An atlas of cells in the human tonsil.

Palatine tonsils are secondary lymphoid organs (SLOs) representing the first line of immunological defense against inhaled or ingested pathogens. We generated an atlas of the human tonsil composed of >556,000 cells profiled across five different data modalities, including single-cell transcriptome, epigenome, proteome, and immune repertoire sequencing, as well as spatial transcriptomics. This census identified 121 cell types and states, defined developmental trajectories, and enabled an understanding of the functional units of the tonsil. Exemplarily, we stratified myeloid slan-like subtypes, established a BCL6 enhancer as locally active in follicle-associated T and B cells, and identified SIX5 as putative transcriptional regulator of plasma cell maturation. Analyses of a validation cohort confirmed the presence, annotation, and markers of tonsillar cell types and provided evidence of age-related compositional shifts. We demonstrate the value of this resource by annotating cells from B cell-derived mantle cell lymphomas, linking transcriptional heterogeneity to normal B cell differentiation states of the human tonsil.

Clinical profile, otologic, and auditory outcomes in patients with Down syndrome.

INTRODUCTION AND OBJECTIVES: Even though the incidence has decreased in recent years, Down syndrome (DS) remains the most common chromosomal disorder today. Despite being a condition with multisystemic involvement, it often tends to affect the head and neck area, making it a frequent reason for consultation with pediatric otolaryngologists or otologists. The purpose of this work is to be one of the first in Spain to characterize and describe the pathology and therapeutic approach typically provided to these patients, analyzing the evolution from a clinical and auditory perspective. MATERIAL AND METHODS: We aim to analyze a sample of 16 pediatric patients recruited over the past 24 years, diagnosed with Down syndrome, and experiencing a wide range of diseases affecting the ear and its auditory function. RESULTS: 62.50% of the patients were women, whose main reason for seeking specialist care was acute and serous otitis media, accounting for 31.25%. These patients have an indication for treatment for various entities within the otological sphere that usually do not differ from those of a healthy child. However, the evolution and response to treatments can take on a torpid character due to the anatomical characteristics of the ears of these patients. CONCLUSIONS: Although the frequency of children with DS in the pediatric otolaryngologist's clinic is decreasing, these patients have a predisposition to ear diseases with auditory repercussions, with variable evolution depending on the disease and the child's intrinsic characteristics.

Promontorial cochleostomy in nonhuman primates. Is it atraumatic?

The purpose of this study is to determine if surgical approach to the inner ear is feasible without generating a hearing loss in an animal model. Five Macaca fascicularis were used as experimental animals and followed up for 27 months. Mastoidectomy, posterior tympanotomy and promontorial cochleostomy were performed on four specimens and one specimen was kept as control animal. Before and after drilling and exposing the endosteal layer and the membranous labyrinth, otoacustic emissions (dPOAE) and auditory brainstem responses (ABR) were used to test hearing. In vivo experimental studies prove it is reliable to expose the membranous labyrinth without causing hearing loss. dPOAE were present after 3, 6, 12, 24 and 26 months of follow-up. Regarding the ABR results from the four M. fascicularis in which a cochleostomy has been carried out, auditory thresholds are within the 20-30 dB interval at 27 months of follow-up. Experimental studies support clinical experiences indicating it is feasible to surgically approach the membranous labyrinth of the cochlea without damaging its hearing function.

Effects of cochlear nuclei electrical stimulation with surface brain stem implants in nonhuman primates.

OBJECTIVES: We undertook morphological evaluation of the cochlear nucleus complex (CNC) after implantation of a surface auditory brain stem implant (ABI). METHODS: We used 14 nonhuman primates (Macaca fascicularis). They underwent translabyrinthine bilateral auditory deafferentation and simultaneous unilateral implantation of an ABI. In 6 cases the ABI was not activated, whereas it was activated in 8 cases. The ABI array consisted of 3 platinum disc electrodes mounted on a silicone pad with the back side covered with polyethylene terephthalate mesh, connected via a cable to an external stimulator in animals undergoing electrical stimulations. RESULTS: All animals tolerated the procedures well. In both groups of animals, neuropathologic lesions or changes attributed to surgical trauma were found. The biotolerance of neural tissue to the materials used was adequate. The stimulation times ranged from 0 to 732 hours. Neuropathologic examination and stereological assessment revealed that the animals showed no signs of significant neural damage after CNC chronic stimulation if this took place within the safety limits. Time of stimulation did not seem to play a significant role in changes. CONCLUSIONS: Besides surgical trauma, the most important factors responsible for CNC changes are the electrical stimulation parameters.

