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Background Skeletal dysplasia (SD) is one of the most common inherited neonatal disorders worldwide, where the recurrent pathogenic mutations in the FGFR2, FGFR3, COL1A1, COL1A2 and COL2A1 genes are frequently reported in both non-lethal and lethal SD. The traditional prenatal diagnosis of SD using ultrasonography suffers from lower accuracy and performed at latter gestational stage. Therefore, it remains in desperate need of precise and accurate prenatal diagnosis of SD in early pregnancy. With the advancements of next-generation sequencing (NGS) technology and bioinformatics analysis, it is feasible to develop a NGS-based assay to detect genetic defects in association with SD in the early pregnancy. Methods An ampliseq-based targeted sequencing panel was designed to cover 87 recurrent hotspots reported in 11 common dominant SD and run on both Ion Proton and NextSeq550 instruments. Thirty-six cell-free and 23 genomic DNAs were used for assay developed. Spike-in DNA prepared from standard sample harboring known mutation and normal sample were also employed to validate the established SD workflow. Overall performances of coverage, uniformity, and on-target rate, and the detecting limitations on percentage of fetal fraction and read depth were evaluated. Results The established targeted-seq workflow enables a single-tube multiplex PCR for library construction and shows high amplification efficiency and robust reproducibility on both Ion Proton and NextSeq550 platforms. The workflow reaches 100% coverage and both uniformity and on-target rate are > 96%, indicating a high quality assay. Using spike-in DNA with different percentage of known FGFR3 mutation (c.1138 G > A), the targeted-seq workflow demonstrated the ability to detect low-frequency variant of 2.5% accurately. Finally, we obtained 100% sensitivity and 100% specificity in detecting target mutations using established SD panel. Conclusions An expanded panel for rapid and cost-effective genetic detection of SD has been developed. The established targeted-seq workflow shows high accuracy to detect both germline and low-frequency variants. In addition, the workflow is flexible to be conducted in the majority of the NGS instruments and ready for routine clinical application. Taken together, we believe the established panel provides a promising diagnostic or therapeutic strategy for prenatal genetic testing of SD in routine clinical practice.

Objectives To compare the efficacy of pentoxifylline with that of conventional steroid therapy in diabetic patients with idiopathic sudden sensorineural hearing loss (ISSNHL) and to compare blood sugar levels during hospitalization. Materials and methods Medical charts were retrospectively reviewed for all diabetic patients admitted to one institution for ISSNHL between 2000 and 2015. We analyzed 298 cases; 50 patients received pulse steroid treatment (steroid group) and 248 received intravenous administration of pentoxifylline only (pentoxifylline group). Hearing change was evaluated by comparing the initial hearing tests with follow-up hearing tests for up to 3 months. Blood sugar levels were also compared between the 2 groups. Results At 3 months post-treatment, the degree of hearing recovery was similar between the 2 groups. The pure-tone average was improved from baseline by 17.9±21.2 dB in the steroid group and 18.9±20.7 dB in the pentoxifylline group (p=0.776); hearing recovery rates were also similar (40% vs 39.1%; p=0.826). During hospitalization, average fasting blood sugar levels were higher (203.9±92.0 vs 174.4±54.8 mg/dL; p=0.033) and acute hyperglycemia was more common (48.0% vs 33.1%; p=0.044) with steroid versus pentoxifylline treatment. Conclusion Hearing recovery rates did not significantly differ between steroid and pentoxifylline treatment in diabetic patients with ISSNHL, but pentoxifylline appeared to be associated with better blood sugar control.

Aim The study evaluated the risk of sudden sensorineural hearing loss (SSHR) in patients with end-stage renal disease (ESRD) undergoing dialysis METHODS: We identified 18 905 patients newly diagnosed with ESRD, comprising 6382 patients on peritoneal dialysis (PD) and 12 523 patients on hemodialysis (HD) using Taiwan's National Health Insurance claims data from 2000 to 2010. A total of 76 520 controls without kidney disease were randomly selected with frequency matched with the ESRD group by age and sex. We further established additional cohorts with 6375 patients on PD and 6375 patients on HD matched by their propensity scores. Cox proportional hazards models were used to examine the effect of ESRD and dialysis modality on the risk of sudden sensorineural hearing loss (SSHL) by the end of 2011. Results The incidences for SSHR were 0.49, 2.37, 2.95, and 2.12 per 1000 person-years in the control, ESRD (PD and HD), PD, and HD cohorts, respectively. The adjusted HRs of SSHR was 2.71, 3.60, and 2.33 for ESRD, PD, and HD groups (95% CI = 2.17-3.38, 2.71-4.78 and 1.81-2.99, respectively) compared with the control cohort. Patients on PD exhibited 1.53-fold (95% CI = 1.14-2.04) and 1.64-fold (95% CI = 1.19-2.27) higher SSHL risk than their age- and sex-matched and propensity score-matched patients on HD, respectively. Conclusion Patients with ESRD exhibit a higher risk of SSHL than people without kidney disease. The SSHL risk is greater for patients on PD than on HD.

