Extranodal natural killer/T-cell lymphoma with tonsil involvement: a case report.

BACKGROUND: Extranodal natural killer/T-cell lymphoma (ENKTL) with tonsil involvement is not common, especially in children. CASE PRESENTATION: A 13-year-old girl presented with an unexplained sore throat for more than 2 months, together with intermittent fever and suppurative tonsilitis. Nasopharyngoscopy revealed a pharyngeal mass. Enhanced computed tomography (CT) scan showed tonsillar hypertrophy and punctate calcification. Chronic pyogenic granulomatous inflammation with pseudoepithelial squamous epithelial hyperplasia was observed in left tonsil, and pyogenic granulomatous inflammation and a small number of T-lymphoid cells were detected in the right tonsil. The immunohistochemical results showed CD2+, CD3+, CD4+, CD5+, CD8+, granzyme B+, and TIA-1+. The Ki-67 proliferation index was 20%. The case showed T cell receptor gene rearrangement. Finally, the case was diagnosed as ENKTL of stage II with tonsil involvement. The patient received 6 cycles of chemotherapy with SMILE regimen, and showed complete response with no recurrence in the follow-up. CONCLUSION: We presented a rare case of ENKTL with tonsil involvement in a child. The patient showed complete response to the SMILE chemotherapy with no recurrence.

Comparison of Superior versus Inferior Canaloplasty and Trabeculotomy Using the OMNI Surgical System.

Purpose: To compare outcomes of ab-interno canaloplasty and trabeculotomy of the superior versus inferior angle. Patients and methods: This was a prospective, non-randomized, interventional comparison study done at the Veteran Affairs Hospital in Long Beach, California. All patients underwent cataract surgery with intraocular lens implantation combined with ab-interno canaloplasty and trabeculotomy with the OMNI Surgical System (SightSciences, Menlo Park, CA, USA), either superiorly or inferiorly. Pre- and post-operative intraocular pressure using Goldmann applanation tonometry and best corrected visual acuity were obtained and compared using paired t-tests. Patients were excluded if they had any prior intraocular surgery or prior laser trabeculoplasty procedures. Results: 38 eyes from 29 patients were analyzed. 19 eyes were included in the superior group and 19 eyes in the inferior group. Mean pre-operative IOP in the superior group was 17.6 ± 5.2 mmHg and in the inferior group was 17.6 ± 4.6 mmHg (p > 0.99). At 12 months, mean postoperative IOP for the superior group decreased 24% to 13.3 ± 2.8 mmHg while the inferior group decreased 26% to 13.1 ± 2.2 mmHg (p = 0.92). Mean preoperative medications in the superior group were 2.2 ± 1.3 and in the inferior group was 2.4 ± 1.3 (p = 0.88). At 12 months, this decreased to 1.3 ± 1.5 post-operatively in the superior group and 2.2 ± 1.6 post-operatively in the inferior group (p = 0.64). Conclusion: There was no statistical difference in efficacy between superior versus inferior canaloplasty/trabeculotomy with OMNI. Therefore, surgeons can perform the procedure in the direction that is most comfortable for them without affecting outcomes.

Clinical Validation of a Handheld Deep Learning Tool for Identification of Glaucoma Medications.

Purpose: To validate a convolutional neural network (CNN)-based smartphone application for the identification of glaucoma eye drop medications in patients with normal and impaired vision. Methods: Sixty-eight patients with visual acuity (VA) of 20/70 or worse in at least one eye who presented to an academic glaucoma clinic from January 2021 through August 2022 were included. Non-English-speaking patients were excluded. Enrolled subjects participated in an activity in which they identified a predetermined and preordered set of six topical glaucoma medications, first without the CNN and then with the CNN for a total of six sequential measurements per subject. Responses to a standardized survey were collected during and after the activity. Primary quantitative outcomes were medication identification accuracy and time. Primary qualitative outcomes were subjective ratings of ease of smartphone application use. Results: Topical glaucoma medication identification accuracy (OR = 12.005, P < 0.001) and time (OR = 0.007, P < 0.001) both independently improved with CNN use. CNN use significantly improved medication accuracy in patients with glaucoma (OR = 4.771, P = 0.036) or VA ≤ 20/70 in at least one eye (OR = 4.463, P = 0.013) and medication identification time in patients with glaucoma (OR = 0.065, P = 0.017). CNN use had a significant positive association with subject-reported ease of medication identification (X2(1) = 66.117, P < 0.001). Conclusion: Our CNN-based smartphone application is efficacious at improving glaucoma eye drop identification accuracy and time. This tool can be used in the outpatient setting to avert preventable vision loss by improving medication adherence in patients with glaucoma.

