Evaluating the Clinical Utility of a Long-Read Sequencing-Based Approach in Prenatal Diagnosis of Thalassemia.

BACKGROUND: The aim is to evaluate the clinical utility of a long-read sequencing-based approach termed comprehensive analysis of thalassemia alleles (CATSA) in prenatal diagnosis of thalassemia. METHODS: A total of 278 fetuses from at-risk pregnancies identified in thalassemia carrier screening by PCR-based methods were recruited from 9 hospitals, and PCR-based methods were employed for prenatal diagnosis. CATSA was performed retrospectively and blindly for all 278 fetuses. RESULTS: Among the 278 fetuses, 263 (94.6%) had concordant results and 15 (5.4%) had discordant results between the 2 methods. Of the 15 fetuses, 4 had discordant thalassemia variants within the PCR detection range and 11 had additional variants identified by CATSA. Independent PCR and Sanger sequencing confirmed the CATSA results. In total, CATSA and PCR-based methods correctly detected 206 and 191 fetuses with variants, respectively. Thus, CATSA yielded a 7.9% (15 of 191) increment as compared with PCR-based methods. CATSA also corrected the predicted phenotype in 8 fetuses. Specifically, a PCR-based method showed one fetus had homozygous HBB c.52A > T variants, while CATSA determined the variant was heterozygous, which corrected the predicted phenotype from ß-thalassemia major to trait, potentially impacting the pregnancy outcome. CATSA additionally identified α-globin triplicates in 2 fetuses with the heterozygous HBB c.316-197C > T variant, which corrected the predicted phenotype from ß-thalassemia trait to intermedia and changed the disease prognosis. CONCLUSIONS: CATSA represents a more comprehensive and accurate approach that potentially enables more informed genetic counseling and improved clinical outcomes compared to PCR-based methods.

Comparison of 2 Different Intratympanic Methylprednisolone Injection Schedules in Combination With Intravenous Dexamethasone for Unilateral Sudden Sensorineural Hearing Loss.

Sudden sensorineural hearing loss is a common otologic disease in clinic. Systemic and intratympanic steroid treatment have been proved to be effective, but the regimens vary from center to center. The purpose of the study is to analyze the effects of the combined application of intravenous dexamethasone and intratympanic methylprednisolone injection in different time strategies for the treatment of unilateral sudden sensorineural hearing loss. A retrospective chart review was performed for the period from March 2016 to June 2018 at our Department of Otorhinolaryngology-Head and Neck Surgery. A total number of 61 patients who met the academy criteria for unilateral sudden hearing loss were included and grouped based on the time to introduce intratympanic methylprednisolone. All the patients received intravenous dexamethasone 10 mg once daily for 5 days, followed 5 mg once daily for the next 7 days. Intratympanic methylprednisolone (40 mg) was injected every other day 4 times into all patients. This regimen was commenced on day 1 in group 1 and on day 6 in group 2. The pre and posttreatment pure-tone audiograms were analyzed. Sixty-one patients met our inclusion criteria. No significant differences were observed between patients' demographics or pretreatment hearing thresholds. In the 3 months posttreatment pure-tone audiogram assessment, the mean hearing threshold improvement were similar between groups with no frequency specificity. The curative rate in both groups were similar and satisfying. Two patients with diabetes mellitus had persistent small perforations. Some patients had other transient discomfort that disappeared before discharge. The different timing of initiation of intratympanic methylprednisolone injection does not significantly affect the outcome of the treatment for sudden sensorineural hearing loss. Thus, we suggest that intratympanic steroid injection should not be applied as a first-line method except for patients who do not respond early to systemic steroid therapy.

Intratympanic dexamethasone injection for sudden sensorineural hearing loss in pregnancy.

BACKGROUND: As sudden sensorineural hearing loss (SSNHL) rarely occurs in pregnant women, there is a lack of knowledge and relevant research on its management. AIM: To investigate the effect of intratympanic dexamethasone injection in the treatment of pregnant patients with SSNHL. METHODS: A retrospective chart review was made for the period between June 2017 and August 2019 at our Department of Otorhinolaryngology-Head and Neck Surgery. Pregnant women who met the criteria for SSNHL were included and grouped based on the therapeutic modalities. The treatment group received intratympanic dexamethasone (2.5 mg) q.o.d. for a total of four times, while the control group received no medication other than bed rest and medical observations. All the patients were under close care of obstetricians. Pure-tone audiograms were performed before and after treatment. RESULTS: Eleven patients who met the inclusion criteria were assigned to the treatment group (n = 7) and the control group (n = 4). The mean age of patients was 31.2 ± 3.8 years; the right ear was affected in seven (63.64%) cases. Two patients (18.2%) suffered from vertigo, 10 (90.9%) suffered from tinnitus and 6 (54.5%) suffered from aural fullness. The time from onset to clinic visit was relatively short, with a mean time of 1.3 ± 0.9 d. All the women were within the second or third trimester; the average gestation period was 26.0 ± 6.2 wk. The pure-tone averages at onset between the two groups were similar. After one wk of therapy, the treatment group had a curative rate of 57.1% and a significantly better hearing threshold and greater improvement compared to the control group (all P < 0.05). Some patients experienced transient discomfort from intratympanic injections that disappeared after getting rest, while none had permanent complications. All patients delivered healthy full-term neonates with an average Apgar score of 9.7 ± 0.5. CONCLUSION: Intratympanic dexamethasone injections can be used as a first-line therapy in pregnant women with SSNHL.