Malawi, as a low-income country in southeastern Africa, severely lacks early identification, diagnosis and intervention measures for hearing loss. Due to its constrained resources, an educational awareness campaign targeted at professionals can be a cost-effective instrument in promoting good health care through awareness, prevention, and early identification of hearing loss. The aim of this study is to assess school teachers’ knowledge of hearing health, audiology services, identification, and management of hearing issues before and after an educational intervention. Methods: A Pre-Survey, followed by an educational intervention, and a Post-Survey were completed by teacher participants. A similar World Health Organization-derived survey was also administered to compare to our locally adapted survey. Trends related to efficacy, performance, and survey improvement were evaluated. Results: A total of 387 teachers participated. The average score on the Post-Survey was significantly improved compared to the Pre-Survey (71% to 97% correct responses) with the educational intervention. The only predictive variable related to performance was the location of the school within the capital of Lilongwe compared to rural sites outside of the capital. Our locally adapted survey compared favorably to the WHO survey. Conclusions: The results suggest that there is a statistically significant improvement in the implementation of an educational program to increase the knowledge and awareness of hearing health care among teachers. Some topics were more poorly understood than others, suggesting the need for targeted awareness interventions. Location within the capital city had some effect on performance but a high rate of correct responses was achievable across the participants independent of age, teaching experience, or gender. Our data support the idea that hearing health awareness interventions can be an effective and low-cost option to equip teachers to effectively serve as an advocate for improved identification, early diagnosis and appropriate referral of students with hearing loss. Hearing loss is prevalent worldwide, with an estimated 34 million children suffering from deafness or hearing loss of which 60% of cases are due to preventable causes . The burAccording to the Global Burden of Diseases in 2019, the top six causes of death in Malawi are communicable diseases, and for the most part, these complications are preventable or treatable with modern medicine . HoweverMoreover, there are plenty of unknowns regarding the state of hearing health in Malawi, and generally, there is a lack of public awareness about hearing health. The prevalence of hearing loss nationwide has not been well elucidated and a centralized hearing screening program does not exist. A study conducted on the pediatric population of a rural community in Malawi found that the prevalence of bilateral hearing loss was as high as 12.5%, unilateral hearing loss 24.5%; and 46.9% of the sample had a potentially reversible etiology . FurtherThe present study sought to assess primary school teachers’ knowledge of hearing health, audiology services, and management of hearing issues before and after a hearing health focused educational intervention. This professional population was selected because of: 1. the burden of likely undiagnosed hearing loss in school-aged children in Malawi; 2. the significant challenges in identifying these individuals; and 3. the potential cost-effective benefit of increasing awareness among the individuals who are most engaged in the care of large numbers of children in Malawi. It is hypothesized that the teachers’ knowledge will be limited but will improve following this educational intervention. With affirmation of this improvement, it will be evident that funding for such a hearing health training program for teachers is necessary to implement nationwide to improve hearing health care and education for all of Malawi’s children and future citizens.This study was undertaken in partnership with the African Bible College (ABC) Audiology team at the ABC Hearing Clinic and Training Centre (ABC HCTC). The educational intervention was developed by the ABC team in consultation with the University of South Florida (USF) Audiology and Otolaryngology collaborators. Data were collected in Malawi by the ABC team and sent for analysis to the USF team in the United States in close consolation with the team in Malawi. IRB approval was obtained from USF and Malawi’s National Health Sciences Research Committee prior to undertaking this study. Permission for engagement of school teachers was also obtained from the District Education Managers for each school within the zones.Teachers were surveyed in five school zones across Malawi: Dedza, Lilongwe Rural and Lilongwe Urban zones , and Salima and Ntchisi zones . As the capital of Malawi, zones in the city of Lilongwe are considered urban relative to the rural zones of Dedza, Salima, and Ntchisi. A total of 25 schools were visited to give a diverse representation of the primary school teachers in the country. Gender, age, school name, school location, and teaching experience were recorded. The sample included approximately 20 primary school teachers selected randomly by the head teacher at the school. The sample of 20 teachers varied due to the school’s size and teachers’ individual schedules. Additionally, the sample was limited to primary school teachers within the five zones permitted by the District Education Managers and excluded student teachers, secondary school, tertiary school educators, and private institutions.This study included a Pre-Survey questionnaire, an educational intervention, and a Post-Survey questionnaire. All surveys were administered on paper immediately before and after the educational intervention, and teachers had 30 min to complete each survey. Only data from teachers who completed both Pre- and Post-Surveys were included for analysis.The Pre-Survey was completed immediately before the educational intervention. The Pre-Survey included a Knowledge Survey assessment comprising ten true-or-false questions that measured the teachers’ knowledge about hearing health, audiology, and hearing care as well as 14 additional true-or-false questions, taken from a World Health Organization (WHO) survey designed to assess hearing health knowledge  13]. Th. Th13]. The educational intervention was presented by two ABC HCTC Audiology students, Grant Kapalamula and Memory Khomera, who traveled to each school to provide optimum accessibility. The students were supervised by an audiologist (Au.D.) registered with the Ministry of Health in Malawi. The intervention was one hour long and completed in a lecture-style format via PowerPoint presentation . Five maThe Post-Survey repeated the Knowledge Survey and a new Opinion Survey comprising 4 Likert-scale-type questions assessing the teachers’ response to the education outreach program.Results of the Opinion Surveys were analyzed by calculating the percentage of agreement and disagreement. The percent agreement included responses for “Strongly Agree” and “Agree” while percent disagreement included responses for “Strongly Disagree” and “Disagree”.p-value was less than 0.05. Statistical analysis was performed using GraphPad Prism version 9.1.0 for Mac, GraphPad Software, San Diego, CA, USA, www.graphpad.com (accessed on 8 November 2022).Results of the Knowledge Surveys were analyzed by comparing percentages correct on the Pre-Survey and Post-Survey. The percent increase was calculated by dividing the difference in Pre- and Post-Survey scores by the Pre-Survey score. Performance on the surveys was compared based on variables thought to have a potential effect on the outcome, including age, sex, teaching experience, and location. Chi-squared analysis was used for comparing the number of correct answers before and after the educational outreach. Comparisons between parametric groups were performed using a Student’s T test while non-parametric comparisons were made using a Mann–Whitney test. Simple linear regression was used to compare performance on the WHO survey  and our A total of 387 teachers participated in this study, 69% of whom were female. The majority of respondents were between 30 and 50 years old. There was a diversity of teaching experience amongst the participants .p < 0.001)  ; a 37% oNotably, some questions were missed more frequently than others, but all showed improvement after the educational intervention. Further, a majority of Post-Survey takers were able to answer the questions correctly. Question 3, evaluating knowledge about a baby’s ability to wear a hearing aid, in particular, was missed more frequently than the rest, with a 24% pass rate on the Pre-Survey. However, this changed significantly following the intervention .The Knowledge Survey scores between schools in Lilongwe, the capital city of Malawi, and the other more rural sites located further from the capital were separately analyzed to compare the effect that site location had on the survey scores. There were 183 participants from schools in Lilongwe and 204 from sites not in Lilongwe. Pre-Survey scores for Lilongwe sites versus non-Lilongwe rural sites were 7.34 and 6.86, respectively .The results of the Pre- and Post-Survey scores were compared by zone and then by school . Kabangon = 14) at 50% agreement, 29% disagreement, and 21% undecided.The Pre-Survey Opinion Survey revealed that most teachers agreed that further hearing care training is necessary, with 97% agreement . Most teThe Post-Survey Opinion Survey revealed that 99% of teachers agreed that the educational intervention was helpful and that they need even more training . It was On the Pre-Survey Opinion Survey, teachers were most confident in their abilities to identify students with hearing difficulties and their understanding of the impact of hearing loss on a child’s education, at 88% and 87% agreements, respectively . The teap < 0.0001). The WHO test results were also normalized to the Malawi test results (divided by 14 and multiplied by 10) to make the scores directly comparable  compared with 7.08 out of 10 questions (70.8%) while the Post-Survey average on the Malawi test was 9.69 out of 10 questions (96.9%). The difference between the Pre- and Post-Malawi Surveys is significant . Location in Lilongwe was the only variable of those tested that had a statistically significant effect on survey performance. Interestingly, participants located in rural sites were more likely to have better performance on the Malawi Post-Survey after the education intervention was completed .The WHO Survey , this study shows the value of educational awareness in improving hearing health literacy.The specific aim of this study was to assess primary school teachers’ knowledge of hearing health, audiology services, and management of hearing issues before and after an educational intervention. As hypothesized, teachers’ level of understanding of some hearing topics was minimal but significantly improved following an educational intervention. This study’s sample of 387 participants spread out across a varied setting is one the largest knowledge studies carried out in Malawi and similar sub-Saharan African settings. From an average Pre-Survey score of 71% to a 97% Post-Survey score  found that, in the United States, teachers