A comprehensive review of small molecule drugs approved by the FDA in 2023: Advances and prospects.

In 2023, the U.S. Food and Drug Administration has approved 55 novel medications, consisting of 17 biologics license applications and 38 new molecular entities. Although the biologics license applications including antibody and enzyme replacement therapy set a historical record, the new molecular entities comprising small molecule drugs, diagnostic agent, RNA interference therapy and biomacromolecular peptide still account for over 50 % of the newly approved medications. The novel and privileged scaffolds derived from drugs, active molecules and natural products are consistently associated with the discovery of new mechanisms, the expansion of clinical indications and the reduction of side effects. Moreover, the structural modifications based on the promising scaffolds can provide the clinical candidates with the improved biological activities, bypass the patent protection and greatly shorten the period of new drug discovery. Therefore, conducting an appraisal of drug approval experience and related information will expedite the identification of more potent drug molecules. In this review, we comprehensively summarized the pertinent information encompassing the clinical application, mechanism, elegant design and development processes of 28 small molecule drugs, and expected to provide the promising structural basis and design inspiration for pharmaceutical chemists.

[The relationship between birth weight and obstructive sleep apnea in children].

Objective:To study the relationship between children's birth weight and obstructive sleep apnea（OSA）. Methods:The sleep data and birth information of children who underwent polysomnography in the Department of Otorhinolaryngology-Head and Neck Surgery of Henan Children's Hospital from October 2020 to July 2022 were retrospectively analyzed. The data of OSA detection rate, OSA severity, sleep structure and respiratory parameters in different birth weight groups were analyzed. Results:A total of 2 778 children met the inclusion criteria, including 1 833 males and 945 females. According to birth weight, the selected children were divided into three groups: 122 small for gestational age（SGA） group, 2 313 appropriate for gestational age（AGA）, and 343 large for gestational age（LGA） group. There was no significant difference in age between different groups（P=0.061）. In each group, boys are significantly more numerous than girls（P=0.001）. The difference in current body mass index（BMI） between groups was statistically significant: the current BMI was higher in the LGA group（17.51±4.01, P<0.001）. The severity of OSA was different in different birth weight groups（P=0.037）. There was a strong positive correlation between the severity of OSA and birth weight（r=0.992）. Children in the SGA group had shorter rapid eye movement（REM） sleep period（19.00[15.18, 23.33], P=0.012）, higher obstructive apnea-hypopnea index（OAHI） values（1.75[0.60, 5.13], P=0.019）, and had lower central apnea hypopnea index（CAHI） values（0.10[0.00, 0.50], P=0.020）. There were no significant differences in sleep structure and respiratory parameters between the LGA group and the AGA group. Multiple regression analysis of the factors affecting the OAHI index showed that the OAHI index of boys was higher than that of girls（95%CI 1.311-2.096, P<0.001）, and age was negatively correlated with the OAHI index（r=-0.105, 95%CI 0.856-0.946, P<0.001）, current BMI and OAHI index were positively correlated（r=0.037, 95%CI 1.010-1.065, P=0.007）. LGA was positively correlated with OAHI index（r=0.346, 95%CI 1.039-1.921, P=0.027）, and the correlation between LGA and OAHI（r=0.346） was higher than that between SGA and OAHI（r=0.340）. Conclusion:There was no significant difference in the incidence of OSA in children with different birth weight groups, but the OSA severity of LGA group was higher. Gender, age, BMI index and large for gestational age were the influencing factors for the occurrence of OSA in children, which should be paid more attention to in clinical practice.

The Clinical Characteristics in Children with Sinonasal Inverted Papilloma: A Case Report and Review of the Literature.

Sinonasal inverted papilloma (SNIP) is one of the most common benign epithelial tumors but rarely occurs in children. The case of a 9-year-old Chinese boy, who presented with a left maxillofacial hump, nasal obstruction, and left nasal cavity and maxillary sinus masses under nasal endoscopy, is reported. The lesion was first diagnosed as a sinonasal tumor. However, to our surprise, the mass was determined to be an inverted papilloma after a detailed histological examination. We retrospectively reported the clinical data of this case and reviewed the relevant literatures on SNIP. This report aims to provide new insights into the clinical characteristics in children with SNIP and improve the understanding of this disease.

A Clinical Analysis of Pharyngeal Bronchogenic Cysts in the Pharynx of Children.

