Phylogeography of a gypsum endemic plant across its entire distribution range in the western Mediterranean.

PREMISE: Gypsum soils in the Mediterranean Basin house large numbers of edaphic specialists that are adapted to stressful environments. The evolutionary history and standing genetic variation of these taxa have been influenced by the geological and paleoclimatic complexity of this area and the long-standing effect of human activities. However, little is known about the origin of Mediterranean gypsophiles and the factors affecting their genetic diversity and population structure. METHODS: Using phylogenetic and phylogeographic approaches based on microsatellites and sequence data from nuclear and chloroplast regions, we evaluated the divergence time, genetic diversity, and population structure of 27 different populations of the widespread Iberian gypsophile Lepidium subulatum throughout its entire geographic range. RESULTS: Lepidium subulatum diverged from its nearest relatives ~3 million years ago, and ITS and psbA/matK trees supported the monophyly of the species. These results suggest that both geological and climatic changes in the region around the Plio-Pleistocene promoted its origin, compared to other evolutionary processes. We found high genetic diversity in both nuclear and chloroplast markers, but a greater population structure in the chloroplast data. These results suggest that while seed dispersal is limited, pollen flow may be favored by the presence of numerous habitat patches that enhance the movement of pollinators. CONCLUSIONS: Despite being an edaphic endemic, L. subulatum possesses high genetic diversity probably related to its relatively old age and high population sizes across its range. Our study highlights the value of using different markers to fully understand the phylogeographic history of plant species.

Intratympanic infliximab is a safe and effective rescue therapy for refractory immune-mediated hearing loss.

PURPOSE: To determine the efficacy and safety of the intratympanic infiltration of infliximab at the hearing threshold of patients in follow-up for refractory immune-mediated hearing loss. METHODS: 17 patients were collected with relapses, despite maintenance treatment with oral azathioprine associated or not with oral prednisone at low doses (between 5 and 7.5 ml/day) or refractory relapses to previous intratympanic corticoid treatment being 19 affected ears infiltrated. We measured the hearing threshold by Pure-Tone Average (PTA) 500-3000 Hz, 125-8000 Hz and 250-8000 Hz in pre-infiltration (baseline) and follow-up 3 weeks post-infiltration with auditory threshold at frequencies 125-8000 Hz. RESULTS: The average age was 50.68 years (±15.23 years). After the administration of intratympanic infliximab, an improvement of the hearing threshold was showed in the Pure-Tone Average (PTA) calculated at 500-3000 Hz (p = 0.004), 125-8000 Hz (p = 0.001) and 250-8000 Hz (p = 0.006). An immediate improvement in low frequencies also was observed: 125, 250 and 500 Hz (p = 0.009, p = 0.002 and p < 0.001 respectively) also at 1000 Hz (p = 0.004) and a persistence of the effect at 3 months in the low frequencies: 125 Hz (p = 0.020), 250 Hz (p = 0.006) and 500 Hz (p = 0.002). CONCLUSIONS: Infliximab intratympanic infiltration improves the hearing threshold in patients with immune-mediated hearing loss. The effect of improving the hearing threshold is higher in low frequencies and persists within 3 months of the infiltration. The administration of intratympanic infliximab is an effective and safe technique.

Ethyl alcohol threshold test: a fast, reliable and affordable olfactory Assessment tool for COVID-19 patients.

