Hypogammaglobulinemia and Infection Events in Patients with Autoimmune Diseases Treated with Rituximab: 10 Years Real-Life Experience.

OBJECTIVES: To investigate predictors of hypogammaglobulinemia (HGG) and severe infection event (SIE) in patients with autoimmune disease (AID) receiving rituximab (RTX) therapy. METHODS: This was a retrospective study conducted in a tertiary medical center in China. Predictors of HGG or SIE were assessed using Cox analysis. Restricted cubic spline (RCS) analysis was applied to examine the correlation between glucocorticoid (GC) maintenance dose and SIE. RESULTS: A total of 219 patients were included in this study, with a cumulative follow-up time of 698.28 person-years. Within the study population, 117 patients were diagnosed with connective tissue disease, 75 patients presented with ANCA-associated vasculitis, and 27 patients exhibited IgG4-related disease. HGG was reported in 63.3% of the patients, where an obvious decline in IgG and IgM was shown three months after RTX initiation. The rate of SIE was 7.2 per 100 person-years. An increase in the GC maintenance dose was an independent risk factor for both hypo-IgG (HR 1.07, 95% CI 1.02-1.12, p = 0.003) and SIE (HR 1.06, 95% CI 1.02-1.1, p = 0.004). Further RCS analysis identified 7.48 mg/d prednisone as a safe threshold dose for patients who underwent RTX treatment to avoid a significantly increased risk for SIE. CONCLUSION: HGG was relatively common in RTX-treated AID patients. Patients with chronic lung disease or who were taking ≥ 7.5 mg/d prednisone during RTX treatment were at increased risk for SIE and warrant attention from physicians.

Development of a prediction nomogram for 1-month mortality in neonates with congenital diaphragmatic hernia.

OBJECTIVES: Although many prognostic factors in neonates with congenital diaphragmatic hernia (CDH) have been described, no consensus thus far has been reached on which and how many factors are involved. The aim of this study is to analyze the association of multiple prenatal and postnatal factors with 1-month mortality of neonates with CDH and to construct a nomogram prediction model based on significant factors. METHODS: A retrospective analysis of neonates with CDH at our center from 2013 to 2022 was conducted. The primary outcome was 1-month mortality. All study variables were obtained either prenatally or on the first day of life. Risk for 1-month mortality of CDH was quantified by odds ratio (OR) with 95% confidence interval (CI) in multivariable logistic regression models. RESULTS: After graded multivariable adjustment, six factors were found to be independently and consistently associated with the significant risk of 1-month mortality in neonates with CDH, including gestational age of prenatal diagnosis (OR, 95% CI, P value: 0.845, 0.772 to 0.925, < 0.001), observed-to-expected lung-to-head ratio (0.907, 0.873 to 0.943, < 0.001), liver herniation (3.226, 1.361 to 7.648, 0.008), severity of pulmonary hypertension (6.170, 2.678 to 14.217, < 0.001), diameter of defect (1.560, 1.084 to 2.245, 0.017), and oxygen index (6.298, 3.383 to 11.724, < 0.001). Based on six significant factors identified, a nomogram model was constructed to predict the risk for 1-month mortality in neonates with CDH, and this model had decent prediction accuracy as reflected by the C-index of 94.42%. CONCLUSIONS: Our findings provide evidence for the association of six preoperational and intraoperative factors with the risk of 1-month mortality in neonates with CDH, and this association was reinforced in a nomogram model.

Construction of MOFs@COFs composite material as stationary phase for efficient separation of diverse organic compounds.

BACKGROUND: The development of efficent chromatographic stationary phases (SP) with mixed-mode or multiple interactions in high-performance liquid chromatography (HPLC) for the separation of complex samples is a challenging task. Metal organic frameworks (MOFs)-based SP can provide desired multiple interactions and enable the separation of a diverse range of solutes, but have limitations of low column efficiency and poor stability. RESULTS: Herein, the hybrid MOFs@Covalent organic frameworks (COFs) materials were used as SP in HPLC due to their synergistic structural features. The SiO2@NH2-UiO-66@CTF SP was synthesized by integration of NH2-UiO-66 and covalent triazine framework (CTF) onto silica surface. Due to the unique structure of SiO2@NH2-UiO-66@CTF with hierarchical-pores, this column showed higher column efficiency (up to 49,369 plates m-1 for alkylbenzenes) than the reported columns packed with MOFs-based SP. Owing to the Zr4+-N coordination bonding between CTF and NH2-UiO-66, the structural stability of SiO2@NH2-UiO-66@CTF can be improved. Furthermore, this new column exhibited remarkable column stability with relative standard deviation of retention time of <0.40% after 400 injections. With the combined advantages of multifunctional properties, high column efficiency, and good stability, SiO2@NH2-UiO-66@CTF SP showed excellent selectivity for the separation of a variety of hydrophobic, aromatic, heteroatomic, and hydrophilic analytes. SIGNIFICANCE AND NOVELTY: This work not only offers a promising SP with multiple retention mechanisms for HPLC, but also provides an efficient strategy for development of high column efficiency MOFs-based SP with good stability. Moreover, the MOFs@COFs hybrid materials were expanded in application area through this study, and the research results can also afford the foundation for further explore its structural characteristics.

