Novel insights into gut health: Cilostazol strengthens gut integrity by adjusting TLR-2/NF-κB/IL-23 and CD44/AKT/GSK-3ß/cyclin-D1 trajectories in methotrexate-induced mucositis model.

Methotrexate (MTX)-induced gastrointestinal mucositis is a common adverse effect characterized by redox imbalance and overproduction of inflammatory mediators that perturb intestinal integrity. Currently, there is no definitive treatment for this condition and its prevention is still far beyond comprehension. Because of its pleiotropic pharmacological actions, we aimed to explore the potential mechanisms through which cilostazol (CILO) can protect against MTX-induced intestinal mucositis. Wistar rats were allocated into 4 groups, control, CILO (100 mg/kg, p.o for 14 days), MTX (7.5 mg/kg for 4 successive days), and CILO + MTX. The improving effect of CILO on the morphological structure was confirmed by an upturn in the histopathological and transition electron microscope examinations evidenced by the increased jejunal villus height/width and the crypt depth besides the maintenance of tight junctions. These findings were verified biochemically; on the molecular level, CILO reduced the MTX-induced lipid peroxidation, cleaved caspase-3, p53, and the inflammatory parameters (TLR-2, NF-κB, IL-23, TNF-α, IL-1ß), while increasing the anti-inflammatory marker IL-10 and the antioxidant enzyme SOD. Moreover, CILO decreased the injurious axis AKT/GSK-3ß/cyclin-D1, and CD44+, but increased the immunoexpression of the cell proliferating marker PCNA. CILO also upheld the intestinal barrier by enhancing the tight junction molecules (ZO-1, claudin-4) and the E-cadherin/ß-catenin complex while abating the mesenchymal marker vimentin. In conclusion, CILO protected gut integrity by reducing the epithelial-mesenchymal transition process, the MTX-induced oxidative, apoptotic, and inflammatory mediators, and turning off the CD44/AKT/GSK-3ß/cyclin D1 trajectory and intensifying the expression of PCNA.

Outcomes of Central Neck Dissection for Papillary Thyroid Carcinoma in Primary Versus Revision Setting.

Introduction: Surgery in the central compartment after previous thyroidectomy involves an increased risk of injury to critical organs, including the parathyroids and recurrent laryngeal nerve. Contrastingly, primary central neck dissection involves a relatively low operative risk. Objective: This study aimed to compare the outcomes of central neck dissection in primary versus revision settings with respect to the lymph node yield and complication rates. Methods: This single-center prospective study included patients who underwent primary or revision neck dissection surgery for histologically confirmed thyroid malignancy between January 2018 and January 2022. Results: We included 30 patients who underwent total thyroidectomy with primary central neck dissection and 29 patients who underwent central neck dissection following remote thyroidectomy with or without previous central dissection. There was no significant between-group difference in postoperative complications, including permanent hypocalcemia and recurrent laryngeal nerve injury. However, both groups showed a significant postoperative decrease in calcium levels even though calcium and parathyroid hormone levels were within reference range. Conclusion: Although many surgeons fear revision central neck dissection, it appears to have similar therapeutic outcomes and complication rates as primary neck dissection for papillary thyroid cancer. Specifically, there were no between-group differences in the lymph node yield, hypoparathyroidism, or recurrent laryngeal nerve paralysis. Patients with normocalcemia showed a significant postoperative reduction in calcium levels, suggesting subclinical parathyroid insufficiency.

Bilateral congenital choanal atresia in a preterm neonate - a rare neonatal emergency: A case report and review of literature.

Congenital choanal atresia results from the developmental failure of the nasal cavity to connect posteriorly with the nasopharynx. Although congenital choanal atresia is a well-recognized developmental disorder, it is an uncommon condition with an overall incidence of approximately 1 per 10,000 live births. The authors aim to highlight that in very preterm neonates, early diagnosis of bilateral congenital choanal atresia needs a high index of suspicion to avoid life-threatening events. It is considered as one of the neonatal emergencies, and repair is recommended in the first few weeks of life. The authors report an uncommon presentation of a very preterm neonate born at 31 weeks of gestation, diagnosed to have bilateral congenital choanal atresia with repeated failure of a trial of extubation. A transnasal endoscopic repair was performed in the eighth week of life to relieve the life-threatening nasal obstruction.

Skull Base Osteomyelitis With Bilateral Acute Otitis Media.

