Association between the C-reactive protein/albumin ratio and mortality in older Japanese patients with dysphagia

BackgroundC-reactive protein-to-albumin ratio (CRP/ALB) has been proven to represent a biomarker for predicting prognosis in many groups of patients with severe diseases. However, few studies have investigated the association between CRP/ALB and mortality in Japan older people with dysphagia patients.ObjectiveThis retrospective cohort study aimed to assess the prognostic value of C-reactive protein/albumin ratio (CAR) in older Japanese patients with dysphagia.MethodsWe analyzed data from 253 patients diagnosed with dysphagia at a single center between January 2014 and January 2017. Cox regression analysis was used to compare the mortality rates across the CAR tertiles. Subgroup analyses were conducted, and Kaplan–Meier curves were used to determine the median survival times.ResultsThe study included 154 female and 99 male patients, with a median age of 83 years. After adjusting for all covariates, the multivariable Cox regression analysis revealed a significant association between increasing CAR (HR = 1.19, 95% CI: 1.03–1.37, P = 0.022) and the risk of mortality. Compared to the reference group T1 (< 0.149), the adjusted hazard ratios for T2 (0.149–0.815) and T3 (> 0.815) were 1.75 (95% CI: 1.07–2.87, P = 0.027) and 2.15 (95% CI: 1.34–3.46, P = 0.002), respectively. Kaplan–Meier curves indicated median survival times of 864, 371, and 223 days for T1, T2, and T3, respectively.ConclusionThe C-reactive protein/albumin ratio was positively related to mortality in Japan older people with dysphagia patients. There was no interaction for the subgroup analysis. The result was stable

Case report: Fatal Legionella infection diagnosed via by metagenomic next-generation sequencing in a patient with chronic myeloid leukemia

Legionella is an aerobic, gram-negative, intracellular pathogen and is an important cause of community-acquired pneumonia. Legionella pneumophila is the most common causative agent of Legionella pneumonia. Clinical diagnosis of Legionella pneumonia is challenging due to the lack of specific clinical manifestations and the low positive rates of conventional pathogen detection methods. In this study, we report a case of a patient with chronic myeloid leukemia who developed rigors and high fever after chemotherapy and immunotherapy. Chest computed tomography revealed consolidation in the left lower lobe of the lung and ground-glass opacities in both lower lobes. Multiple blood cultures showed Escherichia coli, Staphylococcus aureus, Bacillus licheniformis, and positive results in the β-D-glucan test (G test). The patient was treated with various sensitive antimicrobial agents, including meropenem plus fluconazole, meropenem plus carpofungin, and vancomycin. Unfortunately, the patient’s condition gradually worsened and eventually resulted in death. On the following day of death, metagenomic next-generation sequencing (mNGS) of 1whole blood revealed L. pneumophila pneumonia with concurrent bloodstream infection (blood mNGS reads 114,302). These findings suggest that when conventional empirical antimicrobial therapy proves ineffective for critically ill patients with pneumonia, the possibility of combined Legionella infection must be considered, and mNGS can provide a diagnostic tool in such cases

Neoadjuvant Immune Checkpoint Inhibitors in hepatocellular carcinoma: a meta-analysis and systematic review

BackgroundNeoadjuvant immunotherapy has demonstrated beneficial outcomes in various cancer types; however, standardized protocols for neoadjuvant immunotherapy in hepatocellular carcinoma (HCC) are currently lacking. This systematic review and meta-analysis aims to investigate the reliability of neoadjuvant immunotherapy’s efficacy and safety in the context of HCC.MethodsA systematic search was conducted across PubMed (MEDLINE), EMBASE, the Web of Science, the Cochrane Library, and conference proceedings to identify clinical trials involving resectable HCC and neoadjuvant immunotherapy. Single-arm meta-analyses were employed to compute odds ratios and 95% confidence intervals (CIs). Heterogeneity analysis, data quality assessment, and subgroup analyses based on the type of immunotherapy drugs and combination therapies were performed. This meta-analysis is registered in PROSPERO (identifier CRD42023474276).ResultsThis meta-analysis included 255 patients from 11 studies. Among resectable HCC patients, neoadjuvant immunotherapy exhibited an overall major pathological response (MPR) rate of 0.47 (95% CI 0.31-0.70) and a pathological complete response (pCR) rate of 0.22 (95% CI 0.14-0.36). The overall objective response rate (ORR) was 0.37 (95% CI 0.20-0.69), with a grade 3-4 treatment-related adverse event (TRAE) incidence rate of 0.35 (95% CI 0.24-0.51). Furthermore, the combined surgical resection rate was 3.08 (95% CI 1.66-5.72). Subgroup analysis shows no significant differences in the efficacy and safety of different single-agent immunotherapies; the efficacy of dual ICIs (Immune Checkpoint Inhibitors) combination therapy is superior to targeted combined immunotherapy and monotherapy, while the reverse is observed in terms of safety.DiscussionNeoadjuvant immunotherapy presents beneficial outcomes in the treatment of resectable HCC. However, large-scale, high-quality experiments are warranted in the future to provide robust data support

Direct Conversion of Mouse Astrocytes Into Neural Progenitor Cells and Specific Lineages of Neurons