Atraumatic surgical approach to the cochlea with a micromanipulator.

CONCLUSIONS: Our design and preliminary results show that the the micromanipulator could be a great help to the surgeon in the atraumatic surgical approach to the lateral wall of the cochlea at the promontory. OBJECTIVES: Hearing preservation in cochlear implant opens new frontiers in the treatment of sensorineural hearing loss. To preserve the membranous labyrinth intact, new surgical tools are needed, either for cochlear implantation or for other applications. The objectives of this study were to design and test a micromanipulator coupled to a drilling tool for the atraumatic exposure of the spiral ligament. The micromanipulator is designed to increase precision when drilling the otic capsule bone. MATERIALS AND METHODS: A group from the University of Navarra worked on the device design -- based on a compliant mechanism -- and in vitro test. The components and functioning of the micromanipulator are described. It was tested in 10 formalinized temporal bones after a mastoidectomy, a posterior tympanotomy, and a transcanal tympanotomy were performed. The micromanipulator was placed over the cranial surface, and used to expose the endostium, anteriorly to the round window niche. RESULTS: A combined approach through the external auditory canal was feasible, together with a posterior tympanotomy to visually control the work and make complementary manoeuvres. Drilling was easy, and visual control through the posterior tympanotomy was excellent. A high degree of drilling precision was achieved. A little disruption of the membranous labyrinth was found only in the first bone of the series.

Advantages of cochlear implantation in prelingual deaf children before 2 years of age when compared with later implantation.

OBJECTIVES: To compare the auditory abilities and speech performance of children with a profound prelingual bilateral hearing-impairment when subjected to a cochlear implant (CI) before or after 2 years of age. To analyze the complications that arose during, or as a result of, the implantation process in these groups. DESIGN: Prospective cohort single-subject, repeated-measures study of children with profound bilateral hearing impairment subjected to CI. SETTING: Tertiary referral center with a program of pediatric CI from 1991. PATIENTS: This study analyzed 130 children subjected to multichannel CI for profound prelingual bilateral hearing-impairment in two age groups: 0 to 2 (n = 36) and 2 to 6 years of age (n = 94). INTERVENTIONS: The children were evaluated before, and each year after, the intervention (for up to 5 years) with both closed-set and open-set auditory and speech perception tests. Their speech ability was evaluated according to the Peabody Picture Vocabulary and Reynell general oral expression scales. RESULTS: Auditory and speech perception tests improved significantly in all children after CI, regardless of the follow-up time. The infant's performance was better the earlier the implant was performed. Speech tests showed that the development of children treated before 2 years of age was similar to normal children, and no additional complications were observed when compared with CI in older children. CONCLUSIONS: When performed before 2 years of age, CI offers a quicker and better improvement of performance without augmenting the complications associated with such an intervention.

Morphometry of the human cochlear wall and implications for cochlear surgery.

OBJECTIVE: To study the lateral wall of the cochlea in human temporal bones (TBs), in order to evaluate the feasibility of performing micro-dissection of the spiral ligament and an endosteal electrode implantation. MATERIAL AND METHODS: We reviewed the database of the TB bank of The House Ear Institute in search of bones that did not distort the otic capsule or spiral ligament, and selected 36 horizontally sectioned TBs. All bones had been removed using the en bloc technique, fixed in formalin, decalcified in EDTA, embedded in celloidin and cut into 20-pm serial sections. We evaluated sections stained with hematoxylin-eosin under a microscope, and made several measurements of the lateral wall of the cochlea using optical appliances. A total of 20 measurements were made at 3 levels: midmodiolar sections; sections at the round window niche; and sections containing the anterior border of the stapes footplate. RESULTS: The selected sections provide useful data when applied during surgery. All the numerical data were analyzed statistically and, although individual variability occurred, most of the measurements seemed to be quite homogeneous. CONCLUSIONS: A greater understanding of the microscopic anatomy and dimensions of the human TB will help to understand the surgical relationships at the lateral wall of the cochlea. Our study provides some numerical references for the dimensions of the cochlea that may help in cochlear surgery. These dimensions would be of particular interest in cochlear implantation, especially in the design of endosteal electrodes.