[Clinical phenotypic and genetic analysis of syndrome families with EYA1 gene variants].

Objective:To investigate the clinical phenotype of a family with branchio-oto syndrome （BOS） and to explore the genetic etiology of the syndrome in this family. Methods:Clinical data were collected from a child diagnosed with BOS and his family members. Genomic DNA was extracted from peripheral blood of the proband and his family members. Whole-exome sequencing was performed, and the mutation sites were verified and analyzed by Sanger sequencing. Results:The family consists of two generations with four members, three of whom exhibit the phenotype. Two members have hearing loss and bilateral preauricular fistulas and bilateral branchial cleft fistulas. One member has bilateral preauricular fistulas and bilateral branchial cleft fistulas. All of which were in line with the clinical diagnosis of gill ear syndrome, the inheritance mode of the family was autosomal dominant inheritance, genetic testing showed that all members of the family had c. 1744delC（p. L592Cfs*47） mutation in the EYA1 gene, while unaffected members have the wild-type allele at this locus. This mutation is a frameshift mutation, which results in the early appearance of the stop codon, and has not been reported so far. According to ACMG guidelines, the variant was preliminarily determined to be suspected pathogenic. Conclusion:The newly discovered EYA1c. 1744delC（p. L592Cfs*47） mutation in this family is the pathogenic mutant gene of the patients in this family, which further expands the mutation spectrum of EYA1 gene, gives us a new understanding of the disease, and provides an important reference for clinical diagnosis and genetic counseling.

Durable partial response to pembrolizumab, lenvatinib, and letrozole in a case of recurrent uterine carcinosarcoma with ESR1 gene amplification.

•ESR1 gene amplification occurs in 7% of uterine carcinosarcoma.•The presence of ESR1 gene amplification in recurrent uterine carcinosarcoma may be targeted by aromatase inhibitors.•ESR1 gene amplification may be identified through immunohistochemical staining for estrogen receptor followed by fluorescence in situ hybridization or tumor targeted gene sequencing.

Spironolactone for Preventing Contrast-Induced Nephropathy After Percutaneous Coronary Intervention in Patients With Acute Myocardial Infarction and Chronic Kidney Disease.

Patients with acute myocardial infarction (AMI) and chronic kidney disease (CKD) are at high risk of contrast-induced nephropathy (CIN), which can subsequently worsen the overall prognosis. To evaluate the efficacy of spironolactone for CIN prevention, 410 patients with AMI and CKD receiving percutaneous coronary intervention (PCI) were retrospectively analyzed. Among them, 240 and 170 patients were enrolled in the standard treatment and spironolactone groups (spironolactone was administered 2 days before and 3 days after PCI), respectively. The primary endpoint of CIN was defined as a 0.5 mg/dL or >25% increase from the baseline serum creatinine level within 48-72 h post-PCI. CIN incidence was significantly lower in the spironolactone group than in the standard treatment group (11.2 vs 26.7%, P < .001). Further, cardiac re-hospitalization (hazard ratio [HR]: 0.515; 95% CI: 0.382-0.694; P < .001) and cardiac death (HR: 0.612; 95% CI: 0.429-0.872; P = .007) risks were significantly lower in patients who received long-term spironolactone with a median treatment duration of 42 months after discharge. Spironolactone might lower the risk of CIN, and long-term use of spironolactone reduces the risk of cardiac re-hospitalization and cardiac death in patients with AMI and CKD undergoing PCI.

