Development and Validation of a Clinical Score for Predicting the Risk of Tympanosclerosis Before Surgery.

OBJECTIVE: To develop and validate a clinical score to predict the risk of tympanosclerosis before surgery. METHODS: A sample of 404 patients who underwent middle ear microsurgery for otitis media was enrolled. These patients were randomly divided into 2 cohorts: the training cohort (n = 243, 60%) and the validation cohort (n = 161, 40%). The preoperative predictors of tympanosclerosis were determined by multivariate logistic regression analysis and implemented using a clinical score tool. The predictive accuracy and discriminative ability of the clinical score were determined by the area under the curve (AUC) and the calibration curve. RESULTS: The multivariate analysis in the training cohort (n = 243, 60%) identified independent factors for tympanosclerosis as the female sex (odds ratio [OR]: 3.83; 95% CI: 1.66-9.37), the frequency-specific air-bone gap at 250 Hz ≥ 45 dB HL (OR: 3.68; 95% CI: 1.68-8.57), aditus ad antrum blockage (OR: 3.29; 95% CI: 1.38-8.43), type I eardrum calcification (OR: 25.37; 95% CI: 8.41-88.91) or type II eardrum calcification (OR: 18.86; 95% CI: 6.89-58.77), and a history of otitis media ≥ 10 years (OR: 4.10; 95% CI: 1.58-11.83), which were all included in the clinical score tool. The AUC of the clinical score for predicting tympanosclerosis was 0.89 (95% CI: 0.85-0.93) in the training cohort and 0.89 (95% CI: 0.84-0.95) in the validation cohort. The calibration curve also showed good agreement between the predicted and observed probability. CONCLUSIONS: The clinical score achieved an optimal prediction of tympanosclerosis before surgery. The presence of calcification pearls on the promontorium tympani is a strong predictor of tympanosclerosis with stapes fixation.

Analysis of Risk Factors for Myringosclerosis Formation after Ventilation Tube Insertion.

BACKGROUND: This study examined possible risk factors for myringosclerosis formation after ventilation tube insertion (VTI). METHODS: A retrospective study was performed in a single tertiary referral center. A total of 582 patients who underwent VTI were enrolled in this study. Patients were divided into two groups based on the presence or absence of myringosclerosis: MS+ and MS-. Characteristics of patients were collected through medical chart review; these included age, gender, nature and duration of effusion, type of ventilation tube (VT), duration and frequency of VTI, incidence of post-VTI infection, incidence of intraoperative bleeding, and presence of postoperative perforation. Incidences of risk factors for myringosclerosis and the severity of myringosclerosis in association with possible risk factors were analyzed. RESULTS: Myringosclerosis developed in 168 of 582 patients (28.9%) after VTI. Patients in the MS+ group had an older mean age than those in the MS- group. The rates of myringosclerosis were higher in patients with older age, serous otitis media, type 2 VT, post-VTI perforation, and frequent VTI. However, there were no differences in occurrence of myringosclerosis based on gender, duration of effusion, duration of VT placement, incidence of post-VTI infection, or incidence of intraoperative bleeding. The severity of myringosclerosis was associated with the duration of effusion and frequency of VTI. CONCLUSION: Older age, serous effusion, type 2 VT, presence of post-VTI perforation, and frequent VTI may be risk factors for myringosclerosis after VTI; the severity of myringosclerosis may vary based on the duration of effusion and frequency of VTI.

Myringosclerosis in hemodialysis patients with hyperparathyroidism.

Myringosclerosis is the final stage of the middle ear lamina propria inflammation or trauma; it starts with collagen production in excess amounts in the lamina propria of the middle ear mucosa. Then, hyalinization and calcification occur. Later on, metaplasia of bone or cartilage can occur. A similar sequence occurs with hyperparathyroidism in chronic kidney disease. This study is aimed to detect the prevalence of myringosclerosis in patients of our hemodialysis (HD) unit and find out any association between hyperparathyroidism and myringosclerosis in chronic HD patients. A total number of 86 patients were selected according to the inclusion criteria. They were divided into two groups: Group 1 (58 patients myringosclerosis free patients on regular HD), Group 2 (28 patients myringosclerosis-positive patients on regular HD). No statically significant difference was found in serum parathyroid hormone levels between the two studied groups. Serum creatinine was significantly higher in Group 2, serum ferritin was significantly lower in Group 2, and mean corpuscular volume of red blood cells was highly significantly lower in Group 2. Myringosclerosis affects 32% of our HD patients and we could not detect any strong correlation between myringosclerosis and hyperparathyroidism.