are instrumental in the identification, prevention, and early detection of hearing loss in children . It mustHearing health training on teachers, nurses, or other professionals in contact with children can be a viable identification tool for referral to Audiology services in the country. This is especially important considering that conductive hearing losses, largely due to cerumen impaction and middle ear pathologies, are preventable and treatable conditions that individuals living in low-income countries often face . Health Moreover, this study’s findings suggest that the impact of the educational intervention was most prominent in peripheral sites further from the capital city. Individuals from Lilongwe performed better on the Malawi Pre-Survey but participants from more rural sites located further from the capital city performed better on the Post-Survey in a small but statistically significant way. As the capital city, Lilongwe is the largest and best-equipped city in Malawi, with a greater presence of resource centers designed as a measure for helping children with different challenges in school. Therefore, teachers in Lilongwe may already have been exposed to some form of inclusivity training. Additionally, Lilongwe is the location of the ABC HCTC, and subsequently, teachers and schools within the clinic’s catchment area may be more familiar with audiology and the signs of hearing loss in children, and ultimately feel more equipped to manage hearing loss. However, hearing health literacy can be significantly improved in these peripheral areas with limited access to resources as indicated by the current study. Indeed, 99% of teachers believe that further hearing care training is necessary, even after the intervention. The results of the current study provide further evidence that a hearing health training program has the potential for cost-effective disease identification and appropriate referral.The most improved question from the Knowledge Survey regarded early identification of hearing loss: 3. A hearing aid can be worn by a baby. This statistic is a vital indicator of the severity in lack of knowledge of early intervention and viable remedial hearing devices such as hearing aids and cochlear implants especially in reference to infants and children. Although hearing aids, cochlear implants, and other remedial measures may currently be cost prohibitive in lower-income countries such as Malawi, the lack of diagnosis compounds the lack of demand for infrastructure development . It alsoOne aspect of this intervention which is not assessed by the current study is how durable the improvement in knowledge and awareness. Additionally, it is important to note that the surveys that were used have not undergone rigorous validation. The WHO survey is based upon materials developed by the WHO and focuses on key themes in prevention of hearing loss and overall hearing care. While this has been implemented in three separate publications, validation of this base survey and of the adapted Malawi version are important refinements to this work. Our group has planned follow-up investigations to reassess participants over time and to address survey validation more rigorously. There are some additional limitations to the study design, including some potential selection bias due to the randomization of participating teachers by school principals. Additionally, while the current study showed a significant improvement in hearing health awareness future studies could improve upon the intervention material to encompass other critical strategies such as classroom noise management and the effectiveness of early identification and intervention in the classroom. Finally, longitudinal investigation is required to determine if the information gained remains as part of institutional memory or if ongoing educational efforts are required.Overall, a comparison between the teachers in Malawi and the other general populations of Saudi Arabia and the rural areas of the United States of America shows a significant gap in hearing awareness. This is likely due to limited exposure to information, as the current study has proved an instantaneous increase in survey scores after exposure to the educational intervention. It is likely that the hearing awareness gap is even larger in the general public where average literacy rates are lower than those of professionals such as teachers. Moreover, cultural influences, which are more prominent in rural populations with lower literacy rates, have not been considered in this discussion.Hearing loss is among the biggest antagonists to the success of a child in school and in future career development, even in well-developed countries. Improved identification and intervention for hearing loss can greatly assist in connecting hearing-impaired children to care, giving them a better chance of development and future success. Teachers stand at a unique intervention point for identification and referral of students and are a key target for these interventions. By providing teachers with the knowledge and skills to detect children with hearing loss, there now exists a viable means of giving these professionals the tools to aid identifying children in need and connecting them to appropriate care.


When looking only at the severely or profoundly affected ears, young age, low Glascow coma score, pneumococcal aetiology, and ataxia were associated with a worse hearing outcome.Survivors of childhood bacterial meningitis (BM) often develop hearing impairment (HI). In low- and middle-income countries (LMICs), BM continues to be a significant cause of hearing disability. We assessed hearing among BM survivors using auditory steady-state responses (ASSR), providing frequency-specific estimated audiograms, and examined whether ASSR would provide a greater understanding of BM-induced HI. Survivors from two prospective BM trials  from Luanda Children’s Hospital were examined in a follow-up visit with a median duration of 26 months after BM. The hearing of 50 BM survivors and 19 control children was evaluated using ASSR and auditory brainstem response (ABR) after interview and neurological and otorhinolaryngological examinations. The median age of survivors was 80 (IQR 86) months. We diagnosed HI (better ear hearing ≥ 26 dB) in 9/50 (18%) children. Five of the fifty survivors (10%) and 14/100 ears (14%) had profound HI (>80 dB). Severe-to-profound HI affected all frequencies steadily, affecting only the ears of BM survivors (18/100 vs. 0/38,  In low- and middle-income countries (LMICs), survivors of childhood bacterial meningitis (BM) often suffer from multiple sequelae, of which sensorineural hearing impairment (HI) is the most common . BM is aAfter BM, multiple and major sequelae occur, of which HI is the most common, reported in up to 34% of cases and ranging from mild to profound and unilateral to bilateral, typically occurring early on in the disease . In BM-rPure-tone play audiometry and pure-tone audiometry are measurements of hearing requiring the child’s cooperation, typically suitable for a child beyond infancy and over five years of age, respectively. In LMICs, pure-tone audiometry is the most accessible method, while the testing of young children who are most often affected by BM and HI is often lacking . AdditioThe hearing evaluation of young children and disabled individuals who are unable to participate in traditional behavioural tests relies on objective methods. Auditory steady-state response (ASSR) and auditory brainstem response (ABR) are both evoked electric potentials created by acoustic stimuli, and are used to estimate hearing sensitivity. Rapid and repeated auditory stimuli evoke ASSR, which is then detected and analysed using statistical methods to predict the presence or absence of a response that is analysed in the frequency domain . The tec® stimuli are sound stimuli developed to reduce delay related to the cochlear travelling wave. The responses are recorded using electrodes placed on the skull while background noise and biological electric activity are filtered out using a variety of techniques. ASSR has shown feasibility and accuracy in estimating hearing thresholds in young children [The frequency-specific narrow-band CE-Chirpchildren . While Achildren , it may We aimed to test the hearing of patients via ASSR to acquire estimated audiograms to provide accurate counselling for those with hearing loss, and to examine whether ASSR would provide more data on BM-induced HI. To our knowledge, ASSR has not been described in BM before.Survivors from two prospective BM treatment trials  ,17 from We examined the hearing of 50 survivors using ASSR and ABR and the Eclipse platform . A control group of 19 children was also included. The controls were healthy children who had no history of BM visiting the hospital during our study. They were siblings to the BM survivors (N = 11), or healthy children attending the hospital to receive vaccinations (N = 8) for rabies.The families were interviewed using a structured questionnaire in their native language. Our study paediatrician (TP) carried out a clinical and neurological examination on each child. Before the hearing evaluation, the study doctors, residents in paediatrics and otorhinolaryngology, performed a pneumatic otoscopy for each patient after cleaning the ear canal with cotton swabs when necessary. In case of any uncertainty of the ear status, a crosscheck was carried out. Concomitant ear pathology was not defined as an exclusion criterion, as all participants deserved an evaluation of their hearing. Prior to the study, the study doctors received detailed training to perform ASSR and ABR recordings.The hearing evaluation was carried out in a quiet hospital room without other electronic devices turned on, except for the study computers. Between patients, the room was cooled down with an air conditioner. The electrodes were placed on cleaned and rubbed skin on the mastoids (negative electrodes), vertex (positive electrode), and low forehead (ground) for the 2-channel ASSR and ABR recording. Before stimulation, acceptable skin impedance was verified. Infants and young children were held in a comfortable position on the parent’s lap and were encouraged to fall asleep after bottle- or breastfeeding; older participants lay in bed, and were instructed to relax, close their eyes, and stay still, and were allowed to fall asleep. General anaesthesia was not necessary in any case. Hearing testing and electrode placement are illustrated in ® stimuli were delivered binaurally using headphones with intensities of 80, 60, 40, and 20 dB nHL  at a rate of 90 Hz in ASSR. In ABR, the stimuli were delivered to the ears separately with the contralateral side, receiving 20 dB lower masking using the above-mentioned intensities. Recording used the ASSR and ABR modules of the Eclipse platform. In ASSR, the algorithm-guided frequency-specific recording was stopped when the level of significance for a response was reached or if no response was found during six minutes of recording. The thresholds were calculated using proprietary algorithms. In ABR, the in-built algorithm gave a pass/refer result based on a reproducible wave V. The intensities were lowered or raised until the lowest threshold was reached.The narrow-band CE-ChirpFor ASSR, the collected data were estimated