Ionic liquid-functionalized mesoporous multipod silica for simultaneously effective extraction of aflatoxin B1 and its two precursors from grain.

BACKGROUND: Aflatoxin B1 (AFB1) and its precursors contaminate food and agricultural products, posing a significant risk to food safety and human health, but simultaneous and effective extraction and determination of AFB1 and its precursors with varied structures is still a challenging task. RESULTS: In this study, a bisimidazolium-type ionic liquid functionalized mesoporous multipod silica (SiO2@mPMO-IL(im)2) was fabricated to extract AFB1 and its two precursors, i.e., averantin and sterigmatocystin. The SiO2@mPMO-IL(im)2 could simultaneously extract three targets with varied structures based on the multipods, mesopores, and multifunctional groups. The density functional theory calculations further verified the multiple interactions between SiO2@mPMO-IL(im)2 and targets. The fabricated SiO2@mPMO-IL(im)2 could effectively extract and determine three targets in grains by combing with dispersive solid-phase extraction and high-performance liquid chromatography. Good linearity (r2 > 0.9978), low LODs (0.9-1.5 µg kg-1) and LOQs (3.0-4.5 µg kg-1), satisfactory spiked recoveries (92.5%-106.8%) and high precisions (RSD<6.4%) were observed. SIGNIFICANCE AND NOVELTY: This work demonstrates the feasibility of SiO2@mPMO-IL(im)2 for simultaneous and effective extraction of toxins with varied structures and provides a promising sample preparation for the analysis of AFB1 and its precursors in grain samples.

A Novel and Highly Efficient Microextraction Method for the Determination of Aflatoxin Precursor Averantin in Fatty Grain Samples.

Averantin (AVN) is an important aflatoxin biosynthetic precursor and has been listed in the screening range of mycotoxins. Herein, a novel ionic liquid-based one-, two-, and three-phase transition microextraction (IL-OTTPTME) method was combined with high-performance liquid chromatography for the extraction and determination of AVN in fatty grain samples. The formation of a homogeneous solution and three-phase system during the IL-OTTPTME process allowed both efficient extraction and coextracted lipid cleanup. Density functional theory calculations and distribution coefficient determination results demonstrated that AVN extraction by IL mainly occurred through hydrogen-bond and π-π interactions. Under optimized conditions, the LOD and LOQ of the proposed method were 0.5 and 1.5 ng/g, respectively. Finally, the method was used to determine AVN in several grains with different fat contents, achieving satisfactory relative recoveries (86.0-107.8%) and RSDs (1.2-6.2%, n = 3).

The development and initial validation of IgG4-related disease damage index: a consensus report from Chinese IgG4-RD Consortium.

OBJECTIVE: To develop and conduct an initial validation of the Damage Index for IgG4-related disease (IgG4-RD DI). METHODS: A draft of index items for assessing organ damages in patients with IgG4-RD was generated by experts from the Chinese IgG4-RD Consortium (CIC). The preliminary DI was refined using the Delphi method, and a final version was generated by consensus. 40 IgG4-RD cases representing four types of clinical scenarios were then selected, each with two time points of assessment for at least 3 years of follow-up. 48 rheumatologists from 35 hospitals nationwide were invited to evaluate organ damage using the CIC IgG4-RD DI. The intraclass correlation coefficient (ICC) and the Kendall-W coefficient of concordance (KW) were used to assess the inter-rater reliability. The criterion validity of IgG4-RD DI was tested by calculating the sensitivity and specificity of raters. RESULTS: IgG4-RD DI is a cumulative index consisting of 14 domains of organ systems, including a total of 39 items. The IgG4-RD DI was capable of distinguishing stable and increased damage across the active disease subgroup and stable disease subgroup. In terms of scores at baseline and later observations by all raters, overall consistency in scores at baseline and later observations by all raters was satisfactory. ICC at the two time points was 0.69 and 0.70, and the KW was 0.74 and 0.73, respectively. In subgroup analysis, ICC and KW in all subgroups were over 0.55 and 0.61, respectively. The analysis of criterion validity showed a good performance with a sensitivity of 0.86 (95% CI 0.82 to 0.88), a specificity of 0.79 (95% CI 0.76 to 0.82) and an area under the curve of 0.88 (95% CI 0.85 to 0.91). CONCLUSION: The IgG4-RD DI is a useful approach to analyse disease outcomes, and it has good operability and credibility. It is anticipated that the DI will become a useful tool for therapeutic trials and studies of prognosis in patients with IgG4-RD.