Intraoperative bulbocavernosus reflex monitoring for predicting postoperative voiding dysfunction in patients with distal intraspinal tumors.

OBJECTIVE: To investigate the predictive value of intraoperative bulbocavernosus reflex (BCR) monitoring for voiding dysfunction post-operatively in patients with distal intraspinal tumors and to determine an appropriate timing for postoperative follow-up assessment. METHODS: Patients with distal intraspinal tumors who underwent surgery with BCR monitoring were collected. Patients were classified into BCR absent and present groups according to the monitoring responses at the end of surgery. Voiding function was evaluated at 1 week, 2 months, 4 months, and 6 months after surgery. RESULTS: A total of 52 patients were included. There were 30 (57.7 %) males and the mean age was (48.6 ± 17.2) years. Forty-nine (94.2 %) patients were adult. BCR was preserved in 50 (96.2 %) patients and completely disappeared in 2 cases at the end of the surgery. The sensitivity of intraoperative BCR loss for worsened voiding were 20.0 %, 33.3 %, 66.7 %, and 100.0 % at 1 week, 2 months, 4 months, and 6 months post-operatively respectively. The specificity was all 100.0 % at the four follow-ups. Preoperative voiding difficulty was more common in patients suffering from worsened voiding than those maintained at 1 week post-operatively (P < 0.05). CONCLUSIONS: Intraoperative BCR monitoring is a reliable technique to predict the postoperative voiding dysfunction in patients with distal intraspinal tumors. Preservation of the BCR is a robust indication for favorable postoperative urinary function as time goes on and 6-month post-operatively may be an optimal timing for functional assessment with high sensitivity and specificity. Preoperative voiding symptoms may be a risk factor for voiding difficulty at early stage after surgery.

Sputum Metabolomic Signature and Dynamic Change of Cough Variant Asthma.

Cough variant asthma (CVA), a common reason for chronic cough, is a globally prevalent and burdensome condition. The heterogeneity of CVA and a lack of knowledge concerning the exact molecular pathogenesis has hampered its clinical management. This study presented the first sputum metabolome of CVA patients, revealed the dynamic change during treatment, and explored biomarkers related to the occurrence and treatment response of CVA. We found arginine biosynthesis, purine metabolism, and pyrimidine metabolism pathways were enriched in CVA compared to healthy controls. Part of metabolic disturbances could be reversed by anti-asthmatic medication. The levels of dipeptides/tripeptides (alanyltyrosine, Gly-Tyr-Ala, Ala-Leu, and Thr-Leu) were significantly associated with sputum Neu% or Eos% of CVA patients. Differential metabolites pre-treatment between effective and ineffective groups enriched in purine metabolism, thiamine metabolism, and arginine metabolism. 2-isopropylmalate was down-regulated in CVA patients and increased after treatment, and effective group had a lower 2-isopropylmalate level pre-treatment. Random forest and logistic regression models identified glutathione, thiamine phosphate, alanyltyrosine, and 2'-deoxyadenosine as markers for distinguishing CVA from healthy controls (all AUC > 0.8). Thiamine phosphate might also be promising for predicting therapy responsiveness (AUC = 0.684). These findings implied that disturbed mitochondrial energy metabolism and imbalanced oxidation-reduction homeostasis probably underlay the metabolic pathogenesis of CVA.

Efficacy and safety of rituximab induction therapy and effect of rituximab maintenance for IgG4-related disease: a systematic review and meta-analysis.

BACKGROUND: Previous studies have reported that rituximab (RTX) therapy might be beneficial in reducing relapse rates in patients with IgG4-related disease (IgG4-RD). Therefore, we aimed to systematically assess the efficacy and safety of RTX induction treatment and the effect of RTX maintenance in patients with IgG4-RD. METHODS: The protocol was registered in the PROSPERO (CRD42023427352). PubMed, Embase, the Cochrane database, Scopus, and the Web of Science were interrogated to identify studies that evaluated the impact of RTX on prognosis in IgG4-RD. We explored the impact of various subgroups of factors on relapse outcomes and focused on the possible role of maintenance therapy in reducing relapse rates. The pooled incidence of adverse events of RTX therapy and the influencing factors have also been evaluated. RESULTS: Eighteen studies comprising 374 patients (mean age 56.0 ± 8.7 years; male 73.7 %) with a mean follow-up duration of 23.4 ± 16.3 months were included. The pooled estimate of the response rate, complete remission rate, overall relapse rate, adverse event rate, and serious adverse event rate of RTX induction therapy were 97.3 % (95 % CI, 94.7 %-99.1 %), 55.8 % (95 % CI, 39.6 %-71.3 %), 16.9 % (95 % CI, 8.7 %-27.1 %), 31.6 % (95 % CI, 16.7 %-48.9 %) and 3.9 % (95 % CI, 0.8 %-8.9 %), respectively. In subgroup analysis, the pooled relapse rate was significantly lower in studies with maintenance than without maintenance (2.8% vs 21.5 %, p < 0.01). Pooled Kaplan-Meier relapse curves also demonstrated that RTX maintenance therapy provided a better prognosis. CONCLUSIONS: RTX induction therapy appears to have satisfactory efficacy in the induction of remission in IgG4-RD. In addition, prophylactic RTX maintenance therapy after induction may be beneficial in preventing relapse of IgG4-RD.

