Coffee and caffeine intake reduces risk of ulcerative colitis: a case-control study in Japan.

BACKGROUND AND AIM: Although diet is one of the potential environmental factors affecting ulcerative colitis (UC), evidence is not sufficient to draw definitive conclusions. This Japanese case-control study examined the association between the consumption of coffee, other caffeine-containing beverages and food, and total caffeine and the risk of UC. METHODS: The study involved 384 UC cases and 665 control subjects. Intake of coffee, decaffeinated coffee, black tea, green tea, oolong tea, carbonated soft drinks, and chocolate snacks was measured with a semiquantitative food-frequency questionnaire. Adjustments were made for sex, age, pack-years of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, body mass index, and intake of vitamin C, retinol, and total energy. RESULTS: Higher consumption of coffee and carbonated soft drinks was associated with a reduced risk of UC with a significant dose-response relationship (P for trend for coffee and carbonated soft drinks were <0.0001 and 0.01, respectively), whereas higher consumption of chocolate snacks was significantly associated with an increased risk of UC. No association was observed between consumption of decaffeinated coffee, black tea, green tea, or oolong tea and the risk of UC. Total caffeine intake was inversely associated with the risk of UC; the adjusted odds ratio between extreme quartiles was 0.44 (95% confidence interval: 0.29-0.67; P for trend <0.0001). CONCLUSIONS: We confirmed that intake of coffee and caffeine is also associated with a reduced risk of UC in Japan where people consume relatively low quantities of coffee compared with Western countries.

Role of Oxidative Stress in Sensorineural Hearing Loss.

Hearing is essential for communication, and its loss can cause a serious disruption to one's social life. Hearing loss is also recognized as a major risk factor for dementia; therefore, addressing hearing loss is a pressing global issue. Sensorineural hearing loss, the predominant type of hearing loss, is mainly due to damage to the inner ear along with a variety of pathologies including ischemia, noise, trauma, aging, and ototoxic drugs. In addition to genetic factors, oxidative stress has been identified as a common mechanism underlying several cochlear pathologies. The cochlea, which plays a major role in auditory function, requires high-energy metabolism and is, therefore, highly susceptible to oxidative stress, particularly in the mitochondria. Based on these pathological findings, the potential of antioxidants for the treatment of hearing loss has been demonstrated in several animal studies. However, results from human studies are insufficient, and future clinical trials are required. This review discusses the relationship between sensorineural hearing loss and reactive oxidative species (ROS), with particular emphasis on age-related hearing loss, noise-induced hearing loss, and ischemia-reperfusion injury. Based on these mechanisms, the current status and future perspectives of ROS-targeted therapy for sensorineural hearing loss are described.

The Landscape of MYB/MYBL1- and Peri-MYB/MYBL1-Associated Rearrangements in Adenoid Cystic Carcinoma.