OBJECTIVE: COVID-19 patients may present mild symptoms. The identification of paucisymptomatic patients is paramount in order to interrupt the transmission chain of the virus. Olfactory loss could be one of those early symptoms which might help in the diagnosis of COVID-19 patients. In this study, we aim to develop and validate a fast, inexpensive, reliable and easy-to-perform olfactory test for the screening of suspected COVID-19 patients. STUDY DESIGN: Phase I was a case-control study and Phase II a transversal descriptive study. SUBJECTS AND METHODS: Olfaction was assessed with the ethyl alcohol threshold test and symptoms with visual analogue scales. The study was designed in two phases: In Phase I, we compared confirmed COVID-19 patients and healthy controls. In Phase II, patients with suspected COVID-19 infection referred for testing were studied. RESULTS: 275 participants were included in Phase I, 135 in Phase II. The ROC curve showed an AUC of 0.749 in Phase I, 0.737 in Phase II. The cutoff value which offered the highest amount of correctly classified patients was ≥ 2 (10% alcohol) for all age intervals. The odds ratio was 8.19 in Phase I, 6.56 in Phase II with a 75% sensitivity. When cases report normal sense of smell (VAS < 4), it misdiagnoses 57.89% of patients detected by the alcohol threshold test. CONCLUSION: The olfactory loss assessed with the alcohol threshold test has shown high sensitivity and odds ratio in both patients with confirmed COVID-19 illness and participants with suspected SARS-CoV-2 infection.

A revision of the conductive hearing loss in Cranium 4 from the Middle Pleistocene site of Sima de los Huesos (Burgos, Spain).

Pathological conditions have been previously documented in the Middle Pleistocene Sima de los Huesos hominins from northern Spain, and several of these have clear behavioral implications. Within this fossil assemblage, Cranium 4 shows bilateral external auditory exostoses which have been preliminarily interpreted as causing a significant hearing loss in this individual. If confirmed, this would be the oldest recorded case of deafness in human history and could have important implications for the antiquity of this condition, as well as social interactions. To further investigate this case, the current study presents 3D reconstructions of the entire outer and middle ear, based on computed tomography scans of both temporal bones in Cranium 4. We established the degree of stenosis in both external auditory canals, showing that in both cases the degree of stenosis is less than 52% of the original cross-sectional area of each canal. Based on clinical studies in living humans, the buildup of wax due to the degree of stenosis in Cranium 4 is unlikely to have caused frequent external ear infections. In addition, we estimated the pattern of sound power transmission up to 5 kHz in both ears relying on a comprehensive model developed in the bioengineering literature and which has been applied previously to the Sima de los Huesos hominins. The model was modified to account for the peculiar shape of the pathological external ear canals in Cranium 4. The results show that this pathology had little to no influence on the sound power transmission in this individual. Thus, we conclude that the exostoses present in both ears of Cranium 4 did not significantly affect their hearing.

The child who lived: Down syndrome among Neanderthals?

Caregiving for disabled individuals among Neanderthals has been known for a long time, and there is a debate about the implications of this behavior. Some authors believe that caregiving took place between individuals able to reciprocate the favor, while others argue that caregiving was produced by a feeling of compassion related to other highly adaptive prosocial behaviors. The study of children with severe pathologies is particularly interesting, as children have a very limited possibility to reciprocate the assistance. We present the case of a Neanderthal child who suffered from a congenital pathology of the inner ear, probably debilitating, and associated with Down syndrome. This child would have required care for at least 6 years, likely necessitating other group members to assist the mother in childcare.

Genetic diagnosis of childhood sensorineural hearing loss.

INTRODUCTION: Congenital/early-onset sensorineural hearing loss (SNHL) is one of the most common hereditary disorders in our environment. There is increasing awareness of the importance of an etiologic diagnosis, and genetic testing with next-generation sequencing (NGS) has the highest diagnostic yield. Our study shows the genetic results obtained in a cohort of patients with bilateral congenital/early-onset SNHL. MATERIALS AND METHODS: We included 105 children with bilateral SNHL that received genetic testing between 2019 and 2022. Genetic tests were performed with whole exome sequencing, analyzing genes related to hearing loss (virtual panel with 244 genes). RESULTS: 48% (50/105) of patients were genetically diagnosed. We identified pathogenic and likely pathogenic variants in 26 different genes, and the most frequently mutated genes were GJB2, USH2A and STRC. 52% (26/50) of variants identified produced non-syndromic hearing loss, 40% (20/50) produced syndromic hearing loss, and the resting 8% (4/50) could produce both non-syndromic and syndromic hearing loss. CONCLUSIONS: Genetic testing plays a vital role in the etiologic diagnosis of bilateral SNHL. Our cohort shows that genetic testing with NGS has a high diagnostic yield and can provide useful information for the clinical workup of patients.

