Expression of Periostin in Benign Salivary Gland Tumors.

Parotid tumors present a wide range of histological features, from benign to malignant. Periostin, an extracellular matrix protein specifically expressed in the periosteum and periodontal ligament, is isolated from osteoblast cell lines. It regulates fibrosis and collagen deposition and plays an important role in myocardial repair after myocardial infarction. It is also known to be involved in otorhinolaryngological-diseases. This study included 36 patients [38 specimens; 16 men and 20 women, mean age 59.2 (range 26-82) years] who underwent parotid tumor resection at the Division of Otorhinolaryngology, Tohoku Medical and Pharmaceutical University, between April 2017 and March 2022 and were clinically and pathologically diagnosed as having benign parotid tumors. Formalin-fixed, paraffin-embedded sections from the surgical specimens were autoclaved and immunostained with anti-periostin antibodies to evaluate the expression and distribution of periostin. Histologically, the tumors were diagnosed as pleomorphic adenomas in 15 cases (15 specimens), Warthin's tumors in 13 cases (15 specimens), basal cell adenomas in 2 cases (2 specimens), oncocytomas in 4 cases (4 specimens), and myoepitheliomas in 2 cases (2 specimens). An increased expression of periostin was found in 32 of 38 samples (84.2%) in the stroma of benign parotid tumors. Four distinct patterns of periostin expression were observed in benign parotid gland tumors: negative, superficial, infiltrative, and diffuse. Statistically significant differences were found between periostin expression patterns and histological classification of the tumors. Our results suggest that periostin may be involved in the pathogenesis of benign parotid tumors and could serve as a new biomarker for these tumors.

Immunohistochemical localization of CD31, CD34, and periostin in vocal fold polyps.

BACKGROUND: Long-term voice-abuse or sudden vocal fold microvascular disruption can lead to injury and subsequent repair/remodeling of the vocal fold mucosa. Periostin is known to be involved in airway remodeling and in various otolaryngological diseases. In ischemic heart disease, increased CD31 expression has been observed around cardiomyocytes during remodeling, and endothelial proliferation has been reported to occur at these sites. OBJECTIVES: We investigated the expression and the roles of CD31, CD34, and periostin in the formation of vocal fold polyps. MATERIALS AND METHODS: Fifty-seven samples of vocal fold polyps were investigate histopathologically and immunohistochemically. RESULT: Expression of CD31 and CD34 was detected in 41 (71.9%) and 53 (93.0%) samples, respectively, obtained from patients with vocal fold polyp. Expression of periostin was detected in 41 (71.9%) samples obtained from patients with vocal polyps. The vocal polyp samples could be classified into three histological subtypes. Three patterns of CD31 and CD34 expression were observed in the vocal polyp. Four patterns of periostin expression were observed in vocal polyps. An association was observed between the CD31 expression pattern and the histological subtype of vocal fold polyps. CONCLUSION AND SIGNIFICANCE: In vocal fold polyps, evaluation of vascular endothelial markers may be useful for staging.

Correction to "First Total Synthesis of Tanzawaic Acid B".

[This corrects the article DOI: 10.1021/acsomega.3c03634.].

First Total Synthesis of Tanzawaic Acid B.

The first total synthesis of (+)-tanzawaic acid B, a natural polyketide bearing a pentadienoic ester and octalin moiety, has been accomplished. The synthetic improvement from previous synthetic conditions facilitated our gram-scale synthesis of the chiral octalin that possesses seven stereogenic centers and that is the core skeleton of almost all of the tanzawaic acid family.

Effect of second-generation antihistamines on nighttime sleep and daytime sleepiness in patients with allergic rhinitis.

BACKGROUND: The daytime tiredness experienced by the vast majority of allergic rhinitis (AR) sufferers is directly related to the fact that they experience disrupted sleep at night. This study compared the effects of recently marketed second-generation H1 antihistamines (SGAs) on nighttime sleep and daytime sleepiness in patients with AR, with patients grouped into those taking non-brain-penetrating antihistamines (NBP group) and those taking brain-penetrating antihistamines (BP group). METHODS: Patients with AR completed self-administered questionnaire-based surveys to determine Pittsburgh Sleep Quality Index (PSQI) before and after taking SGAs. Statistical analysis was performed on each evaluation item. RESULTS: Of 53 Japanese patients with AR between 6 and 78 years old, median (SD) age was 37.0 (22.4) years old and 21 were men (40%). Of the 53 patients, 34 were the NBP group and 19 were the BP group. In the NBP group, mean (SD) subjective sleep quality score after medication was 0.76 (0.50), which was significantly lower (better) than the score of 0.97 (0.52) before medication (p = 0.020). In the BP group, mean (SD) subjective sleep quality score after medication was 0.79 (0.54), which was not significantly different from the score of 0.74 (0.56) before medication (p = 0.564). In the NBP group, mean (SD) global PSQI score was 3.47 (1.71) after medication, which was significantly lower (better) than the score of 4.35 (1.92) before medication (p = 0.011). In the BP group, mean (SD) global PSQI score was 2.47 (2.39) after medication, which was not significantly different from the score of 3.00 (2.71) before medication (p = 0.125). CONCLUSION: Subjective sleep quality and global PSQI score were improved only in the group taking non-brain-penetrating SGAs.