thresholds in dB at 0.5, 1, 2, and 4 kHz. For an overall estimation of hearing, a mean of thresholds was calculated. WHO hearing loss grades were used to categorise the patients into groups of mild (26–40 dB nHL), moderate (41–60 dB nHL), severe (61–80 dB nHL), and profound HI (>80 dB nHL). A hearing threshold of ≤25 dB nHL indicated normal hearing. A better ear hearing threshold of >30 dB nHL was defined as disabling HI, according to the WHO definition ,19. If aThe ethics committee of Hospital Pediátrico David Bernardino approved both treatment trials, including amendments for the current follow-up study. Before inclusion to the original trials, the child’s guardian gave informed consent. The follow-up evaluation was voluntary for all families. Based on paediatric and hearing evaluations, counselling and appropriate references were given in line with the local health system. During the study, local residents were trained in pneumatic otoscopy and audiological testing.U test to compare medians, and calculated Spearman rho values for correlations. The distribution of the data was graphically analysed, and the Shapiro–Wilk test was applied if needed. We applied statistical significance of p < 0.05.We analysed the data using SPSS 28.0 for MacOS  and used descriptive methods to present the findings. We used Fisher’s exact test to compare dichotomous categorical variables and the nonparametric Mann–Whitney The ASSR evaluation was attempted for 86 children (63 patients and 23 controls). Altogether, 69 children and 138 ears were successfully evaluated using ASSR and ABR . HoweverDuring the follow-up study, the median age of the children was 80 (IQR 86.0) months. The follow-up study was performed 26 months  after BM. For controls, the median age was 85 (IQR 59) months. Eighteen out of fifty survivors (36%) were girls. Nine survivors were recruited from the first clinical trial , while fOut of 50 BM survivors, 9 (18%) had HI (better ear hearing ≥ 26 dB nHL). Disabling HI (>30 dB nHL) affected seven (14%) of the patients. Five of fifty patients (10%) and fourteen of one hundred ears (14%) were diagnosed as having profound HI, i.e., deafness (>80 dB nHL). Additionally, one (2%) suffered from severe HI (61–80 dB nHL), one (2%) suffered from moderate HI (41–60 dB nHL), and mild HI (26–40 dB nHL) occurred in two (4%) children. Any type of HI (of either ear) affected 16 (32%) of the patients. None of the controls had bilateral HI but 4 of 19 (21%) had unilateral HI. p = 0.07. However, using a cut-off of 40 dB, HI was more common in patients’ than controls’ ears . Similarly, using a cut-off of 60 dB, having severe or profound HI was significantly more common in patients’ vs. controls’ ears , and profound HI of ears was more common with patients compared to controls , as seen in The frequency-specific results of all ears (n = 100 in patients) are shown in p = 0.028; p = 0.058; p = 0.02; and p = 0.003 in Mann–Whitney U test, for frequencies 0.5, 1, 2, and 4 kHz, respectively). The mean ASSR threshold correlated with the ABR threshold in patients and controls  and in the ears of patients and controls . The hearing grades obtained using ASSR and ABR are displayed in The frequency-specific hearing threshold estimates of ears differed between patients and controls  had healthy ears in otoscopy while three children (6%) showed middle ear or tympanic membrane pathology on either ear S. pneumoniae aetiology  and low haemoglobin  were associated with a worse hearing outcome. At follow-up, ataxia  and peripheral nystagmus  were associated with HI.Clinical suspicion of HI at follow-up was associated significantly with severe-to-profound HI. Two children were severely handicapped. One older child was attending school for hearing disabled children; another older child had dropped a class twice. These patients are described in greater detail in the HI is a frequent finding after BM, affecting 18% of BM survivors in the present study (better ear hearing ≥ 26 dB nHL). The proportion of disabling HI (>30 dB) in seven (14%) of the survivors, and severe-to-profound HI in six of the survivors (12%), with mostly deafness, is in line with the previous literature from high-BM-prevalence settings . In our However, comparisons to previous data, specifically from similar settings, are challenging, as the youngest children are typically excluded or their testing does not rely on objective measures. Despite these shortcomings, a meta-analysis of BM sequelae in African children reported post-discharge HI of 2–34% . ABR wasThe proportion of any hearing impairment in ears did not differ significantly between BM survivors and controls. The mild-to-moderate HI of 7% in our survivors’ and 11% in our controls’ ears may be attributable in a few cases to impacted cerumen or other acquired causes of HI, such as measles, mumps, other infections, or sickle cell disease, all highly prevalent in Africa . In factS. pneumoniae [As expected, a significant difference in the estimated ASSR frequencies between BM patients and controls was noted across the tested frequencies as the severe-to-profound HI occurred only in BM survivors. In addition, the ASSR showed that HI manifested similarly across the tested frequencies. In animal models of BM, the infection spreads from the subarachnoid space via the patent cochlear aqueduct to the labyrinth, resulting in gradual damage along the base to the axis . Thus, teumoniae ,7,25. Preumoniae .The success rate for performing both ASSR and ABR was quite high: 69/86 (80%) amongst the children included in the study . In 69 cS. pneumoniae aetiology, and low blood haemoglobin were associated with worse hearing outcomes. These have all been previously described as being BM-related risk factors for unfavourable hearing outcomes in LMIC settings [When looking only at the severely or profoundly affected ears, young age, low Glasgow coma score, settings ,27, and settings . The undS. pneumoniae and H. influenzae type b BM, while N. meningitidis more often leaves hearing undamaged [S. pneumoniae was associated with a severe-to-profound HI of ears. Aetiology, however, should not determine the need for auditory testing after BM.In LMICs, the presenting condition of a child during BM has been the determinant factor predicting mortality and severe sequelae overruling many other factors such as the aetiology ,27. The ndamaged ,4. SimilThe limited sample size likely affected our results, as we did not find associations with other risk factors reported in African studies, such as convulsions, associated cranial nerve findings, low blood leukocyte count, and high CSF protein levels ,30. As sThis study has several limitations. We could not recruit all of the survivors of our studies, which may have biased our study population. Additionally, 20% of the children intended for hearing evaluation could not participate, due to either not being able to calm down for the audiometry or technical problems which arrested the testing. In addition, our control group was rather small, which may also affect some of our comparisons stated above. The resources enabled us to examine hearing using only ASSR and ABR.The equipment to clean the ear canal was not optimal, as in 12% of all ears (BM children and controls) cerumen blocked the view in otoscopy even though the median hearing did not statistically differ between ears with or without cerumen. The ear status was normal with mild-to-moderate HI in all except three ears . The very limited resources hampered the possibility to clear the ear canal as cotton swabs were the only available instruments. No suction devices for ear wax removal were available; in addition, the children’s hospital lacks a tympanometer and an otomicroscope. These are limitations that have likely affected our results and need to be taken into account when interpreting our results; however they might reflect the reality in many resource-limited settings.The limited capacity to meet the demands of rehabilitation in cases of severe-to-profound HI was demonstrated with our patients, as none of them had access to hearing aids or cochlear implants, which are lacking in Luanda. However, to tackle these inequalities in Africa, WHO has launched resolutions addressing ear and hearing care by establishing training programmes, improving access to affordable and cost-effective hearing technologies, and promoting alternative communication methods .HI is a major sequela after BM, with severe-to-profound HI distinguishing the patients from controls and occurring in 6/50 (12%) children and in 18/100 (18%) ears. This HI occurred across all ASSR frequencies and did not differ from the ABR results. A young age at time of BM, low Glasgow coma score at presentation, pneumococcal aetiology, and ataxia were all associated with HI. As BM-induced HI often affects children of prelingual age, prompt diagnosis and rehabilitation matters are crucial. The need for accessible ear and hearing care and education after BM in LMIC settings is significant.


Auditory brainstem response (ABR) is the response of the brain stem through the auditory nerve. The ABR test is a method of testing for loss of hearing through electrical signals. Basically, the test is conducted on patients such as the elderly, the disabled, and infants who have difficulty in communication. This test has the advantage of being able to determine the presence or absence of objective hearing loss by brain stem reactions only, without any communication. This paper proposes the image preprocessing process required to construct an efficient graph image data set for deep learning models using auditory brainstem response data. To improve the performance of the deep learning model, we standardized the ABR image data measured on various devices with different forms. In addition, we applied the VGG16 model, a CNN-based deep learning network model developed by a research team at the University of Oxford, using preprocessed ABR data to classify the presence or absence of hearing loss and analyzed the accuracy of the proposed method. This experimental test was performed using 10,000 preprocessed data, and the model was tested with various weights to verify classification learning. Based on the learning results, we believe it is possible to help set the criteria for preprocessing and the learning process in medical graph data, including ABR graph data. Hearing loss refers to a condition in which the ability to hear or understand sounds is more difficult than for people with normal hearing due to abnormalities in the inner, outer, or vestibulocochlear nerves. These symptoms may be temporary or permanent and may affect one or both ears. Auditory brainstem response (ABR) refers to an electrical response that occurs when sound is recognized in the brainstem, which is the path through which sound (audio) reaches the auditory cortex of the brain as a neuroelectric signal of the cochlear tube. The diagnostic process used to assess the hearing threshold by measuring the waveform of the corresponding electrical response is usually referred to as an ABR test.The ABR test, generally performed to evaluate hearing loss, is a non-invasive test that is unaffected by sleep or anesthesia. In particular, the ABR test is a means of objectively measuring the hearing of newborns, infants, and patients with congenital disabilities who have difficulty