Diagnostic yield of genetic testing in adults with sensorineural hearing loss.

INTRODUCTION: The contribution of genetic causes to sensorineural hearing loss (SNHL) in adults is less clear than in children, and genetic diagnosis is still not standardized in adults. In this study we present the genetic results obtained in a cohort of adult patients with SNHL. MATERIALS AND METHODS: We included 63 adults with SNHL that received genetic testing between 2019 and 2022. Whole exome sequencing was performed and variants in genes related to hearing loss (virtual panel with 244 genes) were prioritised and analysed. RESULTS: 24% (15/63) of patients were genetically diagnosed: 87% (13/15) of patients had non-syndromic hearing loss and 13% (2/15) had syndromic hearing loss. We identified pathogenic and likely pathogenic variants in 11 different genes. CONCLUSIONS: Our results show that a significant proportion of adults with SNHL have a genetic origin, and that implementation of genetic testing improves diagnostic accuracy and allows personalized management of these patients.

Phylogenetic and phylogeographic evidence for a Pleistocene disjunction between Campanula jacobaea (Cape Verde Islands) and C. balfourii (Socotra).

Our understanding of processes that led to biogeographic disjunct patterns of plant lineages in Macaronesia, North Africa and Socotra remains poor. Here, we study a group of Campanula species distributed across these areas integrating morphological and reproductive traits with phylogenetic and phylogeographic data based on the obtention of sequences for 4 highly variable cpDNA regions and AFLP data. The phylogeny obtained shows a sister relationship between Campanula jacobaea (endemic to Cape Verde Islands) and C. balfourii (endemic to Socotra), thus revealing a striking disjunct pattern (8300 km). These species diverged around 1.0 Mya; AFLP and haplotype data suggest that no genetic interchange has occurred since then. Their closest taxon, C. hypocrateriformis, is endemic to SW Morocco. The archipelagos of Macaronesia and Socotra have probably acted as refugia for North-African species, leading to speciation through isolation. Although C. balfourii has a restricted distribution, its genetic variability suggests that its populations have suffered no bottlenecks. C. jacobaea is also genetically rich and its distribution across Cape Verde Islands seems to have been influenced by the NE-SW trade winds, which may also have favoured the admixture found among the populations of the three southern islands. Floral features of the morphologically hypervariable C. jacobaea were also measured to assess whether the taxon C. bravensis, described for some of the southeast populations of C. jacobaea, corresponds to a different evolutionary entity. We show that morphological variation in C. jacobaea does not correspond to any genetic or geographic group.

Genetic patterns of habitat fragmentation and past climate-change effects in the Mediterranean high-mountain plant Armeria caespitosa (Plumbaginaceae).

PREMISE OF THE STUDY: Mountain plants are among the species most vulnerable to global warming, because of their isolation, narrow geographic distribution, and limited geographic range shifts. Stochastic and selective processes can act on the genome, modulating genetic structure and diversity. Fragmentation and historical processes also have a great influence on current genetic patterns, but the spatial and temporal contexts of these processes are poorly known. We aimed to evaluate the microevolutionary processes that may have taken place in Mediterranean high-mountain plants in response to changing historical environmental conditions. METHODS: Genetic structure, diversity, and loci under selection were analyzed using AFLP markers in 17 populations distributed over the whole geographic range of Armeria caespitosa, an endemic plant that inhabits isolated mountains (Sierra de Guadarrama, Spain). Differences in altitude, geographic location, and climate conditions were considered in the analyses, because they may play an important role in selective and stochastic processes. KEY RESULTS: Bayesian clustering approaches identified nine genetic groups, although some discrepancies in assignment were found between alternative analyses. Spatially explicit analyses showed a weak relationship between genetic parameters and spatial or environmental distances. However, a large proportion of outlier loci were detected, and some outliers were related to environmental variables. CONCLUSIONS: A. caespitosa populations exhibit spatial patterns of genetic structure that cannot be explained by the isolation-by-distance model. Shifts along the altitude gradient in response to Pleistocene climatic oscillations and environmentally mediated selective forces might explain the resulting structure and genetic diversity values found.

