Clinical and Experimental Medicine最新文献

Background: The combination of azathioprine (AZA) with infliximab (IFX) enhances clinical efficacy in treating Crohn's disease (CD), increasing the risk of adverse events. This study aims to identify the optimal timing for AZA administration in IFX combination therapy to maximize patient benefit.

Methods: This was a retrospective, single-center study, which analyzed patients with CD undergoing IFX treatment from January 2017 to December 2022. Baseline data were collected. To minimize potential confounding effects, we utilized two established propensity score methods: propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). The primary efficacy outcome was defined as the proportion of patients achieving clinical remission at the 54-week follow-up. Safety outcomes were evaluated through comprehensive monitoring and systematic classification of adverse events.

Results: A total of 528 active CD patients were included. Of these, 146 received concomitant AZA (AZA group), while 382 did not (non-AZA group). Following PSM or IPTW, the AZA group demonstrated significantly higher clinical remission rates (PSM: P < 0.001, IPTW: P < 0.001) compared to the non-AZA group. Furthermore, 46 patients used AZA during induction (IP-AZA group) and 100 during maintenance (MP-AZA group). After PSM or IPTW, both groups showed similar remission rates at 54 weeks (PSM: P = 0.793, IPTW: P = 0.508), with comparable safety profiles.

Conclusion: For CD patients treated with IFX, whether AZA was initiated in the induction phase or during the maintenance phase, the impact on clinical outcomes and occurrence of adverse events was similar.

This study aimed to verify whether neutrophil extracellular traps (NETs) was related to the severity of respiratory tract infections (RTI) and establish a prognostic model for severe respiratory infections. Peripheral blood mononuclear cells (PBMC) were isolated from RTI patients for RNA sequencing. Weighted Graph Co-expression Network Analysis was performed to identify gene modules and analyze the correlation between gene modules and clinical features. The prognostic model was established by LASSO regression. The concentration of IL-8 in plasma was measured by Enzyme linked immunosorbent assay (ELISA). The gene expression levels in PBMC were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). In total, 120 patients with RTIs were enrolled between July 2022 and March 2024. Enrichment analysis showed that NETs formation was enhanced during the early stages of pneumonia and sepsis. IL-8 had the strongest correlation with NETs formation, and the concentration of IL-8 in the plasma of patients with sepsis was significantly higher than that in patients with pneumonia and healthy controls (p < 0.001). NET-related genes were positively correlated with the SOFA score and 7-category ordinal scale. The expression level of MPO and PADI4 in sepsis patients were higher than that in community-acquired pneumonia (CAP) alone and healthy controls. The AUC of the prognostic prediction model for severe CAP composed of two genes (PADI4-CD177) showed the best performance, with an AUC of 0.917. This study confirmed that NETs formation was activated in RTI and the 2-gene signature provided a rapid and highly accurate biomarker for predicting the prognosis of severe CAP, which awaits further verification in a prospective cohort.

Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by multifaceted immune dysregulation, which ultimately trigger irreversible damage of tissue and organ. Lupus nephritis (LN) is the most common and life-threatening organ involvement of SLE. Although the prognosis of LN has been dramatically improved with the application of standard-of-care (SoC) regimens, there is an enormous unmet need regarding the global management of refractory LN. Currently, there is no consensus on definition for refractory LN, making early identification and prompt management greatly challengeable. Meanwhile, low remission rate and kidney survival rate, as well as poor prognosis has been longstanding clinical dilemmas for refractory LN. Fortunately, novel treatment options beyond SoC are constantly expanding. To change existing treatment paradigm and pave the way for precise treatment of refractory LN, we summarize current understanding and future considerations of refractory SLE, primarily focusing on the definition, clinical and prognostic characteristics, and emerging treatment strategies.

The prognostic significance of CD15 antigen in acute myeloid leukemia has been evaluated with conflicting results in various studies. However, existing results are limited and further investigation into additional prognostic parameters is necessary. This study aimed to evaluate the impact of CD15 antigen on survival prognosis in patients with de novo AML (dn-AML). We analyzed CD15 antigen expression on diagnostic samples from 676 patients with dn-AML by flow cytometry. Utilizing a 20% positivity threshold, the cohort was stratified into CD15 positivity (56.07%) and CD15 negativity (43.93%) groups. The CD15 negativity group demonstrated a lower complete remission rate (P = 0.006), a higher relapse rate (P = 0.002) and increased mortality (P<0.001) compared to the CD15 positivity group. According to the log-rank test, the CD15 negativity group exhibited significantly shorter overall survival (OS) (P<0.001) and disease-free survival (DFS) (P<0.001). Multivariate analysis identified CD15-positivity, TP53 mutation, European Leukemia Net (ELN) risk category, bone marrow transplant status, white blood cell counts and hemoglobin levels as independent prognostic factors associated with OS. A visualized nomogram was developed to predict OS and demonstrating notable performance with a C-index of 0.778. Compared to the ELN risk model, calibration plots and decision curve analyses indicated superior discrimination, calibration and net benefits. The time-dependent receiver operating characteristic (ROC) curves for 1-, 2-, and 3-year survival also performed robustly (AUC = 0.256, 0.154, and 0.126 respectively). Our study provides a comprehensive perspective on the role of CD15 antigen as an independent prognostic marker in dn-AML patients. To some extent, this prognostic model leverages readily available clinical data to enhance predictive accuracy, identify potential risks and support AML therapeutic decision-making.

