Airway Epithelial Cultures of Children with Esophageal Atresia as a Model to Study Respiratory Tract Disorders.

Esophageal atresia (EA) is a rare birth defect in which respiratory tract disorders are a major cause of morbidity. It remains unclear whether respiratory tract disorders are in part caused by alterations in airway epithelial cell functions such as the activity of motile cilia. This can be studied using airway epithelial cell culture models of patients with EA. Therefore, the aim of this study was to evaluate the feasibility to culture and functionally characterize motile cilia function in the differentiated air-liquid interface cultured airway epithelial cells and 3D organoids derived from nasal brushings and bronchoalveolar lavage (BAL) fluid from children with EA. We demonstrate the feasibility of culturing differentiated airway epithelia and organoids of nasal brushings and BAL fluid of children with EA, which display normal motile cilia function. EA patient-derived airway epithelial cultures can be further used to examine whether alterations in epithelial functions contribute to respiratory disorders in EA.

Bacterial Colonization of the Lower Airways in Children With Esophageal Atresia.

BACKGROUND: Esophageal atresia (EA) is most often accompanied by some degree of tracheomalacia (TM), which negatively influences the airway by ineffective clearance of secretions. This can lead to lower airway bacterial colonization (LABC), which may cause recurrent respiratory tract infections (RTIs). This study aims to evaluate the prevalence and specific pathogens of LABC in EA patients. METHODS: A 5-year retrospective single-site cohort study was conducted including all EA patients that had undergone an intraoperative bronchoalveolar lavage (BAL) during various routine surgical interventions. Concentrations of greater than 10 cfu were considered evidence of LABC. RESULTS: We recruited 68 EA patients, of which 12 were excluded based on the exclusion criteria. In the remaining 56 patients, a total of 90 BAL samples were obtained. In 57% of the patients, at least 1 BAL sample was positive for LABC. Respiratory symptoms were reported in 21 patients at the time of the BAL, of which 10 (48%) had LABC. Haemophilus influenzae (14%) and Staphylococcus aureus (16%) were most frequently found in the BAL samples. The number of respiratory tract infections and the existence of a recurrent fistula were significantly associated with LABC ( P = 0.008 and P = 0.04, respectively). CONCLUSIONS: This is the first study showing that patients with EA have a high prevalence of bacterial colonization of the lower airways which may be a leading mechanism of severe and recurrent respiratory complications.

Injection laryngoplasty for laryngeal cleft type I in an 8-week-old infant.

A laryngeal cleft is a rare anatomical deformity which is increasingly treated with injection laryngoplasty. Since diagnosis of laryngeal cleft type I is often made between 2 and 5 years of age, this treatment is rarely performed on very young children. In this case, we describe how injection laryngoplasty is performed safely on an 8-week-old child, and we illustrate its added value for the diagnostic process and for temporary symptom relief.

Osimertinib and anti-HER3 combination therapy engages immune dependent tumor toxicity via STING activation in trans.

Over the past decade, immunotherapy delivered novel treatments for many cancer types. However, lung cancer still leads cancer mortality, and non-small-cell lung carcinoma patients with mutant EGFR cannot benefit from checkpoint inhibitors due to toxicity, relying only on palliative chemotherapy and the third-generation tyrosine kinase inhibitor (TKI) osimertinib. This new drug extends lifespan by 9-months vs. second-generation TKIs, but unfortunately, cancers relapse due to resistance mechanisms and the lack of antitumor immune responses. Here we explored the combination of osimertinib with anti-HER3 monoclonal antibodies and observed that the immune system contributed to eliminate tumor cells in mice and co-culture experiments using bone marrow-derived macrophages and human PBMCs. Osimertinib led to apoptosis of tumors but simultaneously, it triggered inositol-requiring-enzyme (IRE1α)-dependent HER3 upregulation, increased macrophage infiltration, and activated cGAS in cancer cells to produce cGAMP (detected by a lentivirally transduced STING activity biosensor), transactivating STING in macrophages. We sought to target osimertinib-induced HER3 upregulation with monoclonal antibodies, which engaged Fc receptor-dependent tumor elimination by macrophages, and STING agonists enhanced macrophage-mediated tumor elimination further. Thus, by engaging a tumor non-autonomous mechanism involving cGAS-STING and innate immunity, the combination of osimertinib and anti-HER3 antibodies could improve the limited therapeutic and stratification options for advanced stage lung cancer patients with mutant EGFR.

