 52. CONCLUSION: Dupilumab versus placebo reduced asthma exacerbations in children with type 2 asthma irrespective of evidence of allergic asthma; similar trends were observed in changes in lung function. Significant improvement in asthma control was observed in patients with evidence of allergic asthma, but not in those without.