Approximately 60% of adenoid cystic carcinoma (AdCC) cases are positive for MYB::NFIB or MYBL1::NFIB, whereas MYB/MYBL1 oncoprotein, a key driver of AdCC, is overexpressed in most cases. Juxtaposition of superenhancer regions in NFIB and other genes into the MYB/MYBL1 locus is an attractive oncogenic hypothesis for AdCC cases, either negative or positive for MYB/MYBL1::NFIB. However, evidence supporting this hypothesis is insufficient. We examined 160 salivary AdCC cases for rearrangements in MYB/MYBL1 loci and peri-MYB/MYBL1 areas (centromeric and telomeric areas of 10 Mb each) using formalin-fixed, paraffin-embedded tumor sections. For the detection of the rearrangements, we employed conventional fluorescence in situ hybridization split and fusion assays and a 5 Mb fluorescence in situ hybridization split assay. The latter is a novel assay that enabled us to detect any possible splits within a 5 Mb distance of a chromosome. We found MYB/MYBL1- and peri-MYB/MYBL1-associated rearrangements in 149/160 patients (93%). AdCC cases positive for rearrangements in MYB, MYBL1, the peri-MYB area, and the peri-MYBL1 area numbered 105 (66%), 20 (13%), 19 (12%), and 5 (3%), respectively. In 24 peri-MYB/MYBL1 rearrangement-positive cases, 14 (58%) were found to have a juxtaposition of the NFIB or RAD51B locus into the MYB/MYBL1 loci. On comparing with a tumor group positive for MYB::NFIB, a hallmark of AdCC, other genetically classified tumor groups had similar features of overexpression of the MYB transcript and MYB oncoprotein as detected by semiquantitative RT-qPCR and immunohistochemistry, respectively. In addition, clinicopathological and prognostic features were similar among these groups. Our study suggests that peri-MYB/MYBL1 rearrangements may be a frequent event in AdCC and may result in biological and clinicopathological consequences comparable to MYB/MYBL1 rearrangements. The landscape of MYB/MYBL1 and peri-MYB/MYBL1 rearrangements shown here strongly suggests that juxtaposition of superenhancers into MYB/MYBL1 or peri-MYB/MYBL1 loci is an alteration that acts as a key driver for AdCC oncogenesis and may unify MYB/MYBL1 rearrangement-positive and negative cases.

IL12B rs6887695 polymorphism and interaction with alcohol intake in the risk of ulcerative colitis in Japan.

BACKGROUND: The interleukin (IL)-23/Th17 pathway plays a critical role in ulcerative colitis (UC). The IL-12p40 subunit, which is shared by IL-23 and IL-12, is encoded by the IL12B gene. The current case-control study investigated the association between IL12B SNP rs6887695 and the UC risk. METHODS: There were 384 cases within 4 years of UC diagnosis and 661 controls who were enrolled. Adjustments were made for sex, age, pack-years of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, and body mass index. RESULTS: Subjects with the GG IL12B SNP rs6887695 genotype had a significantly increased risk of UC compared with those with the CC genotype (adjusted odds ratio [AOR], 1.60; 95% confidence interval [CI], 1.08-2.36). This positive association was also significant using the additive and recessive models (AOR, 1.25; 95% CI, 1.03-1.52; AOR, 1.50; 95% CI, 1.08-2.09, respectively). An independent inverse relationship was observed between ever alcohol consumption and the UC risk in those with the CC genotype while no significant association was found in those with at least one G allele (P for interaction = 0.0008). CONCLUSIONS: IL12B SNP rs6887695 was significantly associated with UC. The influence of alcohol consumption might rely on rs6887695.

Generation of DNA-aptamers targeting galectin-7 for the identification of cholesteatoma residue.

PURPOSE: Aiming at complete excision of cholesteatoma during trympanomastoidectomy and therefore reducing the risk of recurrence, intraoperative imaging techniques are required to assist the visualization of cholesteatoma residue. Galectin-7 has been demonstrated to be a biomarker for cholesteatoma matrix and used for intraoperatively identifying the excision margins. METHODS: A galectin-7-targeted DNA-aptamer library was generated for labeling the cholesteatoma matrix using cell-systematic evolution of ligands by an exponential enrichment technique. The binding characteristics of the identified aptamers were analyzed, and structure optimization of the identified aptamers was carried out both in silico and in vitro. FINDINGS: A fluorophore-labeled structure-optimized DNA fragment was commercially synthesized as a non-invasive aptamer-based probe for intraoperative lesion detection. Using galectin-7-aptamer-guided molecular imaging, the excision margins of cholesteatoma matrix and surrounding normal tissue were successfully achieved within 15-20 min. CONCLUSIONS: Galectin-7-targeted aptamers could benefit molecular imaging-guided surgical treatment, which would enable clinicians to not only intraoperatively detect the locations of cholesteatoma matrix in the middle ear, but also assess the postoperative response of the expression profile to therapy. It is highly expected that further efforts for rational design and development should be directed towards the development of clinically translatable aptamer-based imaging agents.