The effect of rosmarinic acid on the prevention of myringosclerosis.

OBJECTIVES: Myringosclerosis commonly occurs as a long-term complication of ventilation during the treatment of otitis media. We aimed to determine the effects of rosmarinic acid as an antioxidant on experimentally induced myringosclerosis. METHODS: Twenty-four male Sprague-Dawley rats, weighing 250-300 g, were unilaterally myringotomized and randomly separated into three groups. Group 1 received no treatment (control group) (n = 8); Group 2 received topical rosmarinic acid (n = 8); Group 3 received oral rosmarinic acid (n = 8). On the twenty-first day, the right ears were examined by otomicroscope and findings of myringosclerosis were recorded. Finally, all of the rats were euthanized and the tympanic membrane (TM) thickness and the severity of middle ear mucosal inflammation were evaluated histopathologically. RESULTS: The myringosclerosis severity, TM thickness, and inflammation scores were found to be significantly higher in the control group than in the topical and systemic treatment groups (p < 0.05). There were no statistically significant differences in terms of TM thickness and inflammation scores between the topical and systemic treatment groups (p > 0.05). While moderate and severe myringosclerosis were higher in the control group, mild myringosclerosis was found to be higher in both treatment groups. CONCLUSION: The local and oral administration of rosmarinic acid suppressed inflammation, reduced TM thickness, and prevented the development of myringosclerosis in myringotomized rats.

Comparison of the Aditus ad Antrum Diameter on CT between Patients with Chronic Otitis Media and Healthy Individuals.

BACKGROUND: The middle ear cavity is ventilated through the aditus ad antrum. Aditus blockage contributes to the pathology of otitis media. OBJECTIVE: To determine the normal values of the aditus ad antrum diameter on computed tomography and to investigate its relationship with chronic otitis media and related pathologies (tympanosclerosis and myringosclerosis). METHODS: The temporal CT images of 162 individuals were evaluated retrospectively. In the axial sections, the inner diameter of the aditus was measured at the narrowest point at the cortex. The differences in diameter were compared between diseased and healthy ears. RESULTS: In healthy individuals, the diameter was narrower in women. There was no difference between the right and left ears in healthy subjects. No correlation was found between age and diameter. In male patients with myringosclerosis, the diameter was slightly narrower on both sides but more marked on the left. In female patients with myringosclerosis, the diameter in both ears was slightly narrower. In cases of otitis media and tympanosclerosis, the diameter was less than that of healthy individuals, despite the lack of statistically significant result in all cases. CONCLUSION: The aditus ad antrum was narrower in diseased ears, indicating that a blocked aditus may contribute to the development of otitis media, as well as mucosal diseases.

Metagenomics Analysis of Bacterial Population of Tympanosclerotic Plaques and Cholesteatomas.

Objective Chronic otitis media can cause cholesteatomas or tympanosclerosis; however, the pathophysiology of such conditions is not completely known. The aim was to identify a bacterial genome that might be present in tympanosclerotic plaques and cholesteatomas using sequence analysis of the gene responsible for the transcription of 16 ribosomal RNA (rRNA). Study Design Metagenomics analysis of the samples. Setting Samples were collected and evaluated at tertiary care centers. Subjects and Methods Sixty-five tympanosclerotic plaques and 37 cholesteatomas were evaluated. The polymerase chain reaction (PCR) was performed using primers designed for the amplification of the gene responsible for the transcription of bacterial 16 rRNA. The PCR-positive samples were sequenced via Sanger method, and 46 selected samples were analyzed with next-generation sequencing (NGS). Results Sanger sequencing revealed the presence of bacterial genomes in a total of 18 of the 102 samples tested. Sequencing of these genomes indicated the presence of Alloiococcus otitis, Staphylococcus aureus, Achromobacter xylosoxidans, Escherichia coli, Staphylococcus sciuri, Staphylococcus caprae, Parvimonas spp., and Bacillus sp. in the tested samples. The NGS showed 1 or more different bacterial genomes in 44 (95.7%) of the 46 samples tested. Predominately, genome of Clostridiales (27 samples), Staphylococcaceae (24 samples), Peptoniphilaceae (12 samples), and Turicella otitidis (9 samples) were identified. Conclusion The middle ear is inhabited by a diverse microbial community than that previously known. With the use of molecular biology, it has become easier to identify the bacterial genomes and improve our understanding of the role of middle ear microbiota in the pathogenesis of chronic inflammatory ear diseases.