accurately measuring hearing level, and due to the objectivity of non-invasive testing, plays an important role in tracking the hearing of children at risk of late-onset or progressive hearing loss, such as those affected by congenital CMV infection ,2. The hThe ABR test is a process by which small electrodes are attached to the forehead and behind the ears to detect electrical activity in the auditory nerve and brainstem in response to sound. The patient hears a series of clicking sounds through earphones inserted into the ears, and the brain waves, which are the brain’s response to the sounds, are detected and automatically recorded on a computer. Therefore, the ABR test can be measured objectively, compared to test methods based on the patient’s subjective response, such as pure tone audiometry. The audiologist judges the hearing threshold of the ABR test with waveform 5, which is detected between 6 and 8 ms, which is the most reliable among waveforms 1 to 5 from each sound stimulus (dB). The ABR test is completed after measuring the EEG for each 30 to 90) dB sound stimulus 0 dB soun.In general, the ABR test results can determine hearing thresholds, the presence of pseudohypacusis, and retro-cochlear hearing loss . DespiteThese problems also occur in the proposed hearing loss classification AI model using ABR data. When the ABR result data of each manufacturer are directly applied to the AI model and trained without refining, low-accuracy prediction results are obtained. In this paper, to develop an AI learning model that automatically classifies hearing loss, the preprocessing process for efficiently learning ABR data is proposed. After applying the proposed preprocessing process, we trained the VGG16 model for data and the classification test for hearing loss patients.The ABR data in this paper were obtained by gathering data from Soonchunhyang University Cheonan Hospital, Asan Medical Center, Samsung Medical Center, Ajou University Medical Center, Seoul National University Hospital, Severance Hospital, Seoul St. Mary’s Hospital, and Konyang University Hospital. The ABR data of 5000 people with normal hearing and 5000 patients with hearing loss were collected and preprocessed. Using the collected data, a deep learning model was applied to analyze the classification performance and accuracy of the deep learning model. This study was reviewed and approved by the Soonchunhyang University Cheonan Hospital’s Investigational Review Board (IRB number: 2021-06-040). We classified ABR image data into hearing loss and normal hearing based on the ABR hearing threshold of 40 dB. The main contribution of this paper is that the proposed method is designed to automatically distinguish between hearing loss patients and normal hearing people using the VGG16 model. The proposed method is expected to be clinically usable with an accuracy of approximately 85%.Medical data is the most actively researched in the field of AI, especially in deep learning technology, and is one of the fields in which many automatic diagnosis systems are currently being developed. Recently, as various medical data have been digitized and a large amount of high-quality medical information has been generated, research on computer-based analysis and automatic diagnosis has been actively conducted ,15,16,17With the advent of deep learning technology, this perception and situation have considerably changed. Deep learning is a concept designed based on an artificial neural network (ANN) that showed limitations due to the initial overfitting problem, but Jeffrey Hinton presented the concept of prior learning in 2006 and the concept of dropout in 2012, and it has been proven that it can overcome the existing problems ,18,19,20By attaching electrodes, the auditory brainstem response (ABR) test records electrical changes occurring in auditory conduction across the auditory nerve and brainstem after sound stimulation through the ear canal. Unlike pure tone audiometry (PTA), the ABR test is a non-invasive test that can objectively evaluate hearing threshold, is not affected by anesthesia or sleep, and is widely used in otolaryngology ,29. As sHearing test results are stored in a medical information system, such as an electronic medical record (EMR), at each hospital. Patients’ personal information is removed manually by using data labelers. Since ABR data is stored in graph form from ABR devices used in each hospital, they should be collected and preprocessed  for feature point marks. Therefore, as shown in 5.Normalization of image sizeX and Y-axis normalization and V-mark removal were already performed in the previous step, ABR image data loss for deep learning training was minimized.To smoothly process the deep learning for graph images, the image size was changed to 573 × 505 px for normalized and preprocessed images. Since In this paper, 10,000 ABR data from 8 different hospitals were collected, preprocessed, and normalized. In addition, a deep learning classification model was applied to the preprocessed ABR image data to classify patients with hearing loss automatically.VGG is a model proposed by the Visual Geometry Group of Oxford. There are two types of VGG structures: VGG16 and VGG19. VGG 19 has three convolution layers, one in front of the pooling layer in layers 3, 4, and 5, compared to VGG 16. For binary classification learning, the model in this paper adopted VGG 16 because too many convolution layers have a high probability of over-integration and may thus be less optimized ,34,35. FInput layer: Basically, an image of size 224 × 224 is delivered to the convolution layer;Convolution layers: VGG16 has 13 convolution layers (conv 1–1~5–3). Each convolution layer consists of a small filter with a size of 3 × 3. Each filter is responsible for extracting features from the input image. After the convolutional layer, a rectified linear unit (ReLU) is used as the activation function;Pooling Layers: After each convolution layer, the max pooling layer is applied. Maximum pooling is responsible for reducing space by extracting only the largest values from each area;Dense Layers: These layers perform a final classification based on the features of the image. After each fully connected layer, the ReLU activation function is also used ,37,38.As shown in In this paper, the VGG16 model for ABR data classification was used to classify hearing loss patients and people with normal hearing. To train the VGG16 model on the collected data, 4500 normal ABR images and 4500 hearing loss ABR images were used. To test the VGG16 model, 500 normal ABR images and 500 hearing loss ABR images were used. To accurately evaluate the performance of the proposed VGG16 model, we tested and compared it under several conditions. In our experimental test of the proposed VGG16 model, the epochs were increased to  for batch sizes (16 and 8). Therefore, six results were derived, and Accuracy indicates the rate at which the proposed model accurately predicted whether the subject was a person with normal hearing (40 dB ≤ hearing threshold) or a patient with hearing loss (40 dB > hearing threshold). Sensitivity represents the rate at which people with normal hearing were properly classified as normal. The false positive rate (FPR) refers to the rate of actual hearing loss patients predicted to be people with normal hearing, while the false negative rate (FNR) refers to the rate of those who were predicted to be hearing loss patients, even though they were people with normal hearing. Precision represents the ratio of cases classified as people with normal hearing to actual people with normal hearing. The F1 score represents the harmonic average of precision and sensitivity. The higher the F1 score value, the more valid the value is. The primary purpose of this paper was to determine whether patients applying for disability-grade screening are people with normal hearing or hearing loss patients. Therefore, high sensitivity, precision, and low FNR, which do not classify people with normal hearing as hearing loss patients as much as possible, are judged as valid values while judging the accuracy value that reliably distinguishes people with normal hearing from hearing loss patients. In addition, the F1 score must also be high to verify the reliability of the corresponding value.The experimental results showed that when the epoch was set to 200 and the batch size was set to 8, it showed the best performance with accuracy results of 84.90% and an F1 score of 85.66%. The batch size refers to the number of data belonging to a small group when learning training image data once. A smaller number requires longer data learning time, but the results of the model used in this paper showed slightly better learning results. Epoch refers to the number of times the entire data passes through the neural network, and it simply refers to the number of learning times. Greater number epochs also require longer learning time, but a better learning rate is achieved when learning is carried out up to a certain upper limit.To prove the effectiveness of the preprocessing performed in this paper, we conducted classification learning and testing for hearing loss patients and people with normal hearing using the VGG16 model. In addition to the best value of epoch 200, epochs 50 and 100 were also sufficiently effective for classification. Therefore, we confirmed that the preprocessing work proposed in this paper is effective in building a hearing loss patient classification model using ABR image data, and in future research, we plan to continue automating the preprocessing work. It is expected that this work will help to distinguish ABR data-based hearing loss between measurement technicians and otolaryngologists.This paper introduced a preprocessing process to automatically classify patients with hearing loss using ABR graph image data using a deep learning model. A result of testing for automatic classification with the VGG16 model after preprocessing the ABR input image of this paper shows accuracy results of 84.90%, specificity of 79.60%, sensitivity of 90.20%, FPR of 20.40%, FNR of 9.80%, precision 81.56%, F1 score 85.66% under epoch 200, and batch size 8 were obtained. Among the 6 learning experimental tests, the FNR is low while the harmonic average F1 score is high, which explains that the rate of normal data classified as hearing loss patient data is low, while the reliability of the learning results is somewhat high. This is expected to help doctors conduct a second review after the first discrimination using the model when classifying the disabled with ABR graph data.Currently, ABR data is measured by an audiologist using a specific ABR device, and then an otolaryngologist diagnoses hearing loss using these data. This study aims to analyze the ABR result automatically using AI technology for the primary classification of hearing loss, and then to proceed with the otolaryngologist’s secondary discrimination. This technique is expected to be of great help in improving the hearing loss diagnosis and analysis process. In a future study, we will present the automation of the ABR data preprocessing process and use the proposed model as new research. In another future study, we will apply an algorithm that automatically detects V waveforms to research a deep learning model to help audiologists evaluate ABR data.


