Fructose intake, endogenous biomarkers and latent metabolic construct in adolescents: Exploring path associations and mediating effects.

BACKGROUND: Uric acid (UA) and homeostatic model assessment of insulin resistance (HOMA-IR) are endogenous biomarkers implicated in metabolic disorders and dysfunction. OBJECTIVES: To investigate the structural associations between sugar-sweetened beverage intake (SSB), UA, HOMA-IR and adolescent latent MetS construct (MetsC) representing paediatric metabolic syndrome (MetS). METHODS: A population-based representative adolescent cohort (n = 1454) was evaluated for risk profiles of MetS. Structural equation modelling was performed to identify multifactor structural associations between study parameters and evaluate mediating effects. RESULTS: Adolescents had a single-factor latent construct representing MetS. Increased SSB intake was associated with higher UA and HOMA-IR levels, and the two biomarkers were positively associated with the MetsC score. UA and HOMA-IR exerted three mediating effects on the association between fructose-rich tea beverage (FTB) intake of >500 mL/day and MetsC: adjusted standardized coefficient and mediating effect (%), FTB → UA → MetsC: 0.071, 23.1%; FTB → HOMA-IR → MetsC: 0.034, 11.0%; FTB → UA → HOMA-IR → MetsC: 0.010, 3.1%. The UA-associated pathways accounted for 31.1% of the overall mediation on the association between bottled sugar-containing beverage intake and MetsC. After accounting for the UA- and HOMA-IR-derived detrimental effects, the fructose-rich tea beverage intake of >500 mL/day had a tea-related beneficial effect on MetsC, with an adjusted standardized coefficient of -0.103. CONCLUSIONS: UA and HOMA-IR individually and jointly mediate the adverse effects of high fructose-rich SSB intake on the mechanisms underlying paediatric MetS. Fructose-free tea-based beverages may have a beneficial effect on latent MetS structure in adolescents.

Betel-quid addictive use disorders and Oral potentially malignant disorders and Oral cancer in south, southeast, and East Asia: A systematic review and meta-analysis.

OBJECTIVE: This study aimed to provide a comprehensive assessment of the measurement and prevalence of betel-quid (BQ) abuse, dependence, and BQ use disorder (BUD), as well as to evaluate the impact of BQ addiction on oral malignant diseases. METHODS: We used the PRISMA guidelines to perform a systematic review and meta-analysis. We searched for relevant publications up to April 2024 in PubMed, Web of Science, and Embase. The articles were evaluated for BQ addiction and its relationship with oral potentially malignant disorders (OPMD) and oral cancer. RESULTS: The prevalence of BQ abuse, dependence, and BUD in South, Southeast, and East Asia varied between 0.8%-46.3%, 0.4%-43.5%, and 4.7%-39.2%, respectively. Among BQ chewers, the corresponding proportions of these disorders ranged from 40.5%-99.6%, 20.9%-99.6%, and 55.2%-99.3%. The pooled risks of OPMD associated with BQ abuse, dependence, and BUD were 16.3, 18.7, and 9.6-35.5, respectively. The risk of oral cancer for mild, moderate, and severe BUD was 8.5, 8.2, and 42.3, respectively. CONCLUSIONS: BUD mediates the link between BQ use and an increased risk of oral malignant disorders. Addressing and treating BQ addiction is an important component of comprehensive OPMD and oral cancer preventive and intervention programs that go beyond simple cessation efforts.

The benefit of dupilumab as a postoperative short-term adjuvant therapy for chronic rhinosinusitis with nasal polyps: A preliminary study.

Introduction: Recent evidence recommends the use of biologics in patients with severe uncontrolled type 2 chronic rhinosinusitis with nasal polyp (CRSwNP) owing to its propensity for recurrence after functional endoscopic sinus surgery (FESS). Among the type 2 biologics used for the treatment of nasal polyps, dupilumab (Dupi, anti-IL-4) exhibited superior efficacy and safety in indirect comparison studies. Objective: This study aimed to evaluate the objective and subjective outcomes of patients with CRSwNP treated with and without adjuvant Dupi therapy after FESS. Methods: Adult patients with type 2 CRSwNP who underwent FESS with adjuvant Dupi after surgery were enrolled. A matched control group without adjuvant Dupi therapy were recruited during the same period. All patients underwent nasal endoscopy and completed the sinonasal outcome test-22 questionnaire evaluations at baseline and 3 months after surgery. Results: A total of 10 patients who received postoperative adjuvant therapy with Dupi and 20 patients who underwent surgery only were included. Patients with add-on Dupi therapy had significantly higher eosinophil cationic protein levels in the serum, eosinophil counts in peripheral blood, prevalence of asthma, and nasal polyp score at baseline. Both treatments were effective in reducing the patient's symptoms by SNOT-22 at 3 months postoperatively. However, patients with adjuvant Dupi therapy exhibited significantly better endoscopic scores than those with surgery only (p = .022). Conclusion: Surgery plays an important role in treating patients with CRSwNP, and adjuvant Dupi use may facilitate objective mucosal recovery postoperatively. Level of Evidence: 4.