A facelift procedure for resection of a branchial cleft cysts.

OBJECTIVES: Branchial cleft cysts (BCCs) are common in daily practice, however, BCC patients suffer aesthetic problems due to postoperative scars on visible parts after surgery. To analyze the feasibility, surgical outcomes and possible risks and complications encountered during a facelift procedure for patients with BCC. METHODS: This retrospective analysis examined patients who had undergone surgery for branchial cleft cyst using a facelift procedure (n = 16) or conventional transcervical resection (n = 20) at our institutes between April 2015 and August 2021. RESULTS: There was no significant difference between the groups that underwent the facelift procedure or conventional transcervical resection as to the average size of the cysts, operating time, bleeding, drain out, or recurrence. None of the patients needed to switch from the facelift procedure to conventional transcervical resection. In all the patients in the facelift procedure group, postoperative scars were fully concealed by the auricle and hair. However, four patients in the facelift procedure group experienced a transient auricular complication after surgery. CONCLUSION: The facelift procedure provides adequate visualization, workspace and excellent cosmetic results in suitably selected cases with BCC.

Periostin is an aggravating factor and predictive biomarker of eosinophilic chronic rhinosinusitis.

BACKGROUND: Patients with eosinophilic chronic rhinosinusitis (ECRS) respond poorly to many treatment modalities. Overproduction of periostin in the nasal mucosa is reported to contribute to polyp formation. This study examined periostin levels in patients with ECRS in comparison with levels in patients with non-ECRS. METHODS: Fifty-nine patients with chronic rhinosinusitis were grouped into those with ECRS and those with non-ECRS. We compared the relationships between peripheral blood eosinophil level, serum periostin level, histopathological findings, clinical and laboratory findings, nose findings, diagnostic score of the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis Study, and postoperative recurrence of nasal polyps in each group. RESULTS: In the ECRS group, a positive correlation was found between peripheral blood eosinophil level and serum periostin level (rs = 0.49, P < 0.01: Spearman's rank correlation coefficient). ROC curve analysis was used to evaluate the serum periostin level that could predict postoperative recurrence of nasal polyps in the ECRS group: the area under the curve (AUC) was 0.95, sensitivity was 92%, and specificity was 100%; the serum periostin cutoff value for postoperative recurrence of nasal polyps was 130 ng/ml. In ROC curve analysis to evaluate peripheral blood eosinophil level, the AUC was 0.73, sensitivity was 69.2%, and specificity was 85.0%; the cutoff value was 8.8%. CONCLUSIONS: periostin was implicated in the pathophysiology of ECRS. Periostin shown to be a more useful biomarker than eosinophils in ECRS. Periostin was shown to likely be an important biomarker for pathological severity of ECRS and postoperative recurrence of nasal polyps.

OK-432 Treatment of Ranula Intruding into the Cervical Region.

OBJECTIVES: Plunging ranula intruding into the cervical region is rare and a standard therapy has not yet been consolidated. This paper investigates the outcomes and side effects of OK-432 treatment in patients with a ranula extending into the cervical region. METHODS: The study design and setting consisted of a planned data collection at Tohoku Medical and Pharmaceutical University and Fukase Clinic. Eight patients with ranula extending into the cervical region received OK-432 treatment between January 2016 and February 2019. OK-432 treatment was performed for patients with ranula extending into the cervical region. RESULTS: In all patients, a total shrinkage and marked reduction in lesions were observed without local scars or deformations after OK-432 treatment. Complications were local swelling and mild fever (37.5-38.5 °C), which lasted a few days in half of the patients. CONCLUSIONS: OK-432 treatment is straightforward, secure, and efficacious and can be substituted for surgery in the treatment of ranula extending into the cervical region.

Cervical Liposarcoma Revisited: A Case Report and Scoping Literature Review.

