Brigatinib in NF2-Related Schwannomatosis with Progressive Tumors.

BACKGROUND: NF2-related schwannomatosis (NF2-SWN, formerly called neurofibromatosis type 2) is a tumor predisposition syndrome that is manifested by multiple vestibular schwannomas, nonvestibular schwannomas, meningiomas, and ependymomas. The condition is relentlessly progressive with no approved therapies. On the basis of preclinical activity of brigatinib (an inhibitor of multiple tyrosine kinases) in NF2-driven nonvestibular schwannoma and meningioma, data were needed on the use of brigatinib in patients with multiple types of progressive NF2-SWN tumors. METHODS: In this phase 2 platform trial with a basket design, patients who were 12 years of age or older with NF2-SWN and progressive tumors were treated with oral brigatinib at a dose of 180 mg daily. A central review committee evaluated one target tumor and up to five nontarget tumors in each patient. The primary outcome was radiographic response in target tumors. Key secondary outcomes were safety, response rate in all tumors, hearing response, and patient-reported outcomes. RESULTS: A total of 40 patients (median age, 26 years) with progressive target tumors (10 vestibular schwannomas, 8 nonvestibular schwannomas, 20 meningiomas, and 2 ependymomas) received treatment with brigatinib. After a median follow-up of 10.4 months, the percentage of tumors with a radiographic response was 10% (95% confidence interval [CI], 3 to 24) for target tumors and 23% (95% CI, 16 to 30) for all tumors; meningiomas and nonvestibular schwannomas had the greatest benefit. Annualized growth rates decreased for all tumor types during treatment. Hearing improvement occurred in 35% (95% CI, 20 to 53) of eligible ears. Exploratory analyses suggested a decrease in self-reported pain severity during treatment (-0.013 units per month; 95% CI, -0.002 to -0.029) on a scale from 0 (no pain) to 3 (severe pain). No grade 4 or 5 treatment-related adverse events were reported. CONCLUSIONS: Brigatinib treatment resulted in radiographic responses in multiple tumor types and clinical benefit in a heavily pretreated cohort of patients with NF2-SWN. (Funded by the Children's Tumor Foundation and others; INTUITT-NF2 ClinicalTrials.gov number, NCT04374305.).

Evolução e desfecho de casos de violência intrafamiliar contra crianças e adolescentes: enfoque fonoaudiológico / Evolution and outcome of cases of intrafamily violence against children and adolescents: Speech, Language Pathology and Audiology approach / Evolución y desenlace de los casos de violencia intrafamiliar contra niños y adolescentes: enfoque de logopedia

Objetivo: investigar as alterações fonoaudiológicas encontradas em casos de violência intrafamiliar contra crianças e adolescentes, bem como analisar a evolução e o desfecho dos casos atendidos por fonoaudiólogos. Método: Estudo transversal, produzido por meio da aplicação de questionários com fonoaudiólogos clínicos que atendiam a crianças e adolescentes nos estados do Paraná e Santa Catarina. A exploração dos dados foi pautada na metodologia de Análise do Conteúdo (AC). Resultados: Dos 75 fonoaudiólogos pesquisados, 52% atenderam a crianças e/ou adolescentes suspeitos ou confirmados de sofrerem violência. Deste número, 59,5% dos profissionais continuaram acompanhado os casos e 40,5% descontinuaram o acompanhamento. Conclusão: As alterações na linguagem foi a queixa fonoaudiológica mais encontrada nas vítimas. Em muitos casos não foi possível obter informações sobre o desfecho da situação de violência, devido ao abandono do trabalho fonoaudiológico. Nas situações com desfechos favoráveis, este acontecimento ocorreu devido à remoção do agressor do contexto familiar, o acompanhamento de todos os envolvidos ou o encaminhamento da vítima para tratamentos interdisciplinares. Com relação ao desenrolar da queixa fonoaudiológica, os casos que tiveram evolução, foram os acompanhados de maneira interdisciplinar, principalmente com tratamento psicólogo dos envolvidos. Pode-se notar, também, que os profissionais que relacionaram a queixa fonoaudiológica com a situação de violência atuaram de forma mais humanizada, olhando o sujeito como um todo, permitindo o seu progresso terapêutico. (AU)