[The prevalence of tympanosclerosis and the effectiveness of its surgical treatment]. / Rasprostranennost' timpanoskleroza i éffektivnost' ego khirurgicheskogo lecheniia.

The objective of the present study was to characterize the epidemiological variants of tympanosclerosis and the effectiveness of the surgical treatment of the patients presenting with this condition. We have undertaken the analysis of the results of 1965 surgical interventions on the patients suffering from different forms of chronic otitis media (COM) performed during the period from 2009 till 2014 with a view to determining the frequency of tympanosclerosis (TSC). In 542 cases, it proved possible to evaluate the intraoperative findings, stages and methods of reconstructive surgery, the anatomical and functional outcomes and effectiveness of the intervention. At present, the signs of tympanosclerosis are identified in 27.6% of the patients presenting with chronic otitis media including 88.7% and 11.3% suffering from the perforating and non-perforating forms of this pathology, respectively. In 74% of the cases its manifestations are diagnosed in the patients having the tubotympanic form of COM. In 53.3% of the patients TSC foci are responsible for the fixation of the ossicular chain whereas in 46.7% of the cases the auditory ossicles retain mobility. As many as 88.6% of the patients underwent the one-step surgical intervention, 10.7% were managed using two-step surgery, and 0.7% of the patients were given the three-stage treatment. Type I tympanoplasty was performed in 62% of the patients, type III tympanoplasty in 30.4%, and various types of stapedoplasty in 4.6% of the cases. The favourable anatomical and functional outcomes at the first stage of the surgical intervention with the use of the autogenous tissues for tympano- and ossiculoplastic surgery were achieved in 87.9% of the patients on the average (by means of the closure of the tympanic defect in 92.2% and by re-fixation of the selected elements of the ossicular chain in 17.3%of the cases). The anatomical and functional effectiveness of the second-stage surgical intervention was estimated at 93.1%.

Does calcemia influence the onset of myringosclerosis after myringotomy with the insertion of ventilation tubes?

INTRODUCTION: Myringosclerosis is one of the most frequent late complications of the insertion of ventilation tubes, and its aetiopathogenesis remains unknown. The calcification that occurs in the formation of myringosclerosis plaque raises the hypothesis of the presence of a calcium metabolism disorder. The objective is to determine whether calcemia contributes to the development of myringoscelerosis after insertion of ventilation tubes. MATERIAL AND METHODS: A longitudinal, prospective, analytical cohort study was conducted in patients undergoing myringotomy with the insertion of ventilation tubes due to otitis media with effusion. Calcemia was evaluated pre-operatively and in the follow-up the appearance of myringosclerosis and the percentage of the tympanum involved were evaluated. RESULTS: The study included 156 patients (297 ears), with calcemia values ranging from 7.6 to 10.2mg/dl. Myringosclerosis was identified in 35.4% of the operated ears. No relationship was found between the appearance of myringosclerosis and calcemia (p=.596). It was found, however, that the greater the percentage of the tympanum affected by myringosclerosis, the lower the calcemia values (p=.014). CONCLUSION: The population studied had calcemia values within the normal range, which allows us to infer that no changes in calcium metabolism are required for the development of myringosclerosis. Moreover, unlike in previous studies, higher calcium levels are not associated with more myringosclerosis. Calcemia did not influence the appearance of myringosclerosis after myringotomy with the insertion of ventilation tubes.

Predictive factors for the appearance of myringosclerosis after myringotomy with ventilation tube placement: randomized study.

Myringotomy with the insertion of ventilation tubes is the most frequent surgical procedure performed in children, and the appearance of myringosclerosis is one of its most frequent long-term complications. The objective of this study is to identify clinical factors and technique variations that may have a relation with the appearance of myringosclerosis, after tube insertion. Patients submitted to myringotomy with transtympanic short-term tube insertion were studied in a longitudinal prospective and analytical cohort study with the prospective randomized open, blinded endpoint (PROBE) methodology, to study the influence of the location of myringotomy (anterior-inferior quadrant or posterior-inferior), directions of the incision (radial or non-radial) and aspiration or not of the middle ear. Our study included 156 patients (297 ears). Myringosclerosis was observed in 35.7 % of the operated ears. It appeared more often in patients with greater number of otitis (p = .001) and with greater number of otorrhea episodes (p = .029) and in patients in whom the tympanogram after the tube extraction was type A (according to Jerger´s classification) (p = 0.016). We identified myringosclerosis in less patients, if the tube was in the tympanic membrane for less than 12 months (p = .009). Myringosclerosis was present more extensively if the tympanic incision was located in the anterior-inferior quadrant, with tympanic involvement superior to 25 % (p = .015). The results observed prove that, underlying the appearance of myringosclerosis, there exists an early inflammatory or infectious process and a final cicatricial process. It was also found that when myringotomy is made in the anterior-inferior quadrant, myringosclerosis appears in a higher percentage of the tympanic membrane; therefore, it is not recommended to do the incision in this quadrant, because it may lead to a reduction of the tympanic membrane vibration.