The cardiovascular-kidney-metabolic (CKM) syndrome is a newly proposed clinical concept that emphasizes the interconnected burden of renal and cardiometabolic dysfunction. However, the impact of metabolic dysfunction-associated fatty liver disease (MAFLD) within the CKM staging framework is still unknown. This cross-sectional study utilized data from the U.S. National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020. Participants aged 18-80 were categorized by CKM staging was applied based on the 2023 American Heart Association classification, MAFLD status, and liver fibrosis was assessed by transient elastography and non-invasive scores. Logistic regression was used to identify independent predictors of advanced CKM stages. Of 6167 participants, 5695 (92.3%) met the CKM Framework, with 3137 (55.1%) having MAFLD (CKM-MAFLD). Those with CKM-MAFLD exhibited significantly higher cardiometabolic risks, particularly for cardiovascular events. Late CKM stages showed a higher prevalence of MAFLD (57.7% vs 53.2%, p < 0.001) and greater steatosis and fibrosis. MAFLD was an independent predictor of CKM risk (OR: 1.2, 95% CI: 1.03-1.5, P 0.04), an effect was more profound in those with liver fibrosis (OR: 1.36, p-value 0.004). MAFLD could be a crucial predictor in CKM risk stratification, emphasizing the need for hepatic evaluation in these frameworks. Early identification of MAFLD-related dysfunction can lead to targeted interventions across the liver-heart-kidney continuum.

The chromosomal translocation t(11;14)(q13;q32) is frequently observed in systemic light-chain (AL) amyloidosis, yet its clinical significance in the era of daratumumab-based therapy remains unclear. To compare clinical and cytogenetic characteristics, we retrospectively analyzed 68 patients with systemic AL amyloidosis and 107 patients with multiple myeloma (MM) newly diagnosed at Kumamoto University Hospital, with the MM cohort serving as a reference cohort. t(11;14) was detected in 55.9% of AL amyloidosis and 28.0% of MM cases. In both diseases, t(11;14) was associated with light chain-only M-protein and elevated CD20 expression on bone marrow plasma cells, suggesting a distinct phenotype. Notably, t(11;14)-positive AL amyloidosis patients exhibited a significantly lower incidence of renal dysfunction, a feature not observed in t(11;14)-positive MM. Among 47 AL amyloidosis patients treated with upfront daratumumab-containing regimens, overall survival did not differ significantly by t(11;14) status. However, event-free survival was significantly shorter in the t(11;14)-positive group (median 41.6 vs. 71.3 months, p = 0.037), accompanied by inferior 3 months hematological and cardiac responses. These findings suggest that t(11;14)-positive AL amyloidosis constitutes a distinct biological and clinical subtype characterized by delayed treatment response to daratumumab. Tailored therapeutic strategies targeting the unique biology of t(11;14)-positive AL amyloidosis is warranted.

A single-center prospective study was conducted at a tertiary care hospital in Kuopio Finland over the past two decades, searching for novel biomarker candidates to predict complicated course of febrile neutropenia (FN) in hematological patients. In Dec 2006‒Dec 2015, 85 patients with acute myeloid leukemia and 179 autologous hematopoietic stem cell transplant recipients were included. More than 20 biomarkers were evaluated in subsequent patient cohorts and compared to C-reactive protein (CRP) and procalcitonin (PCT). The samples were taken on d0-d2 from the beginning of FN. Here, we provide an overview of the results of these studies. Most biomarkers evaluated did not provide additional prognostic benefit compared to CRP or PCT. The most promising biomarkers warranting further studies include soluble cluster of differentiation 14, interleukin-1-receptor antagonist, interleukin-10, tissue inhibitor of matrix metalloproteinase-1, and caspase-cleaved cytokeratin-18. Several biomarkers evaluated in this series of studies are hampered by impaired production by neutrophils/leukocytes (matrix metalloproteinase-8, cell-free plasma DNA and soluble urokinase plasminogen activator receptor) or platelets (vascular endothelial growth factor). For now, these novel biomarkers cannot substitute the conventional markers nor provide additional benefit in routine use. Optimally, the most promising novel markers should be evaluated in prospective multicenter studies with higher patient numbers and several endpoints to more reliably evaluate their performance. At present, close patient monitoring is imperative in hematological patients with FN. The additional information provided by novel FN biomarkers may be useful, but they should be evaluated combined with daily evaluation of sepsis scoring systems.

Patients with hyperthyroidism frequently present with hematological abnormalities; however, the underlying mechanisms remain incompletely understood. This study enrolled 166 treatment-naïve hyperthyroidism patients and 56 age- and sex-matched healthy controls, comparing their complete blood count parameters. Additionally, a murine model of hyperthyroidism was established, and flow cytometry was employed to assess the quantity, proportion, cell cycle status, and apoptosis of hematopoietic stem/progenitor cells (HSPCs) in the bone marrow. Clinical data analysis revealed that, compared to the healthy control group, hyperthyroidism patients exhibited significant reductions in peripheral white blood cell counts-particularly neutrophils, eosinophils, and basophils-as well as in red blood cell parameters, including hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (HCH), and mean corpuscular hemoglobin concentration (MCHC). These alterations were more pronounced in female patients. Animal experiments confirmed that hyperthyroid mice also developed leukopenia and neutropenia. Further investigation demonstrated a decreased number of HSPCs in the bone marrow of hyperthyroid mice. The primary cause was identified as cell cycle arrest rather than increased apoptosis. This study reveals that elevated thyroid hormone levels may lead to alterations in peripheral blood cell counts by inducing cell cycle arrest in bone marrow HSPCs, thereby impairing their proliferation and differentiation capabilities. These findings provide a novel cellular perspective for understanding the mechanisms underlying hematological abnormalities in hyperthyroidism and offer a theoretical foundation for potential clinical intervention strategies.