Friend or Foe? Exploring the Role of Cytomegalovirus (HCMV) Infection in Head and Neck Tumors.

Although not regarded as an oncogenic pathogen, the human cytomegalovirus (HCMV) has been associated with a wide array of malignancies. Conversely, a number of studies report on possible anti-tumor properties of the virus, apparently mediated via HCMV-galvanized T-cell tumor killing; these were recently being investigated in clinical trials for the purposes of anti-cancer treatment by means of dendritic cell vaccines and HCMV-specific cytotoxic T cells. In the present study, we have analyzed the relation between a complement of head-and-neck tumors and HCMV infection across 73 countries worldwide using Spearman correlation, univariate and multivariate regression analysis. Intriguingly, HCMV was found to be pro-oncogenic in patients with nasopharyngeal carcinoma; contrarywise, the virus manifested an inverse (i.e., anti-tumor) association with the tumors of the lip/oral region and the salivary glands. Although this putative protective effect was noted initially for thyroid neoplasia and hypopharyngeal tumors as well, after multivariate regression analysis the connection did not hold. There was no association between laryngeal cancer and HCMV infection. It would appear that, depending on the tissue, HCMV may exert both protective and oncogenic effects. The globally observed protective feature of the virus could potentially be utilized in future therapeutic approaches for salivary tumors and neoplasia in the lip/oral region. As correlation does not necessarily imply causation, more in-depth molecular analyses from comprehensive clinical studies are warranted to substantiate our findings.

Biofilm-producing Bacteria and Quality of Life after Endoscopic Sinus Surgery in Patients with Chronic Rhinosinusitis with Nasal Polyposis.

BACKGROUND: Chronic rhinosinusitis (CRS) is one of the most common health disorders in humans and has a major impact on health-related quality of life (HRQoL). Of the many factors contributing to the etiology of CRS, less is known about the correlation between CRS and bacterial biofilms and their impact on HRQoL. OBJECTIVE: The aim of this prospective study was to investigate the relationship between biofilm-producing bacteria and patients' objective findings and HRQoL. METHODS: Forty-eight patients with CRSwNP were enrolled in a 12-month prospective study. The Lund-Mackay (LM) CT and endoscopic Lund-Kennedy (LK) scores were obtained before endoscopic sinus surgery (ESS), and patients completed the HRQoL instruments: the 22-item Sinonasal Outcome Test (SNOT-22), the 36-item Short Questionnaire (SF-36), and the visual analog scale (VAS). A sinus culture was obtained at ESS, bacteria were isolated, and in vitro quantification of the biofilm was performed. The LK score and HRQoL were determined postoperatively at months 1, 3, 6, and 12. RESULTS: The most common bacterial isolates in patients with CRSwNP were Staphylococcus aureus (28%), coagulase-negative staphylococci (52%), and Pseudomonas aeruginosa (8%). Preoperatively, the highest LM and LK scores were found in patients with strong biofilm producers. Postoperative LK scores were significantly reduced in all patients. Postoperative VAS scores were significantly reduced from month 1 to month 12 postoperatively. Patients with strong biofilm producers had significantly worse nasal blockage, secretion, headache, facial pressure and pain, and loss of smell preoperatively, compared to patients with low biofilm producers. The most significant reduction in preoperative scores SNOT-22 and SF-36 (excluding physical functioning) was seen in patients with S. aureus and P. aeruginosa. CONCLUSIONS: Patients with strong biofilm producers had higher LK and LM scores preoperatively, and greater improvement in LK and HRQoL scores postoperatively. Microbiologic surveillance of all CRS patients is recommended.

In Vitro Antibiofilm Effect of N-Acetyl-L-cysteine/Dry Propolis Extract Combination on Bacterial Pathogens Isolated from Upper Respiratory Tract Infections.

