Age-related hearing loss (ARHL) is a major public health burden worldwide that profoundly affects the daily life of elderly people. Silent information regulator 1 (SIRT1 or Sirtuin1), known as a regulator of the cell cycle, the balance of oxidation/antioxidant and mitochondrial function, has been proven to have anti-aging and life-extending effects, and its possible connection with ARHL has received increasing attention in recent years. This paper provides an overview of research on the connection between SIRT1 and ARHL. Topics cover both the functions of SIRT1 and its important role in ARHL. This review concludes with a look at possible research directions for ARHL in the future. Hearing loss, in its variants conductive, sensorineural or mixed, may be classified according to its etiology as hereditary, traumatic, environmental, and induced by drugs . AccordiAge-related hearing loss (ARHL), also known as presbycusis, is a progressive decline in hearing sensitivity and language comprehension that is associated with aging. Therefore, this can seriously affect the social function and mental health of the elderly individuals . CurrentHearing, as people’s internal sense, is important for daily communication, and hearing impairment can greatly affect social function and mental health. Hearing impairment can seriously affect people’s social functioning and social health. It is now generally accepted that hearing loss is an independent risk factor for cognitive dysfunction . There aThe inner ear pathology of ARHL is characterized by loss of inner and outer hair cells, vascular stripe atrophy, loss of spiral ganglion cells, and degeneration of spiral ligaments . It is cComparing human glucose-6-phosphate dehydrogenase (G6PD) gene-transferred C57BL/6 mice with wild-type mice, G6PD overexpression was found to enhance antioxidant capacity, attenuate oxidative damage and delay the onset of hearing loss . p43 knoSIRT1, a nicotinamide adenine dinucleotide (NAD+)-dependent class III histone deacetylase, is associated with lifespan extension. It is known for its ability to balance oxidation/antioxidation and reduce mitochondrial damage, DNA damage and apoptosis . It has SIRT1 is widely distributed in various organs and tissues throughout the body and is involved in anti-aging, anti-inflammatory, antioxidant, and cell cycle regulation in the brain, liver and other important organs . It has SIRT1 plays a crucial role in hearing loss, especially ARHL. This review elucidates the structure and function of SIRT1 and its localization in the cochlea. Moreover, it mainly explains the relationship between SIRT1 and ARHL, as well as the current research progress related to SIRT1 and the prevention or treatment of ARHL, and provides our own views on future treatment and research strategies for ARHL.Cryptobacterium hidradenum (Sirtuins are (NAD +)-dependent class III histone deacetylases. The family consists of seven members in mammals . These family members are characterized by the possession of the sirtuin core structural domain . Sirtuindradenum , mice  for 12 weeks, where the animals were placed in cages full of toys and encouraged to forage and explore by moving the toys, feeding boxes and water tanks at least once a week. After 12 weeks, they found that EE increased SIRT1 activity in the auditory cortex and improved ARHL . A high-in vitro are preferred. The HEI-OC1 cell line, one of the auditory cell lines, is now commonly used in hearing research (in vitro have also been used to study the effect of drugs on hearing (in vitro do not reflect the systemic effects of a treatment as in vivo do, and administration in vivo may not work well in the inner ear because of the blood-vagus barrier of the inner ear (in vivo and in vitro administration, which is a challenge that needs to be addressed. Hearing loss is not only determined by hair cells but is also closely related to spiral ganglia, spiral ligaments, vascular striae, and endolymph (in vitro cell assays provide information about the cellular response to the treatment and can be used to understand drug effects on hair cells, but they are not representative of drug effects on hearing.Since the acquisition of ARHL in animal models is time-consuming, it increases the difficulty of the experiment, while the modeling time of noise-induced and drug-induced deafness is fast, and the modeling effect is stable. At present, there are many studies on cisplatin-induced hearing loss and noise-induced deafness. The protective effect of SIRT1 in cisplatin-induced hearing loss and noise-induced deafness confirms the potential therapeutic role of SIRT1 in the cochlea . To obtaresearch . Cochlea hearing . Howevernner ear , leadingndolymph . The in Age-related hearing loss is a disease associated with aging, the exact cause of which is unknown and for which there is no clear and effective treatment. Caloric restriction, currently recognized as an effective measure to delay aging, can alter NAD+/NADH and then activate SIRT1 . PerhapsTZ wrote the manuscript and prepared all the figure and table. GT supervised the manuscript writing and editing. Both authors contributed to the article and approved the submitted version.


The National Institute for Health and Care Excellence (NICE) updated its eligibility criteria for unilateral cochlear implants (UCIs) in 2019. NICE claimed this would not impact the cost-effectiveness results used within its 2009 technology appraisal guidance. This claim is uncertain given changed clinical practice and increased healthcare unit costs. Our objective was to estimate the cost-effectiveness estimates of UCIs in UK adults with severe to profound hearing loss within the contemporary NHS environment.A cost–utility analysis employing a Markov model was undertaken to compare UCIs with hearing aids or no hearing aids for people with severe to profound hearing loss. A clinical pathway was developed to estimate resource use. Health-related quality of life, potential adverse events, device upgrades and device failure were captured. Unit costs were derived mostly from the NHS data. Probabilistic sensitivity analysis further assessed the effect of uncertain model inputs.A UCI is likely to be deemed cost-effective when compared to a hearing aid  or no hearing aid . A UCI has an 93.0% and 98.7% likelihood of being cost-effective within the UK adult population when compared to a hearing aid or no hearing aid, respectively. ICERs were mostly sensitive to the proportion of people eligible for cochlear implant, discount rate, surgery and device costs and processor upgrade cost.UCIs remain cost-effective despite changes to clinical practice and increased healthcare unit costs. Updating the NICE criteria to provide better access UCIs is projected to increase annual implants in adults and children by 70% and expenditure by £28.6 million within three years. This increased access to UCIs will further improve quality of life of recipients and overall social welfare. Around 11 million people in the UK live with permanent hearing loss, most of which results from age related damage to the cochlear due to environment and genetic factors –8. WhileImproved hearing from using a UCI also improves quality of life. People have reported improvements in the Geriatric Depression Scale , 13, impMany people in the UK with severe to profound sensorineural hearing loss have missed out on receiving a UCI despite their potential benefits. One study concluded five% of adults eligible for a cochlear implant had received one within the UK, arguing that low provision and utilisation resulted from limited audiological awareness and screening programs . AnotherPrevious National Institute for Health and Care Excellence (NICE) guidance stated that an adult must have severe to profound hearing loss  and not receive adequate benefit from acoustic hearing aids for a cochlear implant to be funded by the National Health Service (NHS). NICE defined adequate benefit from acoustic hearing aids in adults as a score of 50% or greater using BKB sentence testing at a sound intensity of 70 dB SPL .NICE updated its guidance in March 2019 . Severe Updated eligibility criteria are projected to increase annual access to UCIs by around 70% and cost around £28.6 million annually within three years . While sThe cost-effectiveness of UCIs in the UK adult population has not been investigated since. NICE noted that changes to the eligibility criteria within its 2019 technology appraisal guidance update would not impact the cost-effectiveness results presented within the NICE Health Technology Assessment Report. It reasoned that the original cost-effectiveness estimates included the additional population defined under the new eligibility criteria and that device costs had since declined .This claim is uncertain given changes in the NHS environment since the NICE Health Technology Assessment Report was completed. While device costs have recently decreased, they represent only around 39% of the total cost associated with a UCI , with thOur study aims to evaluate the cost-effectiveness of UCIs compared to hearing aids and no hearing aids in UK adults with severe to profound hearing loss within a contemporary NHS environment. Our target population includes adults who had previously received benefits from a hearing aid and adults who had not. Our study represents the first alternative cost-effectiveness estimate of UCIs compared to that presented within the NICE Health Technology Assessment Report in 2009. It is timely given new guidance is expected to significantly increase access to UCIs for UK adults with severe to profound hearing loss.We update previous results from the NICE Health Technology Assessment Report in three important ways. First, we use a contemporary UCI clinical pathway for the UK developed in consultation with clinicians. Our pathway therefore inherently captures change in UCI clinical pathways over the last two decades. While we do not quantify this change directly, there is evidence that the clinical pathway has changed that could significantly impact costs. For example, costs within the NICE Health Technology Assessment Report relied on clinical estimates of time spent in hospital after cochlear implant surgery, which was estimated to be 72 h . Today mSecond, our study differs from the NICE Health Technology Assessment Report by relying on current NHS reported costs and tariffs derived from the NHS National Schedule of Reference Costs . This prA UCI is expected to improve hearing ability over the remaining life of a recipient. There are also ongoing lifetime costs, such as sound processor upgrades, consumables (cables and batteries), audiologist consultations for maintenance and upgrades, and costs to explant and reimplant a cochlear implant if the device fails or due to medical reasons.A Markov model was employed to capture the chronic nature of severe to profound hearing loss in adults, treatment pathways and health outcomes associated with UCIs and hearing aids. It allowed for death from other causes (which increases in likelihood as the cohort ages) to be incorporated.Parameter estimates were incorporated as mean values with an associated prior distribution representing uncertainty surrounding the mean. Distributions were sourced from the literature, along with expert opinion where data on distributions were not available. Assumptions on distributions were made for those remaining parameter estimates, based on the family to which the parameter belonged.The model took an NHS perspective and a lifetime horizon to capture all differences in lifetime benefits and costs associated with a UCI. The discount rate for future health outcomes and costs was 3.5%, with a 1.5% discount rate tested within a sensitivity analysis. Both these discount rates are recommended by NICE guidelines within their Technology Appraisal Programme . A discoThe model explored alternative combinations of interventions and comparators, resulting in several economic evaluation scenarios. These included a UCI versus a hearing aid and a UCI versus no hearing aid. The model incorporated