Objective: This study was designed to summarize the clinical characteristics, diagnosis and treatment of pharyngeal bronchogenic cysts in children to help in making the correct diagnosis and developing an appropriate treatment plan. Methods: The clinical data of 13 children with bronchogenic cysts in the pharynx, who were treated in otolaryngology head and neck surgery department between September 2013 and July 2019, were analyzed retrospectively. The clinical characteristics were evaluated, and the related factors for diagnosis and treatment were analyzed. Clinical characteristics and imaging features of three cases whose lesions located in the nasopharyngeal, oropharynx, and laryngopharyngeal were demonstrated. Results: All 13 children were male, the youngest being 4 days old, the oldest 6 years and 6 months, and the median age being 1 year and 4 months. Eight patients were diagnosed during a physical examination, and five patients visited the doctor with different degrees of upper airway obstruction. The mass was located in the nasopharynx in one patient, in the oropharynx in eight patients, and in the laryngopharynx in the other four patients. Computed tomography (CT) scanning, which is helpful for a topical diagnosis, showed a dense homogeneous mass. Electronic nasopharyngoscopy showed cystic masses of different sizes in the pharynx. All the children underwent cyst resection under general anesthesia, and the postoperative pathology result was a bronchogenic cyst. One child was lost to follow-up, but the remaining 12 children were followed up for between 6 months and 6 years, during which no recurrence of a cyst was found. Conclusion: Bronchogenic cysts are a rare cyst of the head and neck, and the most common site of the cyst is the oropharynx. The impact on airway obstruction depends on the location and size of the cyst. CT scanning is of great significance for diagnosis. Surgical treatment should be carried out as soon as possible after diagnosis, as surgery is the most effective way to treat bronchogenic cysts. Follow-ups should be carried out regularly to prevent cyst recurrence.

Significance of SUV Max for Predicting Occult Lymph Node Metastasis and Prognosis in Early-Stage Tongue Squamous Cell Carcinoma.

OBJECTIVE: Our goal was to clarify the significance of SUV max for predicting occult lymph node metastasis and prognosis in early-stage tongue squamous cell carcinoma (SCC). METHODS: cT1-2N0 tongue SCC patients who underwent a preoperative PET-CT examination were prospectively enrolled. The association between SUV max and occult lymph node metastasis was analyzed. The main study endpoint was locoregional control (LRC). The Cox model was used to determine the independent factors. RESULTS: A total of 120 patients were included for analysis, and the median SUV max was 9.7. In 60 patients with an SUV max ≤9.7, 5 patients had occult metastasis; in 60 patients with an SUV max >9.7, 13 patients had occult metastasis, and the difference was significant (p=0.041). In patients with an SUV max ≤9.7, the 5-year LRC rate was 93%; in patients with an SUV max >9.7, the 5-year LRC rate was 81%, and the difference was significant (p=0.045). CONCLUSION: An SUV max >9.7 was a marker for occult lymph node metastasis and could decrease LRC in patients with cT1-2N0 tongue SCC.

Intraparotid Lymph Node Metastasis Decreases Survival in Pediatric Patients With Parotid Cancer.

PURPOSE: The occurrence of parotid cancer in pediatric patients is uncommon, and the significance of intraparotid lymph node (IPN) metastasis in the pediatric population remains unknown. Therefore, the main goal of the present study was to analyze the effect of IPN metastasis on survival in pediatric patients with parotid cancer. PATIENTS AND METHODS: Pediatric patients with parotid cancer were retrospectively enrolled from multiple medical centers. The association between IPN metastasis and clinicopathologic variables was analyzed using χ2 tests. The main study endpoint was recurrence-free survival (RFS), which was calculated using the Kaplan-Meier method. Independent prognostic factors were evaluated using the Cox proportional hazards method. RESULTS: IPN metastasis was noted in 15 of 77 patients (19.5%). A positive relationship was noted between IPN metastasis and tumor stage, lymphoma history, and disease grade. The 10-year RFS was 91%. Univariate analysis revealed that IPN metastasis, disease grade, resection extent, tumor stage, and lymphoma history were associated with RFS. Cox regression analysis revealed that IPN metastasis (odds ratio [OR], 2.805; 95% confidence interval [CI], 1.697 to 5.119; P = .004) and lymphoma history (OR, 1.742; 95% CI, 1.027 to 3.687; P = .014) were the only 2 independent predictors of recurrence. CONCLUSIONS: IPN metastasis significantly decreased survival in patients with pediatric parotid cancer.

Summary of the Experience in the Diagnosis and Treatment of Complex Preauricular Fistulas in 78 Children.