Bacterial biofilms play an important role in the pathogenesis of chronic upper respiratory tract infections. In addition to conventional antimicrobial therapy, N-acetyl-L-cysteine (NAC) and propolis are dietary supplements that are often recommended as supportive therapy for upper respiratory tract infections. However, no data on the beneficial effect of their combination against bacterial biofilms can be found in the scientific literature. Therefore, the aim of our study was to investigate the in vitro effect of N-acetyl-L-cysteine (NAC) and dry propolis extract in fixed combinations (NAC/dry propolis extract fixed combination) on biofilm formation by bacterial species isolated from patients with chronic rhinosinusitis, chronic otitis media, and chronic adenoiditis. The prospective study included 48 adults with chronic rhinosinusitis, 29 adults with chronic otitis media, and 33 children with chronic adenoiditis. Bacteria were isolated from tissue samples obtained intraoperatively and identified using the MALDI-TOF Vitek MS System. The antimicrobial activity, synergism, and antibiofilm effect of NAC/dry propolis extract fixed combination were studied in vitro. A total of 116 different strains were isolated from the tissue samples, with staphylococci being the most frequently isolated in all patients (57.8%). MICs of the NAC/dry propolis extract fixed combination ranged from 1.25/0.125 to 20/2 mg NAC/mg propolis. A synergistic effect (FICI ≤ 0.5) was observed in 51.7% of strains. The majority of isolates from patients with chronic otitis media were moderate biofilm producers and in chronic adenoiditis they were weak biofilm producers, while the same number of isolates in patients with chronic rhinosinusitis were weak and moderate biofilm producers. Subinhibitory concentrations of the NAC/propolis combination ranging from 0.625-0.156 mg/mL to 10-2.5 mg/mL of NAC combined with 0.062-0.016 mg/mL to 1-0.25 mg/mL of propolis inhibited biofilm formation in all bacterial strains. Suprainhibitory concentrations ranging from 2.5-10 mg/mL to 40-160 mg/mL of NAC in combination with 0.25-1 mg/mL to 4-16 mg/mL of propolis completely eradicated the biofilm. In conclusion, the fixed combination of NAC and dry propolis extract has a synergistic effect on all stages of biofilm formation and eradication of the formed biofilm in bacteria isolated from upper respiratory tract infections.

Oxidative Stress and Inflammation Biomarkers in Postoperative Pain Modulation in Surgically Treated Patients with Laryngeal Cancer-Pilot Study.

(1) Background: Surgical treatment of laryngeal carcinoma includes different types of laryngectomies with neck dissection. Surgical tissue damage triggers an inflammatory response, leading to the release of pro-inflammatory molecules. This increases reactive oxygen species production and decreases antioxidant defense mechanisms, leading to postoperative oxidative stress. The aim of this study was to assess the correlation between oxidative stress (malondialdehyde, MDA; glutathione peroxidase, GPX; superoxide dismutase, SOD) and inflammation (interleukin 1, IL-1; interleukin-6, IL-6; C-reactive protein, CRP) parameters and postoperative pain management in patients surgically treated with laryngeal cancer. (2) Methods: This prospective study included 28 patients with surgically treated laryngeal cancer. Blood samples were taken for the analysis of oxidative stress and inflammation parameters before the operative treatment and after the operative treatment (1st postoperative day and 7th postoperative day). The concentrations of MDA, SOD, GPX, IL-1, IL-6, and CRP in the serum were determined by coated enzyme-linked immunosorbent assay (ELISA). The visual analog scale (VAS) was used for pain assessment. (3) Results and conclusion: There was a correlation between oxidative stress and inflammation biomarkers and postoperative pain modulation in surgically treated patients with laryngeal cancer. Age, more extensive surgery, CRP values, and use of tramadol were predictors for oxidative stress parameters.

Adoption of clinical practice guidelines in cases of benign paroxysmal positional vertigo.

PURPOSE: Despite being one of the most common types of the peripheral vertigo encountered in clinical practice, benign paroxysmal positional vertigo (BPPV) remains underdiagnosed and undertreated, even in affluent health care systems. The publication of fully updated clinical practice guidelines significantly facilitated the diagnosis and treatment of BPPV. This study evaluates the adoption of the guidelines in our clinical setting and reviews further recommendations for quality-of-care improvement. METHODS: This retrospective cross-sectional survey included a total of 1155 adult patients diagnosed with BPPV at the biggest tertiary care center in the country during a 5-year period (2017-2021). The data for the first three years (2017-2020) and 919 patients were collected in full, and for the remaining 236 patients (2020-2021) only partially due to the disturbance in referrals caused by COVID-19 pandemic. RESULTS: The familiarity with and adherence to the published clinical guidelines by physicians judged by patients' charts and our health care database were overall unsatisfactory. The adherence varied from 0 to 40.5% in our sample. The recommendations for making the diagnosis and for repositioning procedure as first-line therapy were followed in only 20-30% of cases. CONCLUSION: There are large opportunities for improvement in quality of care of BPPV patients. Apart from constant and systematic education at the primary health care level, the health care system may need to adopt more advanced measures of ensuring better adherence to guidelines and subsequent reduction in medical costs.