several health states to capture the treatment pathway and potential adverse events and device failures and death from other causes Fig. .Fig. 1MaIndividuals can remain in their initial state (‘UCI’), or experience an adverse event. These were categorised as either short-term adverse events that lasted one cycle , or long-term events that lasted for their remaining lifetime Fig. .Fig. 2TrInternal and external device failure or external device upgrade can either be immediate (in the first cycle) following surgery, or it can occur over time. This was incorporated into the model using a time-dependent probability calculated from cumulative survival values.Individuals who experience an internal device failure may choose to re-operate and replace the device Fig. . These iIndividuals who experience an external device failure may choose to replace the device or remain with a faulty device and cease to use the cochlear implant. There is no risk of death or adverse events with external device failure. Individuals who experience an external device upgrade will have the device replaced. There is no risk of death or adverse events with external device upgrade.Patients who cease to use a cochlear implant can either use a hearing aid, where they can be compliant or non-compliant, or they can choose not to use a hearing aid. ‘Death from surgery or natural causes’ is an absorbing health state, accounting for the risk associated with cochlear implant surgery and general all-cause mortality over time in the UK adult population.Several structural assumptions were required within the Markov model. Persons were assumed to have been diagnosed with severe to profound sensorineural hearing loss in both ears. All persons deemed eligible for a cochlear implant were assumed to receive a cochlear implant . Any future hearing loss the patient experiences does not impact health outcomes given hearing loss is already severe to profound. Those persons using a hearing aid (instead of a UCI) were either compliant users or non-complaint users.Several assumptions were made regarding the device itself. Annual equipment maintenance costs start in the second year from receiving a cochlear implant. The internal component of a cochlear implant lasts a lifetime, unless trauma occurs resulting in device failure, and that all cochlear implants are 3 T MRI compatible.The Markov model required several underlying parameters related to its structure, device failure, probability of re-implantation, and implant type, among other categories Table . Data weLiterature reviews on transition probabilities and utilities associated with hearing aids and cochlear implants were also conducted up to October 2018 to update and supplement data presented in the three primary sources. Search terms used within the NICE Health Technology Assessment Report were reviewed for their appropriateness, and applied to Ovid Medline and Embase. New search terms were developed for the literature review on utilities. No meta-analyses on utilities were performed due to a high degree of clinical heterogeneity in addition to poor reporting of methods in studies of cochlear implants. Expert opinion was used to fill data gaps associated with resource use and costs.Resource use was derived from published literature, grey literature and expert opinion. This information was used to develop a treatment pathway that an average patient is expected to take, from receiving an initial referral to a cochlear implant program from an audiologist, to receiving and using a cochlear implant Fig. . ResourcA systematic literature review was undertaken to extract health state utility values relating to hearing loss, cochlear implants and hearing aids in adults aged 18 years and over. While UK studies were preferred, studies from other countries with similar health care systems were also explored. Utilities derived from persons with severe to profound sensorineural hearing loss within a randomised controlled trial were prioritised, along with studies using the HUI3, given this instrument includes hearing and speech domains –37.Utility decrements from severe to profound sensorineural hearing loss were calculated by subtracting the HUI3 utility score of having no cochlear intervention derived from a UK study , from thA literature review was conducted to identify utility decrements associated with short-term adverse events and long-term adverse events associated with cochlear implant surgery. There were 17 different types of adverse events associated with cochlear implants found within the literature, excluding device complications such as electrode migration. These were allocated to six categories, including infection , neurological complications , pain , tinnitus (worsening or new occurrence), vestibular complications , and other complications . Only those with a prevalence of greater than one% were included in the model, which include dysgeusia (taste disturbance), vertigo, tinnitus and wound infection Table . It was Costs were calculated by multiplying the volume of resource use associated with interventions by their unit cost Tables , 9, 10. Unit costs were derived from clinical expert opinion, literature reviews, NHS National Schedule of Reference Costs, NHS National Tariff: Currencies and Prices, the Personal Social Services Research Unit, and literature.A sensitivity analysis of key model parameters was undertaken to assess the sensitivity of the ICERs to key model parameters. Parameters were chosen based on their expected level of uncertainty and potential influence on ICERs. Their range was dictated by the 95% confidence interval around the estimate (where available), while an arbitrary range was determined for all other parameters .A probabilistic analysis using Monte Carlo simulation was also conducted, using distributions attached to each model parameter, with 10,000 samples drawn at random from these distributions to calculate a distribution of ICERs. Fixed random number seeds were used to minimise random simulation error . A cost-Model validation was undertaken using the Assessment of the Validation Status of Health-Economic decision models (AdViISHE) tool . InternaThe model was checked for external consistency by first comparing ICERs using inputs derived from the NICE Health Technology Assessment Report. This allowed the structure and mathematical logic of the model to be tested, while holding differences in model inputs constant. ICERs generated using model inputs derived within this study were also compared. The model was also validated by clinical experts on whether the assumptions and structure of the model were reliable and could be reasonably explained.A UCI for someone that had previously worn a hearing aid in the ear that received the implant led to an average incremental lifetime cost increase of £37,988, and an additional 3.18 QALYs. This equates to an ICER of £11,946 per QALY gained.A UCI for someone that had not previously worn a hearing aid in the ear that received the implant led to an average incremental lifetime cost increase of £38,449 and an additional 3.66 QALYs. This equates to an ICER of £10,499 per QALY gained  fell into the northeast quadrant of the cost-effectiveness plane, indicating that a UCI is more expensive but also more effective Figs. , 7. MostModelling results suggest a UCI for adults with severe to profound hearing loss is cost-effective when compared to a hearing aid or no hearing aid. ICERs were well below the NICE cost-effectiveness threshold and CEACs suggest the probability of UCIs being cost-effective is between 93.0% and 98.7%. These results align with the NICE Health Technology Assessment Report conducted in 2009 . It founDifferences in the ICERs reported between the two studies may relate to changes in clinical pathways, resource use and unit costs. Our incremental lifetime costs were up to £4493 more (for someone previously not wearing a hearing aid) compared to the estimate in the NICE Health Technology Assessment Report. While pre-surgical costs and post-surgical costs were lower within our study, there were greater costs associated with cochlear implant surgery, device costs and hearing aids. The largest difference was in surgery and device costs, with our study estimating an additional £3142 and £2352, respectively.Our study developed a likely pre-surgical and post-procedural pathway currently operating in the UK, and applied unit costs derived from the NHS to expected resource use, including surgery and device costs. The UK Health Technology Report study estimated resource use and costs from a UK Cochlear Implant Study Group report conducted in 2004 . That stDifferences in methods and assumptions have also impacted results. This study estimated a patient is around three years older when they receive a cochlear implant compared to the NICE Health Technology Assessment Report, and there were differences in the number and types of adverse events a patient could experience. This study undertook a comprehensive literature review on adverse events to populate the model, while the NICE Health Technology Assessment Report relied on two studies to populate their model. The NICE Health Technology Assessment Report assumed reduced costs for internal device failure, repairs and replacement within a warranty period, which this study did not.Differing Markov model structures may have also impacted results. The NICE Health Technology Assessment Report allowed voluntary non-use of the cochlear implant, allowing UCI recipients to revert to their original hearing support. Our model allowed UCI recipients to revert to either their hearing aid or no hearing aid, but only if the device failed internally. Furthermore, our model produced two separate ICERs, one for adults with some benefit from hearing aids and another for adults with no benefit from hearing aids prior to receiving a UCI. The NICE Health Technology Assessment Report reported one ICER for all adults.This study found ICERs were sensitive to the proportion of people eligible for a UCI. This has implications for improving the awareness of access to UCIs after the change in NICE criteria. An influx of people seeking a UCI may increase the ICER if they are deemed ineligible through initial testing. Increased use of audiologists and speech and language therapists would increase costs without a commensurate increase in health outcomes. Improving the quality of referrals from referring clinics through better data collection and education, and carefully managing expectations regarding access to UCIs, is therefore warranted.While a UCI was estimated to be cost-effective, QALYs may have been underestimated given the most reliable utility estimates were taken from a study completed two decades ago . The intOur model represents a simplification of the complex interaction between hearing loss and quality of life. Cost savings were not included with reduced familial support, such as avoiding the need to learn sign language or the potential increase in QALYs for others from the avoidance of stress associated with hearing loss of a family member.Despite research showing severe to profound hearing loss reduces productivity –49, no sThe impact of hearing loss on the severity and onset of dementia were also not considered. While several studies have evaluated the impact of hearing aids on cognitive function , no studIf empirically validated, a reduction in dementia risk from cochlear implants would represent a significant benefit. One study has estimated that even delaying the onset of dementia by one year would decrease the prevalence of dementia around the world by 10% in 2050 . DementiThis study demonstrates that UCIs remain cost-effective since the UK Health Technology Report associated with the original NICE guidance was completed in 2009, despite changes to clinical practice and increased healthcare unit costs. Investment in improved awareness among clinicians and those with severe to profound hearing loss on access to, and potential benefits from, UCIs would further enhance access and improve quality of life and overall social welfare.


