Hearing loss is a significant global health concern, affecting billions of people and leading to various physical, mental, and social consequences. This paper focuses on the risk of noise-induced hearing loss (NIHL) among specific healthcare professionals, especially ear surgeons, orthopaedic surgeons, dentists, and dental hygienists, who frequently use noisy instruments in their professions. While studies on these professionals’ noise exposure levels are limited, certain conditions and factors could pose a risk to their hearing. Measures such as engineering and administrative controls, regular audiometric testing, and the use of hearing protection devices are crucial in preventing NIHL. Early detection and intervention are also vital to mitigate further damage. This paper proposes the results of a modified screening protocol, including questionnaires, audiometry, and additional diagnostic tests to identify and address potential hearing disorders. Specific healthcare professionals should remain aware of the risks, prioritize hearing protection, and undergo regular monitoring to safeguard their long-term auditory well-being. Hearing loss affects around 1.5 billion people globally, with the World Health Organization (WHO) predicting that by 2050, the number will reach nearly 2.5 billion [Occupational noise-induced hearing loss (NIHL) is a symmetrical sensorineural hearing loss that gradually develops after continuous or intermittent noise exposure. Following exposure to loud noise, a temporary threshold shift (TTS) or temporary hearing loss is present for 16 to 48 h. During the initial stages of NIHL, pure tone audiometry may appear normal, and there may be no observable signs of hearing loss on the hearing threshold. The condition referred to as “hidden hearing loss” is characterized by the damage or loss of synaptic connections between hair cells and cochlear neurons .The gradual deterioration of auditory neurons is caused by this synaptopathy, which results in abnormal speech intelligibility and involvement of the hearing threshold at high frequencies (above 3 kHz) ,5.According to the Occupational Safety and Health Administration (OSHA), over 20 million workers are exposed to potentially harmful noise in the workplace every year . MoreoveThe OSHA and the European Agency for Safety and Health at Work have developed a hearing conservation program for individuals exposed to a noise level of 85 dBA or higher, averaged over 8 working hours ,9. The AEX8h exposures of 85, 90, 95, and 100 dBA, covering exposure durations ranging from 10 to 40 years. By utilizing these tables, it becomes feasible to calculate the average estimated NIPTS for the median of a population. According to the ISO 1999 standard, hearing impairment is defined with three definitions [-An average of the hearing threshold levels at 0.5, 1, and 2 kHz that exceeds 25 dB;-An average of the hearing threshold levels at 1, 2, and 3 kHz that exceeds 25 dB;-An average of the hearing threshold levels at 1, 2, 3, and 4 kHz that exceeds 25 dB.The International Organization for Standardization (ISO) 1999:2013, titled “Acoustics—Estimation of noise-induced hearing loss”, provides comprehensive guidelines for assessing and estimating the impact of occupational noise exposure on individuals’ hearing health. The key objectives of ISO 1999:2013 include establishing criteria for classifying noise-induced hearing loss, defining audiometric evaluation procedures, calculating the risk of hearing impairment, and addressing permanent noise damage. It emphasizes the importance of considering factors such as ambient noise levels and exposure duration when evaluating the risk of hearing loss. Included within the standard are tables that present examples of predicted noise-induced permanent threshold shifts (NIPTS) at frequencies of 0.5, 1, 2, 3, 4, and 6 kHz. These predictions are based on LIt is essential to eliminate or minimize the risk of occupational NIHL. Early detection and intervention are crucial in preventing hearing loss, which is irreversible. General prevention principles can help reduce hearing impairment, such as adopting working methods or equipment that require less exposure to noise, using shields or noise-absorbing coverings, conducting periodic audiometric testing, and utilizing hearing protectors .The demanding environment of the operating room presents specific healthcare professionals with numerous challenges, and one often overlooked aspect is the potential risk of noise-induced hearing loss. In the fast-paced world of operative procedures, professionals who use noise-generating tools rely heavily on a variety of instruments to perform intricate procedures. However, the use of noisy instruments poses a unique challenge. Prolonged exposure to high levels of noise during these procedures may have detrimental effects on the professionals’ hearing abilities.This paper provides a concise overview of the hearing risks faced by some specific healthcare workers who are not considered at high risk of developing occupational NIHL.Noise exposure levels have been recorded in various operating rooms and reported in different studies with contrasting results. The levels of noise can vary significantly depending on several factors. The design and layout of the theatres, the types of equipment and instruments utilized, as well as the procedures being performed, all contribute to the overall noise levels experienced by surgical teams .Our focus is on four categories of professionals, including ear surgeons, orthopaedic surgeons, dentists, and dental hygienists, specialities that involve the use of noisy tools.Otorhinolaryngologists, specifically ear surgeons, may face high levels of noise exposure during temporal bone drilling. Although few studies have measured the risk in the operating room, Vaisbuch et al. researched noise exposure during temporal bone drilling, even when multiple individuals were drilling simultaneously in dissection labs . Some stOrthopaedic surgeons use various power tools and loud instruments such as drills, saws, and hammers during surgery ,14. HoweOccupational noise that may be hazardous to dental practitioners and hygienists and has been recorded even in dental healthcare settings ,19,20. PHowever, based on our experience and case series, it is not common for practitioners in these fields to utilize hearing protection devices. This lack of protection leaves them vulnerable to exposure to loud and potentially harmful levels of noise in their work environment .To prevent the progression of auditory damage, early detection of these conditions is essential for individuals who are exposed to loud sounds. We firmly believe that regular audiological screening is necessary for such individuals to detect a hearing impairment.Below, we outline a modified adult screening procedure recommended by the World Health Organization, which is followed at our tertiary referral centre, Policlinico “G. Martino” in Messina   see Fig. Due to A total of 42 individuals, comprising ear surgeons (10 subjects), orthopaedic surgeons (14 subjects), dentists, and dental hygienists (18 subjects), underwent a hearing screening see . These pSimple anamnestic questions regarding hearing are employed as part of the screening process. These questions provide a comprehensive overview of the individual’s hearing health and help direct the screening investigation. A combination of binary (Yes/No) response questions and scored questions are utilized see .These questions allow for quick assessments and are designed to capture specific aspects of the individual’s hearing health. They cover topics such as exposure to loud noise, history of ear infections or trauma, and the use of hearing protection devices. These questions enable healthcare professionals to identify potential risk factors and determine the need for further evaluation.Furthermore, validated questionnaires can be employed to delve deeper into the initial investigation. These questionnaires have been extensively tested and proven to be reliable tools for assessing specific aspects of hearing. By utilizing these validated questionnaires, healthcare professionals can gather more comprehensive data and gain further insights into the individual’s hearing health status.The Self-Efficacy for Situational Communication Management Questionnaire (SESMQ), which measures the perceived self-efficacy for managing communication in individuals with hearing loss. The SESMQ questionnaire consists of 20 questions, each divided into two scales, and the subject is required to respond by assigning a score from 1 to 10. The first scale assesses hearing ability (SESMQH), while the second scale evaluates the level of confidence (SESMQ). Each subscale has a score ranging from 10 to 200. The total score is the sum of the two subscale scores ;Aeq8760h  is equal to or greater than 79 dB [The Noise Exposure Questionnaire (NEQ), which quantifies personal annual noise exposure from both occupational and non-occupational sources. The NEQ questionnaire consists of three sections: the first section includes demographic information, the second section contains six screening questions that assess exposure to high levels of noise, and the third section consists of eleven questions related to participation in noisy activities, on which the annual exposure level is calculated. Three questions in the second section (1-min Noise Screen) serve as a screening tool to assess exposure to high levels of noise, with a score greater than 4 indicating a high risk of developing NIHL (Noise-Induced Hearing Loss). The NEQ questionnaire calculates the annual noise exposure, and the risk of developing NIHL occurs when the Lan 79 dB ;The Hearing Handicap Inventory for the Elderly (HHIE), which assesses the impact of hearing impairment on emotional and social adjustment. The HHIE questionnaire consists of 25 questions. The individual assigns a score ranging from “yes” (4 points), “sometimes” (2 points), to “no” (0 points). The total score ranges from 0 to 100 .Typically, we employ three questionnaires:Pure-tone audiometry, speech audiometry, and the free-field Matrix sentence test are used as audiological screening tests. These are conducted within a soundproof booth that attenuated environmental noise by 40 dB SPL. The tests are performed using the Madsen Astera2 audiometer , which had been calibrated within the last 12 months prior to the measurements. For the audiometric evaluations, TDH39 earphones, a B71 bone vibrator, and speakers are utilized.Pure-tone audiometry is employed to determine the individual’s hearing threshold. Speech audiometry is also conducted using spondaic disyllabic Italian words . The worTo assess speech-in-noise intelligibility, the Italian Matrix sentence test is performed. For this test, two speakers are positioned at a distance of 1 m from the participant, with one on the left side and the other on the right side . This is an adaptive speech-in-noise test that consists of 20 randomly generated sentences, each composed of five words, with a background noise interfering with the speech message. The subject is asked to repeat each word they can hear . If the The purpose of the audiological screening tests is to detect the possible presence of noise-induced hearing loss or other disorders in the auditory system such as tinnitus or abnormal speech intelligibility. Noise-induced hearing loss (NIHL) is a symmetrical sensorineural hearing loss that gradually develops after continuous or intermittent noise exposure .All subjects underwent an anamnestic questionnaire see  to assesWhen questionable results were obtained, an audiological assessment was strongly recommended. For individuals who do not report hearing problems, a second screening test was performed.Subsequently, all subjects underwent otomicroscopic examination to assess the presence of earwax, which was removed if necessary. Following this, pure-tone audiometry, speech audiometry with headphones, and the free-field Matrix Sentence Test were performed.