Effectiveness of the Treatment of Rhinogenic Headache Caused by Intranasal Contact.

OBJECTIVES: The aim of the study is to evaluate the effectiveness of the surgical and nonsurgical treatment of headache caused by contact points (CPs) between the nasal septum and inferior or middle turbinate. METHODS: The research was designed as a prospective clinical case-series study. The patients with CP headaches were offered to choose between 2 treatment options, surgery and medical treatment. Two groups of surgically treated patients (surgery groups 1 and 2, depending on whether there is a contact between nasal septum and inferior turbinate or middle turbinate) were evaluated and compared for headache intensity and frequency. Headache intensity was measured using a visual analog scale value from 0 to 10; the frequency of headache was expressed as the number of days during 1 month with a headache (before surgery, 1 month, and 6 months after surgery). A comparison was also made between surgically and nonsurgically treated patients. RESULTS: We found more intensive and frequent headache in patients who had CP between the nasal septum and the middle turbinate (P = .038 and P = .003, respectively). A significant reduction in headache intensity and frequency was found in both groups of surgically treated patients 6 months after surgery; however, this reduction was more significant in patients with mucosal contact between nasal septum and middle turbinate. The nonsurgical treatment made a significant reduction of headache intensity and frequency at 1-month follow-up (P = .012 and P = .031, respectively), but not at 6-month follow-up (P = .114 and P = .088, respectively). CONCLUSION: Surgery gave a statistically significant reduction in the intensity and frequency of headache, which was assessed 6 months after surgery. Surgery was found as superior to nonsurgical treatment in the therapy of CP headache.

Ketamine, an Old-New Drug: Uses and Abuses.

Ketamine as an old-new drug has a variety of clinical implications. In the last 30 years, ketamine has become popular for acute use in humans. Ketamine in standard doses is principally utilized for the induction and maintenance of surgical procedures. Besides its use in anesthesia and analgesia, recent studies have shown that ketamine has found a place in the treatment of asthma, epilepsy, depression, bipolar affective disorders, alcohol and heroin addiction. Ketamine primarily functions as a noncompetitive antagonist targeting the N-methyl-D-aspartate (NMDA) receptor, but its mechanism of action is complex. It is generally regarded as safe, with low doses and short-term use typically not leading to significant adverse effects. Also, ketamine is known as a powerful psychostimulant. During the past decade, ketamine has been one of the commonly abused drugs.

The Expression of Hypoxia-Related Biomarkers: A Significance of HIF-1α C1772T Polymorphism as Predictor of Laryngeal Carcinoma Relapse.

INTRODUCTION: The association between the expression of HIF-1α in the laryngeal carcinoma and the prognosis of disease is quite well documented, but the significance of HIF-1α C1772T polymorphism and its relation to disease phenotype have to be clarified. The aim of this study was to investigate the influence of C1772T polymorphism on the clinical-pathological characteristics and disease-free survival after initial surgical treatment of patients with laryngeal carcinoma. MATERIALS AND METHODS: The prospective cohort study included 65 patients with laryngeal carcinoma. Two representative tumor tissue specimens were taken in each patient during surgery; 1 specimen was used to asses HIF-1α C1772T polymorphism and the other 1 to determine the immunohistochemical expression of HIF-1α, VEGF, as well as CD 34 proteins. The comparison of polymorphism frequency between study and control population was conducted by collecting a 5 mL of peripheral venous blood samples in each subject. RESULTS: Clinicopathological characteristics of laryngeal carcinoma didn't affect the expression of hypoxia-related biomarkers, such as HIF-1α, VEGF or MVD. The statistically significant association between HIF-1α and VEGF expression was found (P = .034), but not between HIF-1α expression and MVD value (P = .696). The expression of HIF-1α was significantly higher among CT heterozygotes (P = .029). We found a significantly more recurrence among CT heterozygotes compared with patients with CC homozygous alleles (57.10% and 24.30%, respectively; P = .007). Patients with C1772T polymorphic variants had significantly worse disease-free survival compared with patients without polymorphism (Log-rank test, P = .007). CONCLUSION: HIF-1α C1772T polymorphism was significantly associated with worse disease-free survival which nominates it as a predictor of laryngeal carcinoma relapse. The preoperative assessment of hypoxia-related biomarkers should be used in everyday practice in order to determine the treatment modalities for laryngeal carcinoma.