Conclusions: Our data are largely consistent with the literature and most results were expected, one relevant exception being the possible role of NICU as a confounding factor and the limited number of risk factors confirmed in the multivariate analysis.Background: Objectives of the present work were to analyze the prevalence of hearing loss in our population of screened newborns during the first 9 years of the universal newborn hearing screening (UNHS) program at University Hospital Sassari  (AOU Sassari), to analyze the risk factors involved, and to analyze our effectiveness in terms of referral rates and dropout rates. Methods: Monocentric retrospective study whose target population included all the newborns born or referred to our hospital between 2011 and 2019. Results: From 2011 to 2019, a total of 11,688 babies were enrolled in our screening program. In total, 3.9‰ of wellborn babies and 3.58% of neonatal intensive care unit (NICU) babies had some degree of hearing loss. The most frequently observed risk factors among non-NICU babies were family history of hearing loss (3.34%) and craniofacial anomalies (0.16%), among NICU babies were low birth weight (54.91%) and prematurity (24.33%). In the multivariate analysis, family history of hearing loss ( Permanent congenital hearing loss is an epidemiologically relevant condition with a rate among newborns of 1 to 3 per 1000 live births. While in a relevant number of cases a definite cause cannot be established, known etiologies and risk factors include genetic factors (syndromic and non-syndromic), congenital infections, ototoxic medications, hyperbilirubinemia, premature birth, low birth weight, admission to a neonatal intensive care unit, birth injuries, drug and alcohol use during pregnancy, maternal diabetes, preeclampsia, and anoxia , copyright 2013–2021 University of Amsterdam, Netherlands). A descriptive analysis of our data was performed to find both prevalence and distribution of the recorded variables. Pearson’s chi-squared test was used to assess whether there was a statistically significant difference between the frequencies of known and potential risk factors among healthy and hearing-impaired newborns. A logistic regression was performed to ascertain the effects of the total number of concomitant risk factors on the likelihood that newborns had a hearing loss. Only risk factors that were originally recorded during the screening phase and the results of the last diagnostic ABR were included in the analysis, as clinical and audiological follow-up data were often not available or reliable enough. For statistical purposes the hearing loss degree and the hearing loss status were assessed on the last available ABR, if less than three were available. Temporary cases with normal results at the follow-up ABRs were not included in the analysis. A correlation matrix of the dropout and referral rate at each stage and different years of screening was performed, and Pearson’s r and From 2011 to 2019, a total of 11,688 babies (2737 NICU and 8951 non-NICU) were enrolled in our screening program. In total, 35 of the 8951 of non-NICU babies (3.9‰) and 98 of the 2737 NICU babies (3.58%) had some degree of hearing loss, as confirmed with diagnostic ABR. Bilateral cases were 27 among non-NICU babies  and 57 among NICU cases . Cases associated with risk factors were 14 among non-NICU babies  and 98 among NICU cases . Two babies among non-NICU babies  and two among NICU babies  had profound bilateral hearing loss.®, Cochlear Limited, Sydney, Australia), whereas the others through traditional external hearing aids.Of the four babies with profound bilateral hearing loss, two received an indication for cochlear implantation. For a third one, the diagnosis was corrected from profound to moderate hearing loss during follow-up . Finallp-value = 0.002).Refer and drop-out rates by year are shown in p-value < 0.001), with a higher number of concomitant risk factors in NICU newborns.Descriptive statistics including sex, prevalence of each recorded risk factor and audiological features are shown in The results of the comparison of frequency distribution of risk factors among healthy and hearing-impaired babies, both for the whole series and for NICU and non-NICU newborns separately, are displayed in p-value p < 0.001), NICU , craniofacial anomalies , low birth weight (<1500 g) , and HIV  were confirmed as risk factors.The results of the univariate and multivariate logistic regression for the whole series are displayed in In total, 41.35% (55/133) of hearing-impaired babies were bilateral pass at the first stage of screening, and received a diagnostic ABR due to known risk factors. Risk factors among these newborns were NICU , low birth weight (<1500 g) , prematurity , mechanical ventilation for at least 5 days , hyperbilirubinemia , family history of hearing loss , and syndromes . None of them were profound or severe bilateral cases, and 25/55 (45.45%) were unilateral hearing losses. In total, 30.90% (17/55) of these cases had only one risk factor involved; in 12 cases  NICU and in 5 cases  familiarity. Moreover, 40% of non-NICU babies (14/35) with hearing loss did not have any known risk factor.Newborn hearing screening programs are a precious health and social tool that allow early detection and habilitation of hearing-impaired newborns. The data flow coming from programs that keep electronic or paper records has proven to be invaluable in understanding how different approaches impact the UNHS programs, in highlighting critical aspects, and in guiding preventive measures. Our screening program follows a fairly common protocol that involves TEOAEs as the test of choice for the first and second stage of screening and ABR for the definitive diagnosis. TEOAEs and aABRs are the most employed technologies in newborn hearing screening, as they are fast, reliable, and validated. They are both sensitive (85–100%) and specific (91–95%). Nonetheless, depending on the protocol applied, a not negligible number of referrals to audiological centers may be due to false positive results. The combination of TEOAEs and aABRs in the screening have been reported to reduce the referral rate . FactorsReferring newborns with risk factors to ABR testing independently from their first stage TEOAEs result has proven to be of utmost importance in our experience, as 52.04% of NICU hearing-impaired newborns and 14.28% of non-NICU ones would have been missed if not for such a practice, consistently with other reports . More inOne of the most discussed aspects and biggest issues of all UNHS programs is the dropout rate. “Lost to follow-up” rates usually range from 3.7 to 65% , mainly Clinical features showed a higher prevalence of risk factors and a greater number of simultaneous risk factors among NICU babies, as expected. The distribution of risk factors we pointed out might seem atypical, with a low number of genetic anomalies . HoweverHearing loss prevalence was within expectations, albeit in the upper limit of the reported range . In totaIn total, 41.35% of hearing-impaired babies would have been missed if not referred to the diagnostic ABR due to risk factors, being bilateral pass at the first stage of screening, thus supporting the indication of a diagnostic ABR in newborns with risk factors even in case of a negative screening, as advocated by some authors [Our analysis on the whole series showed that most of the currently known risk factors had a statistically significant higher frequency in hearing-impaired newborns. Such risk factors included: family history of hearing loss, low birth weight <1500 g), hyperbilirubinemia, low Apgar score ,10, defi00 g, hypOur study has some limitations. It has an observational design, and thus, it may be plagued by selection bias. However, it discusses a universal newborn hearing screening program that grants access to all newborns, with virtually no excluded newborns in the covered territory. We reckon that it is possible that a small number of patients referred to our hospital from other facilities might choose to perform the screening at private centers, but to the best of our knowledge, this number is negligible. Risk factors were collected at birth and are limited to the ones that were known at delivery time, thus excluding all those discovered later in life . Some of the anamnestic data were collected through questionnaires, thus being at risk of recall bias, among others. The instrument dedicated to the first stage of screening of NICU babies was changed at the beginning of 2019 with a new model, the Madsen AccuScreen Type 1077 TE/DP, but whether it may have had an impact on referral rates is unknown. To assess the overall percentage of hearing-impaired babies, we used the results of the last available ABR. Some babies might have had middle ear effusion at the time of our diagnostical ABR, and although our common practice includes appropriate treatment and retest in these cases, in some of them, the follow-up ABR might have been missed, or the condition might not have resolved by that time, and thus, some babies with middle ear effusion might have been inappropriately included in the count of permanent hearing losses. The relevant number of dropouts, especially in the diagnostic phase, reduces the number of hearing-impaired babies found and our ability to correlate these missing events with risk factors. Moreover, our screening program has not been audited during the whole period. Strengths of this study include the number of newborns enrolled in a single facility, the uniformity of the testing method, the team of technicians (the same throughout the 9 years included), and the consistent collection of data through the years.Our data are largely consistent with the literature, and most results were expected, one relevant exception being the possible role of NICU stay as a confounding factor, the limited number of risk factors confirmed in the multivariate analysis, and the impact this might have on the relevance given to other well-known and assessed risk factors in the future.