Primary Posterior Tracheopexy in Esophageal Atresia Decreases Respiratory Tract Infections.

Background: Esophageal atresia (EA) is often accompanied by tracheomalacia (TM). TM can lead to severe respiratory complaints requiring invasive treatment. This study aims to evaluate if thoracoscopic primary posterior tracheopexy (PPT) can prevent the potential sequelae of TM in patients with EA. Methods: A cohort study including all consecutive EA patients treated between 2014 and July 2019 at the Wilhelmina Children's Hospital was conducted. Two groups were distinguished: (group 1) all EA patients born between January 2014 and December 2016 and (group 2) all EA patients born between January 2017 and July 2019, after introduction of PPT. In the latter group, PPT was performed in EA patients with moderate (33-66%) or severe (67-100%) tracheomalacia, seen during preoperative bronchoscopy. Group differences were assessed using the Fisher's exact test for bivariate variables and the Mann-Whitney U-test for continuous variables. Results: A total of 64 patients were included in this study (28 patients in group 1; 36 patients in group 2). In group 2, PPT was performed in 14 patients. Respiratory tract infections (RTIs) requiring antibiotics within the first year of life occurred significantly less in group 2 (61 vs. 25%, p = 0.004). Brief resolved unexplained events (BRUEs) seemed to diminish in group 2 compared to group 1 (39 vs. 19%, p = 0.09). Conclusion: Thoracoscopic primary posterior tracheopexy decreases the number of respiratory tract infections in EA patients. The clinical impact of reducing RTIs combined with the minimal additional operating time and safety of PPT outweighs the risk of overtreatment.

Thoracoscopic Repair of Esophageal Atresia.

Background: Esophageal atresia (EA) is a rare congenital malformation of the esophagus. Surgical treatment is required to restore the continuity of the esophagus. This can be performed through thoracotomy. However, an increasing number of hospitals is performing minimal invasive surgery (MIS). In this article, we describe the technique of thoracoscopic repair of EA in neonates in more detail and show the outcome of a patient cohort operated by young pediatric surgeons in training. Methods: Between 2014 and 2019 correction was performed in 64 EA type C patients at the UMC Utrecht, Wilhelmina Children's Hospital, mainly by young pediatric surgeons in training. Results: All patients were corrected through MIS, 3 days after birth. The median operation duration was 181 (127-334) minutes. Nasogastric tube feeding was started on the first postoperative day, and oral feeding 6 days postop. Postoperative complications included leakage (14.1%), stenosis (51.1%), and recurrent tracheoesophageal fistula (7.8%). Conclusion: Thoracoscopic repair of EA can be performed safely, with good outcome and all the benefits of MIS. However, it remains a challenging procedure and should be performed only in pediatric centers with a vast experience in MIS, especially when training young pediatric surgeons. These centers must have access to a multidisciplinary team of neonatologists, pediatric anesthesiologists, surgeons, and ENT specialists to ensure the best possible care in hemodynamic, respiratory, and cerebral monitoring and gastrointestinal and developmental outcome.

Retrospective analysis of clinical outcomes in bilateral cleft lip and palate patients after secondary alveolar bone grafting and premaxilla osteotomy, using a new dento-maxillary scoring system.

Evaluation of relevant clinical outcomes in patients with bilateral cleft lip and palate (BCLP) after secondary aveolar bone grafting (SABG) and premaxilla osteotomy (PMO), through the use of a new scoring system. Data were collected retrospectively from all patients with BCLP who were operated on between 2004 and 2014, at the end of follow-up. The treatment protocol consisted of SABG + PMO in patients aged between 9 and 13 years. At the end of follow-up, the following parameters were scored: (un)interrupted dental arch, skeletal sagittal relationship, bone height using the Bergland/Abyholm criteria, and the presence of postoperative fistula. These parameters were combined to produce a dento-maxillary scoring system, giving a final score between 1 and 10. For statistical analysis, the independent t-test was used. Of 55 children, 45 were suitable for analysis. The mean age at time of surgery was 12.0 years (8.9-16.4 yrs), and the mean follow-up time was 11.7 years (5.8-15.8 yrs). The average number of surgeries executed under general anesthesia was 6 (range: 3-11). The average dento-maxillary score in this patient cohort was 7.6 (1-10; median: 8). Among these patients, 31 had an uninterrupted dental arch; the average Bergland/Abyholm score was 2.07; 30 patients exhibited an Angle class I incisor relationship; and, in 38 cases, the oronasal communication was closed after SABG + PMO treatment. A significant effect of fistulas was seen on dento-maxillary score (p = 0.001). Specifically, a significant effect of fistulas was seen on interrupted dental arch (p = 0.002) and on Bergland/Abyholm score (p = 0.037). The proposed dento-maxillary scoring system is a straightforward tool that can be used to describe and analyze the amount of dento-maxillary rehabilitation at the end of the treatment. Persistence of oronasal fistulas in patients with BCLP has a significant impact on interruption of the dental arch, and can influence dental results at the end of the second decade.

