Serum proteomics identify CSF1R as a novel biomarker for postoperative recurrence in chronic rhinosinusitis with nasal polyps.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) presents a high rate of postoperative recurrence, but its recurrent mechanisms are not fully clarified. In this study, we aim to explore biomarkers associated with the recurrence of CRSwNP and shed light on the underlying recurrent mechanisms using serum proteomics. Methods: A prospective cohort of CRSwNP patients was conducted, and serum samples were subjected to proteomic profiling. Participants were followed up for 2 years and divided into non-Recurrence and Recurrence groups and differentially expressed proteins (DEPs) were compared. The top 3 DEPs were validated in the serum and tissue samples in a validation cohort, and their predictive values for recurrence and their associations with macrophages were evaluated. In vitro, circulating macrophages were utilized to explore the influence of candidate proteins on macrophage polarization in underlying recurrent mechanisms of CRSwNP. Results: Sixteen CRSwNP patients completed the follow-up schedule, including 10 patients in the non-Recurrence group and 6 patients in the Recurrence group. Serum proteomics revealed a distinctive protein expression profile between the 2 groups. A validation cohort comprising 51 non-recurrent and 24 recurrent CRSwNP patients was recruited. Enzyme-linked immunosorbent assay (ELISA) results revealed that circulating levels of CSF1R and CDC42 were significantly higher, and DHRS9 levels were lower in the Recurrence group in comparison with the non-Recurrence group. In addition, tissue CSF1R and CDC42 were identified to be enhanced in the Recurrence group compared to the non-Recurrence group. Receiver-operated characteristic (ROC) curves and Kaplan-Meier survival analysis suggest that both serum and tissue CSF1R were associated with the risk of postoperative recurrence. Tissue immunofluorescence (IF) revealed that CSF1R was enhanced in the tissues of patients with recurrence, especially in the mesenchymal region. Multiplex IF highlighted that CSF1R was significantly co-expressed with M2 macrophage markers. In vitro experiments confirmed that CSF1R overexpression promoted macrophage M2 polarization and cytokine production. Conclusion: Serum proteomic signatures may affect postoperative recurrence in CRSwNP patients. CSF1R is a potential biomarker for predicting CRSwNP recurrence. Mechanistically, the recurrence of CRSwNP appears to involve the CSF1R-driven M2 polarization process.

Multiple cytokine analyses identify CSF1 as a robust biomarker for predicting postoperative recurrence in chronic rhinosinusitis with nasal polyps.

OBJECTIVE: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease with a high rate of postoperative recurrence. This study aimed to discover potential biomarkers by analyzing multiple cytokine profiles in serum to predict postoperative recurrence in CRSwNP and to explore the underlying mechanisms. METHODS: In this prospective study, we enrolled 18 healthy controls (HC) and 60 CRSwNP patients and analyzed the baseline serum cytokine profiles using the Luminex assay. Patients were followed up for more than 2 years and divided into non-recurrence and Recurrence groups. The differentially expressed cytokines were validated in the serum and tissue samples in a validation cohort, and their predictive values for recurrence were evaluated. RESULTS: Fifty-four CRSwNP patients completed the follow-up schedule, including 37 patients in the non-Recurrence group and 17 patients in the Recurrence group. Multiple cytokine analyses showed that serum CD40, CD40L, IL-18, IL-8, MCP1, and CSF1 levels were elevated in the CRSwNP group, especially in the Recurrence group, compared to the HC group. Receiver operating characteristic curves (ROC) and Kaplan-Meier survival analysis showed that serum levels of CD40, CD40L, and CSF1 were closely associated with the risk of postoperative recurrence. Further validation results showed that both serum and tissue mRNA levels of CD40, CD40L, and CSF1 were significantly higher in the Recurrence group in comparison with the non-recurrence and HC groups, and tissue CSF1 mRNA expression exhibited a robust value for predicting the CRSwNP recurrence. Immunofluorescence results revealed that CSF1 was enhanced in the recurrent CRSwNP patients, especially in the epithelial cell area, and CSF1 expressions were augmented when patients suffered postoperative recurrence. CONCLUSIONS: Circulating cytokine profiles may affect the risk of postoperative recurrence in CRSwNP patients. Our discovery-validation results suggested that CSF1 might serve as a robust biomarker for predicting CRSwNP recurrence.

Circulating exosomal has-miR-24-3p and has-miR-128-3p reflect early efficacy of sublingual immunotherapy in allergic rhinitis.