Active and passive smoking and risk of ulcerative colitis: A case-control study in Japan.

BACKGROUND AND AIM: Although an inverse relationship between current smoking and the development of ulcerative colitis (UC) has been shown in North America and Europe, evidence is limited in Asian countries, where the incidence of UC is rapidly increasing. This Japanese case-control study examined the association between active and passive smoking and risk of UC. METHODS: A self-administered questionnaire was used to obtain information on smoking and potential confounding factors in 384 cases with a diagnosis of UC within the past 4 years and 665 controls. RESULTS: Compared with having never smoked, having ever smoked was associated with an increased risk of UC (adjusted odds ratio [OR] = 1.70, 95% confidence interval [CI]: 1.23-2.37). No association was observed between current smoking and risk of UC, but former smokers had a significant elevation in risk (adjusted OR = 2.40, 95% CI: 1.67-3.45). There was a positive dose-response relationship with pack-years smoked (P for trend = 0.006). Among never smokers, passive smoking exposure at home was significantly associated with an increased risk of UC (adjusted OR = 1.90, 95% CI: 1.30-2.79). A significant dose-response gradient was also observed between pack-years of passive smoking at home and risk of UC (P for trend = 0.0003). CONCLUSIONS: We confirmed that former smoking elevated the risk of UC, whereas an inverse association between current smoking and the risk of UC did not reach a statistically significant level. Passive smoking may be associated with an increased risk of UC.

Pathological evaluation of tumor grade for salivary adenoid cystic carcinoma: A proposal of an objective grading system.

Three pathological grading systems advocated by Perzin/Szanto, Spiro, and van Weert are currently used for adenoid cystic carcinoma (AdCC). In these systems, the amount or presence of the solid tumor component in AdCC specimens is an important index. However, the "solid tumor component" has not been well defined. Salivary AdCC cases (N = 195) were collected after a central pathology review. We introduced a novel criterion for solid tumor component, minAmax (minor axis maximum). The largest solid tumor nest in each AdCC case was histologically screened, the maximum oval fitting the solid nest was estimated, and the length of the minor axis of the oval (minAmax) was measured. The prognostic cutoff for the minAmax was determined using training and validation cohorts. All cases were evaluated for the four grading systems, and their prognostic impact and interobserver variability were examined. The cutoff value for the minAmax was set at 0.20 mm. Multivariate prognostic analyses showed the minAmax and van Weert systems to be independent prognostic tools for overall, disease-free, and distant metastasis-free survival while the Perzin/Szanto and Spiro systems were selected for overall survival but not for disease-free or distant metastasis-free survival. The highest hazard ratio for overall survival (11.9) was obtained with the minAmax system. The reproducibility of the minAmax system (kappa coefficient of 0.81) was scored as very good while those of the other three systems were scored as moderate. In conclusion, the minAmax is a simple, objective, and highly reproducible grading system useful for prognostic stratification for salivary AdCC.

Hearing Impairment and Prevalence of Mild Cognitive Impairment in Japan: Baseline Data From the Aidai Cohort Study in Yawatahama and Uchiko.

OBJECTIVES: Hearing impairment (HI) in midlife may increase the risk of dementia. However, epidemiological research on the association between HI and mild cognitive impairment (MCI) is very limited. DESIGN: The present cross-sectional study investigated the relationship between HI and MCI using baseline data from the Aidai Cohort Study. Study subjects were 995 Japanese adults aged 36 to 84 years. We used the audiometric definition of HI adopted by the World Health Organization, which identifies the speech-frequency pure-tone average hearing thresholds at 0.5, 1, 2, and 4 kHz tones. HI was defined as present when pure-tone average was >25 dB HL in the better hearing ear. MCI was defined as being present when a subject had a Japanese version of the Montreal Cognitive Assessment score of <26. Adjustment was made for age, sex, smoking status, alcohol consumption, leisure time physical activity, hypertension, dyslipidemia, diabetes mellitus, history of depression, body mass index, waist circumference, employment, education, and household income. RESULTS: Among the 995 study subjects, the prevalence values of HI and MCI were 24.3% and 44.5%, respectively. HI was independently positively associated with MCI: the multivariate-adjusted odds ratio (95% confidence interval) was 1.86 (1.32 to 2.62). HI was independently related to a higher prevalence of MCI in those aged 60 to 69 years and those aged 70 years or older: the multivariate-adjusted odds ratios (95% confidence intervals) were 1.64 (1.03 to 2.62) and 2.30 (1.04 to 5.27), respectively. CONCLUSIONS: HI may be associated with a higher prevalence of MCI.