Otopalatodigital syndrome type I: New temporal bone CT-scan sign in a case with a de novo novel mutation / Síndrome otopalatodigital de tipo I: Nuevo signo de TC en una paciente con mutación de novo no descrita

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A model for auditory brain stem implants: bilateral surgical deafferentation of the cochlear nuclei in the macaque monkey.

BACKGROUND: Patients with extensive bilateral lesions of the auditory nerve have a profound and irreversible sensorineural hearing loss (SNHL), which can only be overcome with individually-fitted auditory brain stem implants that directly stimulate the cochlear nuclei. Despite the enormous potential of this increasingly applied treatment, the auditory performance of many implanted patients is limited, and the variability between cases hinders a complete understanding of the role played by the multiple parameters related to the efficacy of the implant. OBJECTIVES: To mimic the condition of patients who have bilateral lesions of the auditory nerve, we developed an experimental model of bilateral deafferentation of the cochlear nuclei by surgical transection of the cochlear nerves of adult primates. MATERIALS AND METHODS: We performed bilateral transection of the cochlear nerves of six adult, healthy, male captive-bred macaques (Macaca fascicularis). Before surgery, brain stem auditory evoked potentials were recorded. The histological material obtained from these animals was compared with similarly processed sections from seven macaques with intact cochlear nerves. The surgical technique, similar to that used in human neuro-otology, combined a labyrinthectomy and a neurectomy of the cochlear nerves, and caused deafness. We analyzed immunocytochemically the expression in cochlear nerve fibers of neurofilaments (SMI-32), and cytosolic calcium binding proteins calretinin, parvalbumin and calbindin, and also applied a histochemical reaction for acetylcholinesterase. RESULTS: None of the primates had any major complications due to the surgical procedure. The lesions produced massive anterograde degeneration of the cochlear nerves, evidenced by marked gliosis and by loss of both type I fibers (which in this species are immunoreactive for calretinin, parvalbumin and neurofilaments) and type II fibers (which are acetylcholinesterase positive). The model of surgical transection described herein causes extensive damage to the cochlear nerves while leaving the cochlea intact, thus mimicking the condition of patients with profound SNHL due to bilateral cochlear nerve degeneration. CONCLUSIONS: The phylogenetic proximity of primates to humans, and the paramount advantage of close anatomical and physiological similarities, allowed us to use the same surgical technique applied to human patients, and to perform a thorough evaluation of the consequences of neurectomy. Thus, bilateral surgical deafferentation of the macaque cochlear nuclei may constitute an advantageous model for study of auditory brain stem implants.

Prospective long-term auditory results of cochlear implantation in prelinguistically deafened children: the importance of early implantation.

The objectives of this study were to report the long-term auditory results of prelinguistically deafened children with bilateral profound hearing impairment treated with a cochlear implant (CI); to analyze the role of auditory stimulation in the development of communicating abilities in early implanted children; and to define the limits of the auditory critical period. It was designed as a prospective cohort single-subject repeated-measures study of children with bilateral profound hearing impairment treated with a CI at a tertiary referral center with a pediatric CI program since 1991. A total of 182 children with bilateral prelinguistic hearing impairment of profound degree treated with a Nucleus CI were enrolled in the study. Eighty-six children received a Nucleus 22 CI and 74 received a Nucleus 24. For data analyses the children were categorized by ages: 0-3 years of age (n = 94); 4-6 years (n = 36); 7-10 years (n = 30); 11-14 years (n = 22). The children were evaluated with a protocol that included tests of audition and speech perception, with closed-set (Vowel Confusion test, Series of Daily Words) and open-set tests (e.g. bisyllables, CID Sentences, CID Sentences adapted for children). Pure-tone averages significantly improved for all children in all groups with the CI compared with preoperative values. Nevertheless, only children implanted before the age of 6 years developed a high ability for recognition of bisyllables and sentences in an open-set. Results show that the earlier the implantation is undertaken, the better the performance outcome. Children implanted outside of the auditory critical period demonstrated significantly poorer performance, suggesting the occurrence of irreversible changes in the central auditory system. In conclusion, eligible children should receive a CI as soon as bilateral profound hearing impairment is diagnosed. This usually permits them to achieve high-performance levels on speech and language measures and potentially integration into an oral communication environment.