Functional Exercise Capacity and Perceived Exertion in Patients with Empty Nose Syndrome.

Empty nose syndrome (ENS) is a complex condition characterized by symptoms such as dyspnea, nasal discomfort, and emotional challenges. This study aimed to evaluate functional exercise capacity and perceived exertion in patients with ENS. Patients with ENS who presented with a range of severe symptoms were prospectively enrolled. Pulmonary function was evaluated using spirometry, and functional exercise capacity was measured via the 6 min walk test (6-MWT). Perceived exertion was quantified using the Borg scale, and cardiopulmonary function was evaluated by monitoring peripheral oxygen saturation (SpO2). These parameters were assessed before and after nasal reconstruction surgery. A total of 44 patients with ENS were enrolled and classified into mild-to-moderate (n = 20) and severe (n = 24) symptom groups. Spirometry results showed no significant differences before and after surgery in the entire cohort. Perceived exertion showed significant postoperative improvement (p = 0.006). The severe ENS symptom group experienced significant improvement in SpO2 (p = 0.013) and perceived exertion (p = 0.002) at the end of the 6-MWT after surgery. Surgical intervention significantly enhanced functional exercise capacity (p = 0.038) in patients with mild-to-moderate ENS symptoms. Surgical reconstruction positively affected perceived exertion and SpO2 at the end of the 6-MWT in patients with ENS. The severity of ENS symptoms, as assessed by SNOT-25 scores, influenced these outcomes. These findings underscore the potential benefits of surgical intervention for enhancing exercise tolerance and respiratory efficiency.

An Antibody-Drug Conjugate for Multiple Myeloma Prepared by Multi-Arm Linkers.

First-line treatment of multiple myeloma, a prevalent blood cancer lacking a cure, using anti-CD38 daratumumab antibody and lenalidomide is often inadequate due to relapse and severe side effects. To enhance drug safety and efficacy, an antibody-drug conjugate, TE-1146, comprising six lenalidomide drug molecules site-specifically conjugated to a reconfigured daratumumab to deliver cytotoxic lenalidomide to tumor cells is developed. TE-1146 is prepared using the HighDAR platform, which employs i) a maleimide-containing "multi-arm linker" to conjugate multiple drug molecules creating a drug bundle, and ii) a designed peptide with a Zn2+-binding cysteine at the C-termini of a reconfigured daratumumab for site-specific drug bundle conjugation. It is shown that TE-1146 remains intact and effectively enters CD38-expressing tumor cells, releasing lenalidomide, leading to enhanced cell-killing effects compared to lenalidomide/daratumumab alone or their combination. This reveals the remarkable potency of lenalidomide once internalized by myeloma cells. TE-1146 precisely delivers lenalidomide to target CD38-overexpressing tumor cells. In contrast, lenalidomide without daratumumab cannot easily enter cells, whereas daratumumab without lenalidomide relies on Fc-dependent effector functions to kill tumor cells.

Identifying the Risk Factors for Orbital Complications in Isolated Sphenoid Rhinosinusitis.

Background and Objectives: Isolated sphenoid rhinosinusitis may have devastating consequences such as orbital complications due to its anatomical contiguity with vital structures. This study aimed to identify patients with isolated sphenoid inflammatory diseases at high risk for developing orbital complications and requiring aggressive management through investigation of the clinical and computed tomography (CT) characteristics of patients with isolated sphenoid rhinosinusitis. Materials and Methods: The medical records of patients who underwent endoscopic sinus surgery between 2005 and 2022 were retrospectively reviewed. Patients with isolated sphenoid rhinosinusitis were identified based on a manual review of the clinical and histopathological findings. Participants' clinical and CT features were reviewed. Results: Among the 118 patients with isolated sphenoid rhinosinusitis, 15 (12.7%) developed orbital complications, including diplopia, extraocular motility limitation, ptosis, and visual impairment. Headaches and facial pain occurred significantly more frequently in patients with orbital complications than in those without orbital complications (p < 0.001). Patients with diabetes mellitus or malignant neoplasms were more likely to develop orbital complications than those without these comorbidities (p < 0.05). Bony dehiscence on CT images was significantly more common in patients with orbital complications than in those without. In the regression analysis, diabetes mellitus (OR, 4.62), malignant neoplasm (OR, 4.32), and bony dehiscence (OR, 4.87) were significant predictors of orbital complications (p < 0.05). Conclusions: Headaches and facial pain are the most common symptoms of isolated sphenoid rhinosinusitis. Orbital complications of isolated sphenoid rhinosinusitis are more common in patients with comorbidities such as diabetes mellitus or malignancy or in those with bony dehiscence on CT images.