A Novel Risk Stratification-Based Immunomodulatory Treatment Strategy for Vogt-Koyanagi-Harada Disease.

PURPOSE: To develop a more tailored immunomodulatory treatment (IMT) strategy based on a novel 2-arm risk stratification system in Vogt-Koyanagi-Harada (VKH) patients. DESIGN: A retrospective clinical cohort study. METHODS: Seventy-nine VKH patients in the acute stage were stratified into low- (n = 58) and high-risk (n = 21) groups based on their exposure to risk factors. They were treated with oral glucocorticoids (GCs) plus as-needed (PRN) or first-line IMT. Best corrected visual acuity (BCVA), sunset glow fundus (SGF) occurrence, relapse rate, and systemic adverse events were evaluated during follow-up. RESULTS: Compared with the low-risk group, the high-risk group showed poorer BCVA at baseline (estimated difference 0.51, 95% CI 0.30-0.78; P < .001) and 6-month follow-up (estimated difference 0.08, 95% CI 0.00-0.08; P = .006), higher incidence of SGF at 12 months (52% vs 28%; RR 1.9, 95% CI 1.1-3.4; P = .040), and higher relapse rate at 6 months (24% vs 5%; RR 4.6, 95% CI 1.2-17.5; P = .028) and 12 months (52% vs 12%; RR 4.4, 95% CI 1.9-9.7; P < .001). In the low-risk cohort, no significant difference between the 2 IMT strategies was observed in primary outcomes. In the high-risk cohort, patients with the immediate IMT showed better BCVA (estimated difference -0.20, 95% CI -0.3 to -0.08; P = .007), lower incidence of SGF (27% vs 80%; RR 0.3, 95% CI 0.1-0.9; P = .030), and lower relapse rate (27% vs 80%; RR 0.3, 95% CI 0.1-0.9; P = .030) compared with the PRN regimen. Moreover, the immediate IMT regimen had a higher frequency of systemic adverse events than the PRN regimen (47% vs 7%; RR 7.1, 95% CI 2.5-20.4; P < .001). CONCLUSIONS: High-risk stratification at baseline was associated with poor prognosis. The immediate IMT regimen was only beneficial for high-risk VKH patients regarding visual outcome, SGF, and relapse rate. This study suggests a potential need for a customized IMT strategy for VKH patients.

Membrane contact sites orchestrate cholesterol homeostasis that is central to vascular aging.

Chronological age causes structural and functional vascular deterioration and is a well-established risk factor for the development of cardiovascular diseases, leading to more than 40% of all deaths in the elderly. The etiology of vascular aging is complex; a significant impact arises from impaired cholesterol homeostasis. Cholesterol level is balanced through synthesis, uptake, transport, and esterification, the processes executed by multiple organelles. Moreover, organelles responsible for cholesterol homeostasis are spatially and functionally coordinated instead of isolated by forming the membrane contact sites. Membrane contact, mediated by specific protein-protein interaction, pulls opposing organelles together and creates the hybrid place for cholesterol transfer and further signaling. The membrane contact-dependent cholesterol transfer, together with the vesicular transport, maintains cholesterol homeostasis and has intimate implications in a growing list of diseases, including vascular aging-related diseases. Here, we summarized the latest advances regarding cholesterol homeostasis by highlighting the membrane contact-based regulatory mechanism. We also describe the downstream signaling under cholesterol homeostasis perturbations, prominently in cholesterol-rich conditions, stimulating age-dependent organelle dysfunction and vascular aging. Finally, we discuss potential cholesterol-targeting strategies for therapists regarding vascular aging-related diseases. This article is categorized under: Cardiovascular Diseases > Molecular and Cellular Physiology.

X-box Binding Protein 1: An Adaptor in the Pathogenesis of Atherosclerosis.

