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.

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.

Contribution of insulin resistance to the relationship between sugar-sweetened beverage intake and a constellation of cardiometabolic abnormalities in adolescents.

BACKGROUND: Insulin resistance (IR) is a pathophysiological construct that derives a series of metabolic disturbances that promote cardiometabolic dysfunction. This study evaluated mediating and modifying effects of homeostatic model assessment-based IR (HOMA-IR) on the association between sugar-sweetened beverage (SSB) consumption and a constellation of adolescent cardiometabolic abnormalities. METHODS: Comprehensive data on sociodemographics, diet, physical activity, and anthropometric and biochemical parameters for 1454 adolescents were obtained from a large-scale representative study for adolescent metabolic syndrome (MetS) conducted in Taiwan. The original (HOMA1-IR) and updated nonlinear (HOMA2-IR) HOMA-IR indicators were used as IR biomarkers. Principal component (PC) analysis was employed to create reduced groups of variables and risk scores for retained PCs. RESULTS: Higher SSB intake was associated with higher levels of HOMA1-IR and HOMA2-IR, and the two IR biomarkers were positively correlated with metabolic dysfunction clustering. Compared with SSB nondrinkers, adolescents who consumed >500 mL/day of hand-shaken high-fructose corn syrup beverages (HHB) had a 0.22 increase in the number of abnormal MetS components, and HOMA-IR mediation explained 33.9-37.9% of the effect. IR biomarkers accounted for 26.5-31.0% of the relationship between >500 mL/day of SSB consumption and bodyweight-enhanced PC scores. The effects of HOMA-IR indicators on all bodyweight-related factors were consistently intensified among >350 mL/day HHB drinkers (all Pinteraction < 0.05). CONCLUSIONS: Fructose-rich SSB intake correlates with a constellation of cardiometabolic abnormalities in adolescents, and this association may be partly mediated by HOMA-IR levels. The adverse effects of HOMA-IR on bodyweight-associated cardiometabolic risk factors depend on the type of SSB consumption, with enhanced risks observed in the intake of high amounts of HFCS-containing SSBs.

Tissue microbiota in nasopharyngeal adenoid and its association with pneumococcal carriage.

The microbial colonization in the nasopharynx is a prerequisite for the onset of infectious diseases. For successful infection, pathogens should overcome host defenses as well as compete effectively with the resident microbiota. Hence, elucidating the richness and diversity of the microbiome at the site of pathogen colonization is pivotal. Here, we investigated the adenoidal tissue microbiota collected through adenoidectomy to evaluate the impact of Streptococcus pneumoniae. Prospectively, children with sleep-disordered breathing (SDB) and otitis media with effusion (OME) were enrolled. During adenoidectomy, the nasopharyngeal swab and adenoid tissues were collected to determine the pneumococcal carriage and tissue microbiota, using multiplex PCR and 16S ribosomal RNA (16S rRNA) pyrosequencing. A total of 66 pediatric patients comprising 38 children with SDB and 28 children with OME were enrolled. There was no difference between the bacterial cultures from the surface of the nasopharyngeal adenoid in the SDB and OME groups. Thirty-four samples (17 SDB and 17 OME) underwent 16S rRNA pyrosequencing and fulfilled the criteria for further analysis. The Shannon diversity index for the samples from the SDB patients was found to be higher than that observed for the samples from OME patients, although the difference was not significant (p = 0.095). The Shannon diversity index for the samples negative for the pneumococcal carriage was significantly higher than that for the samples positive for pneumococcal carriage (p = 0.038). Alloprevotella, Staphylococcus, Moraxella, and Neisseriaceae were significantly dominant in the samples positive for the pneumococcal carriage. Dialister was significantly less present in the adenoid tissue positive for the pneumococcal carriage. Streptococcus pneumoniae, one of the most common pathogens of the airway, significantly influences the composition and diversity of the microbiota in the nasopharyngeal adenoid. Thus, bacterial community analysis based on 16S rRNA pyrosequencing allows for better understanding of the relationship between the adenoidal microbial communities.

