Incidence rate of recurrent cardiovascular events in patients with radiographic axial spondyloarthritis and the effect of tumor necrosis factor inhibitors.

BACKGROUND: Patients with radiographic axial spondyloarthritis (r-axSpA) are at increased risk of incident cardiovascular events. Tumor necrosis factor inhibitors (TNFi) have shown a protective effect against incident cardiovacular events. However, the incidence of recurrent cardiovascular events in patients with r-axSpA with a history of cardiovascular events, and the effect of TNFi on recurrent cardiovascular events remain unclear. We aimed to assess the incidence rate of recurrent cardiovascular events in patients with r-axSpA with a history of cardiovascular events and evaluate the effect of TNFi on the risk of recurrent cardiovascular events. METHODS: This nationwide cohort study used data from the Korean National Claims Database. Data of patients with r-axSpA who had a history of cardiovascular events after being diagnosed with r-axSpA were extracted from the database. The outcome of interest was the recurrence of cardiovascular events (myocardial infarction or stroke). Patients were followed from the index date (date of the first cardiovascular event) to the date of cardiovascular event recurrence, the last date with claims data, or December 31, 2021, whichever occured first. The incidence rate of recurrent cardiovascular events was calculated. An inverse probability weighted Cox model was used to assess the effect of TNFi exposure on the risk of recurrent cardiovascular events. RESULTS: This study included 413 patients (TNFi non-exposure, n = 338; TNFi exposure, n = 75). The incidence rate of recurrent cardiovascular events was 32 (95% confidence interval [CI] 22-42) per 1,000 person-years (TNFi non-exposure, 36 [95% CI 24-48] per 1,000 person-years; TNFi exposure, 19 [95% CI 2-35] per 1,000 person-years). In the inverse probability weighted Cox model, TNFi exposure was significantly associated with a lower risk of recurrent cardiovascular events (hazard ratio 0.33, 95% CI 0.12-0.94). CONCLUSIONS: The incidence rate of recurrent cardiovascular events in patients with r-axSpA is substantial. TNFi exposure was associated with a lower risk of recurrent cardiovascular events.

The TOX-RAGE axis mediates inflammatory activation and lung injury in severe pulmonary infectious diseases.

Thymocyte selection-associated high-mobility group box (TOX) is a transcription factor that is crucial for T cell exhaustion during chronic antigenic stimulation, but its role in inflammation is poorly understood. Here, we report that TOX extracellularly mediates drastic inflammation upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by binding to the cell surface receptor for advanced glycation end-products (RAGE). In various diseases, including COVID-19, TOX release was highly detectable in association with disease severity, contributing to lung fibroproliferative acute respiratory distress syndrome (ARDS). Recombinant TOX-induced blood vessel rupture, similar to a clinical signature in patients experiencing a cytokine storm, further exacerbating respiratory function impairment. In contrast, disruption of TOX function by a neutralizing antibody and genetic removal of RAGE diminished TOX-mediated deleterious effects. Altogether, our results suggest an insight into TOX function as an inflammatory mediator and propose the TOX-RAGE axis as a potential target for treating severe patients with pulmonary infection and mitigating lung fibroproliferative ARDS.

Recent Advances in CAR-Based Solid Tumor Immunotherapy.

Adoptive cell therapy using chimeric antigen receptor (CAR) technology is one of the most advanced engineering platforms for cancer immunotherapy. CAR-T cells have shown remarkable efficacy in the treatment of hematological malignancies. However, their limitations in solid tumors include an immunosuppressive tumor microenvironment (TME), insufficient tumor infiltration, toxicity, and the absence of tumor-specific antigens. Although recent advances in CAR-T cell design-such as the incorporation of co-stimulatory domains and the development of armored CAR-T cells-have shown promising results in treating solid tumors, there are still challenges that need to be addressed. To overcome these limitations, other immune cells, such as natural killer (NK) cells and macrophages (M), have been developed as attractive options for efficient cancer immunotherapy of solid tumors. CAR-NK cells exhibit substantial clinical improvements with "off-the-shelf" availability and low toxicity. CAR-M cells have promising therapeutic potential because macrophages can infiltrate the TME of solid tumors. Here, we review the recent advances and future perspectives associated with engineered immune cell-based cancer immunotherapies for solid tumors. We also summarize ongoing clinical trials investigating the safety and efficacy of engineered immune cells, such as CAR-T, CAR-NK, and CAR-M, for targeting solid tumors.

Arthroscopic Foveal Repair of the Triangular Fibrocartilage Complex Improved the Clinical Outcomes in Patients With Persistent Symptomatic Distal Radio-Ulnar Joint Instability After Plate Fixation of Distal Radius Fractures: Minimum 2-Year Follow-Up.