“PASS” indicates a condition in which there is no alteration in the audiometric threshold or speech-in-noise intelligibility, as determined by the results of the Matrix sentence test. On the other hand, “REFER” indicates an alteration in one or both of the audiologic tests used.Individuals who receive a “PASS” result in these hearing screening tests will undergo another screening after about two years. Those who receive a “REFER” result will require further evaluation for the presence of any “red flags” alerts, such as rapidly progressive hearing loss, unilateral hearing loss, ear pain, ear discharge, dizziness, or previous diagnosis of ear disease .Doubtful results in these screening tests required more accurate diagnostic approaches, such as auditory brainstem response (ABR), otoacoustic emissions (OAE), magnetic resonance imaging (MRI) of the brain and brainstem, and computed tomography (CT), tympanometry and acoustic reflex testing, etc. Furthermore, overlapping pathological conditions may be present in the patients, and they should not be underestimated.In our case series, a total of 42 subjects  underwent screening. Among them, 10 were ear surgeons, 14 were orthopaedic surgeons, and 18 were dentists or dental hygienists. The average age of these subjects was 48.5 ± 9.5 years, with an average work experience of 22.1 ± 9.5 years see .Analysing the data obtained from the audiometric thresholds, the mean of AC mPTA for the right ear was 19.2 ± 7.6 dB HL, and for the left ear, it was 19.4 ± 7.2 dB HL. As for the word recognition score (WRS), all subjects achieved the 100% intelligibility threshold.Regarding the speech reception threshold (SRT), the average was −6.3 ± 0.9 dB SNR. Two subjects recorded an increased SRT despite having a normal hearing threshold . These values contradicted the normative data presented by Puglisi et al. for the Italian version of the Matrix sentence test .The subjects were then stratified into two groups based on the presence or absence of a hearing handicap. A “hearing handicap” is defined as an impairment in the auditory system that can be objectively measured through the used screening audiological tests or subjectively reported by the person from the anamnestic questions and questionnaires for screening, such as tinnitus or decreased speech-in-noise intelligibility. Thirteen subjects showed evidence of hearing issues: high-frequency notch at 4 kHz (four subjects), otosclerosis (one subject), high-frequency hearing loss (three subjects), tinnitus (three subjects), and elevated SRT with normal hearing threshold (two subjects) see .From the screening anamnestic questions  exposure levels exceeding 79 dB, indicating a risk of developing hearing loss.On the other hand, the 1-min Noise Screen allowed the identification of individuals at higher risk of developing noise-induced hearing loss, considering both recreational and job activities. The average score obtained was 3.3 ± 1.4, indicating that these subjects were not at a high risk of noise-induced hearing loss see . It shouRegarding the HHIE questionnaire, the test was administered to the 13 subjects who reported a hearing handicap; the average score was 17.4 ± 11. Only subjects who had a hearing handicap were administered this test; no other subjects reported any hearing problems.We want to clarify that no statistical analysis has been conducted as the presented article takes the form of an “opinion” rather than a research study aimed at demonstrating the association between the use of noise-emitting tools and noise-induced hearing loss or even other hearing disorders. The screening protocol is currently undergoing validation, and the results presented are only preliminary data. Subjects were stratified solely for descriptive purposes and not for comparison. The literature contains variable data regarding exposure levels, making it unable to definitively state the absence of a real risk for these individuals. Therefore, the possibility of developing noise-induced hearing loss or other auditory issues should always be taken into consideration.The best way to reduce the risk of developing occupational NIHL is through prevention measures, as the condition is irreversible and there are currently no effective treatments available. The prevention program is based on three levels: primary prevention, which involves reducing noise exposure levels below hazardous levels; secondary prevention, which focuses on early detection of hearing loss to prevent further damage; and tertiary prevention, which aims to reduce disability or handicap when significant impairment is already present ,37.The European Agency for Safety and Health at Work emphasizes the importance of maintaining a safe and healthy work environment, including periodic monitoring of noise exposure. When high levels of noise are detected, engineering and administrative controls are necessary to prevent irreversible damage to the inner ear. These controls include: (1) selecting appropriate work equipment; (2) providing adequate information and training to ensure proper use of work equipment; (3) reducing noise levels through technical means; (4) implementing maintenance programs for work equipment, workplace, and workplace systems; (5) organizing work to minimize noise levels; (6) limiting the duration and intensity of noise exposure; (7) establishing work schedules that include adequate rest periods .The risk of developing occupational NIHL can be significantly reduced or eliminated when the noise level is kept below 80 dBA. Legal standards for noise levels have been established by various countries .Elevated noise levels have been observed to have a detrimental impact on patient outcomes and impair the performance of healthcare professionals in the operating room. Despite the increase in decibel levels caused by playing music in the operating room, the majority of surveyed staff expressed a positive inclination towards having music during surgery, believing it to enhance both individual and team performance. Overall, music was not perceived as a distraction or hindrance to communication . Some stOther measures of well-being could be applied in the environments where operative procedures are conducted. In a study that proposed the revitalization of a park, it was highlighted that it is not only necessary to reduce noise exposure levels or introduce positive sounds, but also to implement measures that enhance overall well-being. A similar approach could be employed in the workplaces where the subjects under consideration operate. Further investigation is needed to explore the most effective measures, making this area a promising research field yet to be fully explored .Secondary prevention is achieved through regular audiometric testing. Implementing regular auditory assessments and monitoring programs can help detect any early signs of hearing loss in professionals who use noise-generating tools. Prompt identification of hearing impairment allows for timely intervention and the implementation of strategies to mitigate further damage.However, there is still some uncertainty in the literature regarding noise exposure for these subjects who work with noisy instruments. Although these workers are not typically considered at high risk for developing occupational NIHL, it has been reported that noises below the action level can cause temporary and potentially long-term hearing damage .Animal studies have shown that moderate noise exposure (100 dB SPL for 2 h) can cause a TTS without resulting in hair cell loss. However, repeated TTSs, even with threshold recovery, can alter cochlear responses to suprathreshold sound levels. This can result in a synaptopathy, which is characterized by a reduced number of auditory nerve fibres’ activation and a decrease in their firing rate or synchrony. This condition is known as “hidden hearing loss” and is characterized by a normal hearing threshold but difficulties in complex listening tasks, such as word recognition, accurate speech, and sound detection in noisy environments .According to Moore et al., pure tone and speech audiometry are valuable tests in diagnosing NIHL. NIHL caused by different types of noises can be distinguished. Additionally, it is advisable to compare the patient’s hearing threshold with the age-related hearing levels for a non-noise-exposed population, typically using the 50th percentile as specified in ISO 7029 (2017). The NIHL should be quantified for each ear by considering the mean hearing threshold across the frequencies of 1, 2, and 4 kHz .The diagnosis of hidden hearing loss warrants a separate discussion. Kohrman et al. have described three diagnostic approaches for this. The first approach involves the auditory brainstem response (ABR), which shows a reduction in the amplitude of the ABR I peak without any changes in ABR threshold or latency. This reduction correlates with the degree of cochlear synaptopathy. The second approach involves frequency following responses (FFRs), which demonstrate a decline in modulation frequency near 1 kHz, correlating with synaptic loss. The third approach involves a weaker middle ear muscle reflex response in individuals with hidden hearing loss .In this study, we presented the data related to the screening protocol followed at our tertiary referral centre. It is important to note that these are preliminary findings. The screening program has been ongoing for two years, and concrete data on subject follow-up are not yet available.As mentioned earlier, the subjects were recruited among ear surgeons, orthopaedic surgeons, dentists, and dental hygienists. We deemed it appropriate to select only subjects with more than 10 years of experience, as the risk of noise-induced hearing loss increases with prolonged exposure.As outlined in the Materials and Methods section, the initial step involved collecting subject histories to guide the clinician in the appropriate screening pathway. The SESMQ questionnaire and the 1-min Noise Screen were administered to all subjects, while the HHIE questionnaire was given only to those who reported subjective hearing loss or a hearing handicap. It is important to note that these questionnaires are easy and reliable tools for initial diagnostic assessment but should be integrated with objective tests. Questionnaires provide subjective estimates in a rapid manner, as they can be completed in a few minutes. They also have the advantage of being sent via email or filled in online, allowing for quick data collection and early identification of individuals at risk of hearing loss. However, it should be noted that the 1-min Noise Screen may not identify subjects at risk of noise-induced hearing loss since these people may not perceive their noise exposure as risky. This may necessitate the administration of the full NEQ questionnaire.Regarding the administration of the HHIE questionnaire, in our protocol, it is given only to subjects who perceive hearing loss. In this case, as well, biases may occur as some subjects may perceive hearing loss despite having normal auditory function (not in our case series).Furthermore, questionnaires are tools that should be used to rapidly obtain an effective estimation of the risk of noise-induced hearing loss or deafness. Therefore, a streamlined procedure must be applied when extending the screening protocol to many subjects to ensure compliance.However, in our protocol, all subjects subsequently undergo more reliable tests such as pure-tone audiometry, speech audiometry, and the Matrix sentence test. Subjects with normal results, indicating a PASS, are rescreened after 2 years. Those with hearing problems undergo more comprehensive examinations.In our case series of 42 subjects, 13 individuals demonstrated a hearing handicap: these were referred for further instrumental examinations. The data for these patients are currently unavailable as the diagnostic assessment is still ongoing; hence, concrete results cannot be presented at this time.Aeq8760h of 79 dB: one subject with a notch at 4 kHz and one subject without hearing impairment.Out of the eight subjects who completed the full NEQ questionnaire, only two subjects exceeded an annual LIt is important to reiterate that the data presented in this study are preliminary. The hearing problems observed in these