Sensorineural hearing loss (SNHL) is the most common auditory deficit in older adults and may lead to quality-of-life deterioration. However, few studies have been performed in low/middle-income countries, particularly in Latin America. This study aimed to assess the audiological benefit, quality of life, and factors associated with functional gain in elderly hearing aid users in the Fundación Santa Fe de Bogotá and UNIMEQ-ORL, two otology referral centers in Colombia.Pre-post study that included hearing aid users at the otology consult of the Fundación Santa Fe de Bogotá and UNIMEQ-ORL between June 2017 and December 2020. Glasgow Benefit Inventory (GBI) and Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaires were applied. Audiometric  and speech audiometry results were collected.A total of 75 participants (132 ears) were included. The mean age was 70.73 years (SD: 12.66). The median hearing aid use in years was 0.71 (IQR: 0.64–0.90). Mean change in speech audiometry was − 26.53dB , in functional gain was − 21.75dB . The mean changes in the APHAB domains were Ease of Communication: -37.85 , Background Noise: -3.51 , and Aversiveness of Sounds: -6.9 . The GBI assessment of quality of life showed improvement in 100% of the population after the use of hearing aids. The number of years of hearing aids use was associated with functional gain.The number of years of hearing aids use may impact on the functional gain in these populations. A significant clinical benefit was found in terms of quality of life, communication, and reverberation related to the use of hearing aids. Access to hearing aids should be granted, and public health strategies are needed to grant the access to hearing rehabilitation in these populations.Fundación Santa Fe de Bogotá (Protocol Number: CCEI-12666-2020). Hearing loss affects almost 81.4% of adults 80 years or older in the United States , 3. EarlHearing impairment has commonly been associated with functional disability, quality of life deterioration, and emotional difficulties , 10. In This was an observational, analytical, pre-post study conducted at two otolaryngology referral centers in Bogotá, Colombia: the FSFB and UNIMEQ-ORL, between January 2017 and December 2020. Therefore, this study aimed to assess the possible changes in auditory benefit, quality of life, and factors associated with functional gain in patients with hearing aids. Patients under 70 years old received self-administered written questionnaires, and patients over 70 years old were assessed by their legal tutors to answer the questionnaires. All patients had a clinical diagnosis of sensorineural hearing loss that was supported by audiometric results and was performed by an otolaryngologist and an audiologist. The questionnaires were applied during the audiology appointments by two audiologists trained in the application of these tools. According to the Helsinki Declaration, the ethics committee of the FSFB approved this study (CCEI-12666-2020). Informed consent was obtained from all the participants and/or their legal tutors. No incentives were offered for study participation.The FSFB and UNIMEQ-ORL are both healthcare centers located in Bogotá, the capital city of Colombia. Patients from all over the country visit these institutions seeking for hearing rehabilitation and otology healthcare. Both institutions treat patients affiliated to private Health Promoting Entities which provide health insurance packages to all socioeconomic-status populations.The sample size was calculated based on an average change in the APHAB score in the pretest of -4.9 units with a standard deviation of 12.2 points, a power of 90% , and basWhere:And with an exposed / unexposed ratio equal to 1 (r = 1), the sample size is equal to 75 subjects. Regarding the sample selection method, a non-probabilistic, consecutive sampling was conducted.Audiometry was conducted considering the international standardized protocols to measure the intensity in decibels (dB) at which a tone could be heard by the individuals at a specific frequency . An R37aThe Glasgow Benefit Inventory (GBI) scale was applied to the population study one year after hearing aids indication to assess the quality of life. This scale is sensitive to changes related to otolaryngological interventions. The GBI has 18 questions and 3 domains: 12 questions assess the change in “General benefit”, 3 questions assess “Physical benefit”, and 3 questions are related to the “Social support changes”. It gives a score of -100 (negative benefit), 0 (no benefit), and + 100 (positive benefit) . On the Statistical analysis was performed using Stata 16MP software. The descriptive analysis calculated absolute and relative frequencies for the qualitative variables. Measures of central tendency (mean and median) were estimated for the quantitative variables. Standard deviation (SD) and interquartile range (IQR) were assessed for the dispersion measures. A “change from baseline” measure in audiometry values and APHAB domains was calculated using the differences between the baseline scores obtained before using the hearing aid and the scores after one year. A bivariate and multivariate analysis between pre- and post-measurement data of these scores were analyzed by the paired samples Wilcoxon test. A stratified analysis was performed by age to assess functional benefits for age groups. A GEE analysis using an unstructured correlation matrix was carried out to assess the effect of the functional gain after use and fitting of a hearing aid for one year. This effect was adjusted considering the clinical and demographic variables with clinical relevance or biological plausibility, and those with a P-value ≤ 0.2 in ANOVA/Friedman test. Model assumptions were validated through a linearity test, an estimation of standardized residuals and leverage values, and a comparison between the crude and the adjusted models. Hypothesis testing to determine the level of statistical significance was performed using a 95% confidence interval and a P-value < 0.05.A total of 75 individuals were included, with a mean age of 70.73 years (SD: 12.66 years), 54.67% (n = 41) were female, and 84% were aged over 60 years old. The baseline demographic and clinical characteristics of the study population are described in Table In terms of audiometric values, the pre/post and mean changes for the population were stratified by age group (< 60 years vs. > 60 years) and are described in Table Table Table Table Despite hearing aids having wide scientific evidence to improve functional disability and quality of life deterioration related to hearing loss in elderly populations, few studies have assessed these benefits in low/middle-income Latin American countries. This study described the audiological benefit and the improvement in patients’ quality of life in older patients with SNHL treated with hearing aids in a low/middle-income Latin American country. Direct costs of SNHL include the use of resources for diagnosis, otology and audiology consults, hearing aids, rehabilitation, and intangible costs such as quality of life deterioration –23. A reDespite the Colombian health insurance packages include low-cost hearing aids for the population with SNHL, difficulties in access, quality limitations, and lack of follow-up have been described , 26. ConRegarding the audiometric values, an improvement of at least 13 dB was found for the speech frequencies (250–4000 Hz). Similarly, a prior study reported an improvement up to 7 dB +/- 16 dB for the mean pure-tone average at speech frequencies using bone-anchored hearing aids (BAHA) . These fTo gain insight into the quality-of-life changes of this population, the main domains of the GBI score were assessed . Overall, the results for GBI scores showed a significant benefit for all the domains of the scale, and up to 100% of the participants reported an improvement in the total GBI score. These findings are similar to a prior study among 134 older patients who received BAHA for SNHL in the Netherlands that reported positive GBI scores in 84% of the population, and a general satisfaction reported by 71% of the population  LikewiseIn terms of the BN , and AV  domains, our population reported less favorable results. Thus, these findings could be explained by differences in hearing aids brands, and access to maintenance of the hearing aids. Prior authors have also reported these differences in elderly hearing aid users , 32. On Overall, these findings highlight the importance of addressing sociodemographic factors to support older adults in achieving success with hearing aids. Finally, we stand out that prior studies have described difficulties in reaching otolaryngology specialists in low/middle-income Latin American countries , 35, andAmong the strengths of the study, we highlight that the questionnaires were developed by one otolaryngologist and one audiologist with wide clinical experience, and the sociodemographic information was obtained by trained professionals to minimize measurement bias. Moreover, the otolaryngologist of this study reviewed all the information about outcomes and audiological treatment. We highlight that the intensity of audiological change and quality of life were assessed through validated scales in these constructs, so reporter bias and overestimation of the possible benefits in these outcomes were reduced . MoreoveAbout the limitations of the study, we stand out the cross-sectional design of this study which would also lead to recall bias, considering that most hearing aid patients had to recall their benefit compared to several years ago. However, we also stand out that the most accurate way to evaluate health-related quality of life is to administer the questionnaires before hearing aid fitting and to repeat these measurements after a certain interval which would avoid recall bias . We follA significant clinical benefit was found in terms of audiological benefit, communication, reverberation, and quality of life probably due to the use of hearing aids.


IL10 promotor and CIDP occurrence. Major homozygotes (AA) were more frequent in the HCs compared to CIDP patients (p = 0.049), but the GA genotype prevailed among the patients (p = 0.032). A lower frequency of the C allele was observed for rs1800871 and rs1800872 in CIDP patients compared to the HCs (p = 0.048). A higher proportion of A carriers at position -1082 (rs1800896) (presumed to be a low IL-10 producer) was noted in patients with milder disability (low INCAT). All mild-INCAT patients were C carriers for rs1800871 and rs1800872 in IL10 (p = 0.038). Furthermore, the IL6 rs1800795 GG genotype was more frequent in patients (p = 0.049) and the CG heterozygote in the HCs (p = 0.013). Among the CIDP patients, being a G carrier for this SNP was associated with a higher frequency of type 2 diabetes (T2D) compared to being a non-carrier (p = 0.032). Our data indicate a possible association of the IL10 and IL6 SNPs with CIDP, but also with disease severity and T2D occurrence. Given the paucity of CIDP patients, multicentric studies are necessary to draw definite conclusions on these associations.Innate and adaptive immune responses exert their role in CIDP pathogenesis through cytokine production. Single-nucleotide polymorphisms (SNPs) may alter cytokine gene expression, with a potential influence on the pathogenesis of autoimmune diseases. However, cytokine gene SNPs have not been assessed in CIDP patients yet. We assessed functional SNPs in the genes encoding IL-10 , IL-6 (rs1800795), TNF (rs1800629 and rs361525), IL-12B (rs3212227), IFN-γ (rs2430561), GM-CSF (rs25882) and IL-17F (rs11465553) in a cohort of 88 CIDP patients and 486 healthy controls (HCs) via qPCR. We found an association of SNP in the  Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired immune-mediated neuropathy that is typically characterized by progressive, stepwise, or recurrent symmetric proximal and distal weakness, sensory dysfunction and absent or reduced tendon reflexes in all extremities, developing over at least eight weeks . AlthougGiven the complexity of the immune response in CIDP, it could be that the mechanisms of tissue damage vary patient-to-patient, which may lead to a poor treatment response in