Midlife males with obstructive sleep apnea (OSA) bear a high risk for cardiovascular diseases. However, the association of OSA and hearing impairment is controversial. Our objective was to observe the incidence of hearing loss in middle-aged males with different risks for OSA.794 men aged 40–65 who participated in health examination and pure tone hearing screening between January and June 2021 were recruited in the study. Medical history was collected. Height, weight and blood pressure were tested, and biochemical test including blood lipids and blood glucose was performed. According to the STOP-BANG score, the observed subjects were divided into low, intermediate and high groups for OSA risk. Hearing impairment was defined as failure in responding to any pure tone of 25 dB HL in any ear at the frequencies: 4 kHz for high frequency range and 0.5k, 1k, 2 kHz for low/medium frequency range. The incidence of hearing loss in those groups was compared after adjusting the cardiovascular risk factors.The incidence of hearing impairment in the groups of intermediate, high, and intermediate/high risk for OSA  were higher than that in the group of low risk for OSA . After adjusting cardiovascular risk factors, the risk of hearing impairment in the group of high risk for OSA is 1.64 times of the group of low risk for OSA . The risk of hearing impairment at high frequency(4kHz) in the group of intermediate/high risk for OSA is 1.43 times of the group of low-risk for OSA .The risk of hearing impairment in midlife men with high, intermediate/high risk for OSA is significantly increased, especially at high frequency of 4 kHz. Obstructive sleep apnea (OSA) is characterized by recurrent upper airway collapse during sleep, leading to sleep apnea and intermittent hypoxia. It is considered to be a risk factor for a variety of chronic diseases including hypertension, diabetes, ischemic coronary heart disease, stroke, cancer and cognitive impairment . A studyAs the fourth leading cause for disability, hearing impairment has been focused since it may lead to disturbed interpersonal communication, social loneliness and cognitive impairment. A Study showed that 23% of people aged 12 years or older were suffering from hearing loss . The knoRecently, it has been reported that OSA was related to hearing impairment. However, the results are inconsistent. Vorlova et al  showed aBetween January and October 2021, the cross-sectional, population based research was conducted in Beijing Tongren Hospital. Among the individuals who participated in routine health examination and received hearing screening, 794 men aged from 40 to 65 were recruited . QuestioThe study was approved by the Ethics Committee of Beijing Tongren Hospital, Capital Medical University. All procedures were performed in the study in accordance with the 1964 Helsinki declaration and its later amendments. Informed written consents were obtained from all participants included in this study.2 (m2). NC was measured at the horizontal level of the seventh cervical vertebra. Blood pressure was measured twice at the sitting position after resting for 5 min, and the average was used for analysis. Fasting blood samples were detected within 24 hours. Fasting blood glucose (FBG), creatinine, triglyceride (TG), total cholesterol (TC) and low density lipoprotein cholesterol (LDL) were measured by Immunoassay Systems . CCR  = [(140-age) ×body weight (kg)] /serum creatinine (μmol/L) [BMI was derived by weight (kg) / height(μmol/L) .2 (B), 6. age > 50 years old (A), 7. neck circumference > 40 cm (N), and 8. male (G). Low risk = yes to 0–2 questions; high risk = yes to ≥ 5 STOP-BANG questions, or yes to ≥ 2 STOP questions plus neck circumference > 40 cm; intermediate risk = yes to 3–4 STOP-BANG questions with exclusion of those included in the high risk group.OSA risk was assessed by the STOP-BANG questionnaire  which coPure tone hearing screening was conducted in an independent quiet room with ambient noise less than 40 dB, using a AA20 screening audiometer  and a Sennheiser HDA200 noise-masked headphone . Testing was completed at frequencies of 0.5 kHz, 1 kHz, 2 kHz and 4 kHz for each ear separately. Otolaryngology and otoscopy examination were performed by experienced otolaryngologists before hearing screening test. Definition of hearing screening results: a pass was defined as response in both ears to pure-tone stimuli of 25 dB HL at all frequencies. A fail was defined as no response to 25 dB HL at any frequency in either ear. Hearing impairment in the Low/medium frequency range was defined as a fail at 0.5k, 1k or 2 kHz. Hearing impairment in the high frequency range was defined as a fail at 4 kHz .2 test was used for categorical data, one-way ANOVA or independent t-test was used to compare continuous data. The missing values were filled with the median of the non-missing values. Sensitivity analyses were further carried out by assessing whether the present finding was influenced by compositions of subjects. Subjects in the intermediate/high, intermediate and high risk groups were analyzed respectively. The incidence of hearing impairment was shown as OR and 95%CI by binary logistic regression analysis. Different adjustment models were used to evaluate the incidence of hearing impairment in each OSA risk group. Model 1: no factors were adjusted. Model 2: age and BMI were adjusted. Model 3: model 2 plus smoking status were adjusted. Model 4: model 2 plus cardiovascular risk factors  were adjusted. For the multivariate logistic regression, the continuous data were transformed into categorical data: (1) age: ≤50 and > 50; (2) BMI: < 28 and ≥28kg/m2; (3) hypertension: no self-reported hypertension with SBP < 140 and DBP < 90mmHg vs otherwise; (4) diabetes: no self-reported diabetes with FBG < 7mmol/L vs otherwise; (5) dyslipidemia: no self-reported dyslipidemia with TG < 1.7mmol/L, TC < 5.2mmol/L and LDL < 3.4mmol/L vs otherwise. P values < 0.05 were considered statistically significant. SPSS 13.0 software was used for statistical analysis.The Pearson χA total of 794 middle—aged males enrolled in the study were grouped according to the STOP-BANG score. 457 (57.6%) had scores representing low risk for OSA. 213 (26.8%) had scores of intermediate risk, and 124 (15.6%) had scores of high risk for OSA. Together, the intermediate/high risk group added up to 337 (42.4%) of the study subjects. Subjects in the intermediate, high and intermediate/high risk groups tended to be older, and had higher BMI and higher proportion of hypertension, dyslipidemia and smokers. They also had a higher level of SBP, DBP, FBG, TG and CCR . The comThe percentage of individuals who failed the pure-tone screening in the groups of intermediate, high and intermediate/high risk for OSA were higher than that in the group of low risk . No signThe incidence of hearing impairment at any frequency of any ear: The incidence of hearing impairment in the groups of intermediate, high and intermediate/high risk for OSA was significantly higher as compared to that of low risk , Model 1After adjusting age and BMI, and age, BMI plus cardiovascular risk factors, the incidence of hearing impairment at high frequency in individuals with intermediate/ high risk for OSA was significantly higher than that with low risk . WhereasIn our study, it was revealed that the intermediate/high risk for OSA in middle-aged men assessed by STOP-BANG scores was associated with hearing impairment. Further analysis for subtypes of hearing impairment suggested a stronger association of intermediate/high risk for OSA with hearing impairment at high frequency of 4 kHz. After adjusting the potential cardiovascular risk factors, the association was still statistically significant.2 or NC > 40cm besides STOP-BANG scores of 3–4 as a high-risk population. Then the specificity was increased to 79–85%. Those confirmed the reliability of STOP-BANG questionnaire to screen out the population with moderate to severe OSA. In our study, because individuals with BMI > 35kg /m2 were included in the population with STOP-BANG scores≥5, the STOP scores≥2 + NC > 40cm was used as the standard of two-step method. Individuals meeting the standard or with STOP-BANG scores ≥ 5 were classified as high risk for OSA.The STOP-BANG questionnaire is reliable for screening patients with moderate to severe OSA. The risk of moderate to severe OSA is almost 0 in people with 0–2 points. The sensitivity of a score≥3 to detect OSA with apnea and hypopnea index >15 is 100%, but the specificity is only 43%. In order to improve the specificity, Chung et al  proposedSettings and environment for hearing screening test in our study are in line with the statement of ASHA’s adult hearing screening guidelines . HearingPrior studies on the relationship between OSA and hearing impairment revealed inconsistent results. Chopra et al  presenteIt is speculated that OSA induces hearing loss through multiple mechanisms. Among the risk factors that lead to hearing loss, noise leads to high-frequency hearing loss, while hearing loss caused by cardiovascular risk factors such as smoking and diabetes involves both low and high frequency. Noise trauma leads to the loss of outer hair cells inside the Corti’s organ located in the basilar membrane of the cochlea, where high-frequency hearing is encoded. However, smoking and diabetes may lead to ischemia of the inner ear through the dysfunction of cochlear microcirculation and endothelial inflammation . It may Our study used reliable and easy to execute methods for assessing the risk for OSA and hearing impairment, which can be generalized for large-scale population study. We adjusted several confounding factors that may exist simultaneously in OSA and hearing loss. Our staff working on questionnaire collection and hearing screening test were blind of each other, and unaware of the research hypothesis, so the data were objective enough. Nevertheless, there were some limitations. 1. Future polysomnography should be conducted to explore the association between different degree of OSA and hearing impairment. 2. Pure-tone threshold testing can be used to identify the hearing impairment below 25 db HL.In conclusion, we found in Chinese midlife men, the intermediate/high risk for OSA was associated with hearing impairment, especially at the high frequency of 4 kHz. This finding reminded us of early identifying midlife men with OSA risk as a population at high risk for hearing impairment, hence offering proper intervention to prevent consequent deterioration of hearing loss.S1 Data(XLSX)Click here for additional data file.