Oral tongue leukoplakia: analysis of clinicopathological characteristics, treatment outcomes, and factors related to recurrence and malignant transformation.

OBJECTIVES: The tongue is identified as a high-risk site for oral leukoplakia and malignant transformation. The purpose of this study is to investigate the clinicopathological characteristics and treatment outcomes of tongue leukoplakia and assess the factors related to recurrence and malignant transformation. MATERIALS AND METHODS: One hundred and forty-four patients who received carbon dioxide laser surgery for tongue leukoplakia from 2002 to 2019 were analyzed statistically. RESULTS: The follow-up period was 54.90 ± 54.41 months. Thirty patients showed postoperative recurrence (20.83%), and 12 patients developed malignant transformation (8.33%). The annual transformation rate was 2.28%. Univariate analysis showed that a history of head and neck cancer, size of lesion area, clinical appearance, and pathology were significant factors for both recurrence and malignant transformation. In the multivariate logistic regression, a history of head and neck cancer and size of lesion area were independent prognostic factors for recurrence, and a history of head and neck cancer was the only independent factor for postoperative malignant change. CONCLUSIONS: Clinicians should adopt more aggressive strategies for tongue leukoplakia patients with a history of head and neck cancer. CLINICAL RELEVANCE: These results may help clinicians gain a better understanding of oral tongue leukoplakia.

Human stratum corneum proteomics reveals cross-linking of a broad spectrum of proteins in cornified envelopes.

Defects in keratinocyte transglutaminase (TGM1), resulting in an improper protein scaffold for deposition of the lipid barrier, comprise a major source of autosomal recessive congenital ichthyosis. For that reason, the composition and formation of the cornified (cross-linked) protein envelope of the epidermis have been of considerable interest. Since the isopeptide cross-linked protein components are not individually isolable once incorporated, purified envelopes were analysed by mass spectrometry after trypsin digestion. Quantitative estimates of the identified components revealed some 170 proteins, each comprising at least 0.001% of the total, of which keratins were major constituents accounting for ≈74% of the total. Some prevalent non-keratin constituents such as keratinocyte proline-rich protein, loricrin and late envelope protein-7 were preferentially incorporated into envelopes. The results suggest a model where, as previously observed in hair shaft and nail plate, a diversity of cellular proteins are incorporated. They also help rationalize the minimal effect on epidermis of ablating genes for specific single envelope structural components. The quantitative profile of constituent proteins provides a foundation for future exploration of envelope perturbations that may occur in pathological conditions.

Impact of cigarette smoke and IL-17A activation on asthmatic patients with chronic rhinosinusitis

Background: Cigarette smoke have adverse effects in the control of asthma and chronic rhinosinusitis (CRS). Interleukin (IL)-17A, the signature cytokine of helper T 17 cells and group 3 innate lymphoid cells (ILC3), has been reported to link with resistance to therapy in airway inflammation. This study aimed to investigate the impact of cigarette smoking and IL-17A activation on the clinical outcomes of asthmatic patients with chronic rhinosinusitis. Methods: 33 patients with CRS and asthma, including 15 smokers and 18 non-smokers, and 7 asthmatic patients without CRS and smoking were prospectively recruited. The Sino-Nasal Outcome Test-22 and Asthma Control Test were used to evaluate sinonasal symptoms and the level of asthma control, respectively. Real-time PCR and immunostaining were applied to evaluate the expression levels of IL-17A and associated immunological factors on surgically-obtained nasal tissues. Results: Nasal surgery improved both sinonasal symptoms and asthma control. Compared to non-smokers, smokers showed poorer improvement in asthma control. The expression of IL-17A, IL-22, aryl hydrocarbon receptor (AhR), and ILC3 was increased in the nasal tissues of smokers with asthma and CRS. The expression of IL-17A mRNA was correlated with that of AhR and with positive nuclear AhR-AhR nuclear translocator staining cells, and that of cyclooxygenase-2 enzyme (COX-2). ILC3 cells were associated with IL-17A, IL-22, AhR, and COX-2 mRNA expression. Conclusions: Cigarette smoking was related to lesser improvement in asthma control after nasal surgery and to IL-17A activation in the nasal tissues of patients with inflammatory airways.