Incidence of complications in secondary alveolar bone grafting of bilateral clefts with premaxillary osteotomy: a retrospective cohort study.

OBJECTIVE: To evaluate factors affecting incidence of complications after secondary alveolar bone grafting with premaxillary osteotomy (SABG + PO) in children with complete bilateral cleft of lip and palate (BCLP). MATERIALS AND METHODS: Data were collected from children with BCLP treated with SABG + PO from 2004 to 2014 at our institute. Preoperative parameters included age, donor site, race, gingival health, bone quality around cleft-related teeth, premaxilla position, graft timing, presence of canines in the cleft, and presence of deciduous teeth around the cleft area. Logistic regression and the chi-squared test were used to assess correlations and the incidence of complications. RESULTS: In the 64 patients, a significant correlation was found between complication rate and timing of bone grafting with respect to early versus late SABG + PO (p = 0.041), age > 12 years (p = 0.011; odds ratio (OR) 5.9; 95% confidence interval (CI) 1.49-23.93), malposition of the premaxilla (p = 0.042; OR 3.3; 95% CI 1.04-10.13), and preoperative bone quality around cleft-related teeth (p = 0.005; OR 5.3; 95% CI 1.6-17.2). CONCLUSIONS: The timing of SABG + PO is essential, as early SABG + PO is associated with fewer complications. A malpositioned premaxilla and poor bone quality around cleft-related teeth are associated with more complications. Therefore, preoperative orthodontic repositioning of the malpositioned premaxilla before SABG + PO should be considered. CLINICAL RELEVANCE: Analysis of treatment protocols and complications for BCLP patients underscores that proper timing of SABG + PO and correct premaxilla repositioning help reduce complications.

Detecting intratumoral heterogeneity of EGFR activity by liposome-based in vivo transfection of a fluorescent biosensor.

Despite decades of research in the epidermal growth factor receptor (EGFR) signalling field, and many targeted anti-cancer drugs that have been tested clinically, the success rate for these agents in the clinic is low, particularly in terms of the improvement of overall survival. Intratumoral heterogeneity is proposed as a major mechanism underlying treatment failure of these molecule-targeted agents. Here we highlight the application of fluorescence lifetime microscopy (FLIM)-based biosensing to demonstrate intratumoral heterogeneity of EGFR activity. For sensing EGFR activity in cells, we used a genetically encoded CrkII-based biosensor which undergoes conformational changes upon tyrosine-221 phosphorylation by EGFR. We transfected this biosensor into EGFR-positive tumour cells using targeted lipopolyplexes bearing EGFR-binding peptides at their surfaces. In a murine model of basal-like breast cancer, we demonstrated a significant degree of intratumoral heterogeneity in EGFR activity, as well as the pharmacodynamic effect of a radionuclide-labeled EGFR inhibitor in situ. Furthermore, a significant correlation between high EGFR activity in tumour cells and macrophage-tumour cell proximity was found to in part account for the intratumoral heterogeneity in EGFR activity observed. The same effect of macrophage infiltrate on EGFR activation was also seen in a colorectal cancer xenograft. In contrast, a non-small cell lung cancer xenograft expressing a constitutively active EGFR conformational mutant exhibited macrophage proximity-independent EGFR activity. Our study validates the use of this methodology to monitor therapeutic response in terms of EGFR activity. In addition, we found iNOS gene induction in macrophages that are cultured in tumour cell-conditioned media as well as an iNOS activity-dependent increase in EGFR activity in tumour cells. These findings point towards an immune microenvironment-mediated regulation that gives rise to the observed intratumoral heterogeneity of EGFR signalling activity in tumour cells in vivo.