Atherosclerosis (AS), the formation of fibrofatty lesions in the vessel wall, is the primary cause of heart disease and stroke and is closely associated with aging. Disrupted metabolic homeostasis is a primary feature of AS and leads to endoplasmic reticulum (ER) stress, which is an abnormal accumulation of unfolded proteins. By orchestrating signaling cascades of the unfolded protein response (UPR), ER stress functions as a double-edged sword in AS, where adaptive UPR triggers synthetic metabolic processes to restore homeostasis, whereas the maladaptive response programs the cell to the apoptotic pathway. However, little is known regarding their precise coordination. Herein, an advanced understanding of the role of UPR in the pathological process of AS is reviewed. In particular, we focused on a critical mediator of the UPR, X-box binding protein 1 (XBP1), and its important role in balancing adaptive and maladaptive responses. The XBP1 mRNA is processed from the unspliced isoform (XBP1u) to the spliced isoform of XBP1 (XBP1s). Compared with XBP1u, XBP1s predominantly functions downstream of inositol-requiring enzyme-1α (IRE1α) and transcript genes involved in protein quality control, inflammation, lipid metabolism, carbohydrate metabolism, and calcification, which are critical for the pathogenesis of AS. Thus, the IRE1α/XBP1 axis is a promising pharmaceutical candidate against AS.

Mechanism of oxidized phospholipid-related inflammatory response in vascular ageing.

Vascular ageing is an important factor in the morbidity and mortality of the elderly. Atherosclerosis is a characteristic disease of vascular ageing, which is closely related to the enhancement of vascular inflammation. Phospholipid oxidation products are important factors in inducing cellular inflammation. Through interactions with vascular cells and immune cells, they regulate intracellular signaling pathways, activate the expression of various cytokines, and affect cell behavior, such as metabolic level, proliferation, apoptosis, etc. Intervention in lipid metabolism and anti-inflammation are the two key pathways of drugs for the treatment of atherosclerosis. This review aims to sort out the signaling pathway of oxidized phospholipids-induced inflammatory factors in vascular cells and immune cells and the mechanism leading to changes in cell behavior, and summarize the therapeutic targets in the inflammatory signaling pathway for the development of atherosclerosis drugs.

Risk factors for early seizure after revascularization in patients with moyamoya disease.

BACKGROUND: To investigate the risk factors for early seizure after revascularization in patients with moyamoya disease (MMD). METHODS: A total of 298 patients with MMD diagnosed in our hospital from 2015 to 2018 were analyzed retrospectively. We summarized the characteristics of seizure after revascularization in patients with MMD and analyzed the predictors of early postoperative seizure. RESULTS: We identified 15 patients with MMD who developed seizures within 1 week after revascularization. According to logistic regression analysis, age (OR: 1.04, 95% CI 0.998-1.086; P = 0.060) and infarct side (OR: 1.92, 95% CI 0.856-4.290; P = 0.113) were not significantly associated with incident early seizure. Postoperative infarction (OR: 12.89, 95% CI 4.198-39.525; P = 0.000) and preoperative cerebral infarction (OR: 4.08, 95% CI 1.267-13.119; P = 0.018) were confirmed as risk factors for early seizure. CONCLUSIONS: We believe that a history of preoperative infarction and new infarction are independent risk factors of early seizure in patients with MMD after revascularization.

NF-κB and its crosstalk with endoplasmic reticulum stress in atherosclerosis.

Atherosclerosis (AS) is a common cardiovascular disease with complex pathogenesis, in which multiple pathways and their interweaving regulatory mechanism remain unclear. The primary transcription factor NF-κB plays a critical role in AS via modulating the expression of a series of inflammatory mediators under various stimuli such as cytokines, microbial antigens, and intracellular stresses. Endoplasmic reticulum (ER) stress, caused by the disrupted synthesis and secretion of protein, links inflammation, metabolic signals, and other cellular processes via the unfolded protein response (UPR). Both NF-κB and ER stress share the intersection regarding their molecular regulation and function and are regarded as critical individual contributors to AS. In this review, we summarize the multiple interactions between NF-κB and ER stress activation, including the UPR, NLRP3 inflammasome, and reactive oxygen species (ROS) generation, which have been ignored in the pathogenesis of AS. Given the multiple links between NF-κB and ER stress, we speculate that the integrated network contributes to the understanding of molecular mechanisms of AS. This review aims to provide an insight into these interactions and their underlying roles in the progression of AS, highlighting potential pharmacological targets against the atherosclerotic inflammatory process.