Role of Chlamydia pneumoniae and Helicobacteria pylori in the development of tympanosclerosis.

The etiology of tympanosclerosis (TS) is not known, but TS commonly develops secondary to acute and chronic otitis media (COM). Since calcification process in TS resembles that of atherosclerosis (AS), pathogens that are related to pathogenesis of AS may be involved in development of TS. This prospective and controlled study, performed at a tertiary referral center, investigated a possible relationship between the presence of Chlamydia (C.) pneumoniae and Helicobacter (H.) pylori and the development of a tympanosclerotic plaque. The presence of C. pneumoniae was examined in the surgical specimens of 62 patients (29 females and 33 males; age range 10-70 years, mean age 30.8 ± 13.3 years), including 30 patients with TS, 14 patients with cholesteatoma, and 18 patients with chronic suppurative otitis media (CSOM). The presence of H. pylori was examined in the surgical specimens of 88 patients (41 females and 47 males; age range 6-70 years, mean age 32.5 ± 14.8 years), including 35 patients with TS, 22 patients with cholesteatoma, 20 patients with CSOM, and 11 patients with otosclerosis. Tympanosclerotic plaques and control specimens from the cholesteatoma, polypoid mucosa, or mucosal portion of the perforations and stapes supra structure were examined for the presence of H. pylori and/or C. pneumoniae using real-time polymerase chain reaction analysis. The analysis demonstrated that specimens from the tympanosclerotic plaques and the other types of COM were all negative for C. pneumoniae and H. pylori. An association between C. pneumoniae or H. pylori infection and the development of TS or other types of COM could not be established.

Investigation of myringosclerosis development in different grafting materials after myringo-/tympanoplasty.

OBJECTIVES: This study aims to investigate the prevalence of myringosclerosis in tragal perichondrium (TP) and temporalis fascia (TF) grafts after myringo-/tympanoplasty. PATIENTS AND METHODS: Thirty patients, who were diagnosed with non-suppurative chronic otitis media and administered myringo-/tympanoplasty under general anesthesia using TP or TF as grafting material in our clinic between January 2012 and May 2013, were recruited in this retrospective case-control study. Patients were divided into two groups according to used graft material as group 1 (TP) (9 males, 6 females; median age 35.4 years; range 20 to 62 years) and group 2 (TF) (7 males, 8 females; median age 39.8 years; range 19 to 63 years). Occurrence of myringosclerosis on the intact tympanic membrane grafts was evaluated postoperatively by the same surgeon under surgical microscope. RESULTS: Postoperative myringosclerosis was detected in six patients (40%) in TP group and 13 patients (86.7%) in TF group. CONCLUSION: Prevalence of myringosclerosis on graft materials used in myringo-/tympanoplasty was lower in TP group compared to TF group. We believe that this may be due to different vascular structures of different graft tissues and that the low predisposition of perichondrium towards development of myringosclerosis can be considered as an advantage for this graft. We hope that this study adds a new dimension to etiopathogenesis of myringosclerosis and assists otologists in the prevention and treatment of this lesion.

Effect of caffeic acid phenethyl ester on myringosclerosis development in the tympanic membrane of rat.