subjects cannot be definitively attributed to noise-induced damage: modifiable risk factors  and non-modifiable factors , as well as comorbidities or ototoxic drugs, can influence the possibility of hearing damage. The purpose of this study is not to establish a causal relationship between the “risk factor” of using noise-emitting tools and the “disease” itself, namely noise-induced hearing loss, but rather to raise awareness about the potential impact of the work environments and tools utilized on the individuals’ auditory system. Establishing a potential correlation between noise-induced hearing loss in the considered healthcare workers requires appropriate studies. The noise exposure levels to which the subjects are exposed, necessary according to the ISO 1999–2013 standard to assess the risk of developing noise-induced hearing loss, were not considered in this paper, as the focus is to describe a possible streamlined and rapid screening program. Subjects may be exposed to varying levels of noise, and it is uncertain whether some of these levels are of sufficient intensity to cause auditory damage. Measuring exposure levels requires specific protocols that are challenging to implement in a screening program. However, the purpose of this analysis is to draw attention to a relevant public health issue. We are convinced that the conflicting results present in the literature require further confirmation to avoid underestimating the risk faced by these individuals and to identify the most appropriate screening protocol. Due to the presence of numerous limitations and biases in our work, as a future perspective, and an expansion of the scientific literature, a more refined and validated screening program should be developed. Studies demonstrating the association between noise-emitting operative tools and noise-induced hearing loss, or other hearing impairments, should be conducted, considering the execution of randomized clinical trials with a larger sample size or multicenter studies. Additionally, evaluating noise exposure levels and taking into account human exposure to noise, considering the position of the operator’s head and body, would provide more accurate measurements. Therefore, a binaural measurement approach would be recommended.Noise-induced hearing loss is a real occupational hazard faced by surgeons and other healthcare professionals due to prolonged exposure to high levels of noise in the operating room. Preventing occupational noise-induced hearing loss is crucial as the condition is irreversible and currently has no cure. To achieve this goal, a prevention program is recommended.Creating awareness among professionals who use noise-generating tools about the importance of noise management in the operating room is essential. Education and training programs can emphasize the significance of adopting noise reduction strategies while using these instruments when necessary.Despite being exposed to high noise levels, these subjects may not be considered a high-risk group for developing hearing handicaps. Factors such as the short duration of exposure, distance from noise sources, awareness of the risks, and regular auditory assessments contribute to the preservation of their hearing health.The variability in noise levels underscores the importance of conducting individualized assessments for each operating room. Understanding the specific factors that contribute to noise generation in each specialty can aid in implementing appropriate noise control measures.From the data we collected, out of the 42 subjects analysed, 13 individuals had a hearing handicap. Among these, one case was attributed to otosclerosis and not related to noise exposure. As for the remaining 12 subjects, it cannot be definitively stated that their hearing handicap is solely attributable to noise exposure, but it cannot be ruled out either. These individuals exhibit deficits compatible with noise-induced damage. While we acknowledge that our screening currently lacks validation, the analysis of data from these subjects still revealed the presence of some individuals with a hearing handicap.In this article, we aim to advocate for the importance of regular screenings in these individuals, as there is a lack of awareness, based on our experience, regarding the potential risk of developing hearing impairment. Although the association has not been proven, screening can serve as an early diagnostic tool for identifying potential hearing deficits among these subjects.If a potential association between noise-induced hearing loss and healthcare workers who use noisy instruments is confirmed, efforts should be directed towards optimizing the acoustic environment in operating rooms through the use of sound-absorbing materials, proper room design, and the adoption of quieter surgical instruments where feasible. Additionally, the use of personal protective equipment, such as noise attenuators or hearing protectors, should be considered to minimize the risk of prolonged exposure to high noise levels.We believe that further research and collaboration between healthcare professionals, audiologists, and equipment manufacturers are needed to establish standardized guidelines and best practices for noise control in operating rooms. By addressing the variability in noise levels across different specialties and implementing appropriate mitigation strategies, the overall work environment can be made safer and more conducive to optimal surgical outcomes and the well-being of surgical teams.However, it is crucial for these workers to remain vigilant, prioritize hearing protection, and continue to monitor their hearing to ensure long-term auditory well-being, protecting the “gift of sound”.


Widely documented, megaevolutionary jumps in phenotypic diversity continue to perplex researchers because it remains unclear whether these marked changes can emerge from microevolutionary processes. Here, we tackle this question using new approaches for modeling multivariate traits to evaluate the magnitude and distribution of elaboration and innovation in the evolution of bird beaks. We find that elaboration, evolution along the major axis of phenotypic change, is common at both macro- and megaevolutionary scales, whereas innovation, evolution away from the major axis of phenotypic change, is more prominent at megaevolutionary scales. The major axis of phenotypic change among species beak shapes at megaevolutionary scales is an emergent property of innovation across clades. Our analyses suggest that the reorientation of phenotypes via innovation is a ubiquitous route for divergence that can arise through gradual change alone, opening up further avenues for evolution to explore. Species beaks innovate and elaborate while whole clades mainly innovate. Understanding patterns and constraints in the adaptive evolution of species traits is a major goal of evolutionary research. At macroevolutionary scales, renewed attention has been given to variation in the tempo and mode of trait evolution among lineages  large, multivariate datasets to allow exploration of trait covariances at different scales, (ii) reliable and efficient computational methods to estimate the major axes of beak shape variation, and (iii) a set of mathematical tools that can estimate degrees of elaboration and innovation at any scale. To meet the first challenge, we use an 8D beak shape morphospace based on a geometric morphometric dataset of 8748 species of birds .We tested the expectation, derived from adaptive radiation theory  and the Apodiformes (swifts and hummingbirds). Clades with hooked beaks have highly integrated beaks and brain cases and strong allometric patterns of shape variation, particularly among raptorial clades , or class-wide phylogenetic level  and in further nested analysis of the order Passeriformes (figs. S14 and S15). The extent of both elaboration and innovation tends to reduce as we move from class-wide phylogenetic to within-order comparisons. We regard within-order comparisons as the most informative level of comparison at the macroevolutionary scale because comparisons of species level values derived from the main axis of variation at the level of whole Neornithes might reflect global constraints in beak shape or an axis of innovation among clades (as with the Apodiformes discussed above). The class-wide phylogenetic major axis of beak variation aligns closely with the raw (non phylogenetic) major axis in the trait space and primarily describes variation between short, deep, and wide beaks at one extreme and long, shallow, and narrow beaks at the other. Our results point to the possibility that within clades, the phylogenetic major axes of beak variation follow different directions.Phylogenetic distributions of elaborationspecies is the main mode of beak shape divergence at the macroevolutionary scale  evolutionary rate matrix onto the class-wide phylogenetic major axis of beak variation so that they shared the same origin in the shape space. We then used linear algebra to project a focal clade’s phylogenetic major axis of beak variation onto the class-wide phylogenetic major axis of beak variation  as the clade’s innovationclade score. A high innovationclade score indicates that the direction of evolution of a clade differs from the direction of its parent clade . These scores were calculated for each of 4000 posterior pairs of clade versus evolutionary rate matrix .If deep-time jumps in beak shape . These results are consistent with both divergence in phenotype that is proportional to time  and with the idea that changes in phenotypic correlations are expected to occur over longer periods of time, potentially in response to moving adaptive landscapes . Although the class-wide phylogenetic major axis of beak variation aligns closely with the first dimension of the raw beak shape space  and 7 of the 23 families  align with the Passeriformes phylogenetic major axis of beak variation (fig. S15). In addition to the lack of alignment of clade phylogenetic major axis of beak variation with the class-wide phylogenetic major axis of beak variation for birds, we also found that within clades, beak shape variation is either highly constrained  or higher-dimensional than in some orders or superorder than across the whole class Aves  from the class-wide phylogenetic major axis of beak variation. For example, Accipitriformes  have phylogenetic major axes of beak variation that mainly align with the second dimension of the shape space, suggesting distinct directions of beak evolution for the clade relative to the class-wide phylogenetic level but uniformity in their beak shape within the clade. In contrast, the Podicipediformes (grebes) are highly variable across all dimensions, suggesting that all components of the shape space are necessary to describe their beaks. These observations illustrate multiple routes to innovationclade and imply that within clades, species beak shapes can evolve in many directions [akin to Endler et al.’s  than at the species level . We compared the area under the curve of the scaled density of elaborationspecies, innovationspecies, elaborationclade, and innovationclade. We then measured the difference between both areas and found that there was a significant difference in innovationspecies and innovationclade but no clear difference in elaborationspecies and elaborationclade (R) is more influenced by shifts in the adaptive landscape through time and thus reflecting natural selection in deeper nodes more than in younger nodes (figs. S9 and S10).The disconnect between observations of reorientation of trait space at the macroevolutionary scale and an apparent predominance of elaborationionclade . This dispecies, innovationspecies, elaborationclade, and innovationclade. We ran the PGLS analysis using both single and multiple predictors. Our analyses indicate that the majority of variation  and distance to centroid becomes steeper as innovationclade increases , coupled with elaborationspecies, is a robust explanation for the massive diversity of bird beaks we observe today and is consistent with recent suggestions from univariate analysis that observation of