Immune Cell and Biochemical Biomarkers in Advanced Laryngeal Cancer.

Objective: The aim of this study was to evaluate cell and biochemical biomarkers and establish their prognostic value in patients with advanced laryngeal cancer. Material and Methods: A prospective study included 52 patients with advanced laryngeal carcinoma surgically treated at the tertiary referral center. Tumor tissue was immunohistochemically stained for T-cell markers (CD4 and CD8), and levels of cytokines (IL-6 and IL-8) and C-reactive protein were analyzed from blood samples. Results: Overall 3-year survival (OS) of patients included in the study was 69.2% and the disease specific survival (DSS) 72.5%. Higher expression of CD4+ and CD8+ were significant prognostic factors with positive impact on both OS and DSS in univariate analysis, but not in multivariate analysis. Levels of IL-8 were a significant predictor of 3-year OS and DSS survival in patients with advanced laryngeal cancer but not levels of IL-6 and CRP values. Conclusion: Though high expression of CD4 and CD8 were demonstrated in the tumor tissue, but their prognostic role was not established. Higher values of IL-8 proved to be significant negative predictor of DSS. This could further collaborate the inclusion of combination of biomarkers in assessment of favorable treatment choice in patients with advanced laryngeal carcinoma.

Symptoms of depression, anxiety and stress in patients with chronic otitis media.

PURPOSE: Persistent symptoms of chronic otitis media cause limitations in daily routine and social interactions, influencing significantly patients' quality of life and mental health. The purpose of the study was to assess the intensity depression, anxiety and stress symptoms in patients with chronic otitis media and to examine if patient demographic data, characteristics and reported symptoms of otitis influence reported depression, anxiety and stress symptoms. MATERIAL AND METHODS: The study included 316 adult patients diagnosed with unilateral or bilateral chronic otitis media with or without cholesteatoma. Patients underwent a complete otological, audiological and radiological assessment. Chronic otitis media questionnaire 12 (COMQ-12) was used to assess the impact of COM and Depression Anxiety Stress Scale 21 (DASS-21) was used for depression, anxiety and stress assessment. RESULTS: Some level of anxiety and stress were detected in 70.57% 49.37% of the patients, respectively. 13.29% of the patients had scores indicating depression disorder. The mean value of the COMQ-12 questionnaire for this group of patients was 26.24 (SD±11.47) More intense symptoms of COM were significantly associated (p<0.05) with higher scores on DASS-21 subscales. Multivariate logistic regression analysis indicated that significant positive predictors of higher anxiety scores were pure tone average (PTA) on better and worse hearing ear (p<0.05). Drainage from the ear, hearing problems at home and tinnitus were significant positive predictors of a higher DASS-depression score. (p<0.05). CONCLUSION: The study confirmed positive correlation between reported level of anxiety, depression and stress, severity of COM symptoms and quality of life. Level of hearing on the better and worse hearing ear were significant positive predictors of anxiety and stress in patients with COM.

Is otitis media with effusion associated with Samter's triad a new nosological entity? A preliminary report on inflammatory mediator production.