Variability in the Results of Vestibular Assessment in Patients with Genetically Confirmed Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia Syndrome.

BACKGROUND: Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) presents an unpredictable and uneven clinical development of cerebellar ataxia, neuropathy, and vestibular areflexia. The aim of this study is to report the variability of vestibular test results in genetically confirmed patients with cerebellar ataxia, neuropathy, and vestibular areflexia syndrome. METHODS: Caloric testing, video head impulse test (vHIT), and rotatory chair testing were performed in 7 patients who presented pathogenic repeat expansions in the replication factor complex unit 1 gene related to cerebellar ataxia, neuropathy, and vestibular areflexia syndrome. RESULTS: Reduced vestibulo-ocular reflex (VOR) gain was observed in 100% of the patients in rotatory chair testing. Three of them had bilateral areflexia in caloric testing while 2 showed unilateral hypofunction and 2 had no alterations in the test. Only 1 patient had bilateral abnormal vHIT with gains under 0.6 in both ears. CONCLUSION: Genetic testing allows an early diagnosis of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome, whereby the vestibular system may be affected to different degrees. Rotatory chair testing has a higher sensitivity for the detection of vestibular hypofunction in these patients. Caloric testing can provide additional information. vHIT might underdiagnose patients with mild-to-moderate vestibulopathy.

Facilitated Adaptation as A Conservation Tool in the Present Climate Change Context: A Methodological Guide.

Climate change poses a novel threat to biodiversity that urgently requires the development of adequate conservation strategies. Living organisms respond to environmental change by migrating to locations where their ecological niche is preserved or by adapting to the new environment. While the first response has been used to develop, discuss and implement the strategy of assisted migration, facilitated adaptation is only beginning to be considered as a potential approach. Here, we present a review of the conceptual framework for facilitated adaptation, integrating advances and methodologies from different disciplines. Briefly, facilitated adaptation involves a population reinforcement that introduces beneficial alleles to enable the evolutionary adaptation of a focal population to pressing environmental conditions. To this purpose, we propose two methodological approaches. The first one (called pre-existing adaptation approach) is based on using pre-adapted genotypes existing in the focal population, in other populations, or even in closely related species. The second approach (called de novo adaptation approach) aims to generate new pre-adapted genotypes from the diversity present in the species through artificial selection. For each approach, we present a stage-by-stage procedure, with some techniques that can be used for its implementation. The associated risks and difficulties of each approach are also discussed.

Population origin determines the adaptive potential for the advancement of flowering onset in Lupinus angustifolius L. (Fabaceae).

In the present framework of global warming, it is unclear whether evolutionary adaptation can happen quick enough to preserve the persistence of many species. Specifically, we lack knowledge about the adaptive potential of the different populations in relation to the various constraints that may hamper particular adaptations. There is evidence indicating that early flowering often provides an adaptive advantage to plants in temperate zones in response to global warming. Thus, the objective of this study was to assess the adaptive potential for advancing flowering onset in Lupinus angustifolius L. (Fabaceae). Seeds from four populations from two contrasting latitudes in Spain were collected and sown in a common garden environment. Selecting the 25% of the individuals that flowered earlier in the first generation, over three generations, three different early flowering selection lines were established, involving both self-crosses and outcrosses. All artificial selection lines advanced their flowering significantly with respect to the control line in the northernmost populations, but not in the southern ones. Selection lines obtained from outcrossing had a greater advancement in flowering than those from self-crossing. No differences were found in the number or weight of the seeds produced between control and artificial selection lines, probably because plants in the common garden were drip irrigated. These results suggest that northern populations may have a greater adaptive potential and that southern populations may be more vulnerable in the context of climate warming. However, earlier flowering was also associated with changes in other traits (height, biomass, shoot growth, specific leaflet area, and leaflet dry matter content), and the effects of these changes varied greatly depending on the latitude of the population and selection line. Assessments of the ability of populations to cope with climate change through this and other approaches are essential to manage species and populations in a more efficient way.

