Genetic testing has the potential to impact hearing preservation following cochlear implantation

Abstract

Background: Recent advances in less-invasive surgery and electrode design allow for a high degree of hearing preservation (HP) after cochlear implantation (CI), although residual hearing still deteriorates in some patients. To date, the factors predictive of preserving residual hearing remain a controversial topic.

Objective: The aim of this study was to investigate the predictive factors, including the etiology of hearing loss (HL) as a patient-related factor, influencing residual HP after CI.

Methods: Forty-four patients (50 ears, 41 families) with residual acoustic hearing who underwent CI were included. Auditory thresholds before and at 6 months after initial activation were measured. Genetic testing was performed to identify the responsible genes for HL.

Results: We identified the cause of HL in 21 families (51.2%). HP was marginally correlated with age at implantation, while it was independent of pre-operative low-frequency hearing thresholds, cochlear duct length, and electrode length. We found that patients who had pathogenic variants in the CDH23, MYO7A, or MYO15A gene showed statistically better HP scores compared with patients with HL due to other causes (p?=?.002).

Conclusions: Identification of the etiology of HL using genetic testing is likely to facilitate the prediction of HP after implant surgery.     

A multicenter,open‐label,phase II study of tirabrutinib (ONO/GS‐4059) in patients with Waldenström’s macroglobulinemia

Tirabrutinib is a second‐generation Bruton’s tyrosine kinase inhibitor with greater selectivity than ibrutinib. Here, we conducted a multicenter, phase II study of tirabrutinib in patients with treatment‐naïve (Cohort A) or with relapsed/refractory (Cohort B) Waldenström’s macroglobulinemia (WM). Patients were treated with tirabrutinib 480 mg once daily. The primary endpoint was major response rate (MRR; ≥ partial response). Secondary endpoints included overall response rate (ORR; ≥ minor response), time to major response (TTMR), progression‐free survival (PFS), overall survival (OS), and safety. In total, 27 patients (18 in Cohort A; 9 in Cohort B) were enrolled. The median age was 71 y, and the median serum immunoglobulin M level was 3600 mg/dL. Among the patients, 96.2% had the MYD88^L265P mutation. MRR and ORR were 88.9% and 96.3%, respectively (Cohort A: MRR, 88.9%; ORR, 94.4%; Cohort B: MRR, 88.9%; ORR, 100%). Median TTMR was 1.87 mo. PFS and OS were not reached with a median follow‐up of 6.5 and 8.3 mo for Cohorts A and B, respectively. The most common adverse events (AEs) were rash (44.4%), neutropenia (25.9%), and leukopenia (22.2%), with most AEs classified as grade 1 or 2. Grade ≥ 3 AEs included neutropenia (11.1%), lymphopenia (11.1%), and leukopenia (7.4%). No grade 5 AEs were noted. All bleeding events were grade 1; none were associated with drug‐related atrial fibrillation or hypertension. Although the follow‐up duration was relatively short, the study met the primary endpoint. Therefore, tirabrutinib monotherapy is considered to be highly effective for both untreated and relapsed/refractory WM with a manageable safety profile. (JapicCTI‐173646).     

Influence of SNPs in cytokine-related genes on the severity of food allergy and atopic eczema in children

Although many single nucleotide polymorphism (SNP) studies have reported an association of atopy, allergic diseases and total serum immunoglobulin E (IgE) levels, almost all of these studies sought risk factors for the onset of these allergic diseases. Furthermore, many studies have analyzed a single gene and hardly any have analyzed environmental factors. In these analyses, the results could be masked and the effects of other genes and environmental factors may be decreased. Here, we described the correlation between four genes [interleukin (IL)-4 (C-590T), IL-4 receptor (A1652G), FCER1B (G6842A) and STAT6 (G2964A)] in connection with IgE production; the role of IL-10 (C-627A) as a regulatory cytokine of allergy; and the severity of food allergy (FA) and atopic eczema (AE) in 220 Japanese allergic children. In addition to these SNPs, environmental factors, i.e., patient's attitude, indoor environment, and so on, were also investigated in this study. Our study was retrospective, and the correlation was analyzed by our defined clinical scores divided into three terms: worst symptoms, recent symptoms and general amelioration at the most recent examination during the disease course. Our results indicated that IL-10 AA, the genotype with lower IL-10 production, is associated with higher IgE levels in the serum (p < 0.0001, estimate; 0.912). Marginal liver abnormalities were observed in the subject group with both FA and AE (p < 0.1191, estimate; 0.1490). Our defined clinical scores enabled evaluation of various aspects of disease severity. Based on the scores, while no single SNP selected in this study determined severity, the combination of the SNP with laboratory data and environmental factors appeared to determine severity.     

Dopamine agonists and valvular heart disease in Japanese patients with Parkinson's disease

Journal of Neurology - A high incidence of valvular heart disease in Parkinson's disease (PD) patients treated with ergot-derived dopamine agonists, such as cabergoline and pergolide, has been...     

Characteristics and course of bone mineral densities among fast bone losers in a rural Japanese community: the Miyama Study

The aim of this study was to clarify and compare the temporal course of bone mineral density (BMD) between fast bone losers and normal residents in Miyama Village, a rural Japanese community. BMD was measured over a 10-year period in a cohort study in Miyama Village, Wakayama Prefecture, Japan, to provide information on rate of bone loss in the mature and elderly population. Subjects (n=400) were selected by sex and age stratum from the full list of residents born in 1910–1949, with 50 men and 50 women in each age decade. Baseline BMD of the lumbar spine and proximal femur was measured using dual energy X-ray absorptiometry in 1990, 1993, 1997 and 2000. In the cohort, 171 men and 189 women completed the follow-up survey performed in 1993. After calculating the rate of bone loss between 1990 and 1993, the greatest tertile from the distribution of bone loss was categorized as fast bone losers, with the remainder considered as normal subjects. Changes in BMD were compared between normal subjects and fast bone losers over the 10-year period. Mean rate of change for BMD at both lumbar spine and femoral neck in fast bone losers recovered to levels similar to those in normal subjects over 7 years of observation. By contrast, BMD at the lumbar spine and femoral neck decreased steeply over the 10-year period in both groups, and mean BMD for fast bone losers was significantly lower than that of normal subjects (P<0.05). These differences were apparent only at the lumbar spine in both men and women, even after adjusting for age. These results indicate that fast bone loss is a transient phenomenon rather than a fixed status, although individuals who have been categorized as fast bone losers at some stage continue to display low BMD in the lumbar spine.     

Lymphoepithelial (branchial) cyst and amylase

A case of a branchial cyst with a high amylase activity of the cyst fluid was found in a 58-year-old female. The literature on branchial cysts with high amylase activity is reviewed. Amylase that showed high activity in the cystic fluid was revealed to be due to the salivary isoenzymes (S3 and S4) which migrated more to the anodic side on electrophoresis.