Given the challenges rural cancer patients face in accessing cancer care as well as the slower diffusion and adoption of new medical technologies among rural providers, the aim of our study was to examine trends in gene expression profiling (GEP) testing and evaluate the association between hospital rurality and receipt of GEP testing. N = 43), large rural (N = 16), and small rural (N = 48). Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression to evaluate the association between hospital rurality and GEP test use, adjusting for demographic and clinical characteristics. The association between test result and treatment received was assessed among patients who received Oncotype DX (ODX) testing.  Data from the Iowa Cancer Registry (ICR) were used to identify women with newly diagnosed, histologically confirmed breast cancer from 2010 through 2018 who met eligibility criteria for GEP testing. Patients were allocated to the hospitals where their most definitive surgical treatment was received, and Rural-Urban Commuting Area codes were used to categorize hospitals into urban  underwent testing with 95% receiving ODX. While overall GEP testing rates increased over time from 42% between 2010 and 2012 to 51% between 2016 and 2018 (Ptrend < 0.0001), use continued to be the lowest among patients treated at hospitals in small rural areas. The odds of GEP testing remained significantly lower among patients treated at hospitals located in small rural areas , after adjusting for demographic and clinical characteristics. ODX recurrence scores were highly correlated with chemotherapy use across all strata of hospital rurality.  Of 6,726 patients eligible for GEP test use, 46% ( GEP testing continues to be underutilized, especially among those treated at small rural hospitals. Targeted interventions aimed at increasing rates of GEP testing to ensure the appropriate use of adjuvant chemotherapy may improve health outcomes and lower treatment-related costs. In the United States, breast cancer accounts for 31% of all cancers diagnosed among females (excluding nonmelanotic skin cancers), with an estimated 287,850 new cases expected in 2022 [Historically, treatment decisions related to the use of adjuvant chemotherapy have been made using clinicopathologic characteristics  in combination with the treatment preferences of the patient and clinician(s). However, studies suggest approximately 85% of patients diagnosed with HR+, LN− breast cancer are unlikely to derive significant benefit from the addition of chemotherapy given the low 5-year rate of recurrence associated with endocrine therapy alone along with pathologic features that can make these tumors less responsive to traditional cytotoxic chemotherapy , 5. FurtTo better identify those at high risk for recurrence who would benefit from the addition of adjuvant chemotherapy and minimize avoidable side effects associated with overtreatment among patients with a low risk of recurrence, several GEP assays have been developed including Oncotype DX , MammaPrint , Predictor Analysis of Microarray 50 (Prosigna (PAM50); NanoString Technologies, Seattle, WA), EndoPredict , and the Breast Cancer Index  . StudiesThe use of GEP tests for select patients with early-stage breast cancers is included in clinical practice guidelines published by the National Comprehensive Cancer Network (NCCN)  and the Patients residing in rural areas commonly face challenges in accessing cancer care due in part to increased travel burden, limited availability of oncology specialists, and reduced availability of targeted treatments that may be informed by GEP testing –26, whicA secondary data analysis of female breast cancer patients was performed using data extracted from the ICR. The ICR is a population-based registry that routinely collects information on all newly diagnosed cancers in Iowa and includes patient demographics, tumor characteristics, first course of therapies, and survival data. The ICR has been a member of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program since 1973 .Given the deidentified nature of the data, the Institutional Review Board at the University of Iowa determined that this study did not meet the criteria for human subjects' research and was exempted from further review.th or 7th edition), HR+ (defined as estrogen receptor-positive and/or progesterone receptor-positive), HER2−, LN− breast cancer measuring >0.5 cm were identified by the ICR. Patients were excluded if they had not undergone surgical resection of their tumor via mastectomy or lumpectomy (N = 7). Patients with missing surgical facility were also excluded (N = 88).A total of 6,821 female Iowa residents, aged 20 years and older with histologically confirmed, unilateral, first primary, breast cancer diagnosed between January 1, 2010 and December 31, 2018, who met eligibility criteria for GEP testing defined as stage I/II , which accounted for 95% of our GEP-tested population, were the focus of our subsequent analyses. For patients with ODX testing, RS was categorized as low (RS < 18), intermediate (RS 18–30), or high (RS ≥ 31) risk. Considering the study time frame, the RS categories were chosen based on the validation study conducted by Paik et al. . PatientAdjuvant chemotherapy was defined as the first course of treatment initiated at any facility following surgical resection of the tumor. Patients were considered to have received adjuvant chemotherapy regardless of the type of agent, number of agents, or duration of therapy.Rural-Urban Commuting Area (RUCA) codes , based oth or 7th edition), histology, tumor size, and tumor grade. Insurance status was defined as insured (private or Medicare), Medicaid coverage , and uninsured. Patients with no known insurance coverage at the time of diagnosis (N = 145) were assigned to the uninsured category. Census-tract-level median household income derived from the 2017 American Community Survey was included [Patient-level demographic and clinical characteristics obtained from the ICR included age at diagnosis, race/ethnicity, marital status, insurance status, year of diagnosis, cancer stage  underwent testing. Patients treated at hospitals in small rural areas received testing significantly less often compared to those who underwent treatment at hospitals located in urban or large rural areas . In addition, patients who were older at the time of diagnosis, unmarried, and residing in areas with lower median household income received testing less frequently. There were clinically meaningful differences in GEP test use by tumor histology, size, and grade   , use con 0.0001) .In univariable analysis, the odds of GEP testing were significantly lower among patients treated at hospitals located in large rural and small rural areas. In addition, the odds of GEP testing were lower among older patients and those who were unmarried at the time of diagnosis. The odds of GEP testing increased with increasing median household income, increased over time, and increased with increasing tumor grade. The odds of GEP testing varied by tumor histology and tumor size . In multODX testing accounted for 95% of all GEP testing in our study population . Of 2,91In this population-based study, fewer than half of all breast cancer cases who were eligible for GEP testing, based on national clinical practice guidelines, received it. Women eligible for GEP testing were much less likely to receive testing if they sought care at a hospital in a small rural area. These hospitals accounted for 45% of hospitals in the study area and treated 6% of the study population. Patients who received care at hospitals in larger rural areas, accounting for 15% of hospitals and 13% of the study population, were also less likely to receive testing although not after adjustment for demographic and clinical characteristics. Once tested, women were equally likely to receive adjuvant chemotherapy irrespective of hospital rurality.Our results are consistent with other studies that report testing rates between 25% and 54% among eligible breast cancer patients , 35–37. In multivariable analysis, results demonstrate that patients who undergo treatment at hospitals located in small rural areas are significantly less likely to receive GEP testing compared to those treated at urban hospitals, after adjusting for demographic and clinical characteristics. Our finding of low testing rates among patients treated at rural hospitals helps to explain previously reported associations between GEP testing and rural-urban residence , 35–37 bDemographic and clinical characteristics are known to influence the use of GEP tests for women diagnosed with early-stage breast cancer. Consistent with prior studies , 20, 21,Similar to previous studies , 15, theThis is the first population-based study to evaluate differences in GEP test use by hospital location among guideline-eligible breast cancer patients and, therefore, provides new evidence that patients treated at rural hospitals receive less GEP testing compared to those treated at urban hospitals. While previous studies have adjusted for rurality, they were not designed to examine if hospital rurality influenced the odds of GEP testing in women diagnosed with early-stage breast cancer. Additionally, this study was conducted using data from the ICR, which has been a member of the SEER Program since its inception in 1973. Since 1998, this registry has received and maintained annual Gold Standard certification by the North American Association of Central Cancer Registries (NAACCR) .However, several limitations of this study warrant consideration. Our population included predominantly non-Hispanic white patients residing in Iowa at the time of diagnosis, so results may not be generalizable to those of other racial/ethnic groups or to those living in other geographic regions. In addition, patient-provider decision-making processes that may impact the use of GEP tests were not assessable. Furthermore, our study lacked comorbidity information as well as individual data on socioeconomic factors, including income that have been shown to be associated with GEP testing in prior studies. As such, caution should be taken when interpreting the observed association between GEP test use and census-tract data.In summary, the use of GEP testing has increased significantly over time among Iowa's guideline-eligible breast cancer patients but is still low. Despite the clinical utility and cost-effectiveness of such tests, GEP tests continue to be used in less than half of eligible patients, especially among those treated at hospitals located in small rural areas. Further research is needed to examine patient, provider, and hospital characteristics associated with GEP test use, including patient and provider treatment preferences as well as the ability of the patient to adhere safely to a full chemotherapy regimen. Such research may inform the development of targeted interventions aimed at increasing rates of GEP testing in rural areas to ensure the appropriate use of adjuvant chemotherapy and improve health outcomes.