Congenital Stapes Ankylosis in Children: Surgical Findings and Results in 35 Cases.

OBJECTIVE: To evaluate surgical findings and hearing results in children undergoing middle ear surgery for congenital stapes ankylosis with or without other ossicular malformations (Teunissen and Cremers class I and class II malformations). STUDY DESIGN: A nonrandomized, nonblinded case series of prospectively collected data. SETTING: A tertiary referral center. PATIENTS: Twenty-eight consecutive pediatric patients who underwent 35 surgical procedures for congenital stapes ankylosis with or without other ossicular malformations and had available postoperative pure-tone audiometry. INTERVENTION: Primary stapedotomy with vein graft interposition and reconstruction with a Teflon piston, bucket handle prosthesis or total ossicular replacement prosthesis. MAIN OUTCOME MEASURES: Pre- and postoperative audiometric evaluation using four-frequency (0.5, 1, 2, and 4 kHz) audiometry. Air-conduction thresholds, bone-conduction thresholds, and air-bone gaps (ABGs) were measured. Postoperative audiometry was performed at 3, 6, 9, 12, 18, and 24 months after surgery and at a yearly interval thereafter. RESULTS: Overall, a postoperative ABG closure of 10 dB or less was achieved in 73% of class I cases and in 50% of class II cases. A postoperative ABG closure of 20 dB or less was achieved in 77% of class I cases and 67% of class II cases. Postoperative sensorineural hearing loss occurred in one class I case (4%) and none of the class II cases. CONCLUSION: Stapedotomy is a safe and feasible treatment option in children with congenital stapes ankylosis.

Management of the premaxilla in the treatment of bilateral cleft of lip and palate: what can the literature tell us?

OBJECTIVE: In the treatment of bilateral cleft lip and palate (BCLP) patients, there is discussion about the management of the position of the premaxilla. This literature analysis summarises the literature on managing this condition. MATERIALS AND METHODS: A PubMed, Embase and Cochrane Library search was conducted resulting in 4465 articles which were screened on title and abstract. RESULTS: Seventy-one articles were available in full text, 16 of which were included in this literature analysis. We searched on keywords timing and technique, complications, growth of the maxilla and results after bone grafting the alveolar process. This literature analysis has shown that there are various ways to correct the position of the premaxilla. These can be divided into primary, early, late secondary and tertiary intervention before the age of 8 years, between the ages of 8 and 12 years and older than 12 years. Correction is done with surgery, orthodontics or a combination, with or without bone grafting. CONCLUSIONS: An osteotomy of the premaxilla in combination with secondary alveolar bone grafting appears to be the most successful technique. Combining early secondary alveolar bone grafting with osteotomy creates more room to ensure a watertight closure of the nasal mucosa resulting in fewer postoperative complications. Before surgery, the orthodontist should try to optimise the position of the premaxilla for its surgical correction prior to bone grafting. CLINICAL RELEVANCE: The treatment of BCLP patients is still based on experience and expert opinions. This literature analysis tries to give a summery on how to handle the protruded and displaced premaxilla.

A nonrandomized comparison of the thulium laser and the CO2 laser in primary stapedotomy for otosclerosis.

OBJECTIVE: Comparing hearing results in patients with otosclerosis treated with laser-assisted stapedotomy using the 2-µm thulium laser or the CO2 laser. STUDY DESIGN: Prospective nonrandomized clinical study. SETTING: In a tertiary referral center in France (Jean Causse Ear Clinic, Béziers), 208 primary stapedotomies were performed in 204 patients between March 2008 and November 2009. Sufficient follow-up data were available for 194 procedures. METHODS: The fenestration in the footplate was made with the thulium laser in 98 procedures and with a flexible CO2 laser in 96 procedures. Preoperative and postoperative audiometric results were compared. Side effects, such as vertigo and tinnitus, were scored. RESULTS: Patients treated with the CO2 laser had better hearing outcome compared with those treated with the thulium laser at both 3 and 12 months of follow-up. At 3 months, the success of the surgery, defined as closure of the air-bone gap to within 10 dB, was 90.0% in the thulium group compared with 96.8% in the CO2 group. Bone conduction shift showed an overall deterioration of 1.6 dB (standard deviation, 6.9 dB) in the thulium group compared with an improvement of 1.3 dB (standard deviation, 4 dB) in the CO2 group. In the thulium group, there were four patients with sensorineural hearing loss (4.4%) and three with tinnitus (3.1%) compared with none in the CO2 group. CONCLUSION: Stapedotomy surgery performed with a fiber-delivered thulium laser resulted in a higher chance of inner ear damage measured by bone conduction shift compared with the use of a fiber-delivered CO2 laser. We advise not to use the thulium laser for stapedotomy.