Myringosclerosis is hyalinization and calcification of certain areas of the tympanic membrane, especially the fibrous lamina propria layer and appears as white sclerotic lesions. Ventilation tube insertion is one of the most performed operations in the pediatric otorhinolaryngology practice to treat chronic otitis media with effusion. Myringosclerosis is a very common sequela of ventilation tube insertion. In this experimental study, our aim was to show the histopathological effects of caffeic acid phenethyl ester on myringosclerosis development in rat tympanic membrane after myringotomy. The rats were randomly categorized into four experimental groups including the comparison group (n = 4), non-treated group (n = 7), the saline (control) group (n = 7), the caffeic acid phenethyl ester group (n = 7). Non-treated group did not receive any treatment for 15 days. Saline (2.5 mL/kg, intraperitoneal) was administered to the third group once a day for 15 days. Fourth group received caffeic acid phenethyl ester intraperitoneally once a day at a dose of 10 µmol/kg for 15 days. Myringotomy was performed on the right tympanic membrane of all rats except comparison group using a sterile pick with the help of an operating microscope. Histopathological examination of myringosclerosis formation was done by a pathologist under light microscope. In histopathological analysis of groups, the severity of inflammation was milder in caffeic acid phenethyl ester group compared to non-treated and saline groups (p < 0.05). There was less myringosclerotic plaques in caffeic acid phenethyl ester group than in non-treated and saline groups (p < 0.05). TM thickness measurements were very close to each other in non-treated and saline groups. The tympanic membrane thickness of caffeic acid phenethyl ester group was much thinner than the other two groups (p < 0.05). Caffeic acid phenethyl ester decreases inflammation severity and the formation of myringosclerotic plaques. These two effects resulted in thinner tympanic membranes of rats which were treated with caffeic acid phenethyl ester. As a result, caffeic acid phenethyl ester has potential preventive effects on myringosclerosis development after myringotomy and ventilation tube insertion.

[Tympanosclerosis etiology and treatment].

SUMMARY: Tympanosclerosis is the middle ear tissue hyalinization and calcification caused by chronic middle ear inflammation, which mainly results in conductive deafness with unobvious clinical symptom. Etiology is unclear. The treatment is given priority to surgical treatment at present, while long-term effect reported mostly poor. This article analyzed etiology and treatment of the tympanic cavity sclerosis.

Effect of local use of L-carnitine after myringotomy on myringosclerosis development in rats.

OBJECTIVES: This study aimed to investigate the effect of local and intraperitoneal administration of L-carnitine on the prevention of experimentally induced myringosclerosis, and to compare treatment efficiency. METHODS: Twenty-four Albino-Wistar rats (48 ears) were bilaterally myringotomised and divided randomly into four groups: group one received no treatment, group two received intraperitoneal L-carnitine, group three received local L-carnitine, and group four received both intraperitoneal and local L-carnitine. On the 15th day after treatment, tympanic membranes were harvested and evaluated histopathologically for myringosclerotic plaque formation, fibroblastic proliferation, tympanic membrane thickness and new vessel formation. RESULTS: The group one tympanic membranes showed extensive thickness, and the incidence of myringosclerosis and fibroblast proliferation were greater than in groups two and four. There were statistically significant differences in tympanic membrane thickness between groups three and four, and in myringosclerosis incidence and fibroblast proliferation, comparing groups two, three and four. CONCLUSION: Myringosclerosis development was significantly reduced in rats receiving myringotomy plus intraperitoneal L-carnitine. Intraperitoneal L-carnitine administration prevented fibroblastic proliferation and tympanic membrane thickening (both of which cause further tympanic membrane destruction), thus reducing myringotomy-associated morbidity. Local L-carnitine administration had limited effectiveness in this experimental setting.

Levels of reactive oxygen species in rat tympanic membranes after incisional versus radiofrequency myringotomy.

OBJECTIVE: A close relationship between reactive oxygen species (ROS) and myringosclerosis, which is a common complication of myringotomy, was recently reported. The objective of this study was to measure ROS levels directly in rat tympanic membranes using luminol-aided chemiluminescence (CL) in order to compare the levels of ROS after incisional and radiofrequency (RF) myringotomy. METHODS: Fifteen Sprague-Dawley rats were separated into three groups of five animals each. Bilateral myringotomies were made using an appropriate myringotomy lancet in Group 1 and RF in Group 2. Group 3 served as the control group with no myringotomy. Twenty-four hours after the procedure, all tympanic membranes were inspected with an otomicroscope and then excised for the measurement of ROS using luminol-aided CL. RESULTS: The mean ROS level in Group 1 was significantly higher than that in Groups 2 and 3 (p<0.05 for both). The difference in mean ROS level between Groups 2 and 3 was not significant (p>0.05). Otomicroscopy revealed increased vascularity and vessel dilation in all tympanic membranes that underwent myringotomy. Vascular dilation was observed in the annular region in the vessels that passed along the long arm of the malleus, in addition to the vessels feeding the anterior and posterior tympanomalleolar folds. CONCLUSIONS: Although the relationship between ROS and the development of myringosclerosis after myringotomy has been demonstrated, the present study is the first to compare incisional and RF myringotomy based on the measurement of ROS levels. Our results indicate that the increase in ROS due to myringotomy was greater following incisional myringotomy than RF myringotomy.