Mycoplasma hyopneumoniae (M. hyopneumoniae) infections in breeding animals are often subclinical, their control could have a positive effect on M. hyopneumoniae infection levels in fattening pigs. This study investigated the presence of M. hyopneumoniae in the breeding population of ten Belgian farrow-to-finish farms suspected by the herd veterinarian to be M. hyopneumoniae infected. Gilt vaccination against M. hyopneumoniae prior to first insemination was practiced on nine of the ten farms. At four different time points in the reproductive cycle 20 animals were sampled on each farm, namely 30–40 days of gestation, 75–85 days of gestation, 3–5 days after farrowing, and 1–3 days after weaning. In total, tracheobronchial swabs and blood samples were collected from 344 gilts and 456 sows (n = 80/farm). Swabs were analysed for the presence of M. hyopneumoniae DNA using nested PCR and M. hyopneumoniae-specific antibodies were detected in serum with a commercial ELISA. Generalized linear mixed models with farm as random factor were used to test the effect of time point in the reproductive cycle and parity on M. hyopneumoniae PCR prevalence and seroprevalence.Dam-to-piglet transmission plays an important role in the epidemiology of enzootic pneumonia on farms. Although M. hyopneumoniae PCR prevalence ranged between 0% and 43.8% at the farm level and the seroprevalence between 32.5% and 93.8%. Gilts were significantly more M. hyopneumoniae PCR positive than sows at the 2-4th parity (P = 0.02) and > 4th parity (P = 0.02). At 30–40 days of gestation, significantly more breeding animals were PCR positive as compared to 75–85 days of gestation (P = 0.04), 3–5 days after farrowing (P = 0.02) and 1–3 days after weaning (P = 0.02). Gilts had significantly more often M. hyopneumoniae-specific antibodies than sows (P = 0.03).M. hyopneumoniae PCR prevalence varied a lot between farms and due to gilt vaccination the number of animals with M. hyopneumoniae-specific antibodies was high on most farms. Gilts were more often M. hyopneumoniae PCR positive than sows and positive animals were mostly found at 30–40 days of gestation. This emphasizes the importance of a sufficiently long quarantine period and proper gilt acclimation practices before introducing gilts to the sow herd.The online version contains supplementary material available at 10.1186/s40813-022-00267-w. Mycoplasma hyopneumoniae (M. hyopneumoniae) is the primary agent of enzootic pneumonia (EP) in pigs causing significant economic losses in swine production worldwide [M. hyopneumoniae on the farm. Infections in breeding animals are mostly asymptomatic, but these animals can transmit the pathogen to their offspring in the farrowing unit [M. hyopneumoniae in piglets at weaning is associated with the presence of EP-like lung lesions and the percentage of affected lungs at the moment of slaughter [M. hyopneumoniae positive sows in the farrowing unit are risk factors for a higher M. hyopneumoniae prevalence at weaning [M. hyopneumoniae positive at weaning and the losses at the level of the grow-finishing pigs could decrease. In order to optimize M. hyopneumoniae-specific control measures in the breeding population , it is necessary to gain a better insight in the prevalence and epidemiology of M. hyopneumoniae in breeding animals.orldwide , 2. Thesing unit –5. The olaughter , 7. The  weaning , 9. If tM. hyopneumoniae, the presence of the pathogen and M. hyopneumoniae-specific antibodies in breeding animals may differ a lot between farms [M. hyopneumoniae in sows. Most studies reported a higher PCR prevalence or seroprevalence of M. hyopneumoniae in gilts and/or young sows [M. hyopneumoniae, especially in gilts [M. hyopneumoniae PCR prevalence could not be demonstrated. Previous studies addressing M. hyopneumoniae PCR prevalence or seroprevalence in breeding animals are mostly older studies including only one or a few herds. Furthermore, gestating sows were not moved to a group housing system and often only blood samples  or swabs from the upper respiratory tract were taken. The chance of detecting M. hyopneumoniae is higher when samples are taken from the lower respiratory tract [Although most herds are endemically infected with en farms , 10, 11.ung sows , 13, whiung sows . Besidesin gilts . Weaningin gilts , 17. Strin gilts  influencin gilts . Howeverry tract .M. hyopneumoniae PCR positive at specific TPs in the reproductive cycle under group housing conditions.Since 2013, group housing of breeding animals between four weeks of gestation and one week before farrowing is obligatory in the European Union (Directive 2008/120/EC) . HoweverM. hyopneumoniae seroprevalence and infection status in 800 breeding animals from ten different herds in Belgium. The specific objectives were (1) to investigate the influence of parity on M. hyopneumoniae PCR prevalence and seroprevalence, (2) to investigate the influence of the TP in the reproductive cycle on M. hyopneumoniae PCR prevalence and seroprevalence and (3) to investigate the potential correlation between the infection status and seroprevalence.The present study aimed to investigate the M. hyopneumoniae, at least part of the piglets raised at the same site, and willingness to participate. Farmers were allowed to practice vaccination of gilts against M. hyopneumoniae and both breeding of their own gilts or purchase of gilts was permitted. Farms were selected when the herd veterinarian suspected M. hyopneumoniae circulation in young piglets and/or the sow population based on historical information (serology/presence of the pathogen/coughing problems).The study was performed after approval by the Ethical Committee for Animal Experiments of the Faculty of Veterinary Medicine and the Faculty of Bioscience Engineering, Ghent University . Ten Belgian farrow-to-finish farms were included in the study. The first five farms were sampled in 2020 between January and March and the other five farms in 2021 in the same months. Herd inclusion criteria were: no vaccination of sows against On each farm a cross-sectional sampling was performed by sampling 80 breeding animals equally divided over four different TPs in the reproductive cycle; 30–40 (TP1) and 75–85 (TP2) days of gestation, 3–5 days after farrowing (TP3) and 1–3 days after weaning (TP4). On farms with a one- or three-week-production system all samples were taken on the same day, while two sampling moments were needed with approximately nine days in between for farms working in a four-week-production system. Ten clusters (farms) were needed for both the groups of sows and gilts to achieve a power of 80% to detect a difference in proportion of 0.05 between the two groups. In each cluster for the four selected TPs ten gilts and ten sows had to be sampled, meaning 800 pigs in total. With a cluster auto-correlation of 80% and 120% the power ranged from 0.70 to 0.88, respectively, which both were deemed satisfactory. If a farmer did not have ten gilts in a specific batch, all gilts were sampled and completed with sows until 20 animals were sampled at each TP. In each batch the 10 sampling sows were chosen randomly. In total, 800 breeding animals were sampled of which 344 were gilts and 456 were sows. In the group of the gilts 183 animals had not farrowed yet (TP1 and TP2) and 161 animals had farrowed once (TP3 and TP4). There were 285 2-4th parity animals and 171 > 4th parity animals in the group of the sows. From each animal blood and tracheobronchial swabs (TBS) were collected.vena cava cranialis. Samples were centrifuged at 1000xg and serum was stored at −20 °C until further analysis. To detect the presence of M. hyopneumoniae-specific antibodies, a commercial indirect ELISA  was used following the manufacturer’s instructions. Samples were considered positive if the sample to positive (S/P) ratio was higher than 0.40 and negative if the S/P ratio was equal to or lower than 0.40.Blood was collected in a sterile serum tube (clotted blood) by puncture of the jugular vein or M. hyopneumoniae, DNA was extracted from the TBS using a commercial kit  and a nested PCR was performed according to the protocol described by Stärk et al. [A sterile swab of 60 centimeters  was used for the tracheobronchial sampling . All TBSk et al. .M. hyopneumoniae infection status (PCR). In the first one, the parameter ‘parity’ was used as binary (gilt or sow) and in the second one as categorical . Furthermore, to process the serological data (ELISA), also two models were used including the same parameters as the infection status models. Categorical or binary fixed variables with absence of variability among their categories, meaning that more than 90% of the total samples belonged to a given category, were excluded for further statistical analysis. To correlate PCR and serology results the positive predictive value (PPV) and negative predictive value (NPV) were calculated considering the PCR and ELISA data as binary. When calculating the PPVELISA and NPVELISA the PCR test was considered as gold standard and vice versa. Moreover, a point-biserial correlation was performed to correlate PCR and serology results. Apart from that, a GLMM was used with PCR outcome as dependent, farm as random, TP as fixed variable and the precise optical density (OD) values as fixed variable to investigate the association between PCR and serology results. The higher the OD value, the higher the level of M. hyopneumoniae-specific antibodies in the serum. For all GLMM pairwise comparisons were run post-hoc for all the fixed factors and a sequential Sidak correction was applied to correct for multiple testing.All statistical analyses were performed using IBM SPSS version 27® . Descriptive information  regarding the various parameters included in this study was calculated. Test result (either PCR or ELISA) was selected as the dependent variable. We used generalized linear mixed models (GLMM) and fitted binomial logistic models with farm included as random factor and TP included as fixed factor. Two models were developed for the M. hyopneumoniae on a farm, the ten farms were split in five farms with the highest M. hyopneumoniae prevalence (HPF) and five farms with the lowest M. hyopneumoniae prevalence (LPF) after analyzing the PCR data.To see if differences in housing and management of the breeding animals had an influence on the presence of M. hyopneumoniae negative farm. Purchased gilts were vaccinated against M. hyopneumoniae only in the quarantine unit on four farms, on two farms the gilts were vaccinated at the supplier and in the quarantine unit, and on one farm M. hyopneumoniae vaccination was only done at the supplier. At two out of three farms rearing their own gilts, the gilts were vaccinated against M. hyopneumoniae during rearing and one farm (farm 9) did not practice M. hyopneumoniae vaccination. None of the farms vaccinated the gilts after moving them to the insemination unit. Similarly, none of the farms vaccinated the sows against M. hyopneumoniae. On all farms gilts had contact with the sows for the first time in the insemination unit. Mostly, gestating sows were brought in group housing around four weeks of gestation (8/10), only one farm waited until five weeks. On another farm, gestating animals were housed in group already from three days after insemination onwards. According to the farmer and/or the herd veterinarian there were some coughing problems in the breeding animals and/or in young piglets on six farms.An overview of the herd characteristics is shown in Table M. hyopneumoniae prevalence ranged between 0% and 43.8% at the farm level. The ten farms could be split in five LPF with M. hyopneumoniae prevalence ≤ 7.5% and five other HPF with M. hyopneumoniae prevalence ≥ 18.8% and ≤ 43.8%  and parity > 4 (P = 0.02). Animals with parity 2–4 tended to be more often M. hyopneumoniae positive than animals with parity > 4, although this difference was not statistically significant (P = 0.11). Pairwise