Skull base osteomyelitis is an inflammatory process that usually occurs secondary to necrotizing otitis externa or chronic mastoid infections. The involvement of the external auditory canal is typical of this condition and aids in its diagnosis. The treatment of skull base osteomyelitis is often complex and involves long-term intravenous antibiotics. Skull base osteomyelitis originating from the middle ear is a rare entity. We report a case of skull base osteomyelitis originating from the bilateral otitis media.

INI-1-Deficient Sinonasal Carcinoma: Case Report with Emphasis on Differential Diagnosis.

SMARCB1-deficient sinonasal carcinoma is a newly described entity, with less than 100 reported cases. It is characterized by basaloid or rhabdoid morphology and is diagnosed by complete loss of nuclear SMARCB1 (INI-1). The morphologic appearance, specific immunophenotypic markers, and unique molecular make-up distinguish this entity from other various malignant neoplasms. We present a case of a 55-year-old male that presented with a large progressing palatine mass. Magnetic resonance imaging showed a heterogeneous mass involving the left maxillary space. The initial biopsy was diagnosed as undifferentiated carcinoma. Resection was performed, and immunohistochemical studies revealed a complete loss of INI-1, refining the diagnosis to SMARCB1-deficient sinonasal carcinoma. Diagnosis of SMARCB1-deficient sinonasal carcinoma should be considered in all undifferentiated sinonasal carcinomas. Immunohistochemistry or molecular studies are mandatory to confirm the diagnosis and exclude other morphologically similar entities.

Correlation Between Ultrasound and Cytological Findings of Patients With Suspicious Thyroid Nodules: The King Hamad University Hospital Experience.

Background Thyroid nodules are a common presentation in otolaryngology-head and neck clinics. The detection of thyroid nodules has increased significantly with the advancements in radiological technology such as computed tomography and ultrasound (US). The present study aims to improve the clinical practice and management of thyroid disorders by establishing correlations between US and cytological findings in the diagnosis of thyroid nodules. Methodology A retrospective cohort study was conducted at the King Hamad University Hospital (KHUH), Bahrain. A total of 189 cases met the study criteria. Pathological records for thyroid nodule fine needle aspiration (FNA) cytology and US features of sampled nodules from the patients were obtained. The cytological results were categorized into the Bethesda grading system, while the US features were organized into internationally accepted features using the Thyroid Imaging Reporting and Data System (TIRADS). Results The radiologic characteristics from US showed positive features largely for the composition (76.2%) and vascularity (59.3%). Very few showed echogenicity (6.9%). Most records indicated negatively for the shape (94.7%), margins (76.2%), echogenicity (63.5%), or echogenic foci (66.1%). Of the 47 cases in TIRADS 1 and 2, only two were found to be Bethesda 4 classification, showing that most of these nodules were benign. Among those with TIRADS 3 on US, 85% turned were benign (Bethesda 2), two of the remaining six were grade 3, and the other four were suspiciously malignant. Of the 100 cases in TIRADS 4 and 5, 63% were of Bethesda grade 2, and therefore, benign, 14% were mildly suspicious, and only 23% were in Bethesda grades 4-6. A significant positive correlation was noted between the TIRADS and Bethesda scores (r = 0.338, p ≤ 0.001). Conclusions If the thyroid nodules are classified properly by US using the TIRADS system, the probability of a nodule being malignant can be established with a certain level of confidence. The appropriate management of the nodule can be initiated avoiding unwarranted FNA procedures.

Frequency of migraine as a chief complaint in otolaryngology outpatient practice.

OBJECTIVE: To identify the frequency of typical (headache and dizziness) and common atypical (ear fullness, pressure, pain, tinnitus, facial fullness, and nasal congestion) migraine symptoms as chief complaints among patients presenting to otolaryngology clinic. METHODS: This is a descriptive study of prospectively collected data from a general otolaryngology practice. Typical migraine presentations were diagnosed by applying international headache society (IHS) criteria for migraine headache and Neuhauser's criteria for migrainous vertigo. Atypical otologic and rhinologic migraine symptoms were diagnosed using individualized criteria. Charts were reviewed at 6-month interval from the first presentation. RESULTS: Out of 1002 consecutive patients, 10.8% presented with "migrainous chief complaint." All migrainous chief complaint patients had a history of headache but not all of them presented with headache. Corrected female to male ratio in the migraine group was 3 to 1; age distributions were significantly different between the migraine and nonmigraine groups by applying t-test. Out of the atypical complaints, 86% of the patients had a history of concomitant typical presentation. CONCLUSION: Actual diagnostic criteria for migraine do not satisfy the diversity of its presentation. Investigating the history of migraine is enough to diagnose most atypical presentations. Sound knowledge about migraine seems essential for any ENT practitioner.

