Presence of hyaluronan in lung alveoli in severe Covid-19: An opening for new treatment options?

Severe coronavirus disease 2019 (Covid-19) is characterized by inflammation of the lungs with increasing respiratory impairment. In fatal Covid-19, lungs at autopsy have been filled with a clear liquid jelly. However, the nature of this finding has not yet been determined. The aim of the study was to demonstrate whether the lungs of fatal Covid-19 contain hyaluronan, as it is associated with inflammation and acute respiratory distress syndrome (ARDS) and may have the appearance of liquid jelly. Lung tissue obtained at autopsy from three deceased Covid-19 patients was processed for hyaluronan histochemistry using a direct staining method and compared with staining in normal lung tissue. Stainings confirmed that hyaluronan is obstructing alveoli with presence in exudate and plugs, as well as in thickened perialveolar interstitium. In contrast, normal lungs only showed hyaluronan in intact alveolar walls and perivascular tissue. This is the first study to confirm prominent hyaluronan exudates in the alveolar spaces of Covid-19 lungs, supporting the notion that the macromolecule is involved in ARDS caused by SARS-CoV-2. The present finding may open up new treatment options in severe Covid-19, aiming at reducing the presence and production of hyaluronan in the lungs.

Smartphone threshold audiometry in underserved primary health-care contexts.

OBJECTIVE: To validate a calibrated smartphone-based hearing test in a sound booth environment and in primary health-care clinics. DESIGN: A repeated-measure within-subject study design was employed whereby air-conduction hearing thresholds determined by smartphone-based audiometry was compared to conventional audiometry in a sound booth and a primary health-care clinic environment. STUDY SAMPLE: A total of 94 subjects (mean age 41 years ± 17.6 SD and range 18-88; 64% female) were assessed of whom 64 were tested in the sound booth and 30 within primary health-care clinics without a booth. RESULTS: In the sound booth 63.4% of conventional and smartphone thresholds indicated normal hearing (≤15 dBHL). Conventional thresholds exceeding 15 dB HL corresponded to smartphone thresholds within ≤10 dB in 80.6% of cases with an average threshold difference of -1.6 dB ± 9.9 SD. In primary health-care clinics 13.7% of conventional and smartphone thresholds indicated normal hearing (≤15 dBHL). Conventional thresholds exceeding 15 dBHL corresponded to smartphone thresholds within ≤10 dB in 92.9% of cases with an average threshold difference of -1.0 dB ± 7.1 SD. CONCLUSIONS: Accurate air-conduction audiometry can be conducted in a sound booth and without a sound booth in an underserved community health-care clinic using a smartphone.

A Machine Learning Approach to Screen for Otitis Media Using Digital Otoscope Images Labelled by an Expert Panel.

BACKGROUND: Otitis media includes several common inflammatory conditions of the middle ear that can have severe complications if left untreated. Correctly identifying otitis media can be difficult and a screening system supported by machine learning would be valuable for this prevalent disease. This study investigated the performance of a convolutional neural network in screening for otitis media using digital otoscopic images labelled by an expert panel. METHODS: Five experienced otologists diagnosed 347 tympanic membrane images captured with a digital otoscope. Images with a majority expert diagnosis (n = 273) were categorized into three screening groups Normal, Pathological and Wax, and the same images were used for training and testing of the convolutional neural network. Expert panel diagnoses were compared to the convolutional neural network classification. Different approaches to the convolutional neural network were tested to identify the best performing model. RESULTS: Overall accuracy of the convolutional neural network was above 0.9 in all except one approach. Sensitivity to finding ears with wax or pathology was above 93% in all cases and specificity was 100%. Adding more images to train the convolutional neural network had no positive impact on the results. Modifications such as normalization of datasets and image augmentation enhanced the performance in some instances. CONCLUSIONS: A machine learning approach could be used on digital otoscopic images to accurately screen for otitis media.

Causes of hearing impairment in the Norwegian paediatric cochlear implant program.