The impact of clinicopathological factors on clinical outcomes in patients with salivary gland adenoid cystic carcinoma: a multi-institutional analysis in Japan.

BACKGROUND: Owing to the low incidence of adenoid cystic carcinoma (AdCC), reliable survival estimates and prognostic factors remained unclarified. METHODS: In this multi-institutional retrospective analysis, we collected 192 AdCC cases, and investigated the impact of clinicopathological factors on clinical outcomes of the patients. All AdCC cases were of salivary gland origin and were surgically treated with curative intent. Diagnoses of AdCC were validated by a central pathology review by expert pathologists. RESULTS: The 5-year overall survival (OS) and disease-free survival (DFS) rates were 92.5 and 50.0%, respectively. Treatment failure occurred in 89 patients (46%) with the distant failures in 65 (34%). Multivariate analysis indicated that pN2 and a pathologically positive surgical margin were independent prognostic factors for both OS and DFS. Histological grade III was an independent prognostic factor for OS. A primary site in the submandibular gland, pT3/4, pN1, and histological grade II were independent prognostic factors for DFS. Postoperative radiation therapy (PORT) improved the locoregional control (LRC) rate. Prophylactic neck dissection was not associated with a better OS or better LRC among patients with cN0. Facial nerve dissection did not improve clinical outcomes in parotid AdCC cases without facial nerve palsy. CONCLUSIONS: A higher TN classification, a pathologically positive surgical margin, and a higher histological grade were associated with a lower OS. PORT improved LRC rates but neck dissection failed to improve clinical outcomes in patients with cN0. As the distant metastasis was frequent, effective systemic therapy is imperative to improve the survival of AdCC patients.

Elevated Na+/H+ exchanger-1 expression enhances the metastatic collective migration of head and neck squamous cell carcinoma cells.

Cancer cells can migrate as collectives during invasion and/or metastasis; however, the precise molecular mechanisms of this form of migration are less clear compared with single cell migration following epithelial-mesenchymal transition. Elevated Na+/H+ exchanger1 (NHE1) expression has been suggested to have malignant roles in a number of cancer cell lines and in vivo tumor models. Furthermore, a metastatic human head and neck squamous cell carcinoma (HNSCC) cell line (SASL1m) that was isolated based on its increased metastatic potential also exhibited higher NHE1 expression than its parental line SAS. Time-lapse video recordings indicated that both cell lines migrate as collectives, although with different features, e.g., SASL1m was much more active and changed the direction of migration more frequently than SAS cells, whereas locomotive activities were comparable. SASL1m cells also exhibited higher invasive activity than SAS in Matrigel invasion assays. shRNA-mediated NHE1 knockdown in SASL1m led to reduced locomotive and invasive activities, suggesting a critical role for NHE1 in the collective migration of SASL1m cells. SASL1m cells also exhibited a higher metastatic rate than SAS cells in a mouse lymph node metastasis model, while NHE1 knockdown suppressed in vivo SASL1m metastasis. Finally, elevated NHE1 expression was observed in human HNSCC tissue, and Cariporide, a specific NHE1 inhibitor, reduced the invasive activity of SASL1m cells, implying NHE1 could be a target for anti-invasion/metastasis therapy.