Normative inner ear volumetric measurements.

In the current study, we attempted to determine normative inner ear volumetric measurements generated from three-dimensional computed tomography (CT) images. In addition, we investigated a correlation between the axial length and the volume of the labyrinth and discussed clinical outcomes of this correlation. Amira 5.2.2 software was used to create three-dimensional isosurface images of the human labyrinth using two-dimensional CT images from 35 anatomically normal patients. With the three-dimensional labyrinths, complete dimensional analysis was performed to gain insight into both the volume and the greatest axial length of the inner ear. Paired t test and Pearson correlation were used. Our volume of the inner ear inquiry reported a mean volume of 221.5 with SD of 24.3 µL (0.228 µL for males and 0.218 µL for females). The length showed a mean of 1.713 cm with SD of 0.064 cm (1.753 cm for males and 1.695 cm for females). The length was used to estimate the volume, and the estimates were within 10% of the measured volume 74.3% of the time. Normative volumetric measurements of the inner ear can be obtained by using three-dimensional CT Imaging by Amira 5.2.2 software. There was a statistically significant positive correlation between the axial length of the labyrinth and the volume of the labyrinth. The axial length of the labyrinth could be used to estimate the volume of the labyrinth, which may be clinically important to estimate the concentration of the drug distributed in the inner ear.

Who needs admission among infants with acute otitis media?

AIM: Management of acute otitis media (AOM) in infants younger than 2 months old is controversial. It varies between treatment on an outside basis, and hospitalization for intravenous antibiotics and sepsis work-up based on variability of the reported AOM pathogens in this particular group. Our aim is to identify clinical indicators that may suggest a need for an invasive medical work-up and/or hospitalization of these young patients, and compare their management to that of older infants. METHODS: Retrospective chart review. Admitted infants with AOM and a random sample of infants presenting to the emergency room with AOM over a 20-year period. Infants younger than 2 months were designated as 'young infants', and those older as 'older infants'. Demographic data, relevant history, physical examination, laboratory studies and treatment were reviewed. RESULTS: Twenty-nine admitted infants were included (13 young infants). A sample of 58 outpatients was studied, including two young infants. Compared to older inpatient infants, admitted young infants were less febrile (P < 0.05), had more benign white cell count (P < 0.05) but had more otorrhea (P < 0.05). These grew gram-negative organisms. Sepsis work-up was negative. Young infants were more likely to be admitted (P < 0.05). Admitted older infants had more otorrhea than outpatients (P < 0.05) or a complication (P < 0.05). CONCLUSIONS: Young infants often need admission for intravenous antibiotics, until middle ear culture is out. Sepsis work-up may be necessary only in toxic patients. Older infants need admission when severely ill or have a complication.

Transmastoid middle fossa craniotomy repair of superior semicircular canal dehiscence using a soft tissue graft.

OBJECTIVE: To describe the successful surgical treatment of 5 cases of superior semicircular canal dehiscence via a transmastoid middle fossa craniotomy using a soft tissue graft. DESIGN: Case report. SETTING: Private practice otologic referral center. RESULTS: All patients have experienced reduction in auditory and vestibular symptoms. Pulsatile tinnitus and autophony are now absent in the operated ears. Chronic disequilibrium is subjectively improved. Patients with sound evoked eye movements no longer have sound sensitivity on the operated side. Head thrust testing indicates no obstruction of the operated superior canal in all patients with normal head thrust preoperatively. Audiometry is unchanged from preoperation, and cervical vestibular-evoked myogenic potential thresholds have increased on the operated side in 4 of 4 patients. Three patients had dehiscence at the superior petrosal sinus inaccessible to standard middle fossa repair. All patients were discharged to home the morning after surgery. CONCLUSION: Transmastoid craniotomy repair of the superior semicircular canal dehiscence using a soft tissue graft offers numerous advantages over traditional surgical approaches and can be performed safely in the outpatient setting. The strategy is particularly useful in patients with dehiscence at the superior petrosal sinus. This article will review our strategy and discuss the advantages and disadvantages of the different surgical treatments used for patients with severe symptoms from superior canal dehiscence.

Otalgia associated with migraine.