Effects of insulin resistance on the association between the circulating retinol-binding protein 4 level and clustering of pediatric cardiometabolic risk factors.

OBJECTIVES: Retinol-binding protein 4 (RBP4) and insulin resistance (IR) are clinical parameters associated with cardiometabolic diseases. The mediating and modifying roles of IR on children's susceptibility to cardiometabolic disorders are undetermined. This study investigated the mediating and modifying effects of the homeostatic model assessment of IR (HOMA-IR) on the relationship between the serum RBP4 level and clustering of pediatric cardiometabolic risk factors. METHODS: We assessed the diet, physical activity, cardiometabolic risk factors, and clinical parameters of 272 randomly selected adolescents from a large-scale cross-sectional study (n = 2727). Two HOMA-IRs (HOMA1-IR and HOMA2-IR) were used to evaluate the designated effects. RESULTS: Levels of serum RBP4 positively correlated with the levels of the 2 HOMA-based-IRs, and HOMA-IR correlated to all components of pediatric metabolic syndrome (MetS), the number of abnormal components, and a body-weight-weighted principal component score extracted from 12 cardiometabolic risk factors. Increased RBP4 levels had positive effects on waist circumference (WC), triglyceride, and the number of abnormal MetS components (0.310 cm, 1.384 µg/dL, and 0.021 item elevations, respectively), and the HOMA-IRs explained 17.7% to 21.9%, 11.8% to 27.6%, and 23.8% to 25.0% of these effects. The association of WC and the number of abnormal MetS components with the serum RBP4 level was enhanced by higher HOMA-IR (ß for interaction, 0.13 and 0.01 for HOMA1-IR, and 0.32 and 0.02 for HOMA2-IR, respectively). CONCLUSIONS: HOMA-IR is associated with the circulating RBP4 level and cardiometabolic risk factors in adolescents. Pediatric HOMA-IR may have mediating and modifying effects on the positive correlations between RBP4 and the clustering of MetS components.

Proteomic analysis of hair shafts from monozygotic twins: Expression profiles and genetically variant peptides.

Forensic association of hair shaft evidence with individuals is currently assessed by comparing mitochondrial DNA haplotypes of reference and casework samples, primarily for exclusionary purposes. Present work tests and validates more recent proteomic approaches to extract quantitative transcriptional and genetic information from hair samples of monozygotic twin pairs, which would be predicted to partition away from unrelated individuals if the datasets contain identifying information. Protein expression profiles and polymorphic, genetically variant hair peptides were generated from ten pairs of monozygotic twins. Profiling using the protein tryptic digests revealed that samples from identical twins had typically an order of magnitude fewer protein expression differences than unrelated individuals. The data did not indicate that the degree of difference within twin pairs increased with age. In parallel, data from the digests were used to detect genetically variant peptides that result from common nonsynonymous single nucleotide polymorphisms in genes expressed in the hair follicle. Compilation of the variants permitted sorting of the samples by hierarchical clustering, permitting accurate matching of twin pairs. The results demonstrate that genetic differences are detectable by proteomic methods and provide a framework for developing quantitative statistical estimates of personal identification that increase the value of hair shaft evidence.

MicroRNA-302d targets IRF9 to regulate the IFN-induced gene expression in SLE.