Non-invasive diagnosis of non-alcoholic fatty liver disease: Current status and future perspective.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease throughout the world. Hepatocellular carcinoma (HCC) and liver cirrhosis can result from nonalcoholic steatohepatitis (NASH), the severe stage of NAFLD progression. By some estimates, NAFLD affects almost one-third of the world's population, which is completely new and serious public health issue. Unfortunately, NAFLD is diagnosed by exclusion, and the gold standard for identifying NAFLD/NASH and reliably measuring liver fibrosis remains liver biopsy, which is an invasive, costly, time-consuming procedure and involves variable inter-observer diagnosis. With the progress of omics and imaging techniques, numerous non-invasive serological assays have been generated and developed. On the basis of these developments, non-invasive biomarkers and imaging techniques have been combined to increase diagnostic accuracy. This review provides information for the diagnosis and assessment of NAFLD/NASH in clinical practice going forward and may assist the clinician in making an early and accurate diagnosis and in proposing a cost-effective patient surveillance. We discuss newly identified and validated non-invasive diagnostic methods from biopsy-confirmed NAFLD patient studies and their implementation in clinical practice, encompassing NAFLD/NASH diagnosis and differentiation, fibrosis assessment, and disease progression monitoring. A series of tests, including 20-carboxy arachidonic acid (20-COOH AA) and 13,14-dihydro-15-keto prostaglandin D2 (dhk PGD2), were found to be potentially the most accurate non-invasive tests for diagnosing NAFLD. Additionally, the Three-dimensional magnetic resonance imaging (3D-MRE), combination of the FM-fibro index and Liver stiffness measurement (FM-fibro LSM index) and the machine learning algorithm (MLA) tests are more accurate than other tests in assessing liver fibrosis. However, it is essential to use bigger cohort studies to corroborate a number of non-invasive diagnostic tests with extremely elevated diagnostic values.

Prospective Study of Canaloplasty and Trabeculotomy Performed by Trainees.

Purpose: To evaluate outcomes of new adopters of the OMNI® Surgical System (Sight Sciences, Inc.) by prospectively evaluating intermediate-term outcomes of patients operated by trainees. Patients and Methods: This was a prospective study of surgeries performed by trainees on patients with open angle glaucoma undergoing simultaneous cataract surgery and ab interno canaloplasty and trabeculotomy using the OMNI Surgical System. Pre-operative intraocular pressure (IOP) and number of glaucoma medications were recorded. Only patients with a minimum of 6-month follow up were included. Baseline IOP was used to separate subjects into two groups: Group 1 (IOP ≥18 mmHg) and Group 2 (IOP <18 mmHg). Mean decrease in IOP and medications was calculated and compared with paired t-tests for the overall sample as well as the subgroups. Success was defined as those with a ≥20% reduction from pre-operative IOP or with an IOP ≤18 mmHg and ≥6 mmHg and on the same or fewer number of medications while not requiring additional surgery. Adverse events were also recorded. Results: Forty-two eyes of 31 patients were included. Mean pre-operative IOP was 17.2 ± 4.8 mmHg and mean number of medications was 2.4 ± 1.2. The primary endpoint was reached in 83.3% of patients at 12 months. IOP was reduced by 22.3% to 13.4 ± 2.4 (p<0.001). Mean number of medications decreased to 1.7 ± 1.6 (p<0.001). Group 1 mean IOP decreased 35.4% from 22.2 ± 4.6 mmHg to 14.3 ± 2.8 mmHg (p<0.001). Group 2 mean number of medications decreased from 2.3 ± 1.1 to 1.6 ± 1.5 (p<0.001). Conclusion: When operated on by the novice MIGS surgeon, the OMNI device provides effective IOP and glaucoma medication reduction with minimal adverse events. Efficacy and safety of the device in the hands of trainees was comparable to experienced glaucoma surgeons suggesting its ease of adoption.

Reduced healthcare access contributes to delay of care in endometrial cancer.