OBJECTIVE: To investigate the association of otalgia and migraine. STUDY DESIGN: Retrospective survey with evaluation of otalgia response to migraine treatment. Only patients with minimum symptom duration of 3 months, who accepted migraine treatment and had a minimum follow-up of 3 months, were included. SETTING: Single neurotology practice. SUBJECTS: All patients with otalgia in whom other causes of otalgia had been excluded and who were treated with migraine therapies. INTERVENTION: Standard first-line abortive and prophylactic migraine therapies. MAIN OUTCOME MEASURES: Specific clinical data, as well as pretreatment and posttreatment severity scores, were gathered. Response to treatment was assessed by comparing pretreatment and posttreatment symptom scores using paired t test. RESULTS: A total of 26 patients were included. Ninety-two percent responded to migraine therapy with improved symptom frequency, severity, and duration (p < 0.001). Median duration of symptoms was 5 years. Mean delay to response was 2.3 weeks, and mean follow-up was 20 months. Otalgia was the chief complaint in 77%. Pain was dull in 35%, sharp in 19%, throbbing in 19%, and mixed in 27%. Sixty-five percent demonstrated triggerability of otalgia. A total of 65% had International Headache Society migraine. Patients responded to many classes of migraine preventive and abortive medications. CONCLUSION: Otalgia of unclear cause can be related to migraine mechanisms. Our group showed a high prevalence of migraine characteristics, including headache, migraine-associated symptoms, patterns of triggerability, and response to migraine treatment. Clinical criteria for diagnosis of migraine-associated otalgia are suggested for future prospective study.

Gene expression profiling in head and neck squamous cell carcinoma: Clinical perspectives.

BACKGROUND: To date, more than 60 gene expression profiling (GEP) studies have been published in the field of head and neck squamous cell carcinoma (HNSCC) with variable objectives, methods, and results. METHODS: The purpose of this study was to present a state-of-the-art review of GEP in HNSCC focusing on the current advances and perspectives for clinical applications. RESULTS: Gene expression signatures have been developed to identify screening and diagnostic molecular markers, to improve tumor staging (cervical lymph node and distant metastasis prediction), to differentiate lung metastasis of HNSCC from primary lung squamous cell carcinoma, to predict tumor response to chemoradiotherapy, and to provide outcome predictors. CONCLUSION: Some transcriptional signatures that could improve HNSCC management have been identified, but further analyses are required to properly validate and to precisely evaluate their clinical relevance. After an exploratory phase, the completion of large scale projects with stringent methodology is now necessary to transfer GEP from bench to bedside.

Primary malignant melanoma of the trachea.

Tracheal melanomas represent the rarest type of extracutaneous melanomas. The clinical manifestation is similar to other tracheal tumors and ranges from symptoms of airway obstruction such as dyspnea and stridor to other nonspecific symptoms such as hoarseness, cough and hemoptysis. Bronchoscopy is required to draw the origin of the lesion biopsy is needed to establish histologic diagnosis. Treatment consists of either palliative surgery aiming at restoring the airway or tracheal resection and end to end anastmosis. We would like to present here below a rare case of tracheal melanoma and discuss the various diagnostic and therapeutic means.

Clinical relevance of nine transcriptional molecular markers for the diagnosis of head and neck squamous cell carcinoma in tissue and saliva rinse.

BACKGROUND: Analysis of 23 published transcriptome studies allowed us to identify nine genes displaying frequent alterations in HNSCC (FN1, MMP1, PLAU, SPARC, IL1RN, KRT4, KRT13, MAL, and TGM3). We aimed to independently confirm these dysregulations and to identify potential relationships with clinical data for diagnostic, staging and prognostic purposes either at the tissue level or in saliva rinse. METHODS: For a period of two years, we systematically collected tumor tissue, normal matched mucosa and saliva of patients diagnosed with primary untreated HNSCC. Expression levels of the nine genes of interest were measured by RT-qPCR in tumor and healthy matched mucosa from 46 patients. MMP1 expression level was measured by RT-qPCR in the salivary rinse of 51 HNSCC patients and 18 control cases. RESULTS: Dysregulation of the nine genes was confirmed by the Wilcoxon test. IL1RN, MAL and MMP1 were the most efficient diagnostic markers of HNSCC, with ROC AUC > 0.95 and both sensitivity and specificity above 91%. No clinically relevant correlation was found between gene expression level in tumor and T stage, N stage, tumor grade, global survival or disease-free survival. Our preliminary results suggests that with 100% specificity, MMP1 detection in saliva rinse is potentially useful for non invasive diagnosis of HNSCC of the oral cavity or oropharynx, but technical improvement is needed since sensitivity was only 20%. CONCLUSION: IL1RN, MAL and MMP1 are prospective tumor diagnostic markers for HNSCC. MMP1 overexpression is the most promising marker, and its detection could help identify tumor cells in tissue or saliva.