Capturing thermal, mechanical, and acoustic effects of the diode (980 nm) laser in stapedotomy.

INTRODUCTION: The diode laser, with a wavelength of 980 nm, has promising characteristics for being used for the fenestration during stapedotomy. It is known that at this wavelength absorption in pigmented tissues is high, and absorption in water is relatively low compared with medical lasers in the infrared, making it theoretically an applicable laser for stapes surgery in patients with otosclerosis. Another important advantage is that, with respect to other lasers, this device is relatively inexpensive. Despite the potential advantages, the available literature only shows limited reports of this laser being used in stapes surgery. The present article evaluates the thermal, mechanical, and acoustic properties of the diode laser during stapes surgery. METHODS: For the mechanical effects, high-speed imaging with a frame rate up to 4000 f/s (=250 µs resolution) was performed in an inner ear model. For thermal effects, the high-speed Schlieren technique was used. Acoustics were recorded by a hydrophone, incorporated in the model. Pulse settings were 100 ms, 3 W, which are the same settings used during stapes surgery. RESULTS: The application of the diode laser resulted in limited mechanical and thermal effects. Impulse noise was low with an average of 52 (SD, 7.8) dB (A). Before carbonization of the tip of the delivery laser, fiber enhances ablation of the footplate. CONCLUSION: The 980-nm diode laser is a useful tool for laser-assisted stapedotomy in patients with otosclerosis. Mechanical, thermal, and acoustic effects are limited and well within the safety limits.

Limited evidence for the effect of sodium fluoride on deterioration of hearing loss in patients with otosclerosis: a systematic review of the literature.

OBJECTIVE: To determine the protective effect of sodium fluoride on the deterioration of hearing loss in adult patients with otosclerosis. DATA SOURCES: PubMed, Embase, the Cochrane Library, and CINAHL. STUDY SELECTION: A systematic literature search was conducted. Studies reporting original study data on the deterioration of hearing loss in otosclerosis patients treated with sodium fluoride were included. DATA EXTRACTION: Directness of evidence (DoE) and risk of bias (RoB), using the Cochrane Collaboration's tool for assessing risk of bias, of the selected articles were assessed. Studies with low DoE, high RoB, or both were excluded. Absolute risks, mean deterioration of hearing in decibels, risk differences, and their 95% confidence intervals were extracted from the included studies. DATA SYNTHESIS: Our search yielded 168 original titles, of which, 2 placebo-controlled studies were eligible for data extraction. The results of these 2 studies were conflicting. One of the included studies, with high DoE and moderate RoB, reported an absolute risk reduction for deterioration of hearing loss of 18% [95% CI 17; 19] when treating with sodium fluoride. The other included study, with high DoE and moderate RoB, reported no clinically significant difference in mean deterioration of bone-conduction, air-conduction, or air-bone gap between the sodium fluoride group and the placebo group. CONCLUSION: There is weak evidence from one study with significant limitations that deterioration of hearing loss in otosclerosis patients receiving sodium fluoride treatment is less than in patients treated with a placebo.

An introduction of genetics in otosclerosis: a systematic review.

OBJECTIVE: To present an easy to read systematic review concerning the genetic etiology of otosclerosis to help health care providers in counseling otosclerosis patients more accurately. DATA SOURCES: PubMed, Embase, CINAHL, and the Cochrane Library. REVIEW METHODS: Studies on the genetic etiology of otosclerosis were selected. Association studies and family-based studies were included for further review. After quality assessment (risk of bias), data were extracted from the included studies. When available, odds ratios were presented. In case of corresponding genetic anomalies between the studies, it was the aim to combine results. RESULTS: The number of available studies with low risk of bias is limited to 2 association studies and 1 family-based study. These high-quality studies show that otosclerosis in Japanese patients is not linked to the NOG gene and that a polymorphism in the Sp1 binding site located on the COL1A1 gene is associated with otosclerosis as well as OTSC1. Association and family-based studies with moderate risk of bias show a statistically significant association with the ACE gene, AGT gene, OTSC2, RELN gene, TGFB1 gene, 11q13.1, OTSC2, OTSC5, OTSC8, and OTSC10. These results may be spurious associations due to their bias and low statistical power. CONCLUSION: The present systematic review shows that there is scattered evidence of limited quality and a lack of replication studies. It is not possible to point out 1 or more responsible genes, which play a key role within the genetic pathophysiologic mechanism of otosclerosis.