Severe to profound hearing impairment (HI) is estimated to affect around 1/2000 young children. Advances in genetics have made it possible to identify several genes related to HI. This information can cast light upon prognostic factors regarding the outcome in cochlear implantation, and provide information both for scientific and genetic counselling purposes. From 1992 to 2005, 273 children from 254 families (probands) were offered cochlear implants in Norway. An evaluation of the causes of HI, especially regarding the genes GJB2, GJB6, SLC26A4, KCNQ1, KCNE1, and the mutation A1555G in mitochondrial DNA was performed in 85% of the families. The number of probands with unknown cause of HI was thus reduced from 120 to 68 (43% reduction). Ninety-eight (46%) of the probands had an identified genetic etiology of their HI. A relatively high prevalence of Jervell and Lange-Nielsen syndrome was found. The main causes of severe and profound HI were similar to those found in other European countries. GJB2 mutations are a common cause of prelingual HI in Norwegian cochlear implanted children.

Accuracy and Reliability of Smartphone Self-Test Audiometry in Community Clinics in Low Income Settings: A Comparative Study.

BACKGROUND: There is a lack of hearing health care globally, and tele-audiology and mobile technologies have been proposed as important strategies to reduce the shortfall. OBJECTIVES: To investigate the accuracy and reliability of smartphone self-test audiometry in adults, in community clinics in low-income settings. METHODS: A prospective, intra-individual, repeated measurements design was used. Sixty-three adult participants (mean age 52 years, range 20-88 years) were recruited from ENT and primary health care clinics in a low-income community in Tshwane, South Africa. Air conduction hearing thresholds for octave frequencies 0.5 to 8 kHz collected with the smartphone self-test in non-sound treated environments were compared to those obtained by reference audiometry. RESULTS: The overall mean difference between threshold seeking methods (ie, smartphone thresholds subtracted from reference) was -2.2 dB HL (n = 467 thresholds, P = 0.00). Agreement was within 10 dB HL for 80.1% (n = 467 thresholds) of all threshold comparisons. Sensitivity for detection hearing loss >40 dB HL in one ear was 90.6% (n = 84 ears), and specificity 94.2% (n = 84 ears). CONCLUSION: Smartphone self-test audiometry can provide accurate and reliable air conduction hearing thresholds for adults in community clinics in low-income settings.

[Is the current level of investigation for vestibular schwannoma reasonable?] / Utredningsnivån av vestibulära schwannom måste bli rimlig - Nationella riktlinjer behövs.

The main aim of this study was to evaluate if the level of investigation with MRT or BRA (Brainstem Response Audiometry) is adequate in relation to the number of vestibular schwannomas (VS) found in a county like  Dalarna (277 000 inhabitants) in Sweden. The reason to investigate was asymmetrical sensorineural hearing loss (ASHL) defined as a one-sided hearing loss exceeding 10 dB compared to the contralateral side. Between 2007-2014 a total of 55 patients (incidence 2.5/100 000) were diagnosed with a VS in the county. The local ENT department found two thirds of these patients. In the year of 2010, MRT was advocated by SBU (Swedish Agency for Health Technology Assessment and Assessment of Social Services) as the primary step of investigation. During 2011-2014, 981 patients underwent MRT and 482 patients BRA, because of ASHL. Seventeen VS were found, meaning that 58 MRT and 29 BRA were conducted to find one VS. According to earlier studies, only one third of VS show growth tendency. Taking this into consideration, 174 (58 × 3) investigations with MRT will only diagnose approximately 1 patient with a growing VS. We therefore question today's level of investigation and ask for new uniform recommendations on how to investigate for VS in cases of ASHL.

Hyaluronan in vocal folds and false vocal folds in patients with recurrent respiratory papillomatosis.

BACKGROUND: Hyaluronan (HA) is a glycosaminoglycan with viscoelastic properties necessary for vocal fold (VF) vibration and voice production. Changes in HAs molecular mass, possibly related to human papilloma virus, could affect formation/persistence of recurrent respiratory papillomatosis (RRP). Aims/Objective: Describing mass and localization of HA and localization of HA receptor CD44 in VF and false vocal folds (FVF) in RRP. MATERIALS AND METHODS: Biopsies from VF and FVF from 24 RRP patients. Twelve were studied with histo-/immunohistochemistry for HA and CD44 in epithelium, stroma and RRP lesions. Twelve samples were analyzed for HA molecular mass distribution with gas-phase-electrophoretic-molecular-mobility-analyzer (GEMMA). RESULTS: Three of 23 stains (VF and FVF combined) showed faint HA staining in the epithelium; there was more extensive staining in the stroma. CD44 was present throughout all areas in FVF and VF, it did not concur with HA. GEMMA analysis revealed very high mass HA (vHMHA) with more varying amounts in VF. CONCLUSIONS/SIGNIFICANCE: HA was mainly distributed in the stroma. CD44 not binding to HA might explain the non-inflammatory response described in RRP. Possibly crosslinked vHMHA was seen in VF and FVF, with more variable amounts in VF samples. Counteracting HA crosslinking could become a treatment option in RRP.