a significant portion of cases . Thus, aIL10 rs1800896, as well as the differences in the allele frequencies of IL10 rs1800871, and subsequently, rs1800872, an SNP in complete linkage disequilibrium with the latter. However, these discrepancies did not affect haplotype distribution in the IL10 promotor.Therefore, our aim was to analyze the SNPs of cytokines with previously shown significance in other autoimmune diseases in a cohort of CIDP patients. We focused on SNPs with functional impacts located in cytokines of significance for helper T cell subsets relevant to the pathogenesis of CIDP and genotyped SNPs in genes for: IL-10 , IL-6 (rs1800795), TNF (rs1800629 and rs361525), IL-12B (rs3212227 and rs6887695), IL-17F (rs11465553) and GM-CSF (rs25882). We identified different genotype distributions between CIDP patients and a healthy population for This study included CIDP patients from two Serbian neuromuscular centers: the Neurology Clinic of the University Clinical Center of Serbia and the Neurology Clinic of the Clinical Center of Nis. Patients who regularly visited their neurologists during 2016–2018, or were diagnosed at that time, were sampled. Only patients who fulfilled the EFNS/PNS CIDP diagnostic criteria from 2010 were included in this research [Sociodemographic and diagnostic data were collected from the patients themselves and their medical records at the time of blood sampling. The disease onset was classified as acute when the peak of the disease was reached within four weeks from onset, subacute if it lasted between 4 and 8 weeks, and chronic if the initial progressive phase lasted more than 2 months . All of IFNG rs2430561 [IL10 rs1800872 were inferred from the SNP rs1800871 because these two SNPs are in complete linkage disequilibrium in Caucasians [Genomic DNA was isolated from patients’ peripheral blood using a GeneJET Whole Blood Genomic DNA Purification Mini Kit . Genotyping was performed using a TaqMan genotyping assay  with Maxima Probe qPCR Master Mix (Fermentas Thermo Fisher Scientific Inc.) using a RealPlex2 , under cycling conditions recommended by manufacturer of the oligonucleotide mixture. The cycling conditions were established as recommended by the manufacturer of the oligonucleotide mix or as previously described for ucasians ,32. The ucasians ,33,34. Ap values that were less than 0.05 were considered statistically significant. Distributions of allele, genotype and haplotype frequencies between cases and controls were compared via Pearson’s Chi squared test or Fisher’s exact test where appropriate. Two-tailed p values, odds ratios (OR) and 95% confidence intervals (CI) were calculated. p values less than 0.05 were considered significant. The estimation of haplotype frequencies was carried out via the Expectation-Maximization algorithm using Arlequin 3.5.1.3 [All results were tested for Hardy–Weinberg equilibrium. Comparisons between genotype and allele frequencies in different populations were assessed using the Chi-square test.  3.5.1.3 . The IBMIL10 and TNF).We compared allele and genotype distributions for SNPs with functional impacts within genes of potentially relevant cytokines for CIDP pathogenesis, between HCs and patients with CIDP. Furthermore, we performed a haplotype analysis of genes with more than one genotyped SNP  both in the patient and control groups, and IL6 in the patient group.The results of genotyping for all the investigated SNPs in our study population are shown in IL10 polymorphism. The dominant homozygote AA was underrepresented (p = 0.049), while the GA genotype had a higher frequency in the patient group (p = 0.032). Also, a significantly higher frequency of the T allele was observed for rs1800871, and of the A allele for rs1800872, in IL10 in patients with CIDP compared to the HCs (p = 0.048).We noted a statistically significant difference in genotype frequencies between CIDP patients and the HCs for rs1800896 IL10 and TNF. In IL10, three haplotypes with frequencies greater than 1% in patients and controls were identified  was omitted from the analysis. We did not find any significant differences in TNF dinucleotide haplotype frequencies between patients with CIDP and the HCs.The frequencies of p = 0.013 in favor of the GC genotype in HCs and p = 0.049 in favor of the GG genotype in CIDP patients). Frequencies of alleles and genotypes of polymorphisms of other investigated genes were not significantly different in CIDP patients compared to the HCs.Another disparity was observed for genotype frequencies of rs1800795 polymorphism in the gene encoding IL-6 ), compared to CIDP patients without the G allele. Carriers of the A allele in IL10 rs1800896 were more frequent in the group of patients with mild disability, as measured via INCAT ). Nevertheless, all the patients with mild INCAT were C carriers for rs1800871 in the IL10 gene  compared to 90.0% in the group of patients with severe INCAT .We also assessed whether the distributions of allele carriers and genotypes correlated with the clinical characteristics of patients with CIDP. The associations were observed in relation to the presence of T2D in CIDP and to INCAT at nadir, as a measure of disability. G allele carriers for the rs1800795 polymorphism in the gene encoding IL-6 in the group of CIDP patients were more likely to have T2D , with the treatment response or with CIDP outcome (according to CDAS). Also, we did not find an association of any other assessed characteristic of CIDP with the allele or the genotype of the investigated polymorphism.IL10, IL6, IL12B, TNF, CSF2, IL17F and IFNG genes with CIDP.The genetic basis of CIDP has not yet been sufficiently investigated, and further studies are still needed to determine the association between a precisely selected group of SNPs , which code for different proteins of the immune system, and CIDP pathogenesis. Although the role of cytokines has already been postulated in the pathogenesis of CIDP , no atteIL10 promotor are known to be involved in the modulation of IL-10 production [IL10 gene [IL10 gene and CIDP has not yet been analyzed in the current literature. Thus, for the first time, we have shown the association of the IL10 SNP with CIDP. More precisely, we have observed statistically significant differences in GA and AA genotype frequencies between our CIDP patients and HCs for the rs1800896 polymorphism in the IL10 gene. Considering another investigated IL10 gene SNP, rs1800871, and its susceptibility to different autoimmune diseases, Indhumathi et al. observed a notable difference in the frequencies of the minor C allele between psoriasis patients and healthy controls [IL10 gene SNP might play a role in CIDP susceptibility.IL-10 is considered one of the most important cytokines with anti-inflammatory features; it regulates the functions of different immune components and has an important role in the biology of T and B cells . Polymoroduction  and corroduction . Among toduction . Indeed,L10 gene . The exaL10 gene . Howevercontrols . SimilarIL10 promotor with the amount of secreted cytokine upon the in vitro stimulation of peripheral blood mononuclear cells by concanavalin A [IL10 SNP in other neurological autoimmune disorders, MS and RA, respectively, are in line with our findings. For instance, Luomala et al. determined a protective role of the AG genotype of the IL10 gene against severe MS forms, suggesting that this polymorphism might affect disease severity rather than the onset of the disease [Turner et al. found an association of the above-mentioned SNP in the avalin A . Specifiavalin A  and Schoavalin A  on the r disease . On the  disease .Nevertheless, the role of IL-10 in CIDP has not been elucidated and further investigations are still needed. Data from animal models on the role of IL-10 in CIDP pathogenesis are conflicting. On one hand, B7-2-deficient NOD mice spontaneously develop autoimmune polyneuropathy associated with a decrease in IL-10 ,45. On tIL6 at position −174 (rs1800975) is the functional polymorphism, and the G allele has been associated with higher IL-6 production [Due to its prominent proinflammatory function, IL-6 is regarded as a key player in the regulation of the immune response, and dysregulation of the IL-6/IL-6R system has already been associated with the pathogenesis of several autoimmune diseases ,52. An Soduction . We founoduction . Howevern −174 rs00975 is oduction .IL6 rs1800795 and T2D risk [IL6 gene more frequently had T2D compared to the other CIDP patients. A recent European multicenter study showed a twofold increased relative risk of T2D in CIDP patients when compared with the general population [The assessment of this SNP and susceptibility to T2D yielded opposing data, but the C allele was a risk factor for higher BMI and insulin resistance ,56,57,58T2D risk . In our pulation . Althougpulation .IL6 gene and T2D presence in CIDP, we also observed a correlation between INCAT at nadir (a measure of disability) and rs1800896 and rs1800871 polymorphisms in the IL10 gene. During this analysis, a lower  INCAT score in our cohort was noted at the time of investigation. This finding could be interpreted in two main ways, and the first one was the early establishment of CIDP diagnosis in our patients. As per our recent publication, the mean delay in referring a patient with suspicion of CIDP from secondary to tertiary health centers in Serbia is quite short  [Besides the above-mentioned association between the G allele carriers for rs1800795 polymorphism in the  months) . The sec months) .The main limitations of our study are the fact that we could not exclude eventual ethnic specificities of the Serbian population regarding some of the analyzed SNPs, and the relatively small sample size. Despite these limitations, this is still the first study that has evaluated the relevance of cytokine polymorphisms in a representative number of patients diagnosed with this rare disorder. Considering the prevalence of CIDP, future studies ought to be multicentric studies to rule out the contribution of SNPs in cytokine genes in this disease.IL10 promotor and IL6 gene SNPs as possible CIDP susceptibility biomarkers. These SNPs were associated with a few of the clinical characteristics of patients (INCAT at nadir and the presence of T2D). However, further research is necessary to confirm our findings and to identify potential genetic biomarkers of disease activity and CIDP outcome predictors. Eventually, this can improve our knowledge regarding CIDP pathogenesis and lead to new possibilities for the treatment of this chronic and debilitating disease.Our results expand the data regarding the role of several investigated functional cytokine polymorphisms in CIDP and identify the