Systemic lupus erythematosus (SLE) is a complex disease targeting multiple organs as a result of overactivation of the type I interferon (IFN) system, a feature currently being targeted by multiple biologic therapies against IFN-α. We have identified an estrogen-regulated microRNA, miR-302d, whose expression is decreased in SLE patient monocytes and identify its target as interferon regulatory factor (IRF)-9, a critical component of the transcriptional complex that regulates expression of interferon-stimulated genes (ISGs). In keeping with the reduced expression of miR-302d in SLE patient monocytes, IRF9 levels were increased, as was expression of a number of ISGs including MX1 and OAS1. In vivo evaluation revealed that miR-302d protects against pristane-induced inflammation in mice by targeting IRF9 and hence ISG expression. Importantly, patients with enhanced disease activity have markedly reduced expression of miR-302d and enhanced IRF9 and ISG expression, with miR-302d negatively correlating with IFN score. Together these findings identify miR-302d as a key regulator of type I IFN driven gene expression via its ability to target IRF9 and regulate ISG expression, underscoring the importance of non-coding RNA in regulating the IFN pathway in SLE.

Fructose-Rich Beverage Intake and Central Adiposity, Uric Acid, and Pediatric Insulin Resistance.

OBJECTIVE: To determine the association between sugar-sweetened beverage (SSB) consumption with biomarkers of insulin resistance (IR) and investigate whether/how this relates to obesity and serum uric acid in adolescents. STUDY DESIGN: Adolescents (n = 1454, aged 12-16 years) were assessed in a study conducted to monitor Multilevel Risk Profiles for Adolescent Metabolic Syndrome in Taiwan. Detailed information about demographics, diet, physical, anthropometric, and clinical variables was collected. An original homeostatic model assessment of IR (HOMA1-IR), updated nonlinear homeostatic model assessment of IR (HOMA2-IR) model, and several IR markers were measured. RESULTS: Adolescents who consumed a greater amount of SSBs were more likely to have elevated fasting serum insulin, HOMA1-IR, and HOMA2-IR (P for trends, ≤.028). Compared with SSB nondrinkers, those with >350 mL/d intake of heavy high-fructose corn syrup-containing SSBs had a 0.52 and 0.30 higher multivariate-adjusted HOMA1-IR and HOMA2-IR, respectively. Waist circumference and serum uric acid were correspondingly found to explain 25.4% and 23.6%, as well as 23.2% and 20.6%, of the increases in the 2 IR markers. Both the elevations of HOMA1-IR and HOMA2-IR for high-fructose corn syrup-rich SSB intake were strengthened among obese adolescents (P for interaction, ≤.033). CONCLUSIONS: Fructose-rich SSB intake is associated with elevated levels of IR, and this relationship may be partially mediated by central adiposity and serum uric acid. Obesity may modify the effect of this type of SSB consumption in intensifying the elevation of IR in adolescents.

Parallel responses of human epidermal keratinocytes to inorganic SbIII and AsIII.

SbIII and AsIII are known to exhibit similar chemical properties, but the degree of similarity in their effects on biological systems merits further exploration. Present work compares the responses of human epidermal keratinocytes, a known target cell type for arsenite-induced carcinogenicity, to these metalloids after treatment for a week at environmentally relevant concentrations. Previous work with these cells has shown that arsenite and antimonite have parallel effects in suppressing differentiation, altering levels of several critical enzymes and maintaining colony forming ability. More globally, protein profiling now reveals parallels in SbIII and AsIII effects. The more sensitive technique of transcriptional profiling also shows considerable parallels. Thus, gene expression changes were almost entirely in the same directions for the two treatments, although the degree of change was sometimes significantly different. Inspection of the changes revealed that RYR1 and LRIG1 were among the genes strongly suppressed, consistent with reduced calcium-dependent differentiation and maintenance of EGF-dependent proliferative potential. Moreover, levels of miRNAs in the cells were altered in parallel, with nearly 90% of the 198 most highly expressed ones being suppressed. Among these was miR-203, which is known to decrease proliferative potential. Finally, both SbIII and AsIII were seen to attenuate bone morphogenetic protein 6 induction of dual specificity phosphatases 2 and 14, consistent with maintaining epidermal growth factor receptor signaling. These findings raise the question whether SbIII, like AsIII, could act as a human skin carcinogen.

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.

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.

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.

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.

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.

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.

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.