apparently abrupt phenotypic shifts can be explained by gradual Darwinian processes  taxonomic level and innovation at a higher (clade) taxonomic levels could thus explain the diversity of bird beaks we observe today. However, individual species-level variation in the past could also have led to a shift in a clade’s line of least evolutionary resistance through different evolutionary routes on a dynamic adaptive landscape. Together, our results suggest that the signature of evolutionary reorientations in deep time  across a large number of different phylogenetic trees and concatenates the resulting short posteriors into one larger posterior distribution that contains the phylogenetic uncertainty information. We performed the method using the following protocol (see fig. S1). First, we ran three independent MCMCglmm chains, hereafter the parameterization chains, for 50,000 generations with the trait data and the model described above on the consensus tree from the tree distribution, along with flat priors with a belief parameter of 2%, i.e., with a very low weight on the priors. Next, we extracted the following parameters from the parameterization chains: (i) the conservative burn-in average time across the three chains, defined as the highest number of iterations required to first reach the median posterior likelihood value multiplied by 1.1 and (ii) the mini-chain priors, defined as the median posterior model values from the parameterization chains with a belief parameter of 5%. We then ran 400 mini chains in parallel with the estimated burn-in time and priors to run 10 samples past the burn-in. This resulted in 10 exploitable posterior samples for each tree. We used 400 trees because that was the number of models required to reach an effective sample size of at least 200 for all the estimated parameters (see figs. S3 and S4). Using this approach, we reduced the computational time to around 45 CPU hours and 9 GB of RAM per mini-chain—a 400-fold improvement. The total analysis took around three CPU years using the Sheffield Advanced Research Computer (ShARC) cluster from the University of Sheffield. Code to reproduce the procedure is available in the mcmcmcglmmm vignette  by clades  where we calculated the projections of the phylogenetic major axis of beak variation of each clade onto the class-wide phylogenetic major axis of beak variation  where we calculated the projections of each species onto (a) the class-wide phylogenetic major axis of beak variation and (b) the phylogenetic major axis of beak variation of their parent clade . Code to reproduce the analyses is available in this dispRity vignette nt clade . To makeWe measured the amount of orthogonality of each random term  in our models compared to their parent clade and their parent’s parent clade. For example, for Columbiformes, we measured the amount of orthogonality in the evolutionary ratematrices of (i) the Columbimorphae random terms against the phylogeny random terms, (ii) the Columbiformes random terms against the Columbimorphae random terms (parent), and (iii) the Columbiformes random terms against the whole phylogeny random terms (parent’s parent). To measure the amount of orthogonality, we calculated the angles between the phylogenetic major axis of beak variation of the focal clade and their parent clade for each posterior evolutionary rate matrix and within each clade, by randomly comparing phylogenetic major axes of beak variation within a clade. We converted each angle measurement into a degree of orthogonality metric where 0 corresponds to flat angles (0° or 180°) and 1 to right angles (90° or 270°). We then measured the posterior probability of the angles within a clade being different to the angles among clades. These results are available in species, innovationspecies, elaborationclade, and innovationclade as predictors. The most complex model included all two-way interaction termsWe ran PGLS to test the effects of elaboration and innovation on beak shape divergence. Beak shape divergence was calculated as the Euclidean distance of each species beak shape from the centroid of beak shape of all birds. We then fitted a series of nested models with distance as the response and elaborationspecies and innovationspecies as univariate traits. All models were fitted using the phylolm library using a single phylogeny (We then sequentially removed terms to examine effects on model fit. We initially estimated Pagel’s λ (


Mucormycosis is a serious and often fatal fungal infection that is most commonly observed in immunocompromised individuals. The mortality rate of mucormycosis is high if left untreated, and successful treatment requires a combination of antifungal therapy, surgical intervention, and reversal of the underlying immunocompromised state. The choice of antifungal treatment is crucial and depends on several factors, including the safety profile of the drug, its spectrum of activity, and the species of fungus causing the infection. In this report, we describe a case of a patient who presented with mucormycosis and was successfully treated with a combination of antifungal therapy, surgical excision of affected tissue, and reversal of the underlying immunocompromised state. Our report underscores the importance of early recognition and aggressive treatment of mucormycosis to improve outcomes for affected patients. Zygomycetes in the order Mucorales, with rhino-cerebral mucormycosis being the most common form of the disease. The infection primarily affects immunocompromised individuals and carries a high mortality rate if left untreated. Risk factors for mucormycosis include diabetes mellitus, prolonged steroid use, malignancy, hematological malignancy, and post-transplantation [Mucormycosis is an angio-invasive fungal infection caused by fungi of the class antation . Diagnosantation .Antifungal therapy is the mainstay of treatment, with amphotericin B being the antifungal of choice for decades. However, the side effects of amphotericin B can be detrimental, and newer broad-spectrum antifungal agents such as posaconazole and isavuconazole are emerging as potentially effective treatment options . FurtherA 64-year-old female with a medical history of type 2 diabetes mellitus presented to Hospital Selayang, Selayang, Malaysia, in March 2022 with a chief complaint of right eye redness accompanied by right-sided headache and photophobia over the course of two weeks. One week prior to admission, the patient reported right nasal discharge and pain. She denied any history of preceding trauma or falls and reported residing in a flat equipped with air conditioning, with no contact with soil.On examination, the patient was afebrile with a blood pressure of 124/63 mmHg and a pulse rate of 99 beats per minute. There was no evidence of respiratory distress, and the patient's oxygen saturation was 99% while breathing ambient air. Notably, no facial asymmetry, conjunctivitis, proptosis, or ophthalmoplegia was observed. Additionally, a neurological examination did not reveal any meningism, neurological deficits, or cranial nerve palsies. A rigid nasal endoscopy demonstrated eschar in the middle turbinate  scan of the paranasal sinuses revealed mucosal thickening in the right maxillary and sphenoid sinuses, along with surrounding sphenoid bone thickening, which was indicative of right maxillary and sphenoid sinusitis Figure . AdditioRhizopus arrhizus as the causative organism. Susceptibility testing was subsequently performed, which showed that itraconazole had the lowest minimum inhibitory concentration (MIC) of 0.12 µg/mL, followed by posaconazole and amphotericin B, both with MICs of 0.25 µg/mL.On the fourth day of hospitalization, the patient underwent a right medial antrostomy and middle turbinectomy. During the surgery, an eschar was observed in the right middle turbinate, along with a diseased medial wall of the right maxillary sinus. A biopsy of the affected tissue was taken and sent for histopathological examination. The results revealed the presence of wide-septated fungal hyphae with necrosis, as confirmed by positive staining for fungal elements on both periodic acid-Schiff and Grocott methenamine silver staining Figure . FurtherAfter the diagnosis of mucormycosis, the patient was started on intravenous amphotericin B deoxycholate for a planned total duration of six weeks. However, due to the development of electrolyte imbalance and acute kidney injury despite hydration protocol, amphotericin B had to be discontinued on day 35. As posaconazole and isavuconazole were not available in the hospital, oral itraconazole was initiated as an alternative therapy. The patient responded well to the treatment, and a repeat nasal endoscopy was performed, which revealed no residual fungal debris.The patient was followed up at the outpatient clinic and completed a three-month course of oral itraconazole. As of the time of writing, she was still asymptomatic with no signs of disease relapse. The successful management of this case highlights the importance of a high index of suspicion for mucormycosis in high-risk patients, as well as the need for prompt and appropriate antifungal therapy and adequate surgical debridement.Mucorales, class Zygomycetes. The majority of clinical specimens recovered are from the Rhizopus genera, and Rhizopus arrhizus accounts for 60% of all forms of mucormycosis, making it the most common human pathogen overall [Mucorales are found in decaying organic matter, soil, contaminated foods, and construction work, as well as contaminated air filters and aerosolization remains the primary mode of transmission [Mucormycosis is a rare but rapidly spreading invasive fulminant fungal infection of the order  overall . The Mucsmission .Rhizopus sp. can use it as a siderophore to obtain iron and enhance growth [Several risk factors are associated with mucormycosis. These include diabetes mellitus, hematological malignancies, and bone marrow or solid organ transplantation . A case e growth . Lastly,e growth .Mucormycosis is an aggressive and angio-invasive infection that spreads rapidly, leading to tissue necrosis. The fungal hyphae invade the arteries and lymphatic systems, causing the formation of "mucor thrombi," which results in further occlusion, infarction, tissue necrosis, and the development of black necrotic eschar. The infection can spread to adjacent sinuses, orbit, and cranium. Based on the site of infection, mucormycosis is classified into six major forms: rhino-cerebral, pulmonary, cutaneous, gastrointestinal, disseminated, and uncommon rare forms such as endocarditis, osteomyelitis, peritonitis, and renal infection ,5. Rhizopus arrhizus.Rhino-cerebral mucormycosis presents with symptoms such as headache, rhinorrhea, and epistaxis, and may also cause fever and black eschar formation over the nasal or oral cavity. The infection can invade the maxillary, frontal, and ethmoidal paranasal sinuses, leading to facial numbness and edema. If left untreated, the orbital invasion may cause proptosis, blurred vision, diplopia, orbital pain, and paresthesia. Cerebral invasion is the most severe form of the disease . In our Rhizopus arrhizus, has been reported to be low. However, clinical breakpoints for the Mucorales and any antifungal agent have not been established [The current mainstays of treatment for mucormycosis include amphotericin B, posaconazole, and isavuconazole, in combination with surgical debridement. However, these newer antifungal agents, such as posaconazole and isavuconazole, are expensive and not always readily available . While iablished . In our ablished ,11.In conclusion, this case report highlights the importance of early recognition and prompt management of mucormycosis, which is a rare but potentially fatal fungal infection. The successful outcome of our patient was due to a combination of appropriate antifungal therapy, aggressive surgical debridement, and effective management of the underlying immunocompromised state. It is crucial for healthcare providers to have a high index of suspicion for mucormycosis in immunocompromised patients presenting with symptoms of sinusitis or other invasive fungal infections.