Unravelling genetics at the top: mountain islands or isolated belts?

BACKGROUND AND AIMS: In mountain plant populations, local adaptation has been described as one of the main responses to climate warming, allowing plants to persist under stressful conditions. This is especially the case for marginal populations at their lowest elevation, as they are highly vulnerable. Adequate levels of genetic diversity are required for selection to take place, while high levels of altitudinal gene flow are seen as a major limiting factor potentially precluding local adaptation processes. Thus, a compromise between genetic diversity and gene flow seems necessary to guarantee persistence under oncoming conditions. It is therefore critical to determine if gene flow occurs preferentially between mountains at similar altitudinal belts, promoting local adaptation at the lowest populations, or conversely along altitude within each mountain. METHODS: Microsatellite markers were used to unravel genetic diversity and population structure, inbreeding and gene flow of populations at two nearby altitudinal gradients of Silene ciliata, a Mediterranean high-mountain cushion plant. KEY RESULTS: Genetic diversity and inbreeding coefficients were similar in all populations. Substantial gene flow was found both along altitudinal gradients and horizontally within each elevation belt, although greater values were obtained along altitudinal gradients. Gene flow may be responsible for the homogeneous levels of genetic diversity found among populations. Bayesian cluster analyses also suggested that shifts along altitudinal gradients are the most plausible scenario. CONCLUSIONS: Past population shifts associated with glaciations and interglacial periods in temperate mountains may partially explain current distributions of genetic diversity and population structure. In spite of the predominance of gene flow along the altitudinal gradients, local genetic differentiation of one of the lower populations together with the detection of one outlier locus might support the existence of different selection forces at low altitudes.

Isolation and characterization of 10 microsatellite loci in Cneorum tricoccon (Cneoraceae), a Mediterranean relict plant.

PREMISE OF THE STUDY: The main aim of this study was to isolate and characterize microsatellite loci in Cneorum tricoccon (Cneoraceae), a Mediterranean shrub relict of the early Tertiary, which inhabits western Mediterranean islands and coasts. Microsatellites will be useful for investigating biogeography and landscape genetics across the species distribution range, including current or past gene flow. METHODS AND RESULTS: Seventeen microsatellite loci were characterized, of which 10 were polymorphic and amplified for a total of 56 alleles in three populations of C. tricoccon. The markers revealed average coefficients of expected heterozygosity (H(e) = 0.425), observed heterozygosity (H(o) = 0.282), and inbreeding coefficient value per population (F(IS) = 0.408). CONCLUSIONS: These microsatellite primers will potentially be useful in the study of population and landscape genetics, conservation status of isolated populations, island-continental distribution, current or historical movements between populations, and in the investigation of the consequences of dispersal mechanisms of these plants.

Characterization of microsatellites in the mountain plant Armeria caespitosa (Plumbaginaceae) and transferability to congeners.