Purpose: This study aimed to investigate the speech-language disorders found in cases of domestic violence against children and adolescents and to analyze the evolution and outcome of cases assisted by Speech, Language Pathology and Audiology professionals. Methods: Cross-sectional study, produced through the application of questionnaires to clinical Speech, Language Pathology and Audiology professionals who assisted children and adolescents in the states of Paraná and Santa Catarina. Data exploration was based on the Content Analysis methodology. Results: Of the 75 Speech, Language Pathology and Audiology professionals surveyed, 52% assisted children and/or adolescents suspected or confirmed to be victims of violence. Regarding this number, 59.5% of the professionals continued to monitor the cases, and 40.5% discontinued the follow-up. Conclusion: Language changes comprised the speech-language pathology complaint most found in the victims. In many cases, it was not possible to obtain information about the outcome of the situation of violence due to the abandonment of Speech, Language Pathology and Audiology work. In situations with favorable outcomes, this event occurred due to the removal of the aggressor from the family context, the monitoring of all those involved, or the referral of the victim to interdisciplinary treatments. Regarding the development of the speech-language pathology complaint, the cases that evolved were followed up in an interdisciplinary manner, mainly with psychological treatment for those involved. Professionals who related the speech-language pathology complaint to the situation of violence acted more humanely, looking at the subjects as a whole and allowing their therapeutic progress. (AU)

Propósito: investigar los trastornos del habla y el lenguaje encontrados en casos de violencia doméstica contra niños y adolescentes, así como analizar la evolución y el rechazo de dos casos tratados por logopedas. Método: Estudio transversal, producido a través de la aplicación de cuestionarios con logopedas clínicos que atendían a niños y adolescentes en los estados de Paraná y Santa Catarina. La exploración de datos se basó en la metodología de Análisis de Contenido (CA). Resultados: De los 75 fonoaudiólogos encuestados, el 52% asiste a niños y/o adolescentes sospechosos o confirmados de ser víctimas de violencia. De ese número, 59,5% de los profesionales continuaron con el acompañamiento de los casos y 40,5% interrumpieron el seguimiento. Conclusión: Los cambios en el lenguaje fueron la queja de patología del habla y lenguaje más frecuente en las víctimas. En muchos casos no fue posible obtener información sobre el desenlace de la situación de violencia, debido al abandono del trabajo logopédico. En situaciones con resultados favorables, este evento se produjo por la separación del agresor del contexto familiar, el seguimiento de todos los implicados o la derivación de la víctima a tratamientos interdisciplinarios. En cuanto a la evolución del cuadro patológico del habla-lenguaje, los casos que evolucionaron fueron seguidos de manera interdisciplinaria, principalmente con tratamiento psicológico para los involucrados. También se puede notar que los profesionales que relacionaron la denuncia de fonoaudiología con la situación de violencia actuaron de forma más humana, mirando al sujeto como un todo, permitiendo su progreso terapéutico.(AU)

Occupational and environmental noise exposure during pregnancy and rare health outcomes of offspring: a scoping review focusing on congenital anomalies and perinatal mortality.

As environmental and occupational noise can be health hazards, recent studies have investigated the effects of noise exposure during pregnancy. Despite biological plausibility and animal studies supporting an association, studies focusing on congenital anomalies and perinatal mortality as outcomes of noise exposure are still scarce. We performed a scoping review to collect, summarise, and discuss the existing scientific research about the relationships between noise exposure during pregnancy and congenital anomalies and/or perinatal mortality. We searched electronic databases for papers published between 1970 and March 2021. We included 16 studies (seven on congenital anomalies, three on perinatal mortality, and two on both congenital anomalies and perinatal mortality). We assessed four studies on congenital hearing dysfunction as the definition of congenital anomalies includes functional anomalies. We found few studies on this topic and no studies on the combined effects of occupational and environmental noise exposures. Evidence suggests a small increase in the risk of congenital anomalies in relation to occupational and to a lesser extent environmental noise exposure. In addition, few studies investigated perinatal mortality and the ones that did, used different outcome definitions, so no conclusions could be made. However, a recent big cross-sectional study demonstrated an association between road traffic noise and stillbirth. A few studies suggest a possible association between congenital hearing dysfunction and occupational noise exposure during pregnancy. Future studies with larger samples, better exposure assessments, and better statistical modelling strategies are needed to investigate these relationships further.

Experimental Pain and Auditory Sensitivity in Overactive Bladder Syndrome: A Symptoms of the Lower Urinary Tract Dysfunction Research Network (LURN) Study.

PURPOSE: The objective of this study was to investigate the presence of nonbladder sensory abnormalities in participants with overactive bladder syndrome (OAB). MATERIALS AND METHODS: Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) study participants with OAB symptoms and controls were recruited from 6 U.S. tertiary referral centers. Quantitative sensory testing (QST) was performed to determine pressure pain sensitivity at the thumbnail bed and auditory sensitivity. Fixed and mixed effect multivariable linear regressions and Weibull models were used to compare QST responses between groups. Pearson correlations were used to assess the relationship between QST measures. Associations between QST and self-reported symptoms were explored with linear regression. RESULTS: A total of 297 participants were analyzed (191 OAB, 106 controls; 76% white, 51% male). OAB cases were older than controls (57.4 vs 52.2 years, p=0.015). No significant differences in experimental thumbnail (nonbladder) pain or auditory sensitivity were detected between OAB cases and controls. Correlations between pressure and auditory derived metrics were weak to moderate overall for both groups, with some significantly stronger correlations for cases. Exploratory analyses indicated increased pressure pain and auditory sensitivity were modestly associated with greater self-reported bladder pain and pain interference with physical function. CONCLUSIONS: As a group, no significant differences between OAB cases and controls were observed in experimental nonbladder pain or auditory sensitivity during QST. Associations between QST outcomes and clinical pain raise the possibility of centrally mediated sensory amplification in some individuals with OAB.