OBJECTIVE: We aimed to characterize delays to care in patients with endometrioid endometrial cancer and the role healthcare access plays in these delays. METHODS: A chart review was performed of patients with endometrioid endometrial cancer who presented with postmenopausal bleeding at a diverse, urban medical center between 2006 and 2018. The time from symptom onset to treatment was abstracted from the medical record. This interval was subdivided to assess for delay to presentation, delay to diagnosis, and delay to treatment. RESULTS: We identified 484 patients who met the inclusion criteria. The median time from symptom onset to treatment was 4 months with an interquartile range of 2 to 8 months. Most patients had stage I disease at diagnosis (88.6%). There was no significant difference in race/ethnicity or disease stage at time of diagnosis between different groups. Patients who had not seen a primary care physician or general obstetrician-gynecologist in the year before symptom onset were more likely to have significantly delayed care (27.7% vs 14.3%, p = 0.02) and extrauterine disease (20.2% vs 4.9%, p < 0.01) compared to those with established care. Black and Hispanic patients were more likely to experience significant delays from initial biopsy to diagnosis. CONCLUSIONS: Delays exist in the evaluation of endometrial cancer. This delay is most pronounced in patients without an established outpatient primary care provider or obstetrician-gynecologist.

Genetic and Environmental Contributions of Primary Angle-Closure Glaucoma and Primary Open-Angle Glaucoma: A Nationwide Study in Taiwan.

PURPOSE: To estimate the familial risks of primary angle-closure glaucoma (PACG) and primary open-angle glaucoma (POAG) and assess the relative contributions of environmental and genetic factors to these risks. DESIGN: Retrospective, population-based cohort study. METHODS: We used the 2000-2017 Taiwan National Health Insurance Program database to construct 4,144,508 families for the 2017 population (N = 23,373,209). We used the polygenic liability model to estimate glaucoma's heritability and familial transmission. The degree of familial aggregation of glaucoma was obtained from the adjusted relative risk for individuals whose first-degree relatives had glaucoma using Cox's model. RESULTS: PACG and POAG prevalence rates for individuals whose first-degree relatives had PACG or POAG were 0.95% and 2.40%, higher than those of the general population (0.61% and 0.40%, respectively). The relative risk of PACG in individuals whose first-degree relatives had PACG was 2.44 (95% CI = 2.31-2.58). The relative risk of POAG in individuals whose first-degree relatives had POAG was 6.66 (95% CI = 6.38-6.94). The estimated contributions to PACG and POAG phenotypic variances were 19.4% and 59.6% for additive genetic variance, 19.1% and 23.2% for common environmental factors shared by family members, and 61.5% and 17.2% for nonshared environmental factors, respectively. CONCLUSIONS: These data highlight the relative importance of genetic contribution to POAG and environmental contribution to PACG. Therefore, future work may need to focus on finding more novel environmental determinants of PACG.

Incidence and prevalence of keratoconus in Taiwan during 2000-2018 and their association with the use of corneal topography and tomography.

PURPOSE: The aim of this study was to determine the age- and sex-specific incidence and prevalence of keratoconus (KC) in Taiwan and explore their association with the use of computerized corneal topography and tomography (TG). DESIGN: This nationwide retrospective study included the Taiwanese population (N = 27,540,859) from the National Health Insurance Research Database (NHIRD) between 2000 and 2018. METHOD: We estimated the incidence of KC by identifying patients with newly diagnosed KC and estimated its prevalence by identifying patients who had the ICD9-CM code 371.6 or ICD-10-CM code H18.609 twice or more in NHIRD during 2000-2018. RESULTS: The incidence of KC in Taiwan during 2000-2018 was 7075, with the incidence rate being 1.56 (95% confidence interval [CI]: 1.53-1.60) per 100,000 person-years. The prevalence of KC was 4.29 (95% CI: 4.23-4.35) per 100,000 person-years. The KC incidence rate peaked in patients aged 21-25 (6.40 in males and 3.19 in females). The overall incidence rates in males and females were 2.01 and 1.35, respectively (incidence rate ratio: 1.46), indicating that KC had a significant male predisposition. Moreover, we noted a linear correlation (R2 = 0.7488) between the proportion of the use of TG and the incidence of KC. CONCLUSION: Estimates of nationwide population-based incidence and prevalence can contribute to a better understanding of the risk of ethnic groups and geographic locations in KC, and the trend can help physicians improve the general vision health of the population.