PREMISE OF THE STUDY: The focus of this study is to develop microsatellite markers in Armeria caespitosa, a narrow endemic of central Spain. Microsatellite loci are sought to clarify population structure and estimate gene flux among populations. METHODS AND RESULTS: Enriched microsatellite genomic libraries were used for microsatellite isolation. Sixteen microsatellite loci were characterized, eight of which can be used for successful genotyping. Allele number ranged from two to seven per locus. Observed and expected heterozygosity ranged from 0.300 to 0.800 and from 0.296 to 0.733, respectively. Cross-amplification of seven and six loci was successful for A. maritima and A. cantabrica, respectively. CONCLUSIONS: These microsatellites are suitable in the study of population genetics and gene flow among A. caespitosa populations. The information provided by these markers may be useful in the study of this plant's response to global warming.

Endoscopic endonasal approach to pituitary adenomas: Impact on adenohypophyseal function. Study of 231 cases.

PURPOSE: To identify presurgical and surgical factors associated with the development of hypopituitarism and its recovery after endoscopic endonasal transsphenoidal (EET) resection of pituitary adenomas (PAs). METHODS: Retrospective study of patients with PAs operated by the same neurosurgeon through an EET approach in two Spanish tertiary hospitals in ten years. RESULTS: 242 pituitary surgeries performed in 231 patients were analyzed. In the 154 surgeries performed in 146 patients with non-functioning PAs (NFPAs), 46.8% (n=72) presented presurgical hypopituitarism. After PAs resection, 41 of these (56.9%) normalized pituitary function and 11 of 82 patients with preoperative normal function (13.4%) developed new pituitary deficits. Patients with preoperative visual impairment (OR=3.9, p=0.046) and operated in the first four years of the neurosurgeon's learning curve (OR=5.7, p=0.016) presented a higher risk of developing postoperative hypopituitarism. Of the 88 surgeries in 85 patients with functioning PAs (FPAs), 23.9% presented presurgical hypopituitarism, and 47.6% of those recovered after surgery. 9% of the cases with preoperative normal function developed new pituitary deficit/s. Diabetic patients presented a higher risk of persistence of hypopituitarism (OR=10.5, p=0.024). Patients with presurgical visual impairment (OR=30.0, p=0.010) and PAs>3cm (OR=14.0, p=0.027) had higher risk of developing new pituitary deficits. CONCLUSION: Approximately 50% of patients with PAs and preoperative hypopituitarism recover pituitary function after EET surgery. 10% of patients with normal function develop new deficits. Patients with NFPAs with visual involvement and operated in the first four years of neurosurgeon's learning curve, and FPAs patients with presurgical visual impairment and tumor size>3cm have a higher risk of postoperative hypopituitarism.

Limited effect of a highway barrier on the genetic structure of a gypsum soil specialist.

BACKGROUND: Gypsum ecosystems are edaphic islands surrounded by a matrix that is inhospitable to gypsum soil plant specialists. These naturally fragmented landscapes are currently exacerbated due to man-made disturbances, jeopardising their valuable biodiversity. Concomitant action of other fragmentation drivers such as linear infrastructures may increase the already high threat to these specialists. Although some evidence suggest that gypsophytes are not evolutionary dead-ends and can respond to fragmentation by means of phenotypic plasticity, the simultaneous action of barriers to genetic flow can pose a severe hazard to their viability. Here, we evaluated the effect of a highway with heavy traffic on the genetic flow and diversity in the species Lepidium subulatum, a dominant Iberian shrubby gypsophyte. METHODS: We tested the possible existence of bottlenecks, and estimated the genetic diversity, gene flow and genetic structure in the remnant populations, exploring in detail the effect of a highway as a possible barrier. RESULTS: Results showed variability in genetic diversity, migrants and structure. The highway had a low impact on the species since populations can retain high levels of genetic diversity and genetic parameter, like F ST and F IS, did not seem to be affected. The presence of some level of genetic flow in both sides along the highway could explain the relatively high genetic diversity in the habitat remnants. DISCUSSION: Natural fragmentation and their exacerbation by agriculture and linear infrastructures seem to be negligible for this species and do not limit its viability. The biological features, demographic dynamics and population structures of gypsum species seem to be a valuable, adaptive pre-requisite to be a soil specialist and to maintain its competitiveness with other species in such adverse stressful conditions.