Astragalus membranaceus) being the most important herb. In conclusion, the case and literature demonstrated that TCM treatment might be a more effective, low-cost, and safe option for treating CIDP. Although these preliminary findings are promising, a larger sample size and higher-quality randomized clinical trials are urgently required to confirm our findings.Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated neuropathy. First-line treatments for CIDP include corticosteroids, intravenous immunoglobulin, and plasma exchange. However, the application is always limited by high costs, effectiveness, and adverse events. This study investigated a new potentially effective and safe therapeutic treatment to alleviate CIDP symptoms and improve the quality of life. In the present case, a 47-year-old rural woman presented with weakness and numbness of progressive extremities. She was diagnosed with CIDP based on abnormal cerebrospinal fluid and electromyography. The patient was treated with intravenous dexamethasone for 1 week and with Huangqi-Guizhi-Wuwu and Bu-Yang-Huan-Wu decoctions for 90 days. Surprisingly, after the treatment, the weakness and numbness were eliminated, and the quality of life improved. The varying INCAT, MRC, and BI scores also reflected the treatment effects. After 8 months of discharge, the symptoms did not relapse during the follow-up. We also searched “traditional Chinese medicine (TCM)” and “CIDP” in PubMed, EMBASE, the Web of Science, the Cochrane Library, the Chinese National Knowledge Infrastructure Databases, Wanfang Data, and the Chongqing Chinese Science and Technology Periodical Database. Finally, only ten studies were included in the literature review. Three studies were randomized controlled trials, and seven were case reports or case series. There were 419 CIDP patients, but all study sites were in China. Nine TCM formulas involving 44 herbs were reported, with Huang Qi ( Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare immune-mediated neuropathy in which an abnormal immune response causes peripheral nerve demyelination and axonal damage . It usuaThe guidelines recommended intravenous immunoglobulin (IVIg), corticosteroids, and plasma exchange as first-line treatments for CIDP , 5. HoweAlthough first-line treatments can improve symptoms in some patients, they also require ongoing maintenance therapy and the patient's willingness to tolerate the adverse effects or financial burden. The International CIDP Outcome Study (ICOS) revealed that only one-third of CIDP patients were in remission 1 year after the start of first-line treatment, and residual symptoms and deficits were common regardless of treatment . There iTraditional Chinese medicine (TCM) has a long history of boosting weakness and sensory dysfunction. TCM treatments have been widely used as a supplement to CIDP treatment in China. Many recent clinical trials have found that TCM treatments can improve clinical symptoms and the quality of life in patients with peripheral neuropathy (PN). Furthermore, TCM therapy can also enhance the sensory nerve conduction velocity (SNCV) and motor nerve conduction velocity (MNCV) in PN –13. The However, no English literature reports the clinical efficacy of Chinese herbs for CIDP. In the present study, we attempted to use short-term corticosteroids combined with Chinese herbs on a patient with CIDP. Surprisingly, we identified that this therapeutic regimen completely relieved limb weakness and numbness and improved the quality of life. A literature review for TCM in CIDP was also conducted.This case report was conducted in accordance with the Case Report (CARE) Guidelines .On 25 November 2021, a 47-year-old rural woman complained of progressive weakness and numbness in her extremities. Initially, her symptoms were mild, causing her to experience difficulty grabbing objects or walking. After 3 months, the symptoms gradually worsened; she could not hold anything and only walked with assistance. On 23 February 2022, she was diagnosed with PN at another hospital. However, no IVIg or corticosteroids were administered to her, and her symptoms did not improve. Then, on 10 March 2022, she was transferred to our hospital . Upon arrival, the woman exhibited signs of both fatigue and limb paralysis, and she specifically emphasized that the numbness she was experiencing felt like she was wearing gloves and socks. She had no other particular medical history .The proximal end of the upper and lower limbs had grade 3 muscle strength, while the distal end of all limbs had grade 2 muscle strength. Muscular atrophy was observed in the bilateral first dorsal interosseous. Tendon reflexes decreased or disappeared, and limb muscular tension also decreased. Pain and temperature sensibility on the distal limbs decreased. Pyramidal tract signs were not elicited. There was no problem with eye montraosvement, pupil size, or swallowing function.The cerebrospinal fluid (CSF) result revealed that the white blood cell count was one, and the micro-amount of protein was 652.6 mg/L . Other anti-ganglioside antibodies in CSF and serum were all negative, except for anti-sulfatide (aSF) IgG in CSF. The erythrocyte sedimentation rate (ESR) was 36 mm/h . Antinuclear antibodies, rheumatoid factors, HBsAg, HCV-Ab, rapid plasma regain, and HIV-Ab, were all negative. The routine blood, stool, and urine examinations, renal and liver functions, myocardial enzymes, and thyroid functions were all normal.Multiple nerves in the upper and lower limbs were observed with decreased MNCV, SNCV, and amplitude during an electromyography (EMG) examination. Demyelination and axonal damage were identified in the bilateral median, ulnar, tibial, and peroneal nerves. Furthermore, no waveforms were elicited from the left peroneal motor nerve, the left median sensory nerve, or the bilateral superficial peroneal sensory nerves . The braOver 8 weeks, the patient developed progressive, symmetric upper- and lower-limb weakness and numbness and reduced tendon reflexes in all limbs. In addition, abnormal CSF and EMG were observed. The patient was diagnosed with CIDP using the EFNS/PNS consensus guideline .Astragalus membranaceus), 60 g; guizhi (Cassia Twig), 10 g; chishao (Radix Paeoniae Rubra), 10 g; danggui (Angelica sinensis), 10 g; chuangxiong , 10 g; dilong (Lumbricus), 10 g; weilingxian (Radix Clematidis), 10 g; fuling (Poria Cocos), 10 g; baizhu , 10 g; dangshen (Codonopsis pilosula), 10 g; Roucongrong (Cistanche), 15 g; and gancao (liquorice), 6 g. The quality of these herbs was consistent with the 2020 Chinese Pharmacopeia  was used for 1 week. Simultaneously, the patient was given TCM. The TCM formulas used in this case report were Huangqi-Guizhi-Wuwu and Bu-Yang-Huan-Wu decoctions (HGW and BYHW), which is composed of 12 herbs: Huang Qi  Disability Score was 6. The Medical Research Council (MRC) score was 32. The Barthel Index (BI) was 50. After 20 days of treatment, the MRC and BI scores increased to 38 and 60, respectively. However, the INCAT score remained unchanged. Moreover, 3 months later, the patient reported no limb weakness or numbness, and his limb muscle strength could reach grade 5. INCAT, MRC, and BI scores changed to 0, 60, and 100, respectively . After eMost importantly, no side effects were reported. It was unfortunate that she refused to accept an EMG to assess nerve recovery. The patient was delighted with the treatment outcome and was free of adverse events, and the cost was acceptable for a rural family in a developed country. She stated that, after coming to our hospital, her symptoms improved and her quality of life significantly improved. All follow-ups were conducted face to face.From their inception to 11 November 2022, we screened the following databases for literature reviews: PubMed, EMBASE, Web of Science, the Cochrane Library, the Chinese National Knowledge Infrastructure Databases (CNKI), Wanfang Data, and the Chongqing Chinese Science and Technology Periodical Database (VIP). The search strategy included “traditional Chinese medicine” and “chronic inflammatory demyelinating polyradiculoneuropathy” .TCM decoctions were used in all included studies, and the treatment duration ranged from 4 weeks to 6 months. In 60% of the studies, TCM was combined with corticosteroids or IVIg. The average duration of follow-up ranged from 6 months to 16 months. TCM therapies improved muscular strength, sensory disorders (SNCV and MNCV), daily life ability, and relapse rate. However, many studies did not report any adverse event.Astragalus membranaceus) (100%), Banggui (Angelica sinensis) (77.8%), Baizhu  (44.4%), and Dilong (Lumbricus) (44.4%). We used Gephi 0.9.2 and SPSS Modeler 18.0 to perform a complex network analysis to find the core herb. We identified that Huang Qi was the core herb. The results revealed that the number of triangles, clustering coefficient, and eigenvector centrality were 291, 0.32, and 1, respectively (There have been reports of nine TCM formulas involving 44 herbs . The mosectively . FurtherThree RCT studies had sample sizes ranging from 40 to 115. The risk bias assessment tool (RoB2)  was usedThe typical CIDP is a chronic, progressive, monophasic, or recurrent demyelinating polyradiculoneuropathy with progressive weakness, sensory dysfunction, and absent or reduced tendon reflexes . CIDP vaThe CIDP patient discussed in the above care report presented with symmetrical and progressive weakness, numbness, loss of tendon reflexes, abnormal protein levels in the CSF, and demyelination on the EMG. The progressive phase lasted more than 3 months. Furthermore, this patient responded to corticosteroid treatment, one of the characteristics of CIDP . TherefoInterestingly, the patient's CSF ASF-IgG was positive. One of the glycolipid antibodies against the peripheral nerve membrane surface is aSF. Sulfatides constitute a significant class of myelin-specific lipids, and their depletion can result in region-specific effects on non-compact myelin . Only 1–Almost 20% of the CIDP patients did not respond to first-line therapy . FurtherMeanwhile, some researchers have focused on subcutaneous immunoglobulin, which is well tolerated, effective, and affordable. However, the duration of maintenance treatment is at least 24 weeks, and local reactions at the infusion site are common . Better Traditional Chinese medicine and intravenous dexamethasone were used to treat this case. The intravenous dexamethasone course lasted only 1 week, and TCM was used for 3 months. With no adverse events and an extremely positive response, the combined treatment may be a more effective and safe option. The short-term corticosteroid treatment was well tolerated. Moreover, Chinese herbs were inexpensive, had few or no side effects, and were readily available. In the literature review, 50% of the studies  used TCM in combination with corticosteroids, resulting in improvements in weakness, sensory disorder, daily life ability, and relapse rate. Therefore, it can potentially solve the CIDP dilemma, particularly in developing and rural countries. It is generally known that CIDP is an autoimmune disorder that affects peripheral nerve components. Macrophage and T-cell infiltration into peripheral nerves or nerve roots can result in demyelination and axonal damage .Traditional Chinese medicine treatment of this reported CIDP case included Huangqi-Guizhi-Wuwu (HGW) and Bu-Yang-Huan-Wu (BYHW) decoctions, which are the most famous formulas in ancient TCM books. The network pharmacology analysis revealed that HGW could regulate cytokines and the inflammatory response, elements of the cytokine network, the T-cell receptor, NF-kappa B, HIF-1, and PI3K-Akt signaling pathways . BYHW caThe Inflammatory Neuropathy Cause and Treatment Disability Score, MRC, and BI were used in this case to assess the treatment effect at multiple time points. The INCAT disability score is a valuable tool for evaluating upper and lower limb dysfunctions in inflammatory polyneuropathy studies, with the advantages of feasibility, high face validity, and high reliability . The MRCAdverse effects were common with short-, medium-, and long-term immunotherapy . AdverseTo the best of our knowledge, to date, no English literature has reported the clinical efficacy of Chinese herbs for CIDP. This is the first article to summarize TCM trial or case report findings for CIDP. The article also presented potentially effective herbs or formulas containing specific ingredients. However, evidence of efficacy in case reports is lacking. Longer follow-up efficacy and an EMG exam should be investigated further. All the studies in the review were published in Chinese literature, had a single study site, and had low study quality. Large-sample, multi-center, high-quality studies are required to obtain a high level of evidence for TCM. Therefore, TCM has broad potential applications in CIDP because TCM is well tolerated, effective, inexpensive, and readily available.Astragalus membranaceus) may be important for regulating the inflammatory response. Although these preliminary findings are promising, larger sample sizes and higher-quality RCTs are urgently required to confirm our findings.In conclusion, the case demonstrated that TCM treatment combined with short-term corticosteroid therapy eliminated the weakness and numbness of CIDP and improved her quality of life. Huangqi  for the publication of any potentially identifiable images or data included in this article.The idea for this research was proposed by YX. This protocol's drafting was undertaken by YX and LL. DW and JG revised the manuscript for intellectual content. Data collection and illness discussion were performed by YX, LX, JJ, GM, TY, SW, and AL. All authors approved the final version of the manuscript.