Gefitinib is a potent and selective orally active growth factor receptor (EGFR)-tyrosine kinase inhibitor that is commonly used to treat advanced non-small cell lung cancer patients with activating EGFR mutations. Hearing impairment with gefitinib was sparsely reported. In this report, we describe a case of sensorineural deafness associated with the administration of gefitinib, with a Naranjo score of 7.An 81-year-old female was diagnosed with lung adenocarcinoma with bone metastasis and an EGFR-activating mutation. The patient was prescribed gefitinib tablets at a daily dose of 250 mg for lung adenocarcinoma treatment. However, the patient experienced moderate to severe bilateral sensorineural deafness, primarily in her right ear, after taking gefitinib. Following the cessation of gefitinib administration, the patient exhibited partial restoration of auditory function. Upon resuming the medication, she experienced a worsening of deafness.The otoscopic audiogram and hearing test indicated moderate to severe bilateral sensorineural deafness.The otolaryngologist recommended bilateral hearing aids to enhance hearing function.Throughout our follow-up period, the patient did not receive a hearing aid implant.This article first reported the ototoxicity caused by gefitinib. While rare, our report highlights that gefitinib-induced sensorineural deafness is possible and its mechanisms are still unclear. This adverse reaction should be monitored closely during clinical application of gefitinib to improve patient outcomes. It selectively interferes with EGFR receptor tyrosine kinase activity by competing with adenosine triphosphate for the EGFR binding site, thereby inhibiting tumor neovascularization, blocking blood supply to tumor cells, and inhibiting mitogen-activated protein kinase activation and promoting apoptosis. The most common adverse reactions of gefitinib mainly involve the cutaneous system (rash), digestive system (diarrhea), and hepatobiliary system (elevated transaminase).,5 In recent years, reports of severe adverse reactions of gefitinib in literature mainly include: interstitial lung disease, fulminant purpura, acute cholecystitis, bone marrow suppression, severe diarrhea, retinal hemorrhage, etc. Herein, we report a case of acute sensorineural deafness after the administration of gefitinib in a patient with lung adenocarcinoma. At the same time, the literature on hearing impairment caused by EGFR-TKI was summarized, so as to provide reference for clinical use of EGFR-TKI. Ethics Committee of Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine approved the study, and an informed consent has provided.Multiple randomized controlled studies have shown that first-generation selective EGFR-TKI represented by gefitinib can significantly improve the progression-free survival time of patients with advanced EGFR-mutation-positive non-small cell lung cancer compared with chemotherapy, and the adverse reactions of grade 3 and above are significantly lower than those of chemotherapy. Thus EGFR-TKI is first-line treatment in patients with advanced EGFR-mutation-positive non-small cell lung cancer.The patient in question was an 81-year-old female who presented to our clinic with cough, sputum production, shortness of breath, and decreased activity endurance with no apparent cause. A computed tomography scan revealed a right lung mass, a right upper lung nodule shadow, enlargement of 2 lung hilar shadows, right-sided massive pleural effusion associated with pulmonary atelectasis and incomplete expansion, interstitial changes in both lungs, and multiple tiny nodular shadows. The pleural fluid pathology report indicated adenocarcinoma, while the results of gene testing confirmed an EGFR-activating mutation. The patient was therefore diagnosed with lung adenocarcinoma with bone metastasis and was placed on gefitinib tablets at a dose of 250 mg once daily, beginning on May 15, 2020. The patient also had a preexisting medical history of hypertension, hyperlipidemia, and coronary atherosclerotic heart disease and was receiving regular symptomatic treatment with valsartan, amlodipine, simvastatin, ezetimibe, aspirin, isosorbide mononitrate, and trimetazidine hydrochloride.On October 13, 2020, the patient’s cough and wheezing symptoms worsened and she was admitted to the hospital. The patient presented with a complaint of drug-induced hearing loss following a 4-month duration of gefitinib administration. As a consequence, the patient made an independent decision to discontinue the medication on September 30, resulting in a partial recovery of her auditory function. Despite this improvement, the patient’s cough and asthma symptoms persisted, leading to the resumption of gefitinib treatment as advised by her attending physician. However, after taking gefitinib for 3 days, she reported a worsened deafness, particularly in her right ear. The otoscopic audiogram and hearing test indicated moderate to severe bilateral sensorineural deafness. The otolaryngologist recommended bilateral hearing aids to enhance hearing function. However, throughout our follow-up period, the patient did not receive a hearing aid implant. Meanwhile, her hearing loss did not alleviate during the continuous administration of gefitinib, persisting until her passing. which was developed to standardize the causality assessment of adverse drug reaction, was used to estimate the probability of adverse drug reaction in this case. It was found the final score to be 7, indicating the correlation between sensorineural deafness and gefitinib use was determined as “probable,” that is, supported by objective evidence or quantitative test results. So the clinical pharmacist reported this case of adverse reaction to National adverse drug reaction surveillance system of China.The patient had no history of deafness or hearing loss before taking gefitinib, but hearing loss occurred about 4 months after taking gefitinib. During gefitinib administration, the drugs used were commonly used for previous underlying diseases, and no other drugs were used. The patient’s deafness symptoms relieved after stopping gefitinib, but worsened after resuming the medication. The Naranjo Scale Questionnaire,Sensorineural deafness is an organic disease of Corti’s organ, auditory nerve and auditory center, which leads to various types of hearing loss or loss due to its obstruction of sound perception and analysis or influence of information transmission. There are many causes of sensorineural deafness, including age, noise, heredity and the use of ototoxic drugs. EGFR receptor is expressed in both sensory and non-sensory cells of the inner ear of newborn/adult mice, and is involved in the survival, proliferation, regeneration, synaptic connection, cochlear balance and other processes of inner ear cells. Corti’s organ is an important part of sound perception and is composed of sertoli cells and hair cells, etc. Each hair cell forms a synaptic connection with nerve fibers, and the loss of synaptic conduction between hair cells and sensory neurons is a major factor of sensorineural hearing loss. Studies have found that EGFR receptor is related to the response of rat cochlear Corti’s organ to ototoxic drug. Furthermore, transgenic mice blocked by EGFR signal transduction pathway may produce severe hearing loss. Therefore, EGFR-TKI may affect multiple processes of nerve cells in the inner ear by inhibiting EGFR signaling pathway, and resulting in ototoxicity. However, this mechanism has been rarely reported in the clinical use of EGFR-TKIs. Search through the literature has yielded only 1 report of EGFR-TKI-induced hearing impairment, wherein a 66-year-old patient developed tinnitus, dizziness, and profound bilateral hearing loss within 0.5 hour after administration of 150 mg of oral erlotinib, leading to irrevocable ototoxicity. However, Gefitinib-induced hearing loss has not been reported in the literature.Gefitinib is a selective EGFR TKI. There are only a few reports on the ototoxicity of EGFR-TKI in recent years. Yet, the underlying mechanism is incompletely understood. Some studies showed that it may be related to the expression of EGFR receptor in the inner ear.The elderly patient in this case had a previous history of high blood pressure, hyperlipidemia, and coronary atherosclerotic heart disease. She regularly uses Valsartan, amlodipine, simvastatin, ezetimibe, aspirin, isosorbide mononitrate, and trimetazidine hydrochloride, which are not mentioned as having the potential for hearing impairment in the dispensatory. Gefitinib is mainly metabolized by CYP3A4 and may interact with CYP3A4 inducers, inhibitors, or substrates. Simvastatin and amlodipine, which are substrates of CYP3A4 among the patient’s common medications, may compete with gefitinib for the same metabolic pathway and increase the blood concentration of gefitinib, which may be one of the causes of hearing loss in the patient. This is also a limitation of our study. Due to the multitude of co-administered medications, it is unclear whether the sensorineural hearing loss induced by gefitinib is solely due to the drug’s individual adverse reaction or if it is related to interactions with another medication taken by the patient.This article is the first to report on the ototoxicity of gefitinib. It should be emphasized that gefitinib dosage may lead to irreversible damage to hearing, reinforcing the need for diligent monitoring of patients who are prescribed this medication. Audiometric screening at regular intervals is an essential component of patient care in these instances.Data curation: Bao-chen Zhu, Wen-hua Yang, Mao Huang, Yan Liang, Zhen-zhen Lei, Sha-sha Zhang, Ying Wang, Xiao-di Sun.Supervision: Ying Gong, Chun-miao Xue, Guo-dong Hua.Writing – original draft: Bao-chen Zhu, Wen-hua Yang.Writing – review & editing: Jin-gui Wang.