Auditory Dysfunction Among Individuals With Neurofibromatosis Type 1.

Importance: Neurofibromatosis type 1 (NF1) affects hearing through disruption of central auditory processing. The mechanisms, functional severity, and management implications are unclear. Objective: To investigate auditory neural dysfunction and its perceptual consequences in individuals with NF1. Design, Setting, and Participants: This case-control study included children and adults with NF1 and control participants matched on age, sex, and hearing level. Patients were recruited through specialist neurofibromatosis and neurogenetic outpatient clinics between April and September 2019. An evaluation of auditory neural activity, monaural/binaural processing, and functional hearing was conducted. Diffusion-weighted magnetic resonance imaging (MRI) data were collected from a subset of participants (10 children with NF1 and 10 matched control participants) and evaluated using a fixel-based analysis of apparent fiber density. Main Outcomes and Measures: Type and severity of auditory dysfunction evaluated via laboratory testing and questionnaire data. Results: A total of 44 participants (18 [41%] female individuals) with NF1 with a mean (SD) age of 16.9 (10.7) years and 44 control participants (18 [41%] female individuals) with a mean (SD) age of 17.2 (10.2) years were included in the study. Overall, 11 participants (25%) with NF1 presented with evidence of auditory neural dysfunction, including absent, delayed, or low amplitude electrophysiological responses from the auditory nerve and/or brainstem, compared with 1 participant (2%) in the control group (odds ratio [OR], 13.03; 95% CI, 1.59-106.95). Furthermore, 14 participants (32%) with NF1 showed clinically abnormal speech perception in background noise compared with 1 participant (2%) in the control group (OR, 20.07; 95% CI, 2.50-160.89). Analysis of diffusion-weighted MRI data of participants with NF1 showed significantly lower apparent fiber density within the ascending auditory brainstem pathways. The regions identified corresponded to the neural dysfunction measured using electrophysiological assessment. Conclusions and Relevance: The findings of this case-control study could represent new neurobiological and clinical features of NF1. Auditory dysfunction severe enough to impede developmental progress in children and restrict communication in older participants is a common neurobiological feature of the disorder.

Longitudinal auditory pathophysiology following mild blast-induced trauma.

Blast-induced hearing difficulties affect thousands of veterans and civilians. The long-term impact of even a mild blast exposure on the central auditory system is hypothesized to contribute to lasting behavioral complaints associated with mild blast traumatic brain injury (bTBI). Although recovery from mild blast has been studied separately over brief or long time windows, few, if any, studies have investigated recovery longitudinally over short-term and longer-term (months) time windows. Specifically, many peripheral measures of auditory function either recover or exhibit subclinical deficits, masking deficits in processing complex, real-world stimuli that may recover differently. Thus, examining the acute time course and pattern of neurophysiological impairment using appropriate stimuli is critical to better understanding and intervening in bTBI-induced auditory system impairments. Here, we compared auditory brainstem response, middle-latency auditory-evoked potentials, and envelope following responses. Stimuli were clicks, tone pips, amplitude-modulated tones in quiet and in noise, and speech-like stimuli (iterated rippled noise pitch contours) in adult male rats subjected to mild blast and sham exposure over the course of 2 mo. We found that blast animals demonstrated drastic threshold increases and auditory transmission deficits immediately after blast exposure, followed by substantial recovery during the window of 7-14 days postblast, although with some deficits remaining even after 2 mo. Challenging conditions and speech-like stimuli can better elucidate mild bTBI-induced auditory deficit during this period. Our results suggest multiphasic recovery and therefore potentially different time windows for treatment, and deficits can be best observed using a small battery of sound stimuli.NEW & NOTEWORTHY Few studies on blast-induced hearing deficits go beyond simple sounds and sparsely track postexposure. Therefore, the recovery arc for potential therapies and real-world listening is poorly understood. Evidence suggested multiple recovery phases over 2 mo postexposure. Hearing thresholds largely recovered within 14 days and partially explained recovery. However, midlatency responses, responses to amplitude modulation in noise, and speech-like pitch sweeps exhibited extended changes, implying persistent central auditory deficits and the importance of subclinical threshold shifts.

The effect of coronavirus disease 2019 on the hearing system.