A hearing impairment is one of the most significant issues in such cases. Moreover, the presence of middle and inner ear pathologies combined may represent a surgical challenge. No studies have described a combined surgical approach for these coexisting conditions (VS and cholesteatoma), nor the hearing rehabilitation outcomes of using cochlear implants for these patients. (2) Case Report: This paper is on a female patient who underwent simultaneous surgical treatments for VS and middle ear cholesteatoma in the right ear followed by a cochlear implant, describing the technique and the audiological results. (3) Conclusions: The surgical approach was successful and enabled the resection of lesions with the auditory nerve and cochlea preservation. Cochlear implantation in the right ear showed positive postoperative results, with an improvement in the results with the CI in silent and noisy environments. Vestibular schwannoma (VS) is a benign tumor of the Schwann cells from the vestibulocochlear nerve, which occurs at the cerebellopontine angle (CPA) and/or internal auditory canal (IAC) ,2. Its mRecent studies have shown that cochlear implants (CI) can function in the presence of retrocochlear pathologies, such as vestibular schwannoma ,5,6,7,8.Middle ear cholesteatoma is another type of ear disease that can also manifest with hearing loss. The main symptoms are otorrhea, tinnitus and conductive or mixed progressive hearing loss . It is aThe presence of a middle ear or IAC pathology may represent a challenge to performing CI surgery. When treating Cholesteatomatous Otitis Media, the technique of a subtotal petrosectomy associated with CIs provides protection against infection and the extrusion of the device . It is aA few articles describe the co-occurrence of vestibular schwannoma and cholesteatoma in the same patient. The unilateral manifestation of both diseases at the same time is even more rare ,14,15. TA 54-year-old female was referred to the Department of Otorhinolaryngology complaining of progressive hypoacusis in the right ear for the last 19 years. No previous history of diseases was reported. A physical examination revealed right attic tympanic membrane perforation. Computed Tomography (CT) showed the opacification of mastoid cells and the epitympanum, suggesting cholesteatomatous chronic otitis media in the right ear . MagnetiInitial audiological evaluation with pure tone audiometry (PTA) showed conductive hearing loss in the right ear with a tritone average of 56 dB, and the left ear had normal thresholds. The Right Auditory Brainstem Response (ABR) had waves I, III and V present, with increased absolute latencies and normal inter-peak intervals, which are suggestive of conductive loss. The patient avoided surgery on multiple occasions, was lost during the follow-up and returned after 2 years for reassessment due to a vertiginous crisis. At this point, the patient presented with mixed hearing loss, and an important difficulty in comprehension in noise. Although the PTA had a tritone average of 58 dB, the air–bone gaps had increased considerably , and theNew MRI indicated an increase in the dimensions of the expansive lesion inside the IAC, at this point measuring 2 × 1.3 cm, in contact with the cochlear modiolus. It extended and partially obliterated the cerebellopontine angle cistern and brainstem, also compressing the emergence of the right vagus nerve, but with no change in the brainstem signal .The patient underwent tympanomastoidectomy with the resection of the cholesteatoma  and subtThe follow-up otoscopy revealed blind sac ear canal with a wound in great condition. The patient is currently undergoing weekly aural rehabilitation therapy with a team specialized in cochlear implants. Despite magnetic artifacts due to the cochlear implant in the right ear, postoperative MRI  allowed The 6-months postoperative PTA-aided results demonstrated a tritone average of 26 dB in the right ear, with contralateral masking . The BraThe presence of VS and middle ear cholesteatoma in the same patient represents a surgical challenge. The disease courses and the combined surgical approach are both unlikely to preserve hearing. Aiming to surgically remove both lesions and rehabilitate the patient’s hearing, our team of surgeons had to adapt the classical technique. Thus, the resection of cholesteatoma and a subtotal petrosectomy were successfully performed, followed by the enlarged translabyrinthine approach to treating the neuroma. In addition, the cochlea and auditory nerve were preserved, and subsequent cochlear implantation could be carried out in the right ear.Before the surgical intervention, the patient had moderately severe mixed hearing loss in the right ear and normal tritonal average in the left ear, according to Lloyd and Kaplan . The posEach of the two ears substantially contributes to the action potentials that reach the brainstem, which are referred to as binaural loudness. In a binaural-hearing subject, the number of action potentials may double when both ears are used instead of one. The processing of information is also more sensitive to small differences because the just-noticeable differences in intensity and frequency improve with signal redundancy. Therefore, speech recognition in noisy environments is improved . When spA recent systematic review  on the sOne of the patient’s preoperative complaints was the difficulty of comprehension in noisy environments. After only six months postoperatively, she achieved around 64.50% hearing in fixed-noise environments with the CI ear and 99% with bilateral hearing (NH + CI). Our results support the findings of a recently published randomized controlled trial  that shoAnother question that could be raised is about whether it is better to perform the procedures in sequence or concomitantly. When treating patients with SSD, it is important to evaluate the status of the contralateral ear; if there is a risk of, or an emerging hearing loss in the other ear, the surgeon tends to opt for concomitant auditory rehabilitation. In our case, although the contralateral ear had a normal tritonal average, there was a lowering of the thresholds at high frequencies that necessitated a follow-up.In addition, some other factors should be taken into consideration: (i) the duration of deafness is intimately related to speech perception outcomes, so delaying the rehabilitation may jeopardize the results ; (ii) thAn alternative approach to this case would be to access the VS through the middle fossa or retrosigmoid approach in a first stage and, subsequently, address the cholesteatoma through tympanomastoidectomy. In an optimistic scenario, this sequence could allow reasonable hearing preservation, enabling the patient to use hearing aids in the right ear, instead of CI. Even though this was a viable option in this case, the patient had an active role in this decision. Surgery in two stages was offered to the patient, both via the middle fossa and retrosigmoid access points.The advantages of translabyrinthine access are consistent facial nerve identification, no tumor size limitation, no intradural drilling, the wide exposure of the posterior fossa and low recurrence and headache rates. The disadvantages include complete hearing loss and the need for an abdominal fat graft . The midAfter being thoroughly informed of the risks and advantages of each of each approach, and since the patient did not want to undergo a two-stage procedure, translabyrinthine access was chosen. Furthermore, we pondered whether the preservation of hearing in non-translabyrinthine surgery can be temporary, as some of these patients have long-term hearing degeneration after the surgical manipulation of the internal auditory canal . The mecAnother point worth mentioning is that by the time of the surgery, the patient was already suffering from dizziness (her main complaint). Although, the labyrinthectomy via translabyrinthine access leads initially to vertigo and requires subsequent balance rehabilitation, it is also the surgical procedure of the temporal bone used to treat intractable and refractory vertigo . This prEven though this procedure via the translabyrinthine approach with simultaneous cholesteatoma removal and cochlear implantation was feasible and reached optimal results, we are describing a very specific situation—concomitant middle ear cholesteatoma and VS. The goal of this report is not to attest that this combined approach is the best strategy, but to report a successful path for future reference. Surgeons must individualize their conduct for each case and never underestimate the inherent risks of each procedure.The presence of vestibular schwannoma and middle ear cholesteatoma in the same patient represents a surgical challenge. For such clinical circumstances, the classical technique needed to be adapted to optimize the treatment and enable successful outcomes. We described a case, illustrating how it is possible to perform, at the same time and with safety, the resection of both lesions and cochlear implantation in the same ear and during the same surgical session, demonstrating the successful audiological results that followed.