Efficacy of Multifocal Soft Contact Lenses in Reducing Myopia Progression Among Taiwanese Schoolchildren: A Randomized Paired-Eye Clinical Trial.

INTRODUCTION: To evaluate the efficacy and safety of myopia control using a multifocal soft contact lens designed with high peripheral add power in schoolchildren. METHODS: This 1-year multi-center, prospective, randomized, double-blind, controlled study enrolled myopic schoolchildren aged 6-15 years with refractive errors between - 1.0 D and - 10.0 D. Each participant was randomly allocated to wear a daily disposable multifocal soft contact lens as the treatment in one eye and a single-vision soft contact lens as the control in the other eye. The primary endpoints were changes in the cycloplegic spherical equivalent (SE) and axial length at 1 year. RESULTS: Fifty-two of the 59 participants (88.1%) completed the study protocol. The mean change in SE was - 0.73 ± 0.40 D in the treatment group. and - 0.85 ± 0.51 D in the control group (mean difference: - 0.12 ± 0.34 D, p = 0.012). The mean change in axial length was 0.25 ± 0.14 mm in the treatment group, and 0.33 ± 0.17 mm in the control group (mean difference: 0.08 ± 0.10 mm, p < 0.001). The treatment was well tolerated, and no serious adverse events were observed. CONCLUSIONS: Treatment with multifocal soft contact lenses with high peripheral add power was effective in controlling the progression of myopia and axial length elongation in myopic schoolchildren.

Preoperative and pre-chemotherapy CA-125 levels in high-risk early-stage ovarian cancer - An NRG/GOG study.

OBJECTIVES: To determine clinical significance of preoperative and pre-chemotherapy CA-125 in high-risk early-stage epithelial ovarian cancer patients. METHODS: All patients with stage IA/IB and grade 3, stage IC, clear cell, or completed resected stage II cancer were enrolled in a phase III trial and treated with chemotherapy. Kaplan-Meier method and Cox proportional hazards model were used for statistical analyses. RESULTS: 427 patients with high-risk early-stage ovarian cancer were enrolled. Of 213 patients with preoperative CA-125 data, 79% had elevated CA-125. Median preoperative CA-125 level was 103 U/mL. Patients with ≤10, 11-15, and > 15 cm tumors had median preoperative CA-125 levels of 62, 131 and 158 U/mL, respectively (p = 0.002). For the 350 patients with data for pre-chemotherapy CA-125 level, 69% had elevated pre-chemotherapy CA-125 above 35 U/mL with median value of 65 U/mL. However, age, race, stage, cell type and grade of disease were not correlated with CA-125 levels before and after surgery. On multivariate analysis, elevated pre-chemotherapy CA-125 independently predicted worse recurrence-free survival (HR = 2.13, 95% CI: 1.23-3.69; p = 0.007) and overall survival (HR = 1.99, 95% CI: 1.10-3.59; p = 0.022) after adjusting for age, stage, cell type and grade of disease. Compared to those with normal CA-125, patients with elevated pre-chemotherapy CA-125 had lower recurrence-free survival (RFS, 87% vs. 75%; p = 0.007) and overall survival (OS, 88% vs. 82%; p = 0.02). However, preoperative CA-125 was not prognostic of RFS (p = 0.699) or OS (p = 0.701). CONCLUSIONS: Preoperative CA-125 was elevated in nearly 80% of high-risk early-stage ovarian cancer patients. Pre-chemotherapy CA-125 was associated with recurrence-free and overall survival; however, preoperative CA-125 was not prognostic.

The Rising Importance of Stock-Linked Assets in the Black-White Wealth Gap.