Pure-tone audiometry in otosclerosis: insufficient evidence for the diagnostic value of the Carhart notch.

OBJECTIVE: To evaluate whether the Carhart notch on pure-tone audiometry is reliable as a diagnostic test for predicting otosclerosis in patients with conductive hearing loss. Data Sources PubMed, Embase, the Cochrane Library, CINAHL, and Scopus. METHODS: A systematic search was conducted. Studies reporting original study data were included. After assessment of directness of evidence and risk of bias of the selected articles, the prevalences and the positive and negative predictive values were extracted. RESULTS: A total of 1402 unique studies was retrieved. Three of these satisfied the eligibility criteria. One study provided direct evidence, while all studies carried moderate to high risk of bias. One study with moderate directness of evidence and high risk of bias was not further analyzed. In a study with a high directness of evidence, a high risk of bias, and a low prevalence of otosclerosis (8%) in patients with conductive hearing loss, the presence of a Carhart notch at 2000 Hz increased the risk of otosclerosis with 33%. In a second study with moderate directness of evidence, moderate risk of bias, and a high prevalence of otosclerosis (72%) in patients with a surgically confirmed congenital ossicular anomaly or otosclerosis, the presence of a Carhart notch at 2000 Hz increased the risk of otosclerosis with 2%. CONCLUSION AND RECOMMENDATION: Although there is insufficient high-quality evidence regarding the diagnostic value of the Carhart notch, it seems it is a useful hint for the presence of otosclerosis, but it cannot be used to confirm a diagnosis of otosclerosis.

Clinical practice guidelines on the management of patients with common otologic pathology toward European consensus: outline of approach.

OBJECTIVE: To achieve a European consensus about the best-evidence informed-management of patients with common otologic-related problems. DESIGN: Consensus process, supported by the European Academy of Otology & Neuro-Otology. SETTING: The European Academy of Otology & Neuro-Otology. METHODS: A guideline of a specific disease should include evidence-informed recommendations about questions relating to treatment, prognosis, and diagnosis. A standardized method to design guideline questions to search for evidence and to grade the quality of available evidence results in an overview of the best available literature. Experts achieve a consensus on best practice and articulate recommendations on evidence-based actions to be taken in patient care accordingly. The assets of such evidence-based consensus usually are the opinion of experts and arguments on availability, transferability, applicability, and affordability. DISCUSSION: The volume of new information increases at a staggering pace. As a result, there is an increasing demand for consistent systematic management of the available evidence. Systematic filtering of available evidence will help clinicians to find and apply best available and latest evidence efficiently and quickly. CONCLUSION: Despite the otologic line of approach, the present article provides a step-by-step "guideline development instruction manual," which could be used within other medical specialties.

A nonrandomized comparison of stapes surgery with and without a vein graft in patients with otosclerosis.

OBJECTIVE: To evaluate the effectiveness of primary stapes surgery with and without a vein graft in patients with otosclerosis and to determine the differences in the postoperative gain in air-bone gap (ABG) and air-conduction (AC). STUDY DESIGN: A nonrandomized multicenter clinical evaluation. SETTING: Two tertiary referral centers in The Netherlands and France. PATIENTS: Otosclerosis patients that underwent primary stapedotomy surgery. INTERVENTION: Primary stapedotomy surgery without a vein graft (n = 939, first center) compared with primary stapedotomy surgery with a vein graft (n = 3691, second center). MAIN OUTCOME MEASURES: Preoperative and postoperative audiometric results were compared. An analysis of variance was performed to evaluate differences in postoperative ABG and AC gains between surgeries with and without a vein graft, adjusted for potential confounders. RESULTS: The postoperative ABG was 10 dB or lesser in 72.1% of the patients without a vein graft and in 93.2% of patients with a vein graft. After adjustments for differences at baseline, the mean gain in ABG was 18.6 dB (95% CI, 18.1-19.1) in the group without vein graft, compared with 24.2 dB (95% CI, 23.9-24.6) in the group with vein graft (mean difference, 5.6 dB; 95% CI, 5.0-6.2). The mean gain in AC was 19.5 dB (95% CI, 18.7-20.3) in the group without vein graft, compared with 24.3 dB (95% CI, 23.7-24.7) in the group with vein graft (mean difference, 4.8 dB; 95% CI, 3.8-5.7). CONCLUSION: Patients with otosclerosis undergoing primary stapes surgery may benefit more from a vein graft interposition. LEVEL OF EVIDENCE: 2B.