OBJECTIVE: This study aimed to evaluate different auditory regions with audiological tests, based on the presumption that there may be damage to the structures in the hearing system after coronavirus disease 2019. METHODS: Twenty individuals with no history of coronavirus disease 2019 and 27 individuals diagnosed with coronavirus disease 2019 were compared. Pure tone, speech and extended high-frequency audiometry, acoustic immitansmetry, transient evoked and distortion product otoacoustic emissions testing, and auditory brainstem response testing were conducted. RESULTS: The pure tone audiometry and extended high-frequency mean threshold values were higher in the coronavirus disease 2019 group. The transient evoked otoacoustic emissions signal-to-noise ratios were bilaterally lower at 4 kHz in individuals with a coronavirus disease 2019 history. In the auditory brainstem response test, only the interpeak latencies of waves III-V were significantly different between groups. CONCLUSION: Coronavirus disease 2019 may cause damage to the hearing system. Patients should be followed up in the long term with advanced audiological evaluation methods in order to determine the extent and level of damage.

Incidence of Complications in 25 Adult Patients With X-linked Hypophosphatemia.

CONTEXT: Adults with X-linked hypophosphatemia (XLH) present complications other than osteomalacia. OBJECTIVE: To describe the incidence and severity of comorbidities in adults with XLH. METHODS: This observational retrospective study included a total of 25 adults with XLH with thorough investigations, including spinal computed tomography scans, x-rays of hip/knee joints and Achilles tendons, abdominal ultrasounds, and audiograms. The index of ossification of the anterior/posterior longitudinal ligament and yellow ligament (OA/OP/OY index) and the sum of OA/OP/OY index (OS index) were utilized to evaluate the severity of spinal ligament ossification. The Kellgren-Lawrence (KL) classification was adopted to evaluate the severity of the hip/knee osteophytes. RESULTS: The participants consisted of 13 male patients and 12 female patients from 21 families, with a median age of 43 (range, 18-72) years. In all, 20 patients (80%) showed spinal ligament ossification. The median OA/OP/OY/OS indices were 2 (0-22), 0 (0-15), 6 (0-13), and 12 (0-41), respectively. Hip/knee osteophytes were reported in 24 (96%) and 17 cases (68%). The median KL grade was 3 in the hip joint and 2 in the knee joint, and 18 cases (72%) developed enthesopathy in the Achilles tendon. Nephrocalcinosis and hearing impairment were observed in 18 (72%) and 8 (32%) cases. CONCLUSION: This study revealed a high prevalence and severity of ectopic ossification and disclosed the incidence of nephrocalcinosis and hearing impairment in adults with XLH. In cases with severe spinal ligament ossification or noticeable osteophytes around the hip/knee joints, undiagnosed XLH should be considered as a possible underlying condition.

[Can the SARS-CoV-2 virus damage human hearing and balance?] / Czy wirus SARS-CoV-2 moze uszkadzac sluch i równowage?

In 2019, COVID-19, the disease caused by the SARS-CoV-2 virus, evolved into a pandemic which is still going on. The basic clinical symptoms of the SARS-CoV-2 infection are: fever, dry cough, fatigue, muscle pain, respiratory problems, and the loss of smell or taste. Other symptoms, including those related to hearing and balance organs (hearing loss, tinnitus, dizziness), are reported less frequently by patients. They are especially rarely reported as the first symptoms of this infection. In order to answer the question of whether SARS-CoV-2 can cause hearing and balance damage, the authors reviewed the literature sources from 2019-2020 included in EMBASE and PubMed, entering the following words: "hearing loss," "COVID-19," "coronavirus," "sensorineural hearing loss," "vertigo," and "dizziness." Ultimately, 9 studies on the possible relationship between hearing impairment and SARS-CoV-2, and 4 studies on the possible relationship between damage to the balance and SARS-CoV-2, were qualified for the study. The results of the analysis suggest a possible relationship between COVID-19 and hearing loss, with no evidence of a similar relationship between this virus and the balance system. The possible existence of such a relationship should be especially remembered by hospital emergency room doctors, otolaryngologists and audiologists, especially as regards the possibility of a sudden sensironeural hearing loss as the first symptom of COVID-19. This also applies to doctors of other specialties. The authors indicate the need for further, intensive and multifaceted research on this issue. Med Pr. 2021;72(3):321-5.

Objective assessment of autophony during phonation in the diagnosis of patulous Eustachian tube patients.