Background: Cell replacement therapy has been envisioned as a promising treatment for neurodegenerative diseases. Due to the ethical concerns of ESCs-derived neural progenitor cells (NPCs) and tumorigenic potential of iPSCs, reprogramming of somatic cells directly into multipotent NPCs has emerged as a preferred approach for cell transplantation. Methods: Mouse astrocytes were reprogrammed into NPCs by the overexpression of transcription factors (TFs) Foxg1, Sox2, and Brn2. The generation of subtypes of neurons was directed by the force expression of cell-type specific TFs Lhx8 or Foxa2/Lmx1a. Results: Astrocyte-derived induced NPCs (AiNPCs) share high similarities, including the expression of NPC-specific genes, DNA methylation patterns, the ability to proliferate and differentiate, with the wild type NPCs. The AiNPCs are committed to the forebrain identity and predominantly differentiated into glutamatergic and GABAergic neuronal subtypes. Interestingly, additional overexpression of TFs Lhx8 and Foxa2/Lmx1a in AiNPCs promoted cholinergic and dopaminergic neuronal differentiation, respectively. Conclusions: Our studies suggest that astrocytes can be converted into AiNPCs and lineage-committed AiNPCs can acquire differentiation potential of other lineages through forced expression of specific TFs. Understanding the impact of the TF sets on the reprogramming and differentiation into specific lineages of neurons will provide valuable strategies for astrocyte-based cell therapy in neurodegenerative diseases

Reduced Energy Metabolism Impairs T Cell-Dependent B Cell Responses in Patients With Advanced HBV-Related Cirrhosis

Background and AimsPatients with decompensated HBV-related liver cirrhosis (HBV D-LC) showed compromised immune responses, which manifested as a proneness to develop infections and hyporesponsiveness to vaccines, resulting in accelerated disease progression. The alterations in T cell-dependent B cell responses in this pathophysiological process were not well understood. This study aimed to investigate T cell-dependent B cell responses in this process and discuss the mechanism from the perspective of metabolism.MethodsChanges in phenotypes and subsets of peripheral B cells between HBV D-LC patients and healthy controls (HCs) were compared by flow cytometry. Isolated B cells were activated by coculture with circulating T follicular (cTfh) cells. After coculture, the frequencies of plasmablasts and plasma cells and immunoglobin levels were analyzed. Oxidative phosphorylation (OXPHOS) and glycolysis were analyzed by a Seahorse analyzer. Mitochondrial function and the AKT/mTOR pathway were analyzed by flow cytometry.ResultsThe proliferation and differentiation capacities of B cells after T cell stimulation were impaired in D-LC. Furthermore, we found that B cells from D-LC patients showed reductions in OXPHOS and glycolysis after activation, which may result from reduced glucose uptake, mitochondrial dysfunction and attenuated activation of the AKT/mTOR pathway.ConclusionsB cells from HBV D-LC patients showed dysfunctional energy metabolism after T cell-dependent activation. Understanding the regulations of B cell metabolic pathway and their changes may provide a new direction to rescue B cell hyporesponsiveness in patients with HBV D-LC, preventing these patients be infected and improving sensitivity to vaccines

Assessing the causal relationship between gut microbiota and diabetic nephropathy: insights from two-sample Mendelian randomization

BackgroundThe causal association between gut microbiota (GM) and the development of diabetic nephropathy (DN) remains uncertain. We sought to explore this potential association using two-sample Mendelian randomization (MR) analysis.MethodsGenome-wide association study (GWAS) data for GM were obtained from the MiBioGen consortium. GWAS data for DN and related phenotypes were collected from the FinngenR9 and CKDGen databases. The inverse variance weighted (IVW) model was used as the primary analysis model, supplemented by various sensitivity analyses. Heterogeneity was assessed using Cochran’s Q test, while horizontal pleiotropy was evaluated through MR-Egger regression and the MR-PRESSO global test. Reverse MR analysis was conducted to identify any reverse causal effects.ResultsOur analysis identified twenty-five bacterial taxa that have a causal association with DN and its related phenotypes (p < 0.05). Among them, only the g_Eubacterium_coprostanoligenes_group showed a significant causal association with type 1 DN (p < Bonferroni-adjusted p-value). Our findings remained consistent regardless of the analytical approach used, with all methods indicating the same direction of effect. No evidence of heterogeneity or horizontal pleiotropy was observed. Reverse MR analysis did not reveal any causal associations.ConclusionsThis study established a causal association between specific GM and DN. Our findings contribute to current understanding of the role of GM in the development of DN, offering potential insights for the prevention and treatment strategies for this condition

Local Diffusion Homogeneity Provides Supplementary Information in T2DM-Related WM Microstructural Abnormality Detection

Objectives: We aimed to investigate whether an inter-voxel diffusivity metric (local diffusion homogeneity, LDH), can provide supplementary information to traditional intra-voxel metrics (i.e., fractional anisotropy, FA) in white matter (WM) abnormality detection for type 2 diabetes mellitus (T2DM).Methods: Diffusion tensor imaging was acquired from 34 T2DM patients and 32 healthy controls. Voxel-based group-difference comparisons based on LDH and FA, as well as the association between the diffusion metrics and T2DM risk factors [i.e., body mass index (BMI) and systolic blood pressure (SBP)], were conducted, with age, gender and education level controlled.Results: Compared to the controls, T2DM patients had higher LDH in the pons and left temporal pole, as well as lower FA in the left superior corona radiation (p < 0.05, corrected). In T2DM, there were several overlapping WM areas associated with BMI as revealed by both LDH and FA, including right temporal lobe and left inferior parietal lobe; but the unique areas revealed only by using LDH included left inferior temporal lobe, right supramarginal gyrus, left pre- and post-central gyrus (at the semiovale center), and right superior radiation. Overlapping WM areas that associated with SBP were found with both LDH and FA, including right temporal pole, bilateral orbitofrontal area (rectus gyrus), the media cingulum bundle, and the right cerebellum crus I. However, the unique areas revealed only by LDH included right inferior temporal lobe, right inferior occipital lobe, and splenium of corpus callosum.Conclusion: Inter- and intra-voxel diffusivity metrics may have different sensitivity in the detection of T2DM-related WM abnormality. We suggested that LDH could provide supplementary information and reveal additional underlying brain changes due to diabetes