PURPOSE: Otitis media with effusion (OME) associated with Samter's triad (ST) is a difficult entity to treat. The aim of study was an investigation of the middle ear and nasal production of inflammatory mediators (IM) in patients with ST and analysing differences between them and controls. METHODS: Prospective case-control study. Nineteen patients with OME (five had allergic rhinitis, four had nasopharyngeal lymphoid hyperplasia, five had no evident sino-nasopharyngeal disease and five had confirmed ST) and 15 healthy participants were included. The concentrations of IM interleukin-1 beta (IL-1ß), interferon-alpha 2 (IFN-α2), interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23 and IL-33 were measured in nasal and middle ear secretions. RESULTS: There was a difference that was close to a level of statistical significance only for IL-1ß levels in middle ear fluid (p = 0.052) between the ST subgroup and the other patients with OME. Also, we found a significant difference for IL-23 in nasal secretions between these subgroups (p = 0.040), whereas the difference in nasal fluid IL-33 was close to a level of statistical significance (p = 0.052). There was a significant difference in nasal concentrations of IL-1ß, IFN-α2, MCP-1, IL-8, IL-18 and IL-33 (p < 0.001, p = 0.005, p = 0.008, p = 0.011, p = 0.011 and p = 0.011, respectively) between the OME group and the healthy subjects. There were significant positive correlations between concentrations of IL-1ß, IFN-α2, IFN-γ, TNF-α, MCP-1, IL-17A, IL-18 and IL-33 (p < 0.001, p < 0.001, p = 0.002, p = 0.028, p < 0.001, p < 0.001, p < 0.001 and p < 0.001, respectively) in nasal and middle ear secretions. CONCLUSION: This preliminary report showed some differences in IM production between the patients with OME associated with ST and those without it. Our results suggest a uniformity of the production of nasal and middle ear IM and supported the concept of a united airway respiratory disease.

Predictors of Complications Occurrence Associated With Emergency Surgical Tracheotomy.

OBJECTIVE: In emergency airway management, the occurrence of surgical tracheotomy complications is increased and may be fatal for the patient. However, the factors that play a role in complication occurrence and lead to lethal outcome are not known. The objective of this study was to determine predictors associated with the occurrence of complications and mortality after emergency surgical tracheostomy. STUDY DESIGN: Retrospective study with a systematic review of the literature. SETTING: Tertiary medical academic center. SUBJECTS AND METHODS: We included 402 adult patients who underwent emergency surgical tracheostomy under local anesthesia due to upper airway obstruction. Demographic, clinical, complication occurrence, and mortality data were collected. For statistical analysis, univariable and multivariable logistic regression methods were used. RESULTS: In multivariable analysis, significant positive predictors of complication occurrence were previously performed tracheotomy (odds ratio [OR] 3.67, 95% confidence interval [CI], 0.75-17.88), neck pathology (OR 2.05, 95% CI 1.1-1.77), and tracheotomy performed outside the operating room (OR 5.88, 95% CI, 1.58-20). General in-hospital mortality was 4%, but lethal outcome as a direct result of tracheotomy complications occurred in only 4 patients (1%) because of intraoperative and postoperative complications. CONCLUSION: The existence of neck pathology and situations in which tracheotomy was performed outside the operating room in uncontrolled conditions were significant prognostic factors for complication occurrence. Tracheotomy-related mortality was greater in patients with intraoperative and early postoperative complications. Clinicians should be aware of the increased risk in specific cases, to prepare, prevent, or manage unwanted outcomes in further treatment and care.

Anxiety and depression in patients with vocal fold nodules, edema and polyps.

PURPOSE: To compare the prevalence and severity of depression and anxiety among patients with vocal fold (VF) nodules, polyps and edema. At the same time the aim was to analyse association between severity of distress and the level of vocal handicap as well as to identify other factors related to severity of depression and anxiety in these patients. METHODS: To all participants were given five questionnaires: (1) questionnaire on socio-demographic and some other characteristics of patient; (2) Beck's Depression Inventory (BDI); (3) State-Trait Anxiety Inventory (STAI) 1 (State Anxiety); (4) STAI 2 (Trait Anxiety); and (5) Voice Handicap Index (VHI)-10. RESULTS: A total of 205 patients were included in this study. Mild-to-severe depression, according to BDI was present in 79 (38.6%) patients. Mild-to-severe state anxiety and trait anxiety were present in 199 (97.1%) and 200 (97.6%) patients, respectively. Only 10 patients had VHI-10 score ≤ 11. Multivariate analyses showed that there were no significant differences in the level of depression and anxiety between patients with VF nodules, polyps and edema. The VHI-10 score was significantly higher in patients with VF edema in comparison with VF nodule patients (p = 0.001), as well as in comparison with VF polyp patients (p = 0.001). CONCLUSION: The present study identified a high prevalence of psychological and vocal distress among patients with vocal disorders. Severity of depression and anxiety did not differ between patients with VF nodules, polyps and edema, and it was not related to the level of vocal handicap.