Programmed death ligand-1 expression is associated with poor disease free survival in salivary gland carcinomas.

BACKGROUND AND OBJECTIVES: The immune checkpoint ligand programmed death ligand-1 (PD-L1) is expressed in various carcinomas and allows carcinoma cells to elude the immune system. PD-L1 expression is associated with the response to anti-programmed death 1 (PD-1)/PD-L1 drugs. This study aimed to clarify the relationship between PD-L1 expression and clinicopathological factors of salivary gland carcinomas (SGCs) and identify its clinical significance. METHODS: PD-L1 expression was examined by immunohistochemical analysis using a tissue microarray comprised of 219 surgically resected SGC specimens. Detailed clinicopathological factors, including patient outcome, were available for all cases. RESULTS: A case showing complete membranous expression of PD-L1 in more than 1% of whole carcinoma cells was considered positive by ROC analysis. A total of 50 (22.8%) patients showed PD-L1 expression in SGC cells. Positive PD-L1 expression was significantly associated with poor disease free survival (P < 0.001) and overall survival (P < 0.001). Multivariate analysis revealed that positive PD-L1 expression was one of the independent predictors for poor disease free survival (hazard ratio = 2.287, 95% confidence interval = 1.24-4.15; P = 0.008). CONCLUSIONS: Positive PD-L1 expression was significantly associated with poor disease free survival of SGCs, suggesting that antibody therapies targeting PD-1/PD-L1 may have potential application in SGCs. J. Surg. Oncol. 2016;114:36-43. © 2016 Wiley Periodicals, Inc.

Efficacy of chlorophyll c2 for seasonal allergic rhinitis: single-center double-blind randomized control trial.

Chlorophyll c2 extracted from Sargassum horneri improved allergic symptoms in an animal model of allergic rhinitis. In the present study, we explored the efficacy of chlorophyll c2 in patients with seasonal allergic rhinitis. This was a single-center, randomized, double-blind placebo-controlled trial. Sixty-six patients aged 20-43 years, each with a 2-year history of seasonal allergic rhinitis, were randomly assigned to receive either a single daily dose (0.7 mg) of chlorophyll c2 or placebo for 12 weeks. The use of medications including H1-antihistamines and topical nasal steroids was recorded by rescue medication scores (RMSs) noted after 4, 8, and 12 weeks of treatment. Disease-specific quality of life was measured using the Japan Rhinitis Quality of Life Questionnaire (JRQLQ) both before and after 4, 8, and 12 weeks of treatment. The RMS at 8 weeks was significantly better in the chlorophyll c2 than the placebo group (mean RMS difference = -3.09; 95 % confidence interval = -5.96 to -0.22); the mean RMS at 4 weeks was only slightly better in the chlorophyll c2 group. The JRQLQ scores did not differ significantly between the two groups. Chlorophyll c2 would have a potential to be an alternative treatment for allergic rhinitis.

Use of ambulatory anesthesia with manually assisted ventilation for tympanic membrane regeneration therapy in children.

PURPOSE: To present the utility of ambulatory anesthesia using manually assisted ventilation via a facemask for tympanic membrane (TM) regeneration therapy in children. MATERIAL AND METHODS: The study included 10 children (age 4-11years) in whom the duration of perforation before treatment exceeded 6months and who were followed for at least 1year after treatment between December 2009 and December 2012. Under ambulatory anesthesia using manually assisted ventilation via a facemask, TM regenerative therapy with atelocollagen combined with basic fibroblast growth factor was performed in children who could not tolerate the procedure under local anesthesia alone. RESULTS: All of the children completed the TM regenerative therapy under ambulatory anesthesia in less than 5min. Complete closure was achieved in nine (81.8%) ears after 1year of postoperative follow-up. CONCLUSION: TM regenerative therapy can be performed under local anesthesia in less than 5min without a skin incision. However, local anesthesia is often insufficient in small children undergoing this procedure. Therefore, ambulatory anesthesia using manually assisted ventilation via a facemask is appropriate to complete this procedure safely in small children.