The commonest sites for liposarcoma are the retroperitoneum and lower extremities. Liposarcoma of the head and neck region is a rare and potentially life-threatening malignancy. Tumors originating in the right cervical space cause special diagnostic and therapeutic difficulties. In the present report, we describe a case of differentiated liposarcoma of the right cervical region. The tumor continued to grow slowly over 3 years before a definitive diagnosis was established. Extended extirpation of the tumor was performed and proved efficacious in that no recurrence has been observed for 4 years. Recommendations for earlier and accurate diagnosis and treatment of this rare neoplasm are discussed.

Taste and acoustic reflex after recovery from facial muscle paralysis in patients with facial nerve palsy.

BACKGROUND: There are few studies on taste or acoustic reflex (AR) in patients after recovery from facial muscle paralysis (FMP). OBJECTIVES: To investigate the recovery of AR and taste in patients who have recovered from peripheral facial nerve palsy (FNP). MATERIALS AND METHODS: The study included 25 patients whose FMP had resolved after treatment for FNP. A difference in taste threshold of ≤4 dB between the affected and unaffected sides in the electric taste test was defined as normal; an AR on the affected side was assessed to be ≥90% of the AR on the unaffected side was defined as normal. RESULTS: Six months after treatment, 8% of patients with FNP who had recovered from FMP still showed taste disorders, and 60% of patients showed abnormal AR. The number of subjects whose electric taste threshold was normal after treatment was significantly higher than the number of subjects whose AR assessment was normal (p < .01). CONCLUSION AND SIGNIFICANCE: This study demonstrates that even among subjects whose FMP is resolved after treatment for FNP, there are some whose taste and AR do not recover. Physicians should be aware of ear symptoms persisting after facial muscle recovery.

Endoscopic Treatment of Sinonasal Leiomyosarcoma: A Case Report in Light of the Literature.

A 49-year-old Japanese man presented with a rare case of sinonasal leiomyosarcoma with left nasal bleeding for 12 months. He had no history of irradiation or malignancies, including retinoblastoma. Preoperative histological examination suggested vascular leiomyoma. Complete resection with endoscopic surgery was performed. Histological examination during the operation suggested that the tumor was a leiomyoma. However, immunohistochemical staining for α smooth muscle actin and desmin were helpful in establishing a definitive diagnosis of sinonasal leiomyosarcoma. The resection margins were positive for tumor cells. Staging with CT of the neck and thorax, ultrasound of the abdomen, and MRI of the head ruled out metastases. Second endoscopic tumor resection surgery was performed for positive resection margins. The patient's condition was successfully managed with additional excision, and he remains well with no evidence of recurrence and metastasis 36 months after treatment. Endoscopic management should be considered in suitable cases.

4-(Dimethylamino)pyridine N-Oxide-Catalyzed Macrolactamization Using 2-Methyl-6-nitrobenzoic Anhydride in the Synthesis of the Depsipeptidic Analogue of FE399.

A depsipeptidic analogue of FE399 was efficiently synthesized mainly through macrolactamization using 2-methyl-6-nitrobenzoic anhydride (MNBA), and a detailed investigation of the desired 16-membered macrolactam core of FE399 was performed. It was determined that the combination of MNBA and a catalytic amount of 4-(dimethylamino)pyridine N-oxide exhibits much higher activity than that of conventionally used coupling reagents such as hexafluorophosphate azabenzotriazole tetramethyl uronium and benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate.

OK-432 treatment of pediatric patients with recurrent thyroglossal duct cyst after surgery.

<b>Introduction:</b> Recurrent thyroglossal duct cyst after surgery is not a rare condition and first-line treatment has not been established yet.<br/><br/> <b>Aim:</b> Evaluation of outcomes and complications of OK-432 treatment in patients with recurrent thyroglossal duct cyst after surgery. <br/><br/> <b>Material and methods:</b> This study is designed as a case series with planned data collection at Tohoku Medical and Pharmaceutical University and Fukase Clinic. Five patients with recurrent thyroglossal duct cyst after surgery received this therapy between January 2014 and February 2020 on an outpatient basis, without hospitalization. OK-432 solution was injected into the lesion using an 18- or 27-gauge needle, depending on the location and size of the lesion, as well as on possible complications.<br/> <br/> <b>Results:</b> Lesions showed marked reduction or total shrinkage in all patients, with no local scarring or deformity at the injection site. Side effects manifested as local pain at the site of injection and fever (37.5-38.5°C) observed in three patients, but the symptoms resolved within a few days.<br/> <br/> <b>Conclusions:</b> Since OK-432 therapy is simple, easy, safe and effective, it can be used as an alternative to surgery in the treatment of recurrent thyroglossal duct cyst after surgery.