Studies have examined the racial disparities in household characteristics, homeownership, and familial transfer as primary drivers of the Black-White wealth gap in the United States. This study assesses the importance of stock-linked assets in generating wealth inequality. As financial assets become a growing component of household portfolios, the Black-White wealth gap is increasingly associated with the racial disparity in stock-linked assets. Using data from the Survey of Consumer Finances and the Panel Study of Income Dynamics, this study shows that the contribution of stock-linked assets to the Black-White wealth gap has expanded in both absolute and relative terms, surpassing those of homeownership and business equity. Furthermore, a substantial disparity in financial wealth exists even for otherwise similar Black and White households. Although the disparity is larger among those with more economic resources, a gap remains among those with less. Lastly, our analysis shows that the combination of lower ownership levels and lower returns on financial wealth among Black households could account for a quarter of the Black-White wealth accumulation gap, net of differences in current net worth and household characteristics. Our findings suggest that considering financial assets is critical for understanding contemporary racial wealth inequality.

Synthesis of dienes from pyrrolidines using skeletal modification.

Saturated N-heterocyclic pyrrolidines are common in natural products, medicinal compounds and agrochemicals. However, reconstruction of their skeletal structures creating new chemical space is a challenging task, and limited methods exist for this purpose. In this study, we report a skeletal modification strategy for conversion of polar cyclic pyrrolidines into nonpolar linear dienes through a N-atom removal and deconstruction process. This involves N-sulfonylazidonation followed by rearrangement of the resulting sulfamoyl azide intermediates. This can be an energetically unfavorable process, which involves the formation of active C-C π bonds, the consumption of inert C-N and C-C σ bonds and the destruction of stable five-membered rings, but we have used it here to produce versatile conjugated and nonconjugated dienes with links of varying lengths. We also studied the application of this method in late-stage skeletal modification of bioactive compounds, formal traceless C(sp2)-H functionalization and formal N-atom deletion.

Immunotherapy for ovarian cancer is improved by tumor targeted delivery of a neoantigen surrogate.

Ovarian cancer is known for its poor neoantigen expression and strong immunosuppression. Here, we utilized an attenuated non-pathogenic bacterium Listeria monocytogenes to deliver a highly immunogenic Tetanus Toxoid protein (Listeria-TT), as a neoantigen surrogate, into tumor cells through infection in a metastatic mouse ovarian cancer model (Id8p53-/-Luc). Gemcitabine (GEM) was added to reduce immune suppression. Listeria-TT+GEM treatments resulted in tumors expressing TT and reactivation of pre-existing CD4 and CD8 memory T cells to TT (generated early in life). These T cells were then attracted to the TT-expressing tumors now producing perforin and granzyme B. This correlated with a strong reduction in the ovarian tumors and metastases, and a significant improvement of the survival time compared to all control groups. Moreover, two treatment cycles with Listeria-TT+GEM doubled the survival time compared to untreated mice. Checkpoint inhibitors have little effect on ovarian cancer partly because of low neoantigen expression. Here we demonstrated that Listeria-TT+GEM+PD1 was significantly more effective (efficacy and survival) than PD1 or Listeria-TT+GEM alone, and that more treatment cycles with Listeria-TT+GEM+PD1 significantly increased the survival time compared to Listeria-TT+GEM alone. In summary, the results of this study suggest that our approach may benefit ovarian cancer patients.

The Incidence of Urgent Tube Shunt Surgery for Diabetic Neovascular Glaucoma at a Tertiary Academic Medical Center.

Background: Diabetic neovascular glaucoma is a secondary glaucoma that may require immediate correction of elevated intraocular pressure to control pain and protect the optic nerve. While there is a seasonal trend to glucose levels, it is unknown if a seasonal trend exists for diabetic neovascular glaucoma. Objective: This study evaluates the incidence of urgent glaucoma tube shunt implantation in diabetic neovascular glaucoma in a tertiary academic referral center in Southern California. Methods: Electronic medical records were queried for urgent glaucoma tube shunt surgery from 2014 to 2021. The number of cases were separated by month of occurrence, and average hemoglobin A1c values were calculated per month. Data were analyzed via ANOVA tests and one-tailed t-tests. Results: A total of 127 cases were identified. The months of March and April contained the most cases averaging 3 and 2.75 cases, respectively. April had statistically significant higher case numbers than that of other months (P = .041). ANOVA tests excluding April showed no statistically significant difference between the remaining months (P = .901). Average hemoglobin A1c values were highest in the months of April and March at 9.8 and 9.6%, respectively. Conclusion: Emergency glaucoma tube shunt surgery for diabetic neovascular glaucoma occurs most frequently in April. This observation may provide insight into disease prevention through diabetes management and help improve surgical operations such that staffing and resources are allocated accordingly.