Expression of atrophy-related transcription factors in the process of intrinsic laryngeal muscle atrophy after denervation.

We examined changes in the expressions of three atrophy-related transcription factors (FOXO3a, P-FOXO3a, and PGC-1α) in the process of intrinsic laryngeal muscle atrophy after denervation. In total, 51 Wistar rats were used. After transection of the unilateral recurrent laryngeal nerve, the thyroarytenoid (TA) muscle and the posterior cricoarytenoid (PCA) muscle were excised and subjected to histological and Western blot studies. Relationships between the expressions of transcription factors during atrophy of the intrinsic laryngeal muscles were investigated by comparing the results of the treated side (T) with those of the untreated side (U), and sequential changes in the T/U ratio after denervation were assessed. Loss of wet muscle weight, together with a decrease in muscle fiber cross-sectional area and increase in the number of muscle fibers/mm(2), occurred more quickly in TA muscle than in PCA muscle. Muscle atrophy progressed rapidly between 7 and 28 days after denervation, while expression of FOXO3a was maximal on day 7, in both TA and PCA muscles. By contrast, P-FOXO3a expression decreased gradually after denervation. Expression of PGC-1α increased slowly until day 7, and then it declined. Denervation-induced atrophy of the intrinsic laryngeal muscles was closely linked with the expression of FOXO3a and PGC-1α, suggesting that atrophy of these muscles may involve the actions of these transcription factors. In addition, muscle atrophy progressed faster in TA muscle than in PCA muscle, due mainly to differences in muscle fiber composition.

A randomized controlled clinical trial of topical insulin-like growth factor-1 therapy for sudden deafness refractory to systemic corticosteroid treatment.

BACKGROUND: To date, no therapeutic option has been established for sudden deafness refractory to systemic corticosteroids. This study aimed to examine the efficacy and safety of topical insulin-like growth factor-1 (IGF-1) therapy in comparison to intratympanic corticosteroid therapy. METHODS: We randomly assigned patients with sudden deafness refractory to systemic corticosteroids to receive either gelatin hydrogels impregnated with IGF-1 in the middle ear (62 patients) or four intratympanic injections with dexamethasone (Dex; 58 patients). The primary outcome was the proportion of patients showing hearing improvement (10 decibels or greater in pure-tone average hearing thresholds) 8 weeks after treatment. The secondary outcomes included the change in pure-tone average hearing thresholds over time and the incidence of adverse events. RESULTS: In the IGF-1 group, 66.7% (95% confidence interval [CI], 52.9-78.6%) of the patients showed hearing improvement compared to 53.6% (95% CI, 39.7-67.0%) of the patients in the Dex group (P = 0.109). The difference in changes in pure-tone average hearing thresholds over time between the two treatments was statistically significant (P = 0.003). No serious adverse events were observed in either treatment group. Tympanic membrane perforation did not persist in any patient in the IGF-1 group, but did persist in 15.5% (95% CI, 7.3-27.4%) of the patients in the Dex group (P = 0.001). CONCLUSIONS: The positive effect of topical IGF-1 application on hearing levels and its favorable safety profile suggest utility for topical IGF-1 therapy in patients with sudden deafness. TRIAL REGISTRATION: UMIN Clinical Trials Registry Number UMIN000004366, October 30th, 2010.

Prognostic factors of Bell's palsy: prospective patient collected observational study.