Intrathecal administration of nusinersen for spinal muscular atrophy: report of three cases with severe spinal deformity.

BACKGROUND: Spinal muscular atrophy (SMA) is a genetic disease characterized by degeneration of the spinal cord, resulting in progressive muscle atrophy. Recently, nusinersen has been approved for treating SMA, which should be administered intrathecally. CASE PRESENTATION: Patient 1 was a 36-year-old woman with SMA type 2. Patients 2 and 3 were 10- and 17-year-old girls with SMA type 1. In patients 1 and 2, the needle was inserted into the spinal column, but outflow of cerebrospinal fluid was unable to be confirmed. CT revealed that the dural sac terminated at the L5 level in patients 1 and 3 and at the L5/S1 level in patient 2. CONCLUSIONS: Patients with SMA often present with high-grade scoliosis, making intrathecal administration difficult. In addition, the dural sac may terminate at a level higher than normal. To ensure intrathecal administration, the level of dural sac termination must be confirmed by CT before puncture.

A case of localized tracheobronchial relapsing polychondritis with positive matrilin-1 staining.

BACKGROUND: Relapsing polychondritis (RPC) is a rare progressive autoimmune disease characterized by inflammation in the cartilage of multiple organs. Tracheobronchial involvement appears in nearly half of RPC patients during the course of their disease and represents the main cause of death. Localized tracheobronchial RPC is much rarer, and the pathogenesis remains unclear. Matrilin-1 is a non-collagenous cartilage matrix protein and has been suggested to be a potent autoantigen that induces the airway disease of RPC in animal models. However, the expression of matrilin-1 in tracheobronchial tissue in human remains unclear. Therefore, we examined the expression of matrilin-1 in the tracheal and auricular tissues in a localized tracheobronchial RPC patient. CASE PRESENTATION: A 62-year-old man with systemic sclerosis presented with cough and dyspnea on exertion. The lung function test showed an expiratory flow limitation and chest computed tomography showed diffuse thickness from the trachea to the bronchiole. No other tests showed abnormal findings. To evaluate further, bronchoscopy was performed and endobronchial ultrasonography showed thickness in the fourth-marginal echo layer suggesting inflammation of the cartilage. However, the tracheal biopsy showed no specific findings. The subsequent surgical tracheal biopsies showed inflammatory cell infiltration with destruction of the cartilage. Neither auricular nor nasal deformity, except for a tracheobronchial lesion, was detected. Biopsy from the left auricular cartilage also did not show any inflammatory changes. Finally, we diagnosed the patient with localized tracheobronchial RPC. To address the hypothesis that autoimmunity against matrilin-1 is involved in the pathogenesis of localized tracheobronchial RPC, we evaluated the expression level of matrilin-1 in a tracheal and auricular specimen from this patient. Immunohistochemical staining with anti-matrilin-1 antibody showed matrilin-1 in the tracheal but not in the auricular cartilage. CONCLUSIONS: We first demonstrated the expression of matrilin-1 in tracheal but not in auricular cartilage in a localized tracheobronchial RPC patient. This result supports the possibility that matrilin-1 is involved in the pathogenesis of localized tracheobronchial RPC. However, this is only one case report and further observations will be needed to confirm this result.

Outcomes of regional-based newborn hearing screening for 35,461 newborns for 5 years in Akita, Japan.

OBJECTIVES: Newborn hearing screening (NHS) has been actively performed since 2001 in Akita, Japan. The NHS coverage rate has increased yearly, and performance has been consistently >90% since 2012. The purpose of this study was to summarize NHS outcomes in the Akita prefecture of Japan and to obtain new insights for from our summarized data for the future. METHODS: A total of 35,461 newborns in hospitals and clinics where hearing screening was performed in Akita from 2012 to 2016 were included. The outcome data of NHS were collected for analysis. RESULTS: The overall screening coverage rate for hearing loss was 94.7%. Of the screened infants, 0.53% received a referral on the 2-stage automated auditory brainstem response (ABR), and 80.4% of referred infants had a check-up at the hospital to receive a diagnostic hearing examination. Finally, the prevalence of bilateral congenital hearing loss was 0.14%, that of bilateral moderate to profound hearing loss was 0.12%, and that of unilateral congenital hearing loss was 0.10%. Furthermore, the average consultation period in infants with risk factors was significantly later than that in infants without risk factors (p = 0.0015). Follow-up for infants diagnosed with normal hearing after diagnostic hearing examination revealed that 4.7% suffered bilateral moderate to profound hearing loss later. This percentage is significantly higher than that of the general group (p < 0.001). CONCLUSION: The prevalence of bilateral congenital hearing loss was 0.14% in Akita and 0.12% of infants were diagnosed with bilateral moderate to severe hearing loss. Medical personnel should be enlightened regarding the importance of performing hearing diagnostic examinations until 3 months of age. Even if infants were diagnosed with normal hearing after a diagnostic examination, we strongly suggest continuing follow-up until they are able to perform pure tone audiometry with accuracy.