The human auditory system encodes sound with a high degree of temporal and spectral resolution. When hearing fails, existing neuroprosthetics such as cochlear implants may partially restore hearing through stimulation of auditory neurons at the level of the cochlea, though not without limitations inherent to electrical stimulation. Novel approaches to hearing restoration, such as optogenetics, offer the potential of improved performance. We review signal processing in the ascending auditory pathway and the current state of conventional and emerging neural stimulation strategies at various levels of the auditory system. The pathway, in brief, is as follows: sound pressure waves enter the outer ear and reach the tympanic membrane; the resulting movement of the membrane induces vibration of the middle ear ossicles. The middle ear system concentrates the incoming sound waves as mechanical energy to match the impedance encountered as it is transferred from the air into the incompressible cochlear fluids of the inner ear. Energy transfer within the cochlea induces hair cell depolarization, resulting in auditory nerve firing, with the resultant action potential traveling from the cochlear nerve to the brainstem nuclei, from whence it ascends along the central auditory pathway to eventually reach auditory cortex where the sound is perceived. The central auditory pathway consists of multiple levels of nuclei and tracts where the signal is processed as well as influenced by contralateral pathways, descending inputs, and non-auditory signals .Hearing loss is one of the most pervasive sensory disorders with approximately 430 million people affected worldwide. Disabling hearing loss often leads to social isolation, and has been associated with depression, incident dementia, and reduced quality of life . The etiThe cochlear implant (CI) has consistently been demonstrated to significantly improve hearing, communication, and quality of life in individuals with severe to profound SNHL. Cochlear implants bypass cochlear dysfunction by delivering electrical current from within the cochlear scalae that results in activation of spiral ganglion neurons (SGNs) which is then transmitted up the ascending auditory pathway. Most adults implanted with a CI achieve good hearing performance outcomes, as measured by open-set speech perception . HoweverGiven the limitations of currently available implantable devices for hearing rehabilitation, the development of novel approaches for the treatment of hearing loss has been an area of active investigation. The concept of direct neural stimulation by infrared light has evolved into the study of optogenetics in the auditory system . Here, w2.2.1.CF). The result of this cochlear tonotopic organization is our ability to resolve tones that differ in frequency by only 0.2%  component encoding sound frequency and amplitude, as well as a direct current “summation potential” (SP) generated by potassium flow at the level of the hair cell. The SP may have a positive or negative polarity which is measurable and may vary in healthy and disease states . Indeed,nly 0.2% . Tonotopnly 0.2% . SGN neury cells . In addiry cells . Phase lry cells . Howeverry cells . Phase lry cells .2.2.At the level of the pontomedullary junction along the floor of the lateral recess of the fourth ventricle, SGNs of the auditory nerve branch to innervate two subdivisions of the ipsilateral cochlear nucleus: the dorsal cochlear nucleus (DCN) and ventral cochlear nucleus (VCN). The tonotopic organization established in the cochlea is again reflected in the cochlear nucleus: neurons whose CFs range from high to low are organized from dorsal to ventral in the VCN, and from dorsomedial to ventrolateral in the DCN . Each of2.3.The superior olivary complex (SOC) – whose subdivisions include the LSO, MSO, and MNTB – extends from the rostal medulla to the caudal pons and is the first site of convergence of auditory input from both ears. Tonotopic arrangement of auditory inputs is again maintained at this level of the pathway, though neuronal response patterns to sound stimuli are more complex and varied . Compari2.4.The inferior colliculus (IC) is the main center of convergence in the auditory midbrain. It receives and integrates diverse preprocessed inputs from all major auditory brainstem nuclei, as well as integrating auditory and non-auditory inputs. The IC is divided into three subdivisions: a central nucleus (ICC), external cortex, and dorsal cortex . The ext2.5.The MGB receives most of its auditory input from the ICC, which it then distributes to the auditory cortex located within the superior temporal gyrus, as well as other non-auditory cortical regions. Ventral, dorsal, and medial divisions of the MGB each contain subnuclei receiving ascending and descending innervation from the IC and the auditory cortex . MGB inp3.3.1.When hearing loss is beyond remedy by traditional hearing aids – for example, is severe to profound in degree, or with disproportionately poor speech recognition ability – the only widely available option for hearing restoration is a CI. Cochlear implants use an external processor use an external processor to mimic the spectral decomposition process of the normal cochlea, decoding sound stimuli into multi-frequency bands, and then provide electrical current stimulation through implanted intracochlear electrodes. Signal processing is accomplished through encoding of the speech envelope via continuous interleaved sampling (CIS) of input sound and speech waveforms . CIS offWhen hearing loss is secondary to a defect or impairment of the auditory nerve, an auditory brainstem implant (ABI) is a feasible alternative. The ABI similarly relies on electrical current to produce neural activation. Implanted at the surface of the cochlear nucleus as a flat paddle, the neuronal activation induced by sound that is processed and transmitted via the device is even more crude as a result of both larger electrode contacts (relative to the size of the target structure) and the more nuanced tonotopic and cellular organization at this level of the auditory pathway – frequency selectivity is not achieved. ABI performance may also suffer from more complex intrinsic temporal responses seen in cochlear nucleus neurons, an encoding that is not easily reproduced by the implant stimulation. The prototypical population implanted with the ABI is patients with neurofibromatosis type 2 (NF2), in whom placement is performed concomitant to or following vestibular schwannoma removal. Open-set sentence perception ability is uncommon, though a majority of recipients able to achieve environmental sound awareness through use of the device . By virtEmerging research has explored electrical stimulation of higher regions of the ascending auditory pathway. Direct stimulation of SGNs via an auditory nerve implant (ANI) has been proposed, though achieving frequency selectivity with an implant at this level of the auditory pathway should prove challenging . Such anAs is exemplified by observed ABI outcomes and the theoretical challenges of the ANI and AMI, stimulation of increasingly proximal levels of the auditory pathway in a manner that results in an accurate neuronal representation of the precise spectral components of sound is infeasible with current approaches. The baso-apical tonotopy of the cochlea, uniform firing patterns of SGNs, and surgical ease of access make this first level of the auditory pathway the most attractive target for implantable auditory devices. However, there exist inherent limitations to electrical stimulation at the level of the cochlea, rendering an alternative means of SGN stimulation an appealing target of research.3.2.Optical stimulation of auditory neurons using infrared light – or infrared neural stimulation (INS) – poses the theoretical advantage of improved spatial (and thus frequency) resolution. At high intensity levels, infrared light is thought to directly stimulate neurons to cause depolarization. A photoelectric effect, whereby heating of cochlear fluids generates fluid pressure waves akin to acoustic stimuli, may also contribute to neuronal responses to light stimulation within the cochlea . InfrareThe field of optogenetics involves the study of opsin genes in research; more recently, the field has been co-opted for clinical use in the restoration of vision, olfaction, and auditory perception. Channelrhodopsins (ChR), light-gated channels found in algae, render neurons light-sensitive; their expression can be induced in mammals by transfection of opsin genes using viral vectors . A varieIn addition to the limitations in stimulation specificity, other limitations of an optogenetic approach to hearing restoration arise from the use of viral vectors. When mice are transfected with opsin genes post-natally, protein expression is typically reduced compared to when transfected prenatally (intrauterine) . Off-tar4.The tonotopic organization of the auditory system makes hearing restoration via implantable devices feasible; the CI is widely regarded as the most successful neural prosthesis in existence. However, physiologic limitations which curtail performance make the search for an alternative means of hearing restoration alluring. Devices that act to stimulate neurons at the level of the cochlea are likely to be most successful due to the increasing complexity of neuronal organization encountered at more proximal levels of the auditory pathway. Emerging research in the field of optogenetics suggests improved spectral selectivity compared to electrical neural stimulation. However, the practical feasibility of these approaches for hearing restoration in humans is as of yet unknown.AQ: Investigation, Methodology, Supervision, Writing – original draft, Writing – review & editing. KW: Investigation, Writing – original draft. DA: Writing – review & editing. SE: Writing – review & editing. DKC: Writing – review & editing. JB: Conceptualization, Supervision, Writing – review & editing.


Several methods have been described for the intraoperative evaluation of colorectal anastomotic integrity. Technological evolution has allowed to progress from basic mechanical methods to the use of more sophisticated techniques. This study describes a novel endoluminal modality of colorectal anastomotic assessment through the use of a Disposable Rigid Scope Introducer (DRSI) also allowing for intraoperative endoluminal perfusion evaluation by indocyanine green (ICG) fluoroangiography in patients undergoing left-sided colorectal resection.The DRSI consists of an endoluminal introducer device made up of an insertion tube and port connected to an insufflation bulb to manually insufflate the sigmoid and rectum and is compatible with any laparoscopic camera, also allowing for ICG fluoroangiography for perfusion purposes.The DRSI was successfully used to assess anastomotic integrity after left-sided colorectal resections performed in 16 consecutive patients. The DRSI allowed to visualize by fluoroangiography the quality of tissue perfusion at the anastomotic site in all cases, contributing to the decision of avoiding loop ileostomies in low rectal resections. In 2 cases, the DRSI showed the presence of significant anastomotic bleeding which was successfully controlled by laparoscopic suture placement. No adverse event resulted from the use of this device.The DRSI combines direct endoluminal visualization of the anastomosis together with real-time evaluation of its blood flow. This device holds great potential for prompt intraoperative detection of anastomotic alterations, possibly reducing the risk of postoperative anastomotic bleeding or leaks related to mechanical construction/perfusion issues. Potential advantages of this device warrant larger cohort studies and prospective randomized trials.The online version contains supplementary material available at 10.1007/s00268-023-06915-8. The current colorectal anastomotic leak rate persists to be relatively high, broadly ranging between 5 and 15% , 3. AlthSeveral methods have been described for intraoperative evaluation of the integrity of colorectal anastomoses following left-sided colorectal resections. Technological evolution has allowed to progress from basic mechanical methods to the use of more sophisticated techniques, including oxygen spectroscopy, narrow-band imaging, Doppler flowmetry and fluorescence angiography .The ideal method of anastomotic assessment should allow for a direct visualization of the anastomosis both intra- and extra-luminally, additionally combining the possibility of examining tissue microperfusion at this level.This study describes a novel endoluminal modality of colorectal anastomotic assessment