OBJECTIVE: A system enabling the objective assessment of the transmission of voice sounds to the external auditory canal (EAC) during phonation has recently been revised. Our aim was to evaluate the effectiveness of this new system in the diagnosis of patulous Eustachian tube (PET) patients by comparing the results obtained using this method with those obtained from conventional objective tests to diagnose PET. METHODS: A prospective survey of medical records was included with definite PET, possible PET, and sensorineural hearing loss as control. The measurement system consists of a personal computer, an AD/DA converter (NI 6361, National Instruments), a probe microphone system for recording voice sound (ER-10C, Etymotic Research) and two microphones for measuring noise sound in the EAC (ER-10B+, Etymotic Research). Pronouncing the "Ni" sound for 5 s were recorded with these three microphones. The ratio of the maximum sound pressure of voice sound and noise sound in EAC (EAC/Voice) was simultaneously calculated, and results were displayed on a personal computer for diagnosing. RESULTS: Thirty-one patients of 42 ears with definite PET, 26 patients of 38 ears with possible PET, and 12 patients of 24 ears with sensorineural hearing loss as control were included. The EAC/Voice were 8.63 ± 5.43, 25.41 ± 32.63, and 25.87 ± 24.93 in the control, definite PET, and possible PET group respectively. The control group was significantly different from the definite PET (p < 0.05) and possible PET group (p < 0.05). ROC curve analysis confirmed 14.7 as the best diagnostic cut-off value of EAC/Voice (area under the curve=0.782, 95% CI 0.671-0.894). By adopting this cut-off point, 25 (56.8%) and 22 (61.1%) ears were determined as positive findings in the definite PET and possible PET group, respectively. There was no significant correlation between the positive findings judged by the current method and that of sonotubometry in the control (r = -0.63, p = 0.769), definite PET (r = 0.12, p = 0.451), and possible PET group (r = 0.12, p = 0.451). CONCLUSION: The current system is more useful in the objective assessment of autophony during phonation by calculating the ratio of voice sound and elicited noise sound transmitted in the EAC (EAC/Voice). This method seems promising because it is able to detect cases eluding conventionally used test methods such as sonotubometry performed without phonation, thereby increasing the accuracy of PET diagnoses.

Audiological Performance in Children with Inner Ear Malformations Before and After Cochlear Implantation: A Cohort Study of 274 Patients.

BACKGROUND AND OBJECTIVE: Inner ear malformations (IEMs) are common in children with hearing loss. The different types of IEMs form a unique subgroup of cochlear implant (CI) candidates. We aimed to evaluate the auditory perception outcomes of CI in children with different types of IEMs and compare them with CI users without IEMs. METHODS: The study included 274 CI users with and without IEMs as two groups (n = 137, each). Both groups' chronological age at implantation and duration of CI usage was matched (± 8 months). All subjects were evaluated pre-operatively and post-operatively by the Ling's sound test and the auditory perception test battery, which includes the Meaningful Auditory Integration Scale (MAIS), closed-set Pattern Perception Test (PPT) and open-set Sentence Recognition Test (SRT). Besides, children with IEMs were assessed for language development. RESULTS: Progress in the IEMs' group differed according to the type of ear anomaly. CI users with enlarged vestibular aqueduct had the highest scores, while users with common cavity had the lowest. Children with IEMs performed well on the closed-set test while having difficulty with the open-set test. CONCLUSION: Cochlear implantation outcomes are favourable in IEMs' patients with a cochlear nerve visible on magnetic resonance imaging. Our results indicate that it is critical to take the anatomical differences into account during follow-up and rehabilitation programmes. Each CI user should be evaluated according to his or her individual needs.

Bilateral Auditory Brainstem Implants in Patients With Neurofibromatosis 2.

OBJECTIVE: To discuss indications for bilateral auditory brainstem implants (ABIs), compare audiometric outcomes of unilateral vs bilateral ABIs, and determine if patients have improved outcomes with addition of a second-side implant. STUDY DESIGN: Retrospective review of 24 patients with neurofibromatosis 2 (NF2) who underwent sequential placement of ABIs from 1989 to 2019. SETTING: Tertiary referral center. METHODS: Charts were reviewed for indication for second-side surgery, use of implants, and audiometric outcomes. Implants placed in the past 30 years were included in the study. Northwestern University Children's Perception of Speech (NU-CHIPS) and/or City University of New York (CUNY) sentence scores were compared in unilateral and bilateral conditions. RESULTS: Indications for a second-side implant included first-side implants with severe nonauditory symptoms (11), marginal audiometric results (9), outdated technology (2), or deterioration of first side (2). Seven patients are bilateral users and 1 patient discontinued bilateral use after a year due to no significant improvement over unilateral use. One patient with initial bilateral use was lost to follow-up. Thirteen patients are unilateral users due to nonaudiometric side effects or poor audiometric outcomes with the first side. Two patients are complete nonusers. Seventy-five percent had improved audiometric outcomes after the second-side implant, and 20% had stable findings. CONCLUSIONS: Second-side ABIs should be consider in patients with poor performance from a first-side implant. Most patients demonstrate subjective improvement with the second ABI. More research is needed for better objective assessments of improvements.

[Audiological correlates of age-related manifestations of auditory disorders.]

The aim of the study was a comparative analysis of complaints and audiological findings in patients of the audiological center depending on their age. The results of the examination of 300 firstly consulted patients (random sample) are presented. The group of young patients (19-44 years) included 40 people; middle age (45-59 years) - 62 people; elderly (60-74 years) - 100 people; senile age (75-90 years) - 98 people. The survey included the collection of complaints and anamnesis, ENT checkup, pure tone audiometry, impedancemetry, speech audiometry in headphones to detect the signs of Central Auditory Processing Disorder or in the free sound field to assess the effectiveness of hearing aids. It was found that for early diagnosis of hearing loss and prevention of age-related sensory-cognitive dysfunction, it is advisable to use not only the results of pure tone audiometry, but also the data of speech audiometry, as well as the analysis of subjective complaints. The results of the work indicate the need for hearing screening in the population over 60 years old.