Transcultural Adaptation and Validation of the Voice Handicap Index-10 into the Serbian Language.

BACKGROUND: The Voice Handicap Index-10 (VHI-10) is used in clinics because of its validity and ease of use by patients. OBJECTIVES: The aim of this paper was to evaluate the internal consistency, reliability, and clinical validity of the Serbian version of the VHI-10. METHOD: In this cross-sectional study, we translated the original English version of the VHI-10 into Serbian, after which it was back-translated into English. The Serbian version of the VHI-10 was completed by 161 patients with voice disorders, divided into 4 groups according disease etiology (structural, neurological, functional, and inflammatory) and 73 healthy control subjects. RESULTS: The VHI-10 internal consistency was 0.88. Spearman's rank correlation coefficient for VHI-10 test-retest reliability was ρ = 0.991 (p< 0.001). Patients with voice disorders had higher median total VHI-10 scores compared with controls (p< 0.001). The patients' Grade, Instability, Roughness, Breathiness, Asthenia, and Strain (GIRBAS) scale scores were significantly correlated with the VHI-10 test scores (ρ = 0,682, p < 0.001) and VHI-10 retest scores (ρ = 0.716, p < 0.001). CONCLUSION: The Serbian version of the VHI-10 had good validity and reliability and can be used by Serbian patients with voice disorders.

Management of Orbital Complications of Acute Rhinosinusitis in Pediatric Patients: A 15-Year Single-Center Experience.

BACKGROUND: The major clinical dilemma managing acute rhinosinusitis (ARS) in pediatric population is distinguishing uncomplicated rhinosinusitis from a complicated bacterial ARS and orbital complications, the latter requiring antimicrobials and surgical intervention. However, factors associated with severe orbital complications and the optimum management strategy remains controversial. The objectives of this study were to characterize the clinical outcomes of children with orbital complications of ARS and to identify risk factors associated with disease severity. METHODS: This retrospective cohort analysis evaluated the clinical outcomes of 61 children admitted for orbital complications between January 1, 2002 and December 31, 2017. Descriptive statistics were performed to examine the demographics and clinical findings. We compared groups using Mann-Whitney U test for continuous variables and χ for categorical variables. RESULTS: Although two-thirds of children had received prehospital antibiotics, half of the cohort presented with post-septal orbital complications. While 83% of isolates obtained from the same patients were susceptible to the prehospital antibiotics given, the majority of those who received prehospital antibiotics nevertheless required surgical intervention. We observed significant association between the age of presentation and disease severity. Children >5 years of age presented with more severe orbital complications despite prehospital antibiotics and were more likely to require surgical intervention (P < 0.001). CONCLUSIONS: In this study, stage II/III orbital complications at presentation and older age were the most important determinants of medical treatment failure. Early referral to eye, nose and throat (ENT) should be considered for children >5 years with ARS due to worse orbital complications despite prehospital antibiotics.

Laser transoral microsurgery in treatment of early laryngeal carcinoma.

PURPOSE: Laser transoral laryngeal microsurgery has become widely accepted treatment method because of its organ and function preservation and shorter period of hospitalization. The aim of this study was to examine the overall, disease-specific and disease-free survival in patients with early laryngeal carcinoma treated with laser depending on age, gender, common risk factors (tobacco and alcohol use), histopathological tumor grade, anterior commissure involvement, performed tracheotomy, positive surgical margins, T stage, type of endoscopic cordectomy, postoperative radiotherapy and laryngeal preservation. METHODS: Retrospective study included 234 patients with squamocellular carcinoma of the larynx treated with laser transoral laryngeal microsurgery. 5-year overall, disease-specific and disease-free survival and the prognostic impact of mentioned factors were evaluated using Kaplan-Meier and Cox proportional hazard analyses. RESULTS: 5-year OS and DSS was 92.5% and 95.3%, respectively. OS was significantly lower for older patients and in patients with histologically poorly differentiated tumors, 3 and 5 years postoperatively (Log rank test; p = 0.031). DSS was significantly lower in patients with anterior commissure involvement, positive surgical margins and patients who underwent postoperative RT. DFS was significantly lower in patients with anterior commissure involvement, patients with T1b tumor stage and patients who underwent cordectomies type Vb and VI (Log rank, p < 0.05). Laryngeal preservation significantly influenced 5-year OS, DSS and DFS (Log rank, p ≤ 0.001). Multivariate Cox regression analysis showed that age, histological tumor grade and laryngeal preservation were significant negative prognostic factors for 5-year DSS and DFS. CONCLUSION: Transoral laryngeal microsurgery delivers excellent oncological results, even in selected patients with higher stages of early laryngeal cancer and anterior commissure involvement.