Objective: This study aimed to investigate the application of mini-incisions in complex preauricular fistula resection in children. Methods: A total of 78 children who were diagnosed with preauricular fistula infection between January 2017 and December 2019 were included in the study. Their clinical data were analyzed retrospectively, and surgical treatment with mini-incisions based on plastic surgery principles and techniques was provided. Results: All the patients achieved healing following the first application of the treatment. The patients were followed up for 6-42 months, and no recurrence or local auricular deformation occurred. Conclusion: The application of mini-incisions and plastic surgery techniques in complex preauricular fistula resection in children can achieve a good effect and improve the satisfaction of the children and their parents.

Prognostic Value of the Pretreatment Neutrophil-to-Lymphocyte Ratio in Pediatric Parotid Cancer.

Objective: Our goal was to evaluate the prognostic significance of the neutrophil-to-lymphocyte ratio (NLR) in pediatric patients with parotid cancer. Materials and Methods: Pediatric patients with primary parotid cancer were retrospectively enrolled from several clinical centers. The associations between the clinical-pathologic variables and NLR and the prognostic significance of NLR for recurrence-free survival (RFS) and disease-specific survival (DSS) were analyzed. Results: A total of 123 patients were included. The mean NLR was 2.51 and ranged from 1.7 to 6.1. The tumor stage and disease grade were significantly related to NLR. In patients with NLR < 2.51, the 10-year RFS rate was 97%, and in patients with NLR ≥ 2.51, the 10-year RFS rate was 84%; the difference was significant (p = 0.016). In patients with NLR < 2.51, the 10-year DSS rate was 98%, and in patients with NLR ≥ 2.51, the 10-year DSS rate was 83%; this difference was also significant (p = 0.035). Further Cox model analysis confirmed the independence of NLR in predicting the RFS and DSS rates. Conclusions: NLR is significantly associated with prognosis in pediatric patients with parotid cancer.

Oncologic outcome of parotid mucoepidermoid carcinoma in pediatric patients.

BACKGROUND: The goal of this study was to investigate the long-term oncologic outcome of parotid mucoepidermoid carcinoma (MEC) in pediatric patients. PATIENTS AND METHODS: Patients <19 years old who were diagnosed with MEC from January 1990 to December 2017 were retrospectively enrolled in this study. The main analyzed indexes included intraparotid node (IPN) metastasis, neutrophil-tolymphocyte ratio (NLR), loco-regional control (LRC), and disease-specific survival (DSS) rates. RESULTS: A total of 73 patients were enrolled. IPN metastasis occurred in 13 (17.8%) patients; the mean value of the NLR was 2.48 (range: 1.3-6.1). Loco-regional recurrence occurred in 12 patients, and 7 patients died of the disease. The 10-year LRC and DSS rates were 83% and 88%, respectively. IPN metastasis remained significantly related to recurrence in both univariate and Cox model analyses; a high NLR was significantly associated with recurrence in the univariate analysis but not in the Cox model. IPN metastasis remained significantly related to disease-related death in both the univariate and Cox model analyses; a high NLR was not associated with the DSS in univariate analysis. CONCLUSION: The long-term survival rate was relatively favorable in pediatric MEC. IPN metastasis was an independent risk factor for loco-regional recurrence and DSS. The role of the NLR in predicting survival in parotid cancer requires more research.

Prognosis of osteosarcomas in the mandible: 15-year experience of 55 patients.

Our goal was to evaluate the prognosis of osteosarcomas (OS) in the mandible for finding out the best treatment.Patients diagnosed with OS in the mandible from January 2000 to December 2015 were retrospectively enrolled. Demographic, tumor-specific, treatment, and survival data were collected and analyzed.A total of 55 patients (35 male and 20 female) were included, all patients had first manifestation of swelling. Cachexia occurred in 15 (27.3%) patients. Chondroblastic type was the most common histology subtype followed by osteoblastic type. High grade tumors were found in 30 (63.6%) patients. 33 (60%) patients received an operation of hemimandibulectomy, and free fibula reconstruction was performed in 20 (36.4%) patients. The 5-year recurrence-free survival (RFS) and disease-specific survival (DSS) rates were 73.6% and 66.9%, respectively. Univariate prognostic analysis reported risk factors of tumor grade, reconstruction type (free fibula flap vs non-free flap), and operation extent were significant for the recurrence, and reconstruction type and operation extent were significant for the disease-specific death, but in multivariate analysis, only the factor of operation extent was significantly associated with both the recurrence and death.A wide excision extent such as hemimandibulectomy is suggested for OS in the mandible for achieving good prognosis.