through the use of a rigid scope introducer also allowing for intraoperative perfusion evaluation by indocyanine green (ICG) fluoroangiography in patients undergoing laparoscopic left-sided colorectal resection.The US Food and Drug Administration (FDA)- and European Committee (EC)-approved Disposable Rigid Scope Introducer (DRSI)  device is currently commercially available. The DRSI consists of an endoluminal introducer made up of an insertion tube and insufflation port Fig. . The insThe DRSI is intended to be used in the rectum and distal portions of the colon. It is designed for use with a standard laparoscope, 320 mm in length, 10 mm in diameter, 0 or 30° lens.Once the DRSI/laparoscope complex is assembled, it is inserted just past the anal verge and the rectum is inflated through the insufflation bulb. Under direct visual guidance of the white light image, the device is advanced to the level of the anastomosis which is assessed for staple line disruption, bleeding and fluoroangiographic microperfusion Video S1)..1The ICG dose administered intravenously in the present study group was 0.3 mg/kg diluted in injectable sterile water. ICG injection was performed at two separate time points: at the moment of proximal colonic transection with direct visual inspection and after colorectal anastomotic construction with endoluminal assessment as evaluated through the DRSI device. An air-leak test was routinely performed while using the DRSI, by injecting saline solution in the abdominal field. This is a pilot prospective cohort single-center study designed to evaluate anastomotic integrity through the use of the DRSI with concomitant ICG fluoroangiography. Between January and March 2022, a total of 16 patients affected by colorectal cancer or diverticular sigmoid stricture underwent laparoscopic left colectomy, anterior resection or sigmoidectomy at Sapienza University Hospital in Rome, Italy. Demographics, comorbidities and history of neoadjuvant radiochemotherapy were also recorded and are summarized in Table At the moment of proximal colonic transection and after colorectal anastomotic construction, perfusion was evaluated and judged as either ‘excellent’ ; ‘good’ , ‘poor’  or ‘absent’ (no ICG detected). In case of ‘poor’ or ‘absent’ ICG perfusion, a change in transection point was made based on the area of greater fluorescence. A decision of avoiding loop ileostomies in low anterior resections , regardless of preoperative neoadjuvant radiochemotherapy, was made when a ‘good’ or ‘excellent’ anastomotic perfusion was visualized endoluminally.Considering a mean time between injection and fluorescence visualization of an estimated 30–60 s and the ICG half-life of 150–180 s, we assumed 180 s as an upper time limit to assess fluorescence.To prove the applicability of the DRSI device, we performed laparoscopic left-sided colorectal resections in 16 consecutive patients for malignant or benign conditions with endoluminal anastomotic integrity assessment. All surgical procedures and DRSI usage were performed by the same two surgeons. Institutional Review Board and Ethical Committee approval was obtained. All participants provided written informed consent to participate in the study and before all surgical procedures.The Template for Intervention Description and Replication (TIDieR) guideline was used in the present study for intervention reporting purposes.The DRSI was successfully used to assess anastomotic integrity after all left-sided colorectal resections performed in 16 consecutive patients Table .Table 2PAll procedures were performed laparoscopically. No conversions to open surgery, major intra-/postoperative complications or mortality were recorded. Minor postoperative complications (Clavien–Dindo grade I) included one case of ileus, one wound infection and one urinary tract infection. The DRSI allowed to visualize the anastomotic site in all cases with a ‘good’ or ‘excellent’ quality of tissue perfusion by ICG fluoroangiography Fig. . In two Despite the substantial progress in technologies and refinement of surgical techniques, anastomotic leak rates still continue to complicate an elevated portion of colorectal procedures.No definitive conclusions can yet be drawn from the current literature regarding the most effective modality of assessing anastomotic integrity . A recenAn endoscopic view of the anastomosis allows for a more precise evaluation of tissue viability, as it has been proved that the mucosal layer has a lower tolerance to ischemia compared to the serosal lining . The DRSThe DRSI demonstrated to have several advantages, including safety, limited costs, ease of use and high reproducibility. Additionally, it contributed to effectively indicate the presence of active anastomotic bleeding or adequate tissue perfusion in all cases. In our cohort of patients, the presence of good quality tissue perfusion visualized endoluminally via the DRSI drove the decision of avoiding loop ileostomies in selected cases. The limits we have experienced during the use of the DRSI include the need for an additional laparoscopic tower, the increase in the overall operative time, the possibility of exploring only up to 25 cm from the anal verge and the impossibility of performing operative maneuvers such as clip or suture placement when necessary Table .Table 3CThis device holds great potential for prompt intraoperative detection of anastomotic alterations, possibly reducing the risk of anastomotic leaks related to mechanical construction or perfusion issues. The potential advantages of this device warrant larger cohort studies and randomized trials.Supplementary file1 (DOCX 38 KB)Below is the link to the electronic supplementary material.


This study aimed to analyze the relationship between frailty in older patients with diabetes and audiovisual senses.The survey included (1) basic attributes, (2) diabetes-related items, (3) frailty, evaluated according to the Obu Study of Health Promotion for the Elderly (OSHPE) standard, and (4) audiovisual function. Participants included 157 diabetes patients aged ≥65 years, divided into three groups: robust health (n=50), pre-frail (n=76), and frail (n=31). A simple regression analysis, in which the total OSHPE score was used as the dependent variable and the most relevant audiovisual items were used as independent variables, was performed to analyze the frailty factor. Next, a multiple regression analysis adjusted for age and sex was performed with total OSHPE score as the dependent variable and the items most relevant for audiovisual senses as independent variables.For the robust health, pre-frail, and frail groups, frequencies of hearing loss were 18.4%, 42.1%, and 35.5%, respectively, and were associated with frailty; visual impairment frequencies were 38%, 63.2%, and 58.1%, respectively. In multiple regression analysis, economic difficulties , absence of dyslipidemia , lower MNA score , and worsening hearing in the poor hearing ear  were significantly associated with frailty. Hearing but not vision was associated with frailty in older patients with diabetes. Hyperglycemia in older diabetic patients is a risk factor for frailty, and is associated with reduced muscle mass and medication use.3 Complications of frailty are reported to shorten life expectancy.5 Older diabetic patients with frailty have higher rates of hospitalization and mortality than those without frailty, often requiring attention and management, including glycemic control with medications and nutritional guidance.6In recent years, the relationship between frailty and diabetes in older people has received increasing research attention. The concept of frailty is defined by several factors, including muscle weakness, and is also a predictor of poor outcomes, such as impaired life functioning, death, hospitalization, falls, fractures, and cognitive decline caused by age-related physiological decline,7 and the concept of sensory frailty has been proposed. Both vision impairment and hearing loss are associated with frailty.8 Regular ophthalmic examinations are recommended for retinopathy, a complication associated with diabetes. Hearing loss is more frequent in older diabetic patients.9 A follow-up study of approximately 140,000 women showed a higher risk of hearing loss in those with type 2 diabetes compared with those without diabetes, and those with diabetes ≥8 years in duration were at a higher risk of developing moderate or worse hearing loss.10 In Japan, Uchida et al.11 examined the relationship between diabetes treatment and hearing loss in 90 middle-aged and older diabetes patients and reported that hearing deteriorated as the duration of diabetes increased.Sensory organ function is essential for activities of daily living in older individuals. Audiovisual and frailty assessments are considered to be necessary for the prevention of cognitive decline in older individuals,12 However, reports on frailty in older diabetic patients focusing on audiovisual function are scarce.Risk factors for frailty in older diabetic patients include age, low levels of albumin, high-density lipoprotein cholesterol, systolic blood pressure, glycated hemoglobin (HbA1c), total cholesterol, and weight.This study aimed to analyze the relationship between frailty in older diabetic patients and audiovisual sensory function.This cross-sectional observational study included patients with diabetes aged ≥65 years who did not qualify for long-term care insurance and visited the Diabetes Outpatient Department of Center A from October 2015 to May 2016. This study was only able to enroll 157 patients who underwent an audiovisual test during the period mentioned above.13 The MMSE has a full score of 30, with ≥24 categorized as normal, <10 as severe decline, and <20 as intermediate decline. For nutritional evaluation, the Mini Nutritional Assessment (MNA) was used. Participants who scored ≥12 points were categorized as well-nourished.14 Participants who scored ≤11 were classified as possibly undernourished, a 12-item assessment was performed, and the score was summed with a screening score (maximum 30 points) for evaluation. Usage of insulin, dipeptidyl peptidase-4 (DPP-4), sodium-glucose cotransporter 2 (SGLT2), glucagon-like peptide 1 (GLP-1), sulfonylurea (SU), pioglitazone (Pio), and biguanide (BG) were obtained from electronic medical records.Individual characteristics, including age, sex, height, weight, body mass index (BMI), diabetic complications, and HbA1c level, were obtained from electronic medical records. Additionally, inquiries were made on social background factors and whether they experienced economic difficulty in life. Cognitive function was evaluated using the Mini-Mental State Examination (MMSE) as an item for older functional evaluation.15 including five items from Fried et al.,16 were used to evaluate frailty. The measurement methods for the five items were modified for feasibility in Japan. The validity and reliability of the OSHPE were verified in 5,104 community-dwelling people aged ≥65 years. The number of items that applied to each participant was counted from the following five items: “weight loss,” “fatigue,” “decreased physical activity,” “decreased grip strength,” and “decreased walking speed.” For “Weight loss,” 1 point was given if patient responded “yes” and 0 points were given if the patient responded “no” to the following question: “Have you lost more than 5% of your weight in the last 2 years?” For “fatigue,” 1 point was given if the response was “yes” and 0 if “no.” For “Physical inactivity” 1 point was scored for “not doing light exercise/exercise, regular exercise/sports” and 0 for “doing light exercise/exercise, regular exercise/sports.” If the response to the question regarding “Decrease in grip strength” was “no,” 1 point was scored for “male: <26 kg, female: <17 kg,” and 0 points for “male: ≥26 kg, female: ≥17 kg.” The grip strength of the dominant hand was measured three times, and the average value was used. The grip strength meter used was Smedley’s Dynamometer No. 30548. “Walking speed decrease” was 1 point for “male: <1.0 m/s, female: <1.0 m/s” and 0 points for “male: ≥1.0 m/s, female: ≥1.0 m/s.” Normal walking speed was used for walking speed measurements. A 1-m runway was made before and after the measurement section, and the time taken to walk the 5-m measurement section was recorded. By summing all five items, “frail” was defined by the presence of three or more applicable items, while individuals with one or two applicable items were categorized as “pre-frail” and those with no applicable items were categorized as “healthy.”The Obu Study Health Promotion for the Elderly (OSHPE) criteria,17 Visual acuity assessments