Diagnostic accuracy of a general practitioner with video-otoscopy collected by a health care facilitator compared to traditional otoscopy.

OBJECTIVE: Video-otoscopy is rapidly developing as a new method to diagnose common ear disease and can be performed by trained health care facilitators as well as by clinicians. This study aimed to compare remote asynchronous assessments of video-otoscopy with otoscopy performed by a general practitioner. METHOD: Children, aged 2-16 years, attending a health center in Johannesburg, South Africa, were examined. An otologist performed otomicroscopy and a general practitioner performed otoscopy. Video-otoscopy was performed by a health care facilitator and video sequences were stored on a server for assessment by the same general practitioner 4 and 8 weeks later. At all examinations, a diagnosis was set and the tympanic membrane appearance was graded using the OMgrade-scale. The otologist's otomicroscopic diagnosis was set as reference standard to compare the accuracy of the two otoscopic methods. RESULTS: Diagnostic agreement between otologist's otomicroscopic examination and the general practitioner's otoscopic examination was substantial (kappa 0.66). Agreement between onsite otomicroscopy and the general practitioners asynchronous video assessments were also substantial (kappa 0.70 and 0.80). CONCLUSION: Video-otoscopy performed by a health care facilitator and assessed asynchronously by a general practitioner had similar or better accuracy compared to face-to-face otoscopy performed by a general practitioner.

Hyaluronan in Human Vocal Folds in Smokers and Nonsmokers-A Histochemical Study.

OBJECTIVES/HYPOTHESIS: To study the hyaluronan occurrence in human vocal folds, with special regards to gender and smoking and to discuss the implications of findings. STUDY DESIGN: This is a descriptive/morphologic study. METHODS: Sixteen cadaveric vocal folds from eight individuals between 58 and 90 years old (six women and two men) were removed and studied morphologically. Three of the individuals had been cigarette smokers. A direct method for hyaluronan histochemistry using a hyaluronan-binding protein probe (HABP) was used to visualize the polysaccharide. Five examiners performed an analysis of the intensities of hyaluronan staining, independently. RESULTS: We observed intense hyaluronan staining of the vocal folds of which those from women stained considerably stronger than those from men. Stratified squamous epithelium stained for hyaluronan in all sections, whereas respiratory epithelium only stained weakly or not at all. The highest accumulation of hyaluronan occurred subepithelially in the lamina propria, corresponding to Reinke's space. It was observed that vocal folds from smokers were more intensively stained than those from nonsmokers. CONCLUSIONS: Hyaluronan is found in all layers of the human vocal fold. Contradictory to earlier studies, hyaluronan was visualized in squamous epithelium, where it may function as an impact protector. The occurrence of hyaluronan in smokers may have implications in the development of vocal fold inflammation and tumor initiation as hyaluronan is an important molecule in these processes.

Otitis Media Diagnosis for Developing Countries Using Tympanic Membrane Image-Analysis.

BACKGROUND: Otitis media is one of the most common childhood diseases worldwide, but because of lack of doctors and health personnel in developing countries it is often misdiagnosed or not diagnosed at all. This may lead to serious, and life-threatening complications. There is, thus a need for an automated computer based image-analyzing system that could assist in making accurate otitis media diagnoses anywhere. METHODS: A method for automated diagnosis of otitis media is proposed. The method uses image-processing techniques to classify otitis media. The system is trained using high quality pre-assessed images of tympanic membranes, captured by digital video-otoscopes, and classifies undiagnosed images into five otitis media categories based on predefined signs. Several verification tests analyzed the classification capability of the method. FINDINGS: An accuracy of 80.6% was achieved for images taken with commercial video-otoscopes, while an accuracy of 78.7% was achieved for images captured on-site with a low cost custom-made video-otoscope. INTERPRETATION: The high accuracy of the proposed otitis media classification system compares well with the classification accuracy of general practitioners and pediatricians (~64% to 80%) using traditional otoscopes, and therefore holds promise for the future in making automated diagnosis of otitis media in medically underserved populations.

Viscoelasticity of rabbit vocal folds after injection augmentation.