Local versus general anesthesia in stapes surgery for otosclerosis: a systematic review of the evidence.

OBJECTIVE: To assess hearing results following primary stapes surgery in patients with otosclerosis, comparing local and general anesthesia. DATA SOURCES: PubMed, Embase, the Cochrane Library, CINAHL, and Scopus. REVIEW METHODS: A systematic search was conducted, followed by assessment of directness of evidence and risk of bias. Studies reporting original data on the effect of local anesthesia, compared to general anesthesia, on closure of air-bone gap in patients undergoing stapes surgery for otosclerosis were included. RESULTS: A total of 257 unique studies were retrieved, of which 3 (including 417 procedures) satisfied the eligibility criteria. Assessment showed that all studies carried high risk of bias, and only 1 study provided direct evidence. CONCLUSION: There is no difference in postoperative air-bone gap, worsening of sensorineural hearing loss, and postoperative vertigo between the 2 groups. A statistically significant increased risk of immediate dead ear following stapes surgery performed under general anesthesia was reported in 1 study.

Ossiculoplasty in missing malleus and stapes patients: experimental and preliminary clinical results with a new malleus replacement prosthesis with the otology-neurotology database.

OBJECTIVE: To present the preliminary results of new malleus replacement prosthesis combined with a total ossicular prosthesis in middle ear reconstruction in patients missing the malleus and stapes. STUDY DESIGN: Prospective experimental and nonrandomized clinical study. SETTING: Tertiary referral center. METHODS: An original titanium malleus replacement prosthesis (MRP) was designed to be inserted into the external auditory canal and to replace a missing malleus for various middle ear pathologies. The MRP was tested experimentally and clinically. The vibratory properties of the new prosthesis were measured using laser Doppler vibrometry. Ninety patients with missing malleus and stapes, undergoing 92 ossicular reconstructions were enrolled in this study from September 1994 to March 2012. Comparative analyses were made between a group of 34 cases of ossicular reconstructions with total prosthesis (TORP) positioned from the tympanic membrane to the stapes footplate (TM-to-footplate assembly) and a group of 58 cases of ossicular reconstructions with TORP positioned from a newly designed malleus replacement prosthesis (MRP) to the stapes footplate (MRP-to-footplate assembly). Preoperative and postoperative audiometric evaluation using conventional audiometry, that is, air-bone gap (ABG), bone-conduction thresholds (BC), and air-conduction thresholds (AC) were assessed. RESULTS: Experimentally, the vibratory properties of the MRP are promising and remain very good even when the MRP is cemented into the bony canal wall mimicking its complete osseous-integration, if this were to occur. This finding supports the short-term clinical results as in the TM-to-footplate group; the 3-month postoperative mean ABG was 23.3 dB compared with 12.5 dB in the MRP-to-footplate group (difference, 10.8; 95% confidence interval, 4.0-17.6); 37.0% of patients from the TM-to-footplate group had a postoperative ABG of 10 dB or less, and 48.1% of patients had a postoperative ABG of 20 dB or less, as compared with 58.1% and 79.1%, respectively, in the MRP-to-footplate group. The average gain in AC was 11.0 dB in the TM-to-footplate group as compared with 21.3 dB in the MRP-to-footplate group (difference, -10.3; 95% confidence interval, -18.2 to -2.4). CONCLUSION: The results of this study indicate that superior postoperative hearing thresholds could be achieved using a MRP-to-footplate assembly, compared with a TM-to-footplate assembly in patients with an absent malleus undergoing ossiculoplasty. The postoperative AC thresholds, after 3 months and 1 year, are significantly lower in patients treated with the MRP-to-footplate assembly.