Total Synthesis and Antimicrobial Evaluation of 23-Demethyleushearilide and Extensive Antimicrobial Evaluation of All Synthetic Stereoisomers of (16Z,20E)-Eushearilide and (16E,20E)-Eushearilide.

A novel stereoisomer of eushearilide, 23-demethyleushearilide, was synthesized, and the structure-activity relationships of this compound along with known eushearilide stereoisomers were investigated in order to design novel lead compounds for the treatment of fungal infections. It was discovered that all of these congeners, together with the natural product, exhibited a wide range of antimicrobial activity against not only fungi but also against bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE).

Comprehensive analysis of syndromic hearing loss patients in Japan.

More than 400 syndromes associated with hearing loss and other symptoms have been described, corresponding to 30% of cases of hereditary hearing loss. In this study we aimed to clarify the mutation spectrum of syndromic hearing loss patients in Japan by using next-generation sequencing analysis with a multiple syndromic targeted resequencing panel (36 target genes). We analyzed single nucleotide variants, small insertions, deletions and copy number variations in the target genes. We enrolled 140 patients with any of 14 syndromes (BOR syndrome, Waardenburg syndrome, osteogenesis imperfecta, spondyloepiphyseal dysplasia congenita, Stickler syndrome, CHARGE syndrome, Jervell and Lange-Nielsen syndrome, Pendred syndrome, Klippel-Feil syndrome, Alport syndrome, Norrie disease, Treacher-Collins syndrome, Perrault syndrome and auditory neuropathy with optic atrophy) and identified the causative variants in 56% of the patients. This analysis could identify the causative variants in syndromic hearing loss patients in a short time with a high diagnostic rate. In addition, it was useful for the analysis of the cases who only partially fulfilled the diagnostic criteria.

Possible involvement of interleukin-18 in the pathology of hepatobiliary adverse effects related to treatment with ceritinib.

BACKGROUND: Ceritinib demonstrated a statistically significant effect on the progression-free survival versus chemotherapy in patients with advanced anaplastic lymphoma kinase (ALK) rearrangement in non-small cell lung cancer (NSCLC) as the first therapy or after previous treatment with crizotinib and one or two prior chemotherapy regimens in global phase 3 studies. However, some serious adverse effects related to ceritinib therapy were reported across these clinical studies. Among them, a grade 3 and 4 increase in hepatobiliary enzymes was one of the common adverse events related to treatment with ceritinib. However, the pathology remains unclear. Previously, increased Interleukin (IL)-18 was observed in both biliary duct disease and liver disease. Therefore, we hypothesized that IL-18 is involved in the pathology of hepatobiliary adverse effects related to treatment with ceritinib and evaluated the serum IL-18. CASE PRESENTATION: The patient was a 53-year-old Japanese woman that we previously reported as having severe hepatobiliary adverse effects related to ceritinib therapy. Laboratory data, CT and MRI were obtained at each time point. IL-18 was evaluated by ELISA method at each time point. Immunochemical staining of liver tissue was performed as a standard protocol using antibodies against IL-18. Our records showed that the levels of serum IL-18 increased from the early stage of hepatobiliary adverse effects related to the treatment with ceritinib and were became worse with an increase in hepatobiliary enzymes and the progression of imaging abnormalities in the bile duct. Furthermore, IL-18 positive cells were detected in the inflammatory sites around the interlobular bile duct of the liver tissue. CONCLUSION: Our case report shows that the increase of serum IL-18 had a positive correlation with the progression of severe hepatobiliary adverse effects related to treatment with ceritinib and the involvement of IL-18 in the hepatobiliary inflammation by pathological evaluation. These results suggest that IL-18 could be a useful surrogate marker for the hepatobiliary toxicity of ceritinib. However, this is only one case report and further prospective observations will complement our data in the future.