Tumor de sistema nervoso central e o paciente pediátrico: alterações fonoaudiológicas / Central nervous system tumor and the pediatric patient: speech-language alterations / Tumor del sistema nervioso central y el paciente pediátrico: trastornosdelhabla y ellenguaje

Introdução: Os tumores do sistema nervoso central (SNC) constituem a segunda neoplasia mais frequente na criança. Os distúrbios tratados pela equipe de fonoaudiologia mais observados em pacientes com tumores são: disfagia, disfonia, alterações de linguagem, transtorno da articulação temporomandibular, disacusia, disartria e paralisia facial. A detecção precoce de alterações fonoaudiológicas em pacientes com tumores pediátricos, na fase do diagnóstico ou início do tratamento, é essencial para um manejo terapêutico mais adequado. Objetivo: descrever as alterações fonoaudiológicas de pacientes pediátricos com diagnóstico de tumor de sistema nervoso central em atendimento durante internação hospitalar. Método: Estudo retrospectivo, com coleta realizada através da pesquisa de dados extraídos de prontuário eletrônico, com dados dos pacientes internados de março de 2016 a agosto de 2018. Para avaliar a associação entre as variáveis categóricas, o teste Qui-quadrado de Pearson foi aplicado. O nível de significância adotado foi de 5% (p<0,05). Resultados: Verificou-se maior relevância nos dados relacionados aos distúrbios de deglutição e motricidade orofacial. Observou-se significância estatística na variável local da lesão - em fossa posterior -, com presença de alterações fonoaudiológicas. Conclusão: A amostra de pacientes oncológicos pediátricos demonstrou alterações fonoaudiológicas, principalmente nas áreas de disfagia e de motricidade orofacial.

Introduction: Central nervous system (CNS) tumors are the second most frequent neoplasm in children. The disorders treated by the speech therapy team most observed in patients with tumors are: dysphagia, dysphonia, language disorders, temporomandibular joint disorder, dysacusis, dysarthria and facial paralysis. Early detection of speech-language pathology changes in patients with pediatric tumors, at the stage of diagnosis or initiation of treatment, is essential for a more appropriate therapeutic management. Objective: to describe speech disorders in pediatric patients diagnosed with a tumor of the central nervous system in care during hospitalization. Method: Retrospective study, with collection performed through the research of data extracted from electronic medical records, with data of patients hospitalized from March 2016 to August 2018. To evaluate the association between categorical variables, Pearson's Chi-square test was applied. The level of significance adopted was 5% (p <0.05). Results: There was greater relevance in the data related to swallowing disorders and orofacial motricity. Statistical significance was observed in the local variable of the lesion - in the posterior fossa -, with the presence of speech-language disorders. Conclusion: The sample of pediatric cancer patients demonstrated speechlanguage disorders, especially in the areas of dysphagia and orofacial motricity.

Introducción: Los tumores del sistema nervioso central (SNC) son la segunda neoplasia maligna más frecuente em niños. Los trastornos tratados por el equipo de terapia del habla más observados en pacientes con tumores son: disfagia, disfonía, transtornos del lenguaje, trastorno de la articulación temporomandibular, disacusis, disartria y parálisis facial. La detección temprana de los câmbios em la patologia del habla y el linguaje en pacientes con tumores pediátricos, em la etapa de diagnóstico o inicio del tratamiento, es esencial para un manejo terapéutico más adecuado. Objetivo: describir los transtornos del habla y el lenguaje de los pacientes pediátricos diagnosticados con tumor del sistema nervioso central em la atención durante la hospitalización. Método: Estudio retrospectivo, com recopilación realizada a través de la investigación de datos extraídos de registros médicos electrónicos, com datos de pacientes hospitalizados de marzo de 2016 a agosto de 2018. Para evaluar la asociación entre variables categóricas, se aplico la prueba de Chi-cuadrado de Pearson. El nivel de significancia adoptado fue del 5% (p<0,05). Resultados: Hubo mayor relevância em los datos relacionados com los trastornos de la deglución y la motricidad orofacial. Se observo importancia estadística em la variable local de la lesión, em la fosa posterior, com la presencia de alteraciones de la patologia del habla y el lenguaje. Conclusión: La muestra de pacientes com cáncer pediátrico demostró la presencia de transtornos del habla y el lenguaje, especialmente em las áreas de disfagia y motricidad orofacial.

Hearing and Other Neurologic Problems.