Pain Management After Surgical Tonsillectomy: Is There a Favorable Analgesic?

The aim of this study was to examine how ibuprofen and paracetamol prevent pain after cold-steel extracapsular tonsillectomy in children. Also, we examined the relation between age, gender, nausea, postoperative bleeding, antibiotic use, type of diet, and postoperative pain intensity and the type of administered analgesic. A prospective study was conducted on 147 children (95 males and 52 females, aged 7-17 years) who underwent tonsillectomy in the Clinical-Hospital Center "Dragisa Misovic" from January 1 to June 30, 2016. The degree of pain was measured using a visual analog scale (VAS). We did not observe any significant differences in postoperative nausea, hospitalization rate postoperative bleeding, and antibiotic use between the paracetamol and ibuprofen groups. A test of within-patient effects showed that VAS scores changed significantly during the postoperative follow-up period (P = .00), but there were no significant differences between the groups (P = .778). After 12 hours, 29.3% of the patients on paracetamol and 21.8% on ibuprofen were transferred to a soft diet; after 24 hours, 84.8% of the paracetamol group and 85.5% of the ibuprofen group were on a soft diet (χ2 test, P < .05). There was a statistically significant correlation between VAS scores measured 4 hours after the surgery and the time of transference to the soft diet (Spearman ρ test, P < .001). The transfer to soft and normal diets was not significantly different between the 2 groups as assessed by the VAS scores (Pearson χ2 test, P = .565).There is still no consensus on the most effective postoperative pain-control regiment after tonsillectomy. This study showed that satisfactory pain management was achieved equally with both paracetamol and ibuprofen.

Antibiofilm effects of amoxicillin-clavulanic acid and levofloxacin in patients with chronic rhinosinusitis with nasal polyposis.

PURPOSE: Microbial biofilms have been implicated in the pathogenesis of chronic rhinosinusitis with nasal polyposis (CRSwNP). The aim of our study was to evaluate in vitro effects of amoxicillin-clavulanic acid and levofloxacin on biofilm formation by bacterial species isolated from sinus tissue in patients with CRSwNP. METHODS: The sinus mucosal specimens were harvested from the upper parts and roof of ethmoid cavity of 48 patients with CRSwNP. Each sample was washed thoroughly in three separate beakers of sterile saline to remove any planktonic bacteria and further subjected to microbiology analysis. The biofilm-forming capacity of isolated strains was detected by microtiter-plate method and the effects of subinhibitory (1/2× to 1/16× MIC) and suprainhibitory concentrations (4, 8, 16, 32, and 64 µg/ml) of amoxicillin-clavulanic acid and levofloxacin on biofilm production were investigated. RESULTS: Bacterial strains were isolated in 42 (87.5%) patients: one microorganism in 80.9% and two microorganisms in 19.1% of patients. The most prevalent bacteria in CRSwNP biofilms were Staphylococcus epidermidis (34%) and S. aureus (28%) followed by S. haemolyticus (12%), Pseudomonas aeruginosa (8%), Moraxella catarrhalis (6%), Streptococcus pneumoniae (6%), and other staphylococci (6%). Subinhibitory concentrations of amoxicillin-clavulanic acid and levofloxacin significantly reduced biofilm formation (p < 0.01 and p < 0.05, respectively), with better efficacy of amoxicillin-clavulanic acid (1/2-1/8× MIC) on staphylococci and levofloxacin (1/2- 1/4× MIC) on M. catarrhalis and P. aeruginosa biofilm formation. Suprainhibitory concentrations of both tested antibiotics (4-64 µg/ml) significantly eradicated mature biofilms of staphylococci (p < 0.01). The effect of levofloxacin on eradication of staphylococcal biofilms was more noticeable, compared to the effect of amoxicillin-clavulanic acid (p < 0.01). Suprainhibitory concentrations of both tested antibiotics had no effect on eradication of previously formed M. catarrhalis and P. aeruginosa biofilms (p > 0.05). CONCLUSIONS: The amoxicillin-clavulanic acid and levofloxacin are shown to be potent antibiofilm agents in patients with CRSwNP. The effects of tested compounds depend on bacterial species and the volume of formed biofilm.