The purpose of this study was to evaluate various parameters potentially influencing poor prognosis in Bell's palsy and to assess the predictive value for Bell's palsy. A single-center prospective patient collected observation and validation study was conducted. To evaluate the correlation between patient characteristics and poor prognosis, we performed univariate and multivariate analyzes of age, gender, side of palsy, diabetes mellitus, hypertension, and facial grading score 1 week after onset. To evaluate the accuracy of the facial grading score, we prepared a receiver operating characteristic (ROC) curve and calculated the area under the ROC curve (AUROC). We also calculated sensitivity, specificity, positive/negative likelihood ratio, and positive/negative predictive value. We included Bell's palsy patients who attended Ehime University Hospital within 1 week after onset between 1977 and 2011. We excluded patients who were less than 15 years old and lost-to-follow-up within 6 months. The main outcome was defined as non-recovery at 6 months after onset. In total, 679 adults with Bell's palsy were included. The facial grading score at 1 week showed a correlation with non-recovery in the multivariate analysis, although age, gender, side of palsy, diabetes mellitus, and hypertension did not. The AUROC of the facial grading score was 0.793. The Y-system score at 1 week moderate accurately predicted non-recovery at 6 months in Bell's palsy.

Effect of intranasal administration of concentrated growth factors on regeneration of the olfactory epithelium in an olfactory dysfunction-induced rat model.

OBJECTIVE: The development of treatments that promote the regenerative capacity of the olfactory epithelium (OE) is desirable. This study aimed to evaluate the effects of intranasal administration of concentrated growth factors (CGFs) in a rat model of olfactory dysfunction. STUDY DESIGN: Animal study. METHODS: Nineteen male rats were used. Fourteen olfactory dysfunction models were created by intraperitoneal administration of 3-methylindole. We randomly divided the rats from the olfactory dysfunction model after 1 week into the CGF or saline group; CGFs were administered to seven animals and saline to seven animals. Behavioral assessments using the avoidance test were conducted until day 28 after CGF/saline administration. On day 28, histological evaluation was conducted to determine olfactory epithelial thickness and the olfactory marker protein (OMP)-positive cell count. Five animals were intraperitoneally injected with saline as the control group. RESULTS: The avoidance rate remained decreased until 28 days after CGF/saline administration, and there was no significant difference between the two groups. Olfactory epithelial thicknesses on day 28 were 38.64 ± 3.17 µm and 32.84 ± 4.50 µm in the CGF and saline groups, respectively. OE thickness was significantly thicker in the CGF group than in the saline group (P = 0.013). The numbers of OMP-positive cells were 40.29 ± 9.77/1.0 × 104 µm2 and 31.00 ± 3.69/1.0 × 104 µm2 in the CGF and saline groups, respectively. The number of OMP+ cells in the CGF group was significantly increased compared with that in the saline group (P = 0.009). Both groups showed no improvement compared with the control group (OE thickness: 54.08 ± 3.36 µm; OMP+ cell count: 56.90 ± 9.91/1.0 × 104 µm2). CONCLUSIONS: The CGF group showed improved olfactory epithelial thickness and OMP-positive cell numbers compared with that in the saline group.

Oral Intake Difficulty and Aspiration Pneumonia Assessment Using High-Resolution Manometry.

OBJECTIVE: The sequential generation of swallowing pressure (SP) from the nasopharynx to the proximal esophagus is important for the bolus to pass from the oral cavity to the esophagus. The purpose of this study was to investigate the correlation of the SP sequence mode on high-resolution manometry (HRM) with oral intake difficulty and aspiration pneumonia. METHODS: Consecutive patients with dysphagia who were admitted to our dysphagia clinic between November 2016 and November 2020 were enrolled in this cross-sectional study. We classified the HRM pressure topography data according to the SP sequence mode into type A, normal; B, partially decreased; C, totally decreased; and D, sequence disappeared, and according to the upper esophageal sphincter (UES) during pharyngeal swallowing into type 1, flattening and 2, non-flattening. Clinical dysphagia severity was determined based on oral intake difficulty and aspiration pneumonia. RESULTS: In total, 202 patients with dysphagia (mean [standard deviation] age, 68.3 [14.5] years; 140 [69.8%] male) were enrolled. Type C (odds ratio [OR], 10.48; 95% confidence interval [CI], 2.89-51.45), type D (OR, 19.90; 95% CI, 4.18-122.35), and type 2 (OR, 6.36; 95% CI, 2.88-14.57) were significantly related to oral intake difficulty. Type C (OR, 3.23; 95% CI, 1.08-11.12) and type 2 (OR, 4.18; 95% CI, 1.95-9.15) were significantly associated with aspiration pneumonia. CONCLUSION: The failure of sequential generation of SP was associated with higher risk of oral intake difficulty and aspiration pneumonia. These assessments are useful in understanding the pathophysiology and severity of dysphagia and in selecting safety nutritional management methods. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:2127-2135, 2024.