PURPOSE: To investigate the longitudinal trend of symptomatic distal radioulnar joint (DRUJ) instability after plate fixation for distal radius fractures (DRFs), determine which factors are associated with persistent symptomatic DRUJ instability, and evaluate the postoperative outcomes of arthroscopic foveal repair of the triangular fibrocartilage complex (TFCC) in patients with persistent symptomatic DRUJ instability after plate fixation for DRF. METHODS: All consecutive patients who underwent plate fixation for DRF between January 2014 and December 2017 and were followed up for a minimum of 1 year were included in this retrospective study. DRUJ instability was evaluated by subjective ulnar wrist pain and physical examination that included foveal sign and ballottement testing every 2 months after surgery. In patients with persistent symptomatic DRUJ instability lasting >6 months, arthroscopic transosseous foveal repair was performed with consent. Clinical outcomes were evaluated at a minimum of 2 years after surgery. The Generalized Estimating Equation model was used to analyze the incidence rate trend of symptomatic DRUJ instability. RESULTS: Overall, 204 patients were included. The incidence of symptomatic DRUJ instability decreased gradually with time after fixation for DRF until 6 months and was maintained thereafter. Thirty-four of 204 patients (16.6%) had persistent symptomatic DRUJ instability. In multivariable analysis, only high-energy injury was an independent risk factor for persistent symptomatic DRUJ instability (P = .003; odds ratio = 3.599). Seventeen patients underwent arthroscopic foveal repair. The mean follow-up period thereafter was 28.6 months. All clinical outcomes improved significantly compared with preoperative values, and no patient had residual DRUJ instability. CONCLUSION: In patients who had persistent symptomatic DRUJ instability for >6 months after plate fixation for DRFs, arthroscopic foveal repair of the TFCC is considered as a treatment option. Arthroscopic foveal repair of the TFCC to stabilize the DRUJ provided satisfactory clinical and functional outcomes and decreased ulnar-side pain. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Translation and validation of the Korean Version of the Reflux Symptom Score.

OBJECTIVES: To assess the validity and reliability of the Korean version of the reflux symptom score (K-RSS). MATERIALS AND METHODS: The English version of the RSS was translated into Korean and completed by 77 people (44 and 33 people in the patient group and control group, respectively). They completed the K-RSS (K-RSS-1) and reflux symptom index (RSI) questionnaires and answered questions about age, sex, underlying disease, smoking history, and alcohol and coffee consumption. They completed the K-RSS once more (K-RSS-2) after 1 - 2 weeks. Internal consistency was evaluated using Cronbach's α and test-retest reliability using the intraclass correlation coefficient (ICC). External validity was evaluated using the Spearman rank test between the RSI and K-RSS. The Mann-Whitney U test was used to assess internal validity by comparing the K-RSS-1 scores between the patient and control groups. RESULTS: The most common symptoms were globus sensation, throat clearing, and throat pain. The K-RSS reported high internal consistency (α = 0.894). The ICC for the total score was 0.883, indicating excellent test-retest reliability. According to the Spearman analysis, there was a significant correlation between the total score of the K-RSS and that of the RSI (rs = 0.902; P < 0.001), demonstrating strong external validity. Furthermore, the patient group showed significantly higher values than the control group in all K-RSS scores, suggesting high internal validity. CONCLUSION: The K-RSS is a patient-reported outcome questionnaire with excellent criterion-referenced validity and ideal reliability.

Surgical management in a severe OSA patient diagnosed with Stickler syndrome.

Stickler syndrome is a genetic disorder of connective tissue. One of the major symptoms associated with this disorder is an oro-facial malformation, which may cause a submucous cleft or a complete cleft of the hard palate. A 32-year-old man diagnosed with Stickler syndrome and a submucosal cleft palate (SMCP) visited our hospital with a chief complaint of excessive daytime sleepiness. The patient was diagnosed with severe obstructive sleep apnea (OSA), and administration of a polysomnography test revealed an apnea-hypopnea index (AHI) of 30.9 events/hour (h). Auto-titrating continuous positive airway pressure was initiated to control the OSA symptoms and subsequently the patient showed some improvement. However, due to continuous velopharyngeal insufficiency symptoms, intravelar veloplasty was performed. Three months after surgery, the AHI had decreased to 12.4 events/h. Recent studies have described a greater risk for OSA in individuals with cleft palate, than in the general population. The present case demonstrates surgical success in a patient with OSA and SMCP, suggesting that palatal surgery may be considered an optional surgical treatment for OSA patients with SMCP.