OBJECTIVES/HYPOTHESIS: Vocal fold function is related to the viscoelasticity of the vocal fold tissue. Augmentation substances used for injection treatment of voice insufficiency may alter the viscoelastic properties of vocal folds and their vibratory capacity. The objective was to compare the mechanical properties (viscoelasticity) of various injectable substances and the viscoelasticity of rabbit vocal folds, 6 months after injection with one of these substances. STUDY DESIGN: Animal model. METHODS: Cross-linked collagen (Zyplast), double cross-linked hyaluronan (hylan B gel), dextranomers in hyaluronan (DHIA), and polytetrafluoroethylene (Teflon) were injected into rabbit vocal folds. Six months after the injection, the animals were killed and the right- and left-side vocal folds were removed. Dynamic viscosity of the injected substances and the vocal folds was measured with a Bohlin parallel-plate rheometer during small-amplitude oscillation. RESULTS: All injected vocal folds showed a decreasing dynamic viscosity with increasing frequency. Hylan B gel and DiHA showed the lowest dynamic viscosity values, and vocal folds injected with these substances also showed the lowest dynamic viscosity (similar to noninjected control samples). Teflon (and vocal folds injected with Teflon) showed the highest dynamic viscosity values, followed by the collagen samples. CONCLUSION: Substances with low viscoelasticity alter the mechanical properties of the vocal fold to a lesser degree than substances with a high viscoelasticity. The data indicated that hylan B gel and DiHA render the most natural viscoelastic properties to the vocal folds. These substances seem to be appropriate for preserving or restoring the vibratory capacity of the vocal folds when glottal insufficiency is treated with augmentative injections.

Cross-linked hyaluronan used as augmentation substance for treatment of glottal insufficiency: safety aspects and vocal fold function.

OBJECTIVE: To examine safety aspects and vocal fold function after vocal fold augmentation with a cross-linked hyaluronan derivative (hylan B gel) as compared with bovine collagen. STUDY DESIGN; A prospective, randomized trial. METHODS: Eighty-three patients with glottal insufficiency were treated with injection augmentation with hylan B gel and bovine collagen and were examined at 1, 6, and 12 months after treatment. Seventy patients with unilateral vocal fold paresis (n = 35) or atrophy (n = 35) were randomly assigned to receive either hylan B gel (n = 47) or collagen (n = 23) injections into one vocal fold. Thirteen patients with glottal insufficiency caused by scar defects or paresis resulting from malignant disease were included in a nonrandomized group and were treated only with hylan B gel. Evaluations were made from patients' subjective ratings (visual analogue scales), digitized videostroboscopic measurements, phonetograms, maximum phonation time, and phonation quotients. RESULTS: Twelve months after injections, the patients' self-ratings were significantly improved for both the hylan B gel and the collagen groups. In addition, the videostroboscopic measurements showed significantly improved glottal closure for both groups. However, for the hylan B gel group, vibration amplitude and glottal area variations were preserved, and this group showed significantly less resorption at the injected vocal fold edge. Furthermore, maximum phonation time had increased significantly for the hylan B gel patients (collagen, nonsignificant). No serious adverse events were observed; three patients injected with hylan B gel had temporary inflammation at the injection site, which resolved without sequelae. CONCLUSIONS: The results showed that both hylan B gel and collagen can be safely used for injection treatment of glottal insufficiency. Both treatments resulted in significantly improved voice as rated by the patients. However, the patients treated with hylan B gel showed better vocal fold status and longer maximum phonation time at 12 months after treatment as compared with patients treated with collagen.

Viscoelastic properties of rabbit vocal folds after augmentation.

BACKGROUND: Vocal fold function is closely related to tissue viscoelasticity. Augmentation substances may alter the viscoelastic properties of vocal fold tissues and hence their vibratory capacity. OBJECTIVES: We sought to investigate the viscoelastic properties of rabbit vocal folds in vitro after injections of various augmentation substances. STUDY DESIGN AND SETTING: Polytetrafluoroethylene (Teflon), cross-linked collagen (Zyplast), and cross-linked hyaluronan, hylan b gel (Hylaform) were injected into the lamina propria and the thyroarytenoid muscle of rabbit vocal folds. Dynamic viscosity of the injected vocal fold as a function of frequency was measured with a Bohlin parallel-plate rheometer during small-amplitude oscillation. RESULTS: All injected vocal folds showed a decreasing dynamic viscosity with increasing frequency. Vocal fold samples injected with hylan b gel showed the lowest dynamic viscosity, quite close to noninjected control samples. Vocal folds injected with polytetrafluoroethylene showed the highest dynamic viscosity followed by the collagen samples. CONCLUSIONS: The data indicated that hylan b gel in short-term renders the most natural viscoelastic properties to the vocal fold among the substances tested. This is of importance to restore/preserve the vibratory capacity of the vocal folds when glottal insufficiency is treated with injections.