This study investigated the development of subcortical pitch processing, as reflected by the scalp-recorded frequency-following response, during early infancy. Thirteen Chinese infants who were born and raised in Mandarin-speaking households were recruited to partake in this study. Through a prospective-longitudinal study design, infants were tested twice: at 1–3 days after birth and at three months of age. A set of four contrastive Mandarin pitch contours were used to elicit frequency-following responses. Frequency Error and Pitch Strength were derived to represent the accuracy and magnitude of the elicited responses. Paired-samples t tests were conducted and demonstrated a significant decrease in Frequency Error and a significant increase in Pitch Strength at three months of age compared to 1–3 days after birth. Results indicated the developmental trajectory of subcortical pitch processing during the first three months of life.

Nontuberculous mycobacterial otomastoiditis is rare and can be easily confused with various different forms of otitis media. We describe the case of a 50-year-old woman who presented with left-sided chronic otitis media that had persisted for more than 1 year. It was not eradicated by standard antimicrobial therapy and surgical debridement. After appropriate antibiotic therapy for nontuberculous mycobacteria was added to the therapeutic regimen, the patient improved significantly and the lesion had healed by 6 months. Based on our experience with this case, we conclude that early bacterial culture and staining for acid-fast bacilli in ear drainage material or granulation tissue should be performed when standard antimicrobial therapy fails to eradicate chronic otitis media of an un-determined origin that is accompanied by granulation tissue over the external auditory canal or middle ear. Polymerase chain reaction testing is also effective for rapid diagnosis. Surgical debridement and removal of the foreign body can successfully treat nontuberculous mycobacterial otomastoiditis only when effective antimicrobial therapy is also administered.

To investigate whether adenotonsillectomy reduces upper respiratory tract infections (URIs) in the pediatric population.We identified 415 children, aged ≤18 years who had undergone adenoidectomy and/or tonsillectomy during the period from 1999 to 2006, from the Taiwan National Health Insurance Research Database. The comparison group consisted of 1630 children without the surgery randomly selected from the same database frequency matched with sex, age and the surgery date (index date). Changes in physician visits for URIs 2-year period before and 2-year period after the index date were compared between the two groups of children.The number of outpatient visits for URIs decreased with time, children with tonsillectomy and/or adenoidectomy had a greater reduction than comparison children (mean changes, -14 times and -6 times, respectively) in the 2-year period after the index date. Multivariate analyses using generalized estimated equation revealed a significant effect in reducing URIs visits from the surgery (relative ratio=0.85, p0.0001), strongest for children undergoing both tonsillectomy and adenoidectomy (relative ratio=0.76, p0.0001). The association between surgery and the decrease in URIs was more pronounced for children aged 12 years and less.This population-based study suggests that tonsillectomy and/or adenoidectomy is associated with fewer physician visits for URIs. The association is weakened in old children.

This study investigated the development of subcortical pitch processing, as reflected by the scalp-recorded frequency-following response, during early infancy. Thirteen Chinese infants who were born and raised in Mandarin-speaking households were recruited to partake in this study. Through a prospective-longitudinal study design, infants were tested twice: at 1–3 days after birth and at three months of age. A set of four contrastive Mandarin pitch contours were used to elicit frequency-following responses. Frequency Error and Pitch Strength were derived to represent the accuracy and magnitude of the elicited responses. Paired-samples t tests were conducted and demonstrated a significant decrease in frequency error and a significant increase in pitch strength at three months of age compared to 1–3 days after birth. Results indicated the developmental trajectory of subcortical pitch processing during the first three months of life.