Physical therapy for peripheral facial palsy: A systematic review and meta-analysis.

OBJECTIVE: This study aimed to reveal the efficacy of physical therapy for patients with peripheral facial palsy. METHODS: A literature search was conducted using PubMed, Ichushi-Web, and Cochrane Central Register of Controlled Trials. Published randomized controlled trials comparing the physical therapy versus placebo/non-treatment for peripheral facial palsy such as Bell's palsy, Ramsay Hunt syndrome, and traumatic facial palsy were included for meta-analysis. The primary outcome was non-recovery at the end of the follow-up. Non-recovery was defined according to the authors' definition. The secondary outcomes were the composite score of the Sunnybrook facial grading system and sequelae (presence of synkinesis or hemifacial spasm) at the end of the follow-up. Data was analyzed using Review Manager software and pooled risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI) were calculated. RESULTS: Seven randomized controlled trials met the eligible criteria. The data on non-recovery from four studies was obtained and included 418 participants in the meta-analysis. Physical therapy might reduce non-recovery (RR = 0.51 [95% CI = 0.31-0.83], low quality). Pooling the data of composite score of the Sunnybrook facial grading system from three studies (166 participants) revealed that physical therapy might increase the composite scores (MD = 12.1 [95% CI = 3.11-21.0], low quality). Moreover, we obtained data on sequelae from two articles (179 participants). The evidence was very uncertain about the effect of physical therapy on reduction of sequelae (RR = 0.64 [95% CI = 0.07-5.95], very low quality). CONCLUSION: The evidence suggested that physical therapy reduces non-recovery in patients with peripheral facial palsy and improves the composite score of the Sunnybrook facial grading system, whereas the efficacy of physical therapy in reducing sequelae remained uncertain. The included studies had high risk of bias, imprecision, or inconsistency; therefore, the certainty of evidence was low or very low. Further well-designed randomized controlled trials are needed to confirm its efficacy.

Dysphagia in patients with severe COVID-19: a retrospective study.

To investigate dysphagia after extubation in patients with severe coronavirus disease 2019 (COVID-19). We retrospectively examined patients with severe COVID-19 treated in our hospital between August 2021 and March 2022. Feeding outcomes were categorized into two groups-(1) total oral intake, and (2) difficulty in oral intake. To assess the feeding outcome, we used modified water-swallowing test (MWST) for all patients. However, in cases where aspiration or recurrent laryngeal nerve palsy was suspected, we conducted the fiberoptic endoscopic evaluation of swallowing after MWST. Patient data were collected from medical records. Forty-six patients with severe COVID-19 were included. Among the 46 patients, 14 (30.4%) experienced difficulties with oral intake. Older age, longer length of hospitalization, duration of mechanical ventilation, tracheostomy, diabetes, and higher serum levels of C-reactive protein (CRP) and procalcitonin (PCT) at the time of intubation were associated with difficulty in oral intake. The rate of difficulty with oral intake in patients with severe COVID-19 was 30.4%, which is not as high as reported in previous studies. Older age, longer duration of mechanical ventilation, tracheostomy, diabetes, and higher levels of CRP and PCT were associated with the prevalence of oral intake difficulty, suggesting that early attention should be paid to high-risk patients who have preexisting deterioration of swallowing function due to aging and comorbidities, or who have prolonged intubation or tracheostomy to prevent aspiration pneumonia.