A 3-year follow-up study after nasal reconstruction surgery in patients with empty nose syndrome.

KEY POINTS: Empty nose syndrome (ENS) is characterized by a patent nasal airway and a sense of nasal obstruction. ENS and psychological symptoms improved after surgery and remained stable for up to three years. Identifying residual disease is necessary for enhancing therapeutic outcomes in ENS patients.

Computed Tomographic Evaluations in Patients with Empty Nose Syndrome.

OBJECTIVE: We aimed to evaluate computed tomography (CT) images of patients with empty nose syndrome (ENS), investigate the impact of reconstruction surgery on sinus inflammation, and identify the optimal airspace diameter after surgery. METHODS: We conducted a retrospective case series analysis, identifying and enrolling patients with ENS with perioperative CT findings. The clinical characteristics of the participants were collected, and the modified Lund-Mackay (mLM) CT scores were determined. The anterior airspace diameter was evaluated by measuring the distance between the septum and the lateral nasal wall on the coronal plane at the level of the nasolacrimal duct. RESULTS: Twenty patients with ENS and perioperative CT images were enrolled. The mean total mLM CT score and all subsite scores showed no significant changes after surgery. The Empty Nose Syndrome 6-item Questionnaire (ENS6Q) score, Sino-nasal Outcome Test-25 (SNOT-25) score, sleep symptoms domain, psychological domain, and empty nose symptoms domain were significantly associated with anterior airspace diameter in the regression analysis. CONCLUSION: There was no significant difference in sinus inflammation between preoperative and postoperative CT evaluations. The anterior airspace diameters were significantly associated with ENS6Q and SNOT-25 scores. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:2105-2110, 2024.

Clinical Characteristics of Eosinophilic Chronic Rhinosinusitis with Nasal Polyps in Adolescents.

Introduction: Eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) is frequently associated with greater inflammation, poorer prognosis, and a high recurrence rate after sinus surgery. Objective: This study evaluated the clinical and imaging characteristics of eosinophilic CRSwNP in patients aged 12-17. Methods: We retrospectively enrolled 139 patients aged 12-17 with bilateral CRSwNP. Clinical characteristics, computed tomography (CT) features, tissue eosinophil counts, and eosinophil activity were evaluated. Results: Twenty-three (16.5%) patients had recurrent nasal polyps that required revision surgery. Patients requiring revision surgery had higher tissue eosinophil infiltration in the sinus mucosa than those not requiring revision surgery. The optimal cut-off value to distinguish the need for revision surgery was a tissue eosinophil count > 21.5/high-power field determined by the receiver operating characteristic curve. The Lund-Mackay and olfactory cleft opacification scores on CT images were significant predictors of tissue eosinophil count in the univariate analysis, and only olfactory opacification scores remained statistically significant in the multivariate analysis. Conclusion: This study revealed that the CT feature of the olfactory cleft opacification score could be a significant characteristic of eosinophilic CRSwNP in adolescents.

Predicting the Probability of the Incidence of Maxillary Sinus Fungus Ball in Patients Using Nomogram Models.

Maxillary sinus fungal ball (MSFB) is the most common type of non-invasive fungal rhinosinusitis. Since MSFB requires a unique treatment strategy and is associated with potentially severe complications, timely and precise diagnosis is crucial. Computed tomography (CT) is the first-line imaging tool for evaluating chronic rhinosinusitis. Accordingly, we aimed to investigate the clinical and CT imaging characteristics of MSFB. We retrospectively enrolled 97 patients with unilateral MSFB and 158 with unilateral non-fungal maxillary rhinosinusitis. The clinical characteristics, laboratory data, and CT imaging features of participants were evaluated. Older age, female sex, lower white blood cell and neutrophil counts, and CT imaging features (including an irregular surface, erosion of the medial sinus wall, sclerosis of the lateral sinus wall, and intralesional hyperdensity) were significantly associated with MSFB. The presence of adjacent maxillary odontogenic pathology was associated with a decreased likelihood of the incidence of MSFB in unilateral maxillary rhinosinusitis. Separate nomograms were created for patients, without and with the use of CT scan, to predict the probabilities of MSFB in patients with unilateral maxillary rhinosinusitis. We proposed two nomograms based on the clinical and CT characteristics of patients with MSFB. These could serve as evaluation tools to assist clinicians in determining the need for undergoing CT and facilitate the accurate and timely diagnosis of MSFB.