The Allele 2 of the VNTR Polymorphism in the Gene That Encodes a Natural Inhibitor of IL-1ß, IL-1RA Is Favorably Associated With Chronic Otitis Media.

OBJECTIVES: Chronic otitis media (COM) is followed by irreversible tissue damage and destruction of the middle ear structures, with the possibility of complications under the maintenance of inflammation. Inflammatory mediators such as cytokines play a crucial role in the initial stage of inflammation. The aim of this study was to evaluate the association of the polymorphisms in two innate immunity/inflammation cascade genes from interleukin-1 (IL-1) gene cluster with COM with regard to cholesteatoma. METHODS: In the cross-sectional case-control study, DNA samples were collected from 189 patients with COM and 119 controls from a population of Serbia. The +3953 C/T (rs1143634), TaqI polymorphism in interleukin-1 beta (IL-1ß) gene and 86 bp variable number tandem repeat (VNTR, rs2234663) polymorphism in the IL-1 receptor antagonist (IL-1RA) gene were analyzed by polymerase chain reaction. RESULTS: The IL-1ß TaqI polymorphism was not significantly different in patients compared with the control group. The significant difference between patients and controls was observed for both, genotype and allele frequencies of IL-1RA VNTR polymorphism (chi-square P<0.01). We found that carriers of IL-1RA allele 2 (odds ratio, 0.47; 95% confidence interval, 0.29 to 0.76; P=0.004) have a favorable association with COM, using multivariate logistic analysis that included both polymorphisms, age and sex. The IL-1RA allele frequency distribution was significantly different with regard to cholesteatoma. CONCLUSION: The carriers of allele 2 of VNTR IL-1RA polymorphism had a decreased odds ratio for COM, which is in agreement with findings in other inflammatory disease and its previous association with higher IL-1RA levels. Possible down-regulation of IL-1 mediated proinflammatory signaling pathways via IL-1RA in COM as well as results of our study should be further investigated and replicated.

Antibiofilm effects of topical corticosteroids and intranasal saline in patients with chronic rhinosinusitis with nasal polyps depend on bacterial species and their biofilm-forming capacity.

Microbial biofilms have been implicated in the pathogenesis of chronic rhinosinusitis with nasal polyposis (CRSwNP). Intranasal application of corticosteroids and saline is a reliable option for their management. The aim of our study was to evaluate in vitro antibiofilm effects of corticosteroids and isotonic and hypertonic nasal saline in CRSwNP patients. The sinus mucosal specimens were harvested from the ethmoid cavity of 48 patients with CRSwNP and further subjected to hematoxylin-eosin staining and microbiology analysis. The biofilm-forming capacity of isolated bacterial strains was detected by microtiter-plate method and the effects of therapeutic doses of mometasone, fluticasone, isotonic and hypertonic saline on biofilm production were investigated. Bacterial strains were isolated in 42 (87.5%) patients: one organism in 34 (80.9%) and two organisms in 8 (19.1%). Staphylococcus epidermidis (34%) and Staphylococcus aureus (28%) were the most prevalent bacteria in biofilms of CRSwNP patients. Corticosteroids and saline solutions significantly reduced biofilm formation (p < 0.01 and p < 0.05, respectively) with better efficacy of fluticasone and isotonic nasal saline. Treatment with fluticasone, mometasone, isotonic and hypertonic nasal saline completely prevented biofilm production in 66, 50, 84 and 38% of bacterial strains, respectively. The most significant density reduction was observed in biofilm formed by Staphylococcus aureus, Pseudomonas aeruginosa and Streptococcus pneumoniae compared to other bacterial species (p < 0.01, p < 0.05, p < 0.05, respectively). The antibiofilm effects of corticosteroids and saline solutions also greatly depended on bacterial biomass (p < 0.05), with the most significant effect on high compared to small amount of formed biofilm. The topical steroids and nasal saline are shown to be potent antibiofilm agents in patients with CRSwNP. The effects of tested compounds depend on bacterial species and volume of formed biofilm.