[Analysis of 59 cases of large vestibular aqueduct syndrome SLC26A4gene mutation frequency and new mutation sites].

Objective:To study the frequency of SLC26A4 gene mutation sites in children with enlarged vestibular aqueduct deafness in Yunnan, report the new mutation sites of SLC26A4 gene, further clarify the mutation spectrum of SLC26A4gene, and explore the association between biallelic and monoallelic mutations of SLC26A4 gene and CT phenotype of inner ear, so as to provide basis for clinical and genetic diagnosis of deafness. Methods:Review the results of temporal bone CT examination of 390 children after cochlear implantation in the Department of Otolaryngology, Kunming Children's Hospital from August 2016 to September 2021. Sanger sequencing of SLC26A4 gene was performed in 59 children with enlarged vestibular aqueduct. According to the genetic test results, the children who underwent temporal bone CT examination were divided into two groups: SLC26A4 biallelic mutation group（homozygous mutation and compound heterozygous mutation）, monoallelic mutation group, and the association with inner ear CT phenotype was analyzed, and the new sites were summarized and analyzed. Results:The c.919-2a>g mutation was the most common mutation in children with enlarged vestibular aqueduct with SLC26A4 gene mutation. Three new variants of SLC26A4 gene were found; CT examination combined with genetic testing found that a part of children with enlarged vestibular aqueduct was associated with SLC26A4 monoallelic mutation or no SLC26A4 gene mutation was detected. Further research is needed to investigate the involvement of other pathogenic factors in the pathogenesis of EVA.

[TCOF1 Gene variation in Treacher Collins syndrome and evaluation of speech rehabilitation after bone bridge surgery].

Objective:By analyzing the clinical phenotypic characteristics and gene sequences of two patients with Treacher Collins syndrome（TCS）, the biological causes of the disease were determined. Then discuss the therapeutic effect of hearing intervention after bone bridge implantation. Methods:All clinical data of the two family members were collected, and the patients signed the informed consent. The peripheral blood of the proband and family members was extracted, DNA was extracted for whole exome sequencing, and Sanger sequencing was performed on the family members for the mutation site.TCOF1genetic mutations analysis was performed on the paitents. Then, the hearing threshold and speech recognition rate of family 2 proband were evaluated and compared under the sound field between bare ear and wearing bone bridge. Results:In the two pedigrees, the probands of both families presented with auricle deformity, zygomatic and mandibular hypoplasia, micrognathia, hypotropia of the eye fissure, and hypoplasia of the medial eyelashes. The proband of Family 1 also presents with specific features including right-sided narrow anterior nasal aperture and dental hypoplasia, which were consistent with the clinical diagnosis of Treacher Collins syndrome. Genetic testing was conducted on both families, and two heterozygous mutations were identified in the TCOF1 gene: c. 1350_1351dupGG（p. A451Gfs*43） and c. 4362_4366del（p. K1457Efs*12）, resulting in frameshift mutations in the amino acid sequence. Sanger sequencing validation of the TCOF1 gene in the parents of the proband in Family 1 did not detect any mutations. Proband 1 TCOF1 c. 1350_1351dupGG heterozygous variants have not been reported previously. The postoperative monosyllabic speech recognition rate of family 2 proband was 76%, the Categories of Auditory Performance（CAP） score was 6, and the Speech Intelligibility Rating（SIR） score was 4. Assessment using the Meaningful Auditory Integration Scale（MAIS） showed notable improvement in the patient's auditory perception, comprehension, and usage of hearing aids. Evaluation using the Glasgow Children's Benefit Inventory and quality of life assessment revealed significant improvements in the child's self care abilities, daily living and learning, social interactions, and psychological well being, as perceived by the parents. Conclusion:This study has elucidated the biological cause of Treacher Collins syndrome, enriched the spectrum of TCOF1 gene mutations in the Chinese population, and demonstrated that bone bridge implantation can improve the auditory and speech recognition rates in TCS patients.