from the cohort were converted into log MAR units.A near vision chart was used for the simple visual acuity test, and bilateral visual acuity was measured 30 cm away. If necessary, customary corrections were used, such as eyeglasses and contact lenses. The cutoff value for the left or right eye was set to 0.5 according to the distribution, and participants were categorized into two groups: <0.5  and ≥0.5 (without impairment).Regarding the subjective evaluation of poor vision, we asked participants if they were aware of their vision loss using the question, “Do you find it difficult to see?”, then asked if they used eyeglasses and/or had a history of cataract surgery.9 This test was performed twice on both sides of the right and left ears. For participants who regularly used hearing aids, detection of finger rubs was measured while they were using their hearing aids.A pure tone hearing test was performed using an audiometer . The AA-78 had an inspection sound level of –20–105 dB, and bilateral hearing was measured twice at frequencies of 500, 1,000, 2,000, and 4,000 Hz. A soundproof room was used for testing. In the finger rub hearing test, the dry index finger and thumb were rubbed together to make a sound from the back, and the presence or absence of the participant’s reaction was examined. For presentation of the finger rub sound, the inspector stood 30 cm behind the participant and performed a finger rub with a volume of approximately 40 dB; the distance between the fingertip and ear was 5 cm. A sound level meter  was used in advance to confirm that the finger rubbing sound of the inspector nurse was approximately constant at approximately 40 dB.Participants were asked the question, “Do you think you have difficulty hearing?” Responses were given as either “yes” or “no.” Regarding the evaluation of hearing by others, participants were asked the question, “Have others mentioned that you have poor hearing?” Participants responded with “yes” or “no” regarding their hearing loss (referred to hereafter as an indication of hearing loss). Finally, we asked participants if they were using hearing aids.The definition of moderate hearing loss or higher according to World Health Organization (WHO) standards was used. Better average hearing of 500, 1,000, 2,000, and 4,000 Hz sounds that exceeded 40 dB was considered hearing loss.18 or the Kruskal-Wallis test19 for continuous variables.On the basis of the OSHPE criteria, participants were divided into three groups according to the level of frailty , and comparisons of the survey items among them were analyzed using the chi-square test for nominal variablesFor visual function, we analyzed the history percentage of cataract surgery. The left and right hearing levels were categorized as good or poor, and descriptive statistics were calculated.The rates of diabetic complications and insulin use were analyzed for each group.A simple regression analysis, in which the total OSHPE score was used as the dependent variable and the most relevant audiovisual items were used as independent variables, was performed to analyze the frailty factor. Next, a multiple regression analysis adjusted for age and sex was performed with the total OSHPE score as the dependent variable and the items most relevant for audiovisual sensory function as independent variables. Furthermore, a multiple regression analysis was performed after adjusting for age and sex with the total OSHPE score as the dependent variable and all of the items found to have an association in univariate and regression analyses as independent variables. The most dominant items in vision status and hearing status were entered into the regression analysis. SPSS version 22 was used for the statistical analysis, with a significance level of 5%.Of the 200 diabetes patients aged ≥65 years who visited Center A, this study included 157  who underwent audiovisual evaluation .Frail diabetic patients were significantly older, had more economic difficulties, and lower MMSE and MNA scores than non-frail diabetic patients.Participants’ height and weight decreased from the healthy group, to the pre-frail group, to the frail group. The three major complications were neurosis, retinopathy, and nephropathy, occurring in 75 (47.4%), 46 (29.3%), and 87 (55.4%) patients, respectively. The proportion of neurosis tended to increase, leading to frailty in 31.8%, 48.4%, and 19.7% of participants in the healthy, pre-frail, and frail groups, respectively. There were significant associations between OSHPE score and height, weight, and dyslipidemia.There was no association between diabetes medications and frailty, and no patients were using SGLT2. No frail patients were using Pio.Of the 157 patients with near vision , 85 (54.1%) had visual impairment. More than 95.5% of participants had a history of cataract surgery on either the left or right side; 49 (31.2%) participants were subjectively aware of vision loss, and 78 (49.7%) used eyeglasses. Visual evaluation revealed a significant association between the three frailty groups and visual impairment. Compared with patients in the healthy group, 63.2% and 58.1% of participants were visually impaired in the pre-frail and frail groups, respectively.Moderate to high hearing loss according to the WHO classification was observed in 8 (24.2%), 31 (32.3%), and 13 (48.1%) patients in their 60s, 70s, and 80s, respectively.The three frailty groups significantly differed in the percentage of participants with poor hearing, finger rub hearing test performance loss, WHO hearing loss, and indication of hearing loss. There was a significant difference in the frequency of all hearing measures between robust, pre-frail, and frail groups, in all evaluation methods.Further analysis was performed, focusing on the hearing ability of the poor hearing ear that showed the highest correlation with frailty for each audiovisual sense item. In univariate analysis, the poor hearing ear value was significantly associated with the OSHPE score  Model 1.In Model 3, regression analysis was performed with OSHPE score as the dependent variable, age and gender as adjustment variables, and poor hearing ear value, simple vision cutoff value of 0.5, neurosis, economic difficulty in life, dyslipidemia, cerebrovascular disease, MNA score, and MMSE score as independent variables.Economic difficulties , absence of dyslipidemia , MNA , and worsening hearing in the poor hearing ear  were significantly associated with frailty , Model 3The current study investigated the correlation between frailty and audiovisual sensory function in older adults with diabetes and diabetic complications, and identified factors that contribute to frailty in patients with diabetes. The results of this study indicate that poor hearing, dyslipidemia, MNA score, and economic difficulties are associated with frailty in older adults with diabetes.In the current study, the factors associated with frailty in older diabetic patients were not only basic attributes like age, and sex, or diabetes-related factors like insulin and other drug use, HbA1c and other values, and the presence of diabetes-related complications, but also focused on audiovisual impairment. Additionally, the methods of assessing audiovisual impairment were examined using multiple models. We examined several methods for evaluating audiovisual impairment. When these were examined in the input model, a strong association with frailty was found in the presence or absence of hearing loss in the poor hearing ear.20 The link between hearing loss and social frailty has been reported among older women in the South Korean population.22Reports show a significant association between frailty and hearing loss.9 and is associated with a tendency toward frailty, with decreased input of sound information, cognitive decline, depression, and social isolation.23 Additionally, hearing loss reduces social participation and interaction. Decreased outings and other activities because of social frailty are also associated with muscle weakness and physical frailty, and people with hearing loss are currently more likely to become frail. In other words, older people with diabetes are at increased risk of frailty because of hearing loss.Hearing loss is common in older people with diabetes,24 although they may be reluctant to go out because of their concerns about their poor hearing, and as a result, may be more likely to become frail.Because a person with normal hearing in one ear but poor hearing in the other ear may have a lower subjective evaluation of their hearing,3Previous literature reviews have focused on the impact of good hearing. In one-on-one conversations, if good hearing is present in one ear, there is typically no difficulty in overall hearing. However, in noisy situations, if a person has hearing loss in one ear, significant hearing difficulty is often experienced. With aging, a person’s good hearing ear may also develop age-related hearing loss, increasingly requiring repetition of speech. Cochlear microangiopathy caused by diabetes can cause hearing loss, and the auditory system, which has high energy demands because of complex signal processing, is more likely to be a target of hyperglycemic adverse effects.Because subjective evaluation is sometimes inaccurate in older individuals, we conducted an objective evaluation. However, because pure tone audiometry is time-consuming, we also performed the finger rub test, in the hope that the results would also show a significant association. Although the final model included the presence or absence of hearing loss in the poor hearing ear on the basis of pure tone audiometry, univariate analysis showed that finger rub test performance was significantly associated, providing a potential surrogate measure.26 Although there is a paucity of literature assessing frailty and objective visual acuity, a 5-year longitudinal study evaluating the association between self-reported frailty in older people reported a 2.5-fold incidence of frailty with self-reported visual impairment.27 In the present logistic regression analysis, visual impairment and frailty based on a cutoff of 0.5 were not significantly associated, but it is possible that objective longitudinal evaluation would reveal an association.Regarding visual impairment, a cutoff value of 0.5 is used to assess visual acuity in many countries, and has been reported in various guidelines. An association between dementia and a visual impairment cutoff value of 0.5 has been reported in many studies.The incidence of frailty tends to increase with age. Various complications may occur with a long-term history of diabetes, resulting in a poor prognosis and further promotion of frailty.28In the current study, frailty was associated with economic difficulties and undernutrition . Additio29 In a study examining the prevalence and income of diabetes in 119,666 adults, the risk of diabetes increased 1.9-fold in males25; although this report was not specifically focused on older people, low income is also likely to be associated with undernutrition and diabetes in older populations.In older people, nutritional balance tends to be poor, and the frequency of dyslipidemia tends to decrease.30 Further attention should be paid to diabetes patients because dyslipidemia, undernutrition, and financial distress that increase with age are independently associated with frailty.The causes and background of undernutrition in older people include decreased oral intake, decreased activity, and various overlapping background factors, such as comorbidity, medication, decreased oral function, psychological changes, social environment , and economic problems such as poverty.Because the current study employed a cross-sectional design, the findings should be investigated further using longitudinal evaluation. Additionally, because the sample population consisted solely of older adults with diabetes who consume alcohol, comparisons with the broader community of older adults will be necessary to establish the generalizability of the current findings.The strengths of this study included a focus on audiovisual senses to elucidate the factors associated with frailty in older patients with diabetes, thorough measurement of physical functions, and an analysis of complications. Thus, the factors mentioned above strengthened our study of physical aging in older patients with diabetes, which is an underlying factor in frailty. Further clarifying the lifestyle and physical and social factors associated with frailty in this population will improve current understanding of its causes.Hearing but not vision was associated with frailty in older people with diabetes.The authors declare no conflict of interest.