Ototoxicity and other neurologic toxicities are potential consequences of exposure to common therapeutic agents used during treatment of childhood cancer, including platinum and vinca alkaloid chemotherapy, cranial radiation, surgery involving structures critical to cochlear and neurologic function, and supportive care medications such as aminoglycoside antibiotics and loop diuretics. This article provides an overview of ototoxicity and other neurologic toxicities related to childhood cancer treatment, discusses the challenges that these toxicities may pose for survivors, and presents an overview of current recommendations for surveillance and clinical management of these potentially life-altering toxicities in survivors of childhood cancers.

PREVALENCE OF HEARING SYMPTOMS RELATED TO PATULOUS EUSTACHIAN TUBE AFTER BARIATRIC SURGERY.

BACKGROUND: Rapid and severe weight loss can result in the reduction of the ear tube lining fat tissue and it becomes patent, leading to symptoms such as autophony, aural fullness and tinnitus. Patients after bariatric surgery have, in theory, a predisposition to the development of such alteration. AIM: To evaluate the presence of patent tuba-related complaints in patients undergoing bariatric surgery, correlating with weight and body mass index (BMI) values, as well as demographic data. METHODS: Cross-sectional study composed of the evaluation of patients undergoing bariatric surgery through a standardized questionnaire about the presence of symptoms compatible with ear tube patency. RESULTS: Eighty patients were evaluated, 77 female and three males. The main comorbidity was systemic arterial hypertension (37.5%). Fifteen (18.75%) presented symptoms compatible with patent auditory/Eustachian tube - aural fullness and autophony - postoperatively. In symptomatic individuals the initial weight was 112 kg on average and the preoperative BMI was 45 kg/m², while in asymptomatic individuals the weight was 117 kg and BMI 47 kg/m². There was statistical significance in the comparison between individuals with and without symptoms in the variables of initial weight (p=0.00000), current weight (p=0.00029), preoperative BMI (p=0.00219) and postoperative BMI (p=0.00148). CONCLUSION: The presence of symptoms compatible with patent auditory/Eustachian tube was 18.75% of the patients submitted to bariatric surgery in the evaluated sample. Both preoperative weight and BMI were lower in symptomatic patients when compared with the asymptomatic group.

Pneumococcal Meningitis and Its Sequelae - A Devastating CNS Disease.

INTRODUCTION: In countries where Haemophilus influenzae type B vaccine is used, Streptococcus pneumoniae is the most common cause of bacterial meningitis in young children and notable cause of morbidity/mortality. The authors present material of magnetic resonance imaging (MRI) of patients with pneumococcal meningitis from archive of Department of Diagnostic Imaging of Institute of Mother and Child in Warsaw. MATERIALS AND METHODS: We performed 27 brain MRI scans and 1 follow-up computed tomography (CT) in 10 children (2 girls and 8 boys) aged from neonate to 5 years at disease onset with proven pneumococcal infection. RESULTS: Follow-up period range was 0-12 years. Two children underwent only one MRI, one of them died before follow-up and the other was lost from further observation. There was one case of relatively benign disease course with mild changes on MRI. In another seemingly benign case, acute transient hydrocephalus was observed. Six children developed hydrocephalus, and two required ventriculoperitoneal shunting complicated by neuroinfection, shunt malfunction and revisions. Two patients developed epilepsy. In six children, spastic paresis of various severity was diagnosed, up to quadriplegia in one who is under the longest observation (>12 years) and survived in vegetative state. Three other children suffer from delayed psychomotor development to severe intellectual disability. CONCLUSIONS: MRI shows perfectly the degree of central nervous system (CNS) damage during and after pneumococcal invasion. Despite appropriate treatment, disease course may be unpredictably serious. Attempts to eliminate the obligation to vaccinate are extremely irresponsible taking into account potential danger of death, vegetative state or another form of severe damage to CNS. Social and financial costs of care of survivors are very high with shunts placements and changes, (neuro)infections, rehabilitation, families breakdown, etc.

Quantitative definition of neurobehavior, vision, hearing and brain volumes in macaques congenitally exposed to Zika virus.

Congenital Zika virus (ZIKV) exposure results in a spectrum of disease ranging from severe birth defects to delayed onset neurodevelopmental deficits. ZIKV-related neuropathogenesis, predictors of birth defects, and neurodevelopmental deficits are not well defined in people. Here we assess the methodological and statistical feasibility of a congenital ZIKV exposure macaque model for identifying infant neurobehavior and brain abnormalities that may underlie neurodevelopmental deficits. We inoculated five pregnant macaques with ZIKV and mock-inoculated one macaque in the first trimester. Following birth, growth, ocular structure/function, brain structure, hearing, histopathology, and neurobehavior were quantitatively assessed during the first week of life. We identified the typical pregnancy outcomes of congenital ZIKV infection, with fetal demise and placental abnormalities. We estimated sample sizes needed to define differences between groups and demonstrated that future studies quantifying brain region volumes, retinal structure, hearing, and visual pathway function require a sample size of 14 animals per group (14 ZIKV, 14 control) to detect statistically significant differences in at least half of the infant exam parameters. Establishing the parameters for future studies of neurodevelopmental outcomes following congenital ZIKV exposure in macaques is essential for robust and rigorous experimental design.