Hyaluronan and alpha-atrial natriuretic polypeptide in human nasal polyps: contributing factors to oedema formation and polyp growth?

OBJECTIVES: To identify and localize hyaluronan (HYA) and alpha-atrial natriuretic polypeptide (ANP) in human nasal polyps and to measure the HYA concentrations. MATERIAL AND METHODS: Twelve nasal polyps were collected during routine polypectomies and processed histochemically and biochemically to determine the occurrence of HYA. The distribution of ANP was investigated using an immunocytochemical method. RESULTS: HYA was unevenly distributed, being found abundantly in the surface epithelium and basement membrane and around fibres and vessels in the lamina propria. It was also present around seromucinous glands and in the secretion of cysts in the stroma. The HYA concentration was 1,000-fold higher than in serum. ANP was abundant in the apical part of ciliated surface epithelial cells and extracellularly in the basement membrane. In the stroma, ANP was confined to apical acinar cells of the seromucinous glands. CONCLUSIONS: Osmotically active HYA and numerous ANP-immunoreactive cells, active in fluid and/or ion transport functions, are present in human nasal polyps. These substances may well be involved in oedema formation and the successive growth of nasal polyps. The high concentrations of HYA in nasal polyps may be of clinical significance for the future development of a local enzyme treatment for nasal polyposis.

Cross-linked hyaluronan versus collagen for injection treatment of glottal insufficiency: 2-year follow-up.

OBJECTIVES: To evaluate the long-term (24 months) clinical performance (vocal fold function) and safety of hylan B gel as compared with bovine cross-linked collagen in the treatment of patients with glottal insufficiency. MATERIAL AND METHODS: In a prospective trial, 70 patients with glottal insufficiency due to unilateral vocal fold paresis (n =35) or atrophy (n =35) were randomized to received either hylan B gel (n =47) or collagen (n =23) injections into 1 vocal fold. Forty-two of the patients were examined 24 months after treatment. Evaluations were made based on patients' subjective ratings, digitized videostroboscopic measurements, maximum phonation time and phonation quotient. RESULTS: The patients' self-ratings were significantly improved in both the hylan B gel and collagen groups. Videostroboscopic measurements of glottal closure were significantly improved for both groups. The hylan B gel group showed a trend towards less resorption at the injected vocal fold edge in comparison with the collagen group (p =0.05). No serious adverse events were observed. Twenty-eight patients dropped out of the study after 12 months: 18 had been re-injected or operated on with medialization laryngoplasty due to insufficient voice and 10 had either died of causes unrelated to the study or refused to attend follow-up. CONCLUSIONS: No long-term side-effects were found for either the hylan B gel or collagen groups after injection treatment. Both treatments resulted in significantly improved voice as rated by the patients and significantly improved glottal closure. Some resorption was noted for both substances, and approximately 25%, of the patients chose re-treatment 2 years after the initial treatment.

Ear involvement in ligneous conjunctivitis: a rarity or an under-diagnosed condition?

Conjunctivitis lignosa, a rare affliction of the conjunctiva, is sometimes associated with other disturbances. We present two children with concurrent conjunctivitis lignosa and ear involvement. In these two cases, there were histopathologically verified ligneous changes of the middle ears. Routine haematoxylin and eosin, van Gieson, periodic acid-Schiff (PAS) and alcian blue staining of specimens from the eyes and middle ears revealed findings typical for ligneous conjunctivitis. In addition, new histochemical and immunohistochemical studies for glycosaminoglycans on specimens from the eyes and middle ears showed that the accumulations of the amorphous, cell-deficient material stained strongly but heterogeneously for hyaluronic acid and weakly but uniformly for keratin sulphate. The staining for other glycosaminoglycans, e.g. chondroitin-4-sulphate and dermatan sulphate was confined to vessels and areas rich in collagen fibres and fibroblasts. In patients with conjunctivitis lignosa, the ear involvement may remain undiagnosed due to its resemblance to secretory otitis media with effusion. Since isolated ear involvement may occur, we advocate biopsies for routine haematoxylin and eosin, and specific staining for hyaluronic acid and keratin sulphate, also in children with protracted, refractory otitis media with atypical effusion.