comparisons of the different TPs showed that breeding animals in general were significantly more M. hyopneumoniae positive at TP1 compared to TP2 (P = 0.04), TP3 (P = 0.02) and TP4 (P = 0.02). Within the group of gilts, the same significant results were observed when TP1 was compared to TP2 (P = 0.04), TP3 (P = 0.02) and TP4 (P = 0.02). Pairwise comparisons between the other TPs were not statistically significant. For the group of sows, there were no statistically significant differences between the TPs. Detailed results of the different statistical models are provided as supplementary data , while the seroprevalence for the other farms was higher than 66% , and significantly less sows with parity > 4 were seropositive compared to sows with parity 2–4 (P = 0.02) and gilts (P = 0.02). Pairwise comparisons showed no statistically significant differences for the seroprevalence in breeding gilts or sows at the different TPs. Detailed results of the different statistical models are provided as supplementary data  and the NPVPCR was 23.0% (152/660). The PPVELISA was 20.0% (127/635) and the NPVELISA was 92.1% (152/165). An overview of the test results is shown in Table 2=0.27) but statistically significant (P < 0.01) correlation was observed between the OD-values of the ELISA and a PCR positive result. M. hyopneumoniae PCR positive gilts had more often a high OD-value compared to M. hyopneumoniae PCR positive sows (P = 0.03). Considering that the farms had identical random effects and holding TP4 fixed, the odds for M. hyopneumoniae PCR positive gilts to have a high OD-value was 5.5 (P = 0.001), while the odds for PCR positive sows to have a high OD-value was 0.36 (P < 0.001).To investigate whether the PCR prevalence of s 90.7% 17/140 andM. hyopneumoniae circulation were included. Consequently, the results might not be extrapolated to the entire Belgian population of farrow-to-finish farms as only suspected EP-problem farms were included. Furthermore, samples were taken in winter period to have a higher chance of finding M. hyopneumoniae positive animals. When pigs are raised during cold, rainy periods, the chance on being infected with M. hyopneumoniae is higher [Ten Belgian farrow-to-finish farms were visited in this study and all samples were taken between January and March in either 2020 or 2021. Only farms where the veterinarian suspected that there was s higher , 25.M. hyopneumoniae PCR prevalence, but this could not be confirmed. The HPF were larger and they had more breeding animals. Animals on large farms, purchasing a larger number of gilts each year, have a higher risk of being infected with M. hyopneumoniae [M. hyopneumoniae free farm. The duration of the quarantine period might be important but lasted on average five weeks in both groups [M. hyopneumoniae PCR prevalence or seroprevalence in sows and suckling pigs [M. hyopneumoniae was practiced on all farms except one. It is recommended to vaccinate gilts against M. hyopneumoniae to reduce shedding and transmission, but vaccination will not prevent infection [M. hyopneumoniae infected animals on a farm can be high.Based on PCR prevalence the farms could be divided in five HPF (≥ 18.8%) and five LPF (≤ 7.5%). On all the HPF and one LPF coughing problems were observed by the farmer and/or the herd veterinarian in the breeding animals and/or in young piglets. Unfortunately, coughing was not observed nor quantified during the samplings and the presence of other respiratory pathogens in the breeding population was not investigated. Therefore, coughing problems might be associated with eumoniae , 26. Forh groups . Furthering pigs , 10, whenfection , 28–30. M. hyopneumoniae PCR prevalence was high. Although M. hyopneumoniae circulation was suspected, the PCR prevalence was low or even zero in the breeding animals on some farms [M. hyopneumoniae. Due to gilt vaccination, it is not surprising that the number of breeding animals with M. hyopneumoniae-specific antibodies decreased with increasing parity. The concentration of antibodies in blood will decrease over time in the absence of a natural infection boosting the antibody response. On the farm not practicing gilt vaccination (farm 9), the seroprevalence in gilts was 73.9%, meaning that M. hyopneumoniae infections were present in the gilt population and the antibodies in these animals were due to natural infections. On the other farms, it is not known whether serum antibodies were due to vaccination, infection, or both. This highlights the need to develop DIVA compliant vaccines against M. hyopneumoniae [M. hyopneumoniae, and gilts had more often M. hyopneumoniae-specific antibodies compared to sows, which is in line with previous findings [M. hyopneumoniae PCR prevalence or seroprevalence was investigated in breeding animals only to draw conclusions on their offspring [M. hyopneumoniae DNA were mostly taken in the upper respiratory tract using PCR analysis while the sensitivity of TBS is higher [M. hyopneumoniae seropositive sows and the TP in the reproductive cycle had no influence on the seroprevalence, which is in line with our findings [M. hyopneumoniae vaccination status of the breeding population. In their study, Fablet et al. [M. hyopneumoniae on every farm (4/5) and breeding animals were more often PCR positive at 9 weeks before farrowing compared to later TPs in the reproductive cycle, but this result was not significant [M. hyopneumoniae positive farm were followed from birth till weaning of their first litter, the highest M. hyopneumoniae PCR prevalence was seen shortly before first insemination [M. hyopneumoniae PCR positive in the first half of gestation compared to the remainder of their reproductive cycle [Between the farms the variation of me farms . For theeumoniae . In thisfindings , 12, 13.ffspring , 32. Onlffspring , 13. Furs higher . In the findings , 11. Howmination . In lineve cycle . Howeverve cycle  were lonM. hyopneumoniae PCR prevalence was the highest at 30–40 days of gestation in gilts (significant) as well as in sows (not significant). This supports the theory that merging gilts and sows increases the risk for being M. hyopneumoniae PCR positive. Since no samples were taken in our study from the gilts in the quarantine stable or before insemination, it is not possible to indicate if M. hyopneumoniae positive sows infected the new gilts or vice versa. However, before introducing gilts to the sow population good acclimation of the gilts is necessary [M. hyopneumoniae negative source into an endemically infected farm, good immunization is even more important [M. hyopneumoniae is the most commonly applied immunization, as other methods like contact with culled sows are less controlled [On all ten farms gilts were introduced to the sow herd in the insemination unit and gestating sows were housed in group from approximately four weeks of gestation onwards on eight farms. ecessary . A suffiecessary . When gimportant . Vaccinantrolled , 33.M. hyopneumoniae-specific antibodies is commonly practiced to perform herd-level monitoring. Nevertheless, the use of serology has its limitations to assess M. hyopneumoniae epidemiology. First, seroconversion after a natural M. hyopneumoniae infection is variable making it difficult to detect an infection in the early-stage [M. hyopneumoniae is frequently practiced and ELISA tests cannot distinguish antibodies induced by vaccination or by natural infection [M. hyopneumoniae seronegative, it was also M. hyopneumoniae PCR negative in 92.1% of the cases (NPVELISA). Animals being seronegative but PCR positive might have been in the early stages of infection [ELISA) were positive for M. hyopneumoniae on PCR. The outcome of the test characteristics for both PCR and ELISA were obviously influenced by the fact that on nine farms gilts were vaccinated against M. hyopneumoniae. However, the results of the PPVELISA and NPVELISA are of value for the field as M. hyopneumoniae vaccination of gilts is commonly practiced. Most gilts will have M. hyopneumoniae-specific antibodies even if the pathogen is not circulating on the farm. This demonstrates that to estimate the M. hyopneumoniae prevalence in breeding animals on farms endemically infected with the pathogen and practicing gilt vaccination, it is necessary to take swabs and perform a PCR.Serological testing for the presence of ly-stage –37. Seconfection . If an anfection , 36. MorM. hyopneumoniae infected than sows and the highest proportion of infected breeding animals was found in the first half of gestation. Therefore, good acclimation practices for gilts, like proper vaccination and a sufficiently long quarantine period, remain necessary to lower the risk of transmission of M. hyopneumoniae in the breeding population and to control the prevalence of M. hyopneumoniae in their offspring. Furthermore, vaccination of gilts against M. hyopneumoniae is commonly practiced resulting in a high proportion of animals with M. hyopneumoniae-specific antibodies. Therefore, methods relying on direct detection of (parts of) the pathogen, such as PCR analysis on TBS are recommended to investigate the M. hyopneumoniae infection status of breeding herds.Gilts were more frequently Additional file 1. Detailed results from the statistical models used to analyse the infection status (PCR) data.Additional file 2. Detailed results from the statistical models used to analyse the serology (ELISA) data.


Hearing impairment may make responding to phone-based memory tests difficult. Words with fricative consonants may pose particular difficulty, as telephones exclude high-frequency sounds necessary for their intelligibility. We hypothesized that recall would be impacted by hearing ability and word type (fricative vs. non-fricative) in a phone-based word list task.Participants  in the 2016 and 2018 waves of the Health and Retirement Study completed a phone-based word list recall task evenly split (5 each) between fricative and nonfricative words. Hearing was measured objectively (OH) and subjectively (SH), and each were dichotomized into ‘good’ and ‘poor’ hearing. Covariates included age, sex, race, education, depression, a subjective health rating, and functional limitations. Separate mixed-design ANCOVAs were used for OH and SH, where word type recall was within-subject, and hearing ability was between-subject. For OH, there was a main effect of word type =5.67, p=.02) and hearing ability =87.76, p<.001) but no interaction (p>.05). Participants recalled 0.35 fewer fricative words than nonfricative words, and participants with poor OH recalled 0.12 fewer words on average (ps<.001). For SH, there was still a main effect of word type =5.39, p =.02), but no effect of hearing ability (p>.05). OH and SH classifications had low agreement . Hearing ability and word acoustic properties can affect word recall in phone-based tests. Objective hearing tests are important, as subjective ratings do not necessarily agree. Researchers should be careful when constructing telephone-based cognitive tests in order to avoid memory impairment misestimation.


Mucormycosis also known as black fungus, it is relatively rare, but also very serious. It commonly infects the nose, sinuses, eye, and brain resulting in a runny nose, one-sided facial swelling and pain, headache, fever, blurred vision, bulging or displacement of the eye (proptosis), and tissue death. Other forms of disease may infect the lungs, stomach and intestines, and skin. In India, prevalence of mucormycosis is approximately 0.14 per 1000 population. A 58-year-old male came with the complaints of severe headache since a week, nasal congestion, black lesion on nasal bridge and upper inside of mouth that progressively became severe within 2 weeks. Physician inspected the patient and suggested for computed tomography (CT) and magnetic resonance imaging (MRI) scans. After all investigations patient was diagnosed as a case of mucormycosis and had undergone endoscopic debridement.