Long-term outcomes in children with and without cleft palate treated with tympanostomy for otitis media with effusion before the age of 2 years.

BACKGROUND: Long-term outcomes of children with and without cleft palate receiving early treatment for otitis media with effusion (OME) are unclear. OBJECTIVES: To compare long-term otological and audiological outcomes between children with and without cleft palate treated with tympanostomy for OME before the age of 2 years. MATERIAL AND METHODS: Ninety-five children (180 ears) with cleft palate (study group) and 97 children (185 ears) without (control group) were followed-up to a maximum age of 7 years. We retrospectively analyzed the audiological outcomes at the age of 7 years, and the otological outcomes at the last examination. RESULTS: The percentages of children with OME resolution before the age of 7 years were 47.4% and 60% in the study and control groups, respectively, and those of ears with healed tympanic membrane were 71.7% and 79.5% in the corresponding groups. Significantly more ears were subjected to retympanostomy in the study (31.1%) than in the control group (21.6%). Mean pure-tone average (0.5‒4 kHz) was 15.6 dB HL and 14.3 dB HL for the corresponding groups. CONCLUSIONS/SIGNIFICANCE: Otological and audiological outcomes in both groups were similar. The audiological prognosis was favorable regardless of the cleft palate condition.

Effects of Liberal vs Restrictive Transfusion Thresholds on Survival and Neurocognitive Outcomes in Extremely Low-Birth-Weight Infants: The ETTNO Randomized Clinical Trial.

Importance: Red blood cell transfusions are commonly administered to infants weighing less than 1000 g at birth. Evidence-based transfusion thresholds have not been established. Previous studies have suggested higher rates of cognitive impairment with restrictive transfusion thresholds. Objective: To compare the effect of liberal vs restrictive red blood cell transfusion strategies on death or disability. Design, Setting, and Participants: Randomized clinical trial conducted in 36 level III/IV neonatal intensive care units in Europe among 1013 infants with birth weights of 400 g to 999 g at less than 72 hours after birth; enrollment took place between July 14, 2011, and November 14, 2014, and follow-up was completed by January 15, 2018. Interventions: Infants were randomly assigned to liberal (n = 492) or restrictive (n = 521) red blood cell transfusion thresholds based on infants' postnatal age and current health state. Main Outcome and Measures: The primary outcome, measured at 24 months of corrected age, was death or disability, defined as any of cognitive deficit, cerebral palsy, or severe visual or hearing impairment. Secondary outcome measures included individual components of the primary outcome, complications of prematurity, and growth. Results: Among 1013 patients randomized (median gestational age at birth, 26.3 [interquartile range {IQR}, 24.9-27.6] weeks; 509 [50.2%] females), 928 (91.6%) completed the trial. Among infants in the liberal vs restrictive transfusion thresholds groups, respectively, incidence of any transfusion was 400/492 (81.3%) vs 315/521 (60.5%); median volume transfused was 40 mL (IQR, 16-73 mL) vs 19 mL (IQR, 0-46 mL); and weekly mean hematocrit was 3 percentage points higher with liberal thresholds. Among infants in the liberal vs restrictive thresholds groups, the primary outcome occurred in 200/450 (44.4%) vs 205/478 (42.9%), respectively, for a difference of 1.6% (95% CI, -4.8% to 7.9%; P = .72). Death by 24 months occurred in 38/460 (8.3%) vs 44/491 (9.0%), for a difference of -0.7% (95% CI, -4.3% to 2.9%; P = .70), cognitive deficit was observed in 154/410 (37.6%) vs 148/430 (34.4%), for a difference of 3.2% (95% CI, -3.3% to 9.6%; P = .47), and cerebral palsy occurred in 18/419 (4.3%) vs 25/443 (5.6%), for a difference of -1.3% (95% CI, -4.2% to 1.5%; P = .37), in the liberal vs the restrictive thresholds groups, respectively. In the liberal vs restrictive thresholds groups, necrotizing enterocolitis requiring surgical intervention occurred in 20/492 (4.1%) vs 28/518 (5.4%); bronchopulmonary dysplasia occurred in 130/458 (28.4%) vs 126/485 (26.0%); and treatment for retinopathy of prematurity was required in 41/472 (8.7%) vs 38/492 (7.7%). Growth at follow-up was also not significantly different between groups. Conclusions and Relevance: Among infants with birth weights of less than 1000 g, a strategy of liberal blood transfusions compared with restrictive transfusions did not reduce the likelihood of death or disability at 24 months of corrected age. Trial Registration: ClinicalTrials.gov Identifier: NCT01393496.