Remote evaluation of video-otoscopy recordings in an unselected pediatric population with an otitis media scale.

BACKGROUND: A recently validated image-based grading scale for acute otitis media (OMGRADE) can be used to assess tympanic membrane (TM) status. The aim of this study was to evaluate the validity and reliability of this scale for remote assessments of TM status using video-otoscopy recordings in an unselected pediatric population. METHOD: Children 2-16 years attending a South African primary health clinic were offered an ear examination by an otologist using otomicroscopy. An ear and hearing telehealth facilitator then made video-otoscopy recordings (9-33s) of the ears and uptakes were uploaded to a secure server for remote assessments in Sweden by an otologist and general practitioner at four- and eight-weeks post onsite assessment. TM appearance was judged according to the OMGRADE scale. Concordance between onsite otomicroscopy and asynchronous assessments of video-otoscopy recordings was calculated together with intra- and inter-rater agreements. RESULTS: One hundred and eighty ears were included. Concordance of TM classifications using the OMGRADE scale was found to be substantial (weighted kappa range 0.66-0.79). Intra- and inter-rater agreement (test-retest) was found to be substantial to almost perfect (weighted kappa range 0.85-0.88 and 0.69-0.72, respectively). CONCLUSION: The OMGRADE scale can be used to accurately assess the normal TM and secretory otitis media (SOM) remotely using video-otoscopy recordings in an unselected pediatric population.

Video-otoscopy recordings for diagnosis of childhood ear disease using telehealth at primary health care level.

We studied the diagnoses made by an otologist and general practitioner (GP) from video-otoscopy recordings on children made by a telehealth facilitator. The gold standard was otomicroscopy by an experienced otologist. A total of 140 children (mean age 6.4 years; 44% female) were recruited from a primary health care clinic. Otomicroscopic examination was performed by an otologist. Video-otoscopy recordings were assigned random numbers and stored on a server. Four and eight weeks later, an otologist and a GP independently graded and made a diagnosis from each video recording. The otologist rated the quality of the video-otoscopy recordings as acceptable or better in 87% of cases. A diagnosis could not be made from the video-otoscopy recordings in 18% of ears in which successful onsite otomicroscopy was conducted. There was substantial agreement between diagnoses made from video-otoscopy recordings and those from onsite otomicroscopy (first review: otologist κ = 0.70 and GP κ = 0.68; second review: otologist κ = 0.74 and GP κ = 0.75). There was also substantial inter-rater agreement (κ = 0.74 and 0.74 at the two reviews) and intra-rater agreement (κ = 0.77 and 0.74 for otologist and GP, respectively). A telehealth facilitator, with limited training, can acquire video-otoscopy recordings in children for asynchronous diagnosis. Remote diagnosis was similar to face-to-face diagnosis in inter- and intra-rater variability.

Comparison of bilateral and unilateral cochlear implants in children with sequential surgery.

OBJECTIVE: The objective of this study was to evaluate the effect of bilateral versus unilateral cochlear implants and the importance of the inter-implant interval. METHODS: Seventy-three prelingually deaf children received sequential bilateral cochlear implants. Speech recognition in quiet with the first, second and with both implants simultaneously was evaluated at the time of the second implantation and after 12 and 24 months. RESULTS: Mean bilateral speech recognition 12 and 24 months after the second implantation was significantly higher than that obtained with either the first or the second implant. The addition of a second implant was demonstrated to have a beneficial effect after both 12 and 24 months. Speech recognition with the second implant increased significantly during the first year. A small, non-significant improvement was observed during the second year. The inter-implant interval significantly influenced speech recognition with the second cochlear implant both at 12 and 24 months, and bilateral speech recognition at 12 months, but not at 24 months. CONCLUSIONS: A small, but statistically significant improvement in speech recognition was found with bilateral cochlear implants compared with a unilateral implant. A major increase in speech recognition occurred with the second cochlear implant during the first year. A shorter time interval between the two implantations resulted in better speech recognition with the second implant. However, no definitive time-point was found for when the second implant could no longer add a positive effect.