Sellar Diaphragm Reconstruction with Tachosil During Endoscopic Endonasal Surgery: Technical Note.

This report introduces a new closure technique for the management of intraoperative cerebrospinal fluid (CSF) leakage during endoscopic endonasal surgery. The procedure is based on the combination of a traditional autologous tissue flap with a heterologous fibrin graft (TachoSil). We performed a retrospective analysis on 121 patients with pituitary adenomas treated in our center by the senior neurosurgeon (author V.R.B) in the previous 4 years. Only one patient (0.8%) developed a CSF leakage and no adverse events were found related to the use of TachoSil. Compared with other techniques used previously, sellar diaphragm reconstruction with TachoSil seems to be an effective and inexpensive alternative.

Herbivore corridors sustain genetic footprint in plant populations: a case for Spanish drove roads.

Habitat fragmentation is one of the greatest threats to biodiversity conservation and ecosystem productivity mediated by direct human impact. Its consequences include genetic depauperation, comprising phenomena such as inbreeding depression or reduction in genetic diversity. While the capacity of wild and domestic herbivores to sustain long-distance seed dispersal has been proven, the impact of herbivore corridors in plant population genetics remains to be observed. We conducted this study in the Conquense Drove Road in Spain, where sustained use by livestock over centuries has involved transhumant herds passing twice a year en route to winter and summer pastures. We compared genetic diversity and inbreeding coefficients of Plantago lagopus populations along the drove road with populations in the surrounding agricultural matrix, at varying distances from human settlements. We observed significant differences in coefficients of inbreeding between the drove road and the agricultural matrix, as well as significant trends indicative of higher genetic diversity and population nestedness around human settlements. Trends for higher genetic diversity along drove roads may be present, although they were only marginally significant due to the available sample size. Our results illustrate a functional landscape with human settlements as dispersal hotspots, while the findings along the drove road confirm its role as a pollinator reservoir observed in other studies. Drove roads may possibly also function as linear structures that facilitate long-distance dispersal across the agricultural matrix, while local P. lagopus populations depend rather on short-distance seed dispersal. These results highlight the role of herbivore corridors for conserving the migration capacity of plants, and contribute towards understanding the role of seed dispersal and the spread of invasive species related to human activities.

Azathioprine reduces the risk of audiometric relapse in immune-mediated hearing loss. / La azatioprina reduce el riesgo de recaída audiométrica en hipoacusia inmunomediada.

INTRODUCTION: Current schemes for treatment of immune-mediated hearing loss with sporadic short-course, low-dose corticosteroids, are insufficient. METHODS: To determine the role of azathioprine in the control of auditory impairment, a longitudinal, observational, descriptive study was performed with 20 patients treated with azathioprine (1.5-2.5mg/kg/day into two doses) for 1year. The loss of 10dB on two consecutive frequencies or 15dB on an isolated frequency was considered as relapse. RESULTS: The mean age of the patients was 52.50years (95%CI: 46.91-58.17), half were women. Bilateral affectation was 65%. 75% had organ specific disease and 25% had systemic autoimmune disease. The difference between baseline PTA (46.49dB; DS18.90) and PTA at 12months (45.47dB; DS18.88) did not reach statistical significance (P=.799). There was a moderate positive correlation between female sex and the presence of systemic disease (R=.577). By applying Student's t for paired data, a significant difference (P=.042) was obtained between the PTA in frequencies up to 1000 Hz (PTA125-1000Hz). The relative incidence rate of relapse per year was .52 relapses/year (95%CI: .19-1.14]). The median time to audiometric relapse-free was 9.70months (DS1.03). CONCLUSIONS: Azathioprine maintains the hearing threshold, decreases the risk of relapse, and slows down the rate at which patients relapse, altering the course of immune-mediated inner ear disease.