OBJECTIVE: Sublingual immunotherapy (SLIT) can improve the symptoms of allergic rhinitis (AR) and modify its natural course, but its effectiveness varies among individuals. This study aims to analyze miRNAs from serum exosomes and evaluate their predictive values for the early response of SLIT in AR. METHODS: RNA sequencing was performed to investigate the differential expressions of serum exosomal miRNAs between ineffective and effective AR patients who treated with SLIT. The identified candidate miRNAs were validated in two independent cohorts, and the predictive capabilities of these miRNAs and alterations of their expression levels between pre- and 1 year post-SLIT were evaluated. RESULTS: The serum exosome-derived miRNA profiles were significantly different between the effective and ineffective groups. The five most up-regulated and down-regulated miRNAs were verified in the first validation cohort, and the results demonstrated that serum exosomal has-miR-24-3p and has-miR-206 were reduced, while has-miR-128-3p was increased in the effective group compared to the ineffective group (P < 0.05). Additionally, the receiver operating characteristic (ROC) curves revealed that serum levels of has-miR-24-3p and has-miR-128-3p displayed potential values for predicting the early efficacy of SLIT (P < 0.05). In the second validation cohort, it was observed that the baseline levels of serum exosomal has-miR-24-3p were significantly lower, while has-miR-128-3p levels were significantly higher in the effective group compared to the ineffective group (P < 0.05). After 1 year of SLIT, there was a significant decrease in serum exosomal levels of has-miR-24-3p compared to baseline. On the other hand, effective patients showed a notable increase in serum exosomal levels of has-miR-128-3p (P < 0.05). CONCLUSION: Serum exosome-derived miRNAs have the potential to impact the efficacy of SLIT in AR patients. Among them, serum exosomal has-miR-24-3p and has-miR-128-3p show promise as biomarkers for predicting the early effectiveness of SLIT and monitoring therapeutic outcomes.

Subthalamic deep brain stimulation for primary dystonia: defining an optimal location using the medial subthalamic nucleus border as anatomical reference.

Introduction: Although the subthalamic nucleus (STN) has proven to be a safe and effective target for deep brain stimulation (DBS) in the treatment of primary dystonia, the rates of individual improvement vary considerably. On the premise of selecting appropriate patients, the location of the stimulation contacts in the dorsolateral sensorimotor area of the STN may be an important factor affecting therapeutic effects, but the optimal location remains unclear. This study aimed to define an optimal location using the medial subthalamic nucleus border as an anatomical reference and to explore the influence of the location of active contacts on outcomes and programming strategies in a series of patients with primary dystonia. Methods: Data from 18 patients who underwent bilateral STN-DBS were retrospectively acquired and analyzed. Patients were assessed preoperatively and postoperatively (1 month, 3 months, 6 months, 1 year, 2 years, and last follow-up after neurostimulator initiation) using the Toronto Western Spasmodic Torticollis Rating Scale (for cervical dystonia) and the Burke-Fahn-Marsden Dystonia Rating Scale (for other types). Optimal parameters and active contact locations were determined during clinical follow-up. The position of the active contacts relative to the medial STN border was determined using postoperative stereotactic MRI. Results: The clinical improvement showed a significant negative correlation with the y-axis position (anterior-posterior; A+, P-). The more posterior the electrode contacts were positioned in the dorsolateral sensorimotor area of the STN, the better the therapeutic effects. Cluster analysis of the improvement rates delineated optimal and sub-optimal groups. The optimal contact coordinates from the optimal group were 2.56 mm lateral, 0.15 mm anterior, and 1.34 mm superior relative to the medial STN border. Conclusion: STN-DBS was effective for primary dystonia, but outcomes were dependent on the active contact location. Bilateral stimulation contacts located behind or adjacent to Bejjani's line were most likely to produce ideal therapeutic effects. These findings may help guide STN-DBS preoperative planning, stimulation programming, and prognosis for optimal therapeutic efficacy in primary dystonia.

Bilateral subthalamic nucleus deep brain stimulation for refractory isolated cervical dystonia.

Subthalamic nucleus (STN) deep brain stimulation (DBS) has been proven to be an alternative target choice for refractory isolated cervical dystonia (CD). However, assessments of its short and long-term safety, efficacy, and sustained effectiveness have been limited to few reports. Here, we evaluated nine consecutive refractory isolated CD patients who underwent bilateral STN DBS and accepted to short and long-term follow-up in this retrospective study. Seven time points were used to see the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) scores (pre-operation [baseline], 1, 3, 6, 12, 24 months post-operation and last follow-up) to assess improvement of dystonic symptoms. The 36-item Short-Form General Health Survey (SF-36) scores obtained at pre-operation and last follow-up to assess the changes in quality of life. All patients tolerated surgery well and acquired observable clinical benefits from STN DBS therapy. All patients achieved a considerable improvement in quality of life at the last follow-up. The hardware-related adverse events can be tolerated and the stimulation-related adverse events can be ameliorated by programming. Our data support the idea that bilateral STN DBS is a safety and effective method for the treatment of refractory isolated CD, with persistent and remarkable improvement in both movement and quality of life.