Reference gene selection for head and neck squamous cell carcinoma gene expression studies.

BACKGROUND: It is no longer adequate to choose reference genes blindly. We present the first study that defines the suitability of 12 reference genes commonly used in cancer studies (ACT, ALAS, B2M, GAPDH, HMBS, HPRT, KALPHA, RPS18, RPL27, RPS29, SHAD and TBP) for the normalization of quantitative expression data in the field of head and neck squamous cell carcinoma (HNSCC). RESULTS: Raw expression levels were measured by RT-qPCR in HNSCC and normal matched mucosa of 46 patients. We analyzed the expression stability using geNorm and NormFinder and compared the expression levels between subgroups. In HNSCC and/or normal mucosa, the four best normalization genes were ALAS, GAPDH, RPS18 and SHAD and the most stable combination of two genes was GAPDH-SHAD. We recommend using KALPHA-TBP for the study of T1T2 tumors, RPL27-SHAD for T3T4 tumors, KALPHA-SHAD for N0 tumors, and ALAS-TBP for N+ tumors. ACT, B2M, GAPDH, HMBS, HPRT, KALPHA, RPS18, RPS29, SHAD and TBP were slightly misregulated (<1.7-fold) between tumor and normal mucosa but can be used for normalization, depending on the resolution required for the assay. CONCLUSION: In the field of HNSCC, this study will guide researchers in selecting the most appropriate reference genes from among 12 potentially suitable reference genes, depending on the specific setting of their experiments.

Vocal symptoms and acoustic changes in relation to the expanded disability status scale, duration and stage of disease in patients with multiple sclerosis.

Vocal symptoms and acoustic measures of patients with multiple sclerosis (MS) are investigated in relation to the duration of the disease, stage of the disease and the degree of disability. Eighty-two patients were enrolled in this study (40 MS, 42 controls). In the MS group, the most common vocal symptoms were vocal breaks and vocal fatigue present in 10. None of the patients in the control group had voice breaks. In the male group, there was a significant decrease in the fundamental frequency, habitual pitch and maximum phonation time with a significant increase in Shimmer. In the female group, there was a significant decrease in the maximum phonation time only. There was no correlation between vocal symptoms and acoustic measures versus duration of the disease and extent of disability except for vocal fatigue which significantly associated with EDSS (expanded disability status scale) score. Patients with MS may develop vocal symptoms irrespective of the EDSS score, duration and stage of the disease. Vocal fatigue and vocal breaks are more common than hoarseness.

The role of beta-2 agonists in foreign body aspiration.

Foreign body aspiration is a relatively common problem encountered in children during the first 3 years of life. Presentation may include a variety of symptoms and signs that may include wheezing, stridor and cough. Removal of the foreign body via rigid bronchoscopy is the main treatment. Inhaled or nebulized beta-2 agonists are sometimes used in these patients to comfort their breathing and relieve some of their symptoms but can sometimes result in relief or worsening of the obstruction. We hereby report a case of peanut aspiration that was coughed out by the patient directly after treatment with nebulized salbutamol.

Vocal changes in patients using nasal continuous positive airway pressure.

The aim of this prospective study is to assess the vocal changes in patients using nasal continuous positive airway pressure (CPAP). A total of 18 subjects using nasal CPAP were assessed by grading their voice perceptually as G0 for normal voice and G3 for severe hoarseness. Acoustic analysis was also performed and the following parameters were measured: fundamental frequency, habitual pitch, shimmer, relative average perturbation, voice turbulence index, and noise-to-harmonic ratio. The same was done for a control group matched according to age and gender. There was a statistically significant difference in the perceptual evaluation between the CPAP group and controls, with more patients in the former group having moderate hoarseness. There was also an increase in the perturbation parameters and a decrease in the fundamental frequency and habitual pitch in the CPAP group compared to controls. The increase in shimmer was statistically significant. The usage of nasal CPAP seems to induce vocal changes that are perceived as mild to moderate hoarseness, together with an increase in the perturbation parameters. These seem to be secondary to the upper airway dryness reported in these patients. The hypothetical effect of nasal CPAP on the sol layer of the vocal folds is discussed.