The last two decades have demonstrated that preoperative functional acoustic hearing  can be preserved during cochlear implant (CI) surgery. However, the relationship between the electrode array length and postoperative hearing preservation (HP) with lateral wall flexible electrode variants is still under debate.This is a systematic literature review that aims to analyze the HP rates of patients with residual hearing for medium-length and longer-length lateral wall electrodes.https://www.ncbi.nlm.nih.gov/pubmed/) was performed using the search terms “hearing preservation” or “residual hearing” and “cochlear implant” in “All fields.” Articles published only in English between January 01, 2009 and December 31, 2020 were included in the search.A systematic literature review methodology was applied following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) recommendations to evaluate the HP rates of medium-length and longer-length lateral wall electrodes from one CI manufacturer . A search using search engine PubMed (p = 0.689) and 12 months (p = 0.219). In the medium-length electrode group, patients under the age of 45 years had better HP than patients above the age of 45 years.The HP rate was similar between medium-length (93.4%–93.5%) and longer (92.1%–86.8%) electrodes at 4 months (Both medium-length and longer electrode arrays showed high hearing preservation rates. Considering the hearing deterioration over time, implanting a longer electrode at primary surgery should be considered, thus preventing the need for future reimplantation. The current technological and clinical state-of-the-art cochlear implant (CI) surgery is the result of the last 30 years of translational research between CI manufacturers and clinicians . Today, In 1997, Von Illberg et al. introduced the concept of combining electric and acoustic stimulation (EAS) as a mode of treating patients with nonprogressive partial deafness, demonstrating the feasibility of performing CI surgery without totally losing the residual hearing . The iniThese studies encouraged the development of hearing preservation (HP) surgical techniques, such as the application of corticosteroids, slow electrode insertion, avoidance of blood and bone dust entering the scala tympani, and avoidance of perilymph aspiration .From then on, specific electrode arrays dedicated for EAS were developed with medium-length electrodes of 24 mm, reporting encouraging HP rates –10. To aLater on, hearing preservation with long 28 mm and 31 mm electrodes was reported –17.The rationale for these long electrodes was to provide electrical coverage to the entire spiral ganglion in case residual hearing was lost over time , 17, as Moreover, placing the electrode in the LF residual hearing region overlapping electric and acoustic stimulation has been shown to achieve the most benefit with EAS . With prThe rationale for implanting longer electrodes in patients with partial deafness to achieve EAS is controversial; hence, this systematic literature review compares medium-length electrodes with longer electrodes with regard to their respective hearing preservation outcomes.https://www.ncbi.nlm.nih.gov/pubmed/) was performed using the search terms “hearing preservation” or “residual hearing” and “cochlear implant” in “All fields.” Articles published only in the English language between January 01, 2009 and December 31, 2020 were included in the review.A systematic literature review methodology was applied following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)  recommenStudies with pre- and postop audiograms were included in the study. Studies must report on the HP rates by applying the HEARRING group’s HP classification  with preOnly studies reporting on the FLEX24 (flexible 24 mm electrode) or FLEX28/FLEXSOFT electrodes (flexible 28 and 31 mm electrode)  were included in this review. For the FLEX24 studies, a minimum electrode insertion depth of 20 mm was required (to reach 360° of electrode insertion), and for the FLEX28/FLEXSOFT studies, a postoperative CT evaluation or operative report confirming full insertion of FLEX28  or a minimum of 28 mm insertion depth was required.Only MED-EL FLEX electrodes were chosen due to their design similarities and to reduce the effect of electrode design differences on the HP result’s comparison.Further on, the term medium-length electrode will be used for the 24-mm FLEX24 electrode, being designed to reach the first turn of the cochlea. Longer electrodes are those that always reach the second turn, irrespective of the cochlear size, and comprises the 28-mm FLEX28 and the 31-mm FLEXSOFT electrodes.Mean electrode insertion angular depths by the three different electrode lengths are depicted in The review included only patients with LF preoperative pure tone average (PTA) measured ≤65 dBHL across frequencies from 125 to 750 Hz with a minimum follow-up of 4 months and 12 months after cochlear implantation. The motivation for these audiological criteria was that such patients are considered EAS candidates.post-PTApre) / (PTAmax-PTApre))The HEARRING group , 29 proppost is the pure tone average measured postoperatively, PTApre is the pure tone average measured pre-operatively, and PTAmax is the maximal output limits of the audiometer. PTA is calculated for all characteristic frequencies attempted to measure the audiogram .where PTAThe classification based on this equation is independent of the initial hearing level and can be used for all CI users with measurable preoperative residual hearing (PTA: 0–120 dB). The misleading tendency of poorer preoperative hearing showing better postoperative HP results is eliminated because the classification is scaled to the preoperative audiogram. The equation also presents the relative change as a percentage of hearing loss, which is a user-friendly concept. The intervention-induced hearing loss is converted to hearing preservation (HP) by calculating 100%−relative change in %:max was substituted with 110 dB HL. Finally, the numerical scale is converted to a categorical scale for easy reporting. The categorization is defined in In our case, if HP classification was not calculated, PTAAccording to this classification, we defined HP if the patient reached complete or partial hearing preservation.HP is evaluated in those subjects when the postoperative (audiogram) PTA measured is ≤65 dBHL across all frequencies from 125 Hz to 750 Hz. If no measurements at 125 Hz were provided, we assume that the 125 Hz threshold is the same as for 250 Hz. If 750 Hz was not measured and subjects were measured at 500 Hz and 1,000 Hz, linear approximation was performed to obtain the 750 Hz threshold. We extracted the number of patients reported with HP when they fell under the defined HP to calculate the HP rates with each electrode length taken for analysis .The HP rates at a minimum of 4-month and 12-month follow-up were obtained in all patients fulfilling the minimum preoperative LF PTA of 65 dBHL. The overall HP rate was the HP rate with all subjects included. In all evaluations, it was at a minimum 4-month follow-up.Data were collected on the surgical approach, specifically round window (RW) or cochleostomy. Some clinicians use the term “extended round window” approach; however, as this information is not available in all studies, this surgical approach was included in the RW approach. In general, an RW approach was defined as the approach used when the electrode was inserted via the round window membrane and in cases when the RW approach required an anterior-inferior extension to insert the electrode due to either the size of the round window, the insertion angle, or the electrode diameter.Data from studies that were from clinical trials were reported separately. Prospective studies have more control over the subjects and data generation as compared to retrospective studies.Additionally, we calculated and reported the complete HP rates. Complete HP rates were calculated by selecting the number of patients with complete HP divided by the total number of patients implanted with CI.In addition, the age at implantation was assessed as to whether it plays an important role in HP. For this reason, subjects were split into two groups: one group up to and including 45 years of age and another group 45 years of age and above at the time of surgery. The age of 45 years was selected as it was an approximate mean in both groups, the group of patients implanted with a medium-length electrode and the group of patients implanted with a longer electrode.http://tibco.com). A criterion of α = 0.05 for the comparisons was set. The criterion for statistical power was >0.9. Power calculations for two proportions, Z-test have been done in STATISTICA 14.0 to estimate, which min. difference would have been detected as significant with 90% probability (Power).For the given pairwise comparisons, common statistical tests for significant differences were performed as implemented in STATISTICA 14.0 (TIBCO Software Inc. (2020) Data Science Workbench, version 14. https://www.microsoft.com/en-us/microsoft-365/excel). Confounding factors were the electrode type/insertion depth, surgical approach, and age at implantation.Risk of bias assessment helps to establish transparency of evidence synthesis results and findings. Evidence syntheses strive to eliminate bias in the findings. Therefore, the risk of bias was independently assessed by the fourth and the last authors (LL and MP). Included studies were assessed using the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) Tool. . This toThirty-three peer-reviewed publications reporting on HP with the FLEX24 or FLEX28/FLEX SOFT electrodes were identified using the search strategy. A total of 25 peer-reviewed articles published between 2009 and 2020 reporting on HP were identified from the database and are listed in Out of the 304 cases implanted with the FLEX24 electrode, 284 had HP, giving an overall HP rate of 93.4%. Within this group, 20 cases with minimum or no hearing were followed-up to 4 months and 12 months postoperatively. The HP rate with FLEX24 in the 4-month group was 93.4% and 93.5% in the 12-month group at follow-up postoperatively .Seventy-six cases were implanted using the cochleostomy approach, and the remaining 228 cases were implanted with the RW approach of electrode insertion. In the cochleostomy patients, the HP rate was 89.5% (68 of 76 patients) and 95.2% in the RW patients (217 of 228 patients), as shown in Among the 25 articles reviewed, 3 were prospective clinical trial studies. A total of 109 cases were implanted with the FLEX24 electrode, out of which 103 cases had HP, giving an overall HP rate of 94.5%. This gave an HP rate with FLEX24 in the 4-month group of 94.5% and 94.5% in the 12-month group at follow-up postoperatively.A total of 15 peer-reviewed articles published between 2009 and 2020 reporting on HP were identified from the database and are listed in Of the 76 cases implanted with the FLEX28/FLEXSOFT electrode, 70 had HP as per the definition given in the Methods section, giving an overall HP rate of 92.1%. Within this group, 76 cases were followed-up for 4 months and 38 cases were followed-up for 12 months postoperatively. The HP rate with FLEX28/FLEXSOFT in the 4-month group was 90.8% and 86.8% in the 12-month group at follow-up post-operatively.Of the 40 cases implanted with the FLEX28 electrode, 37 had HP, giving an overall HP rate of 92.5%. Within this group, 40 cases were followed-up for 4 months and 15 cases were followed-up for 12 months post-operatively. The HP rate with FLEX28 in the 4-month group was 92.5% and with FLEX28 in the 12-month group was 88.9% at follow-up postoperatively .Of the 36 cases implanted with the FLEXSOFT electrode, 33 had HP, giving an overall HP rate of 91.7%. Within this group, 36 cases were followed-up for 4 months and 23 cases were followed-up for 12 months postoperatively. The HP rate with FLEXSOFT in the 4-month group was 91.7% and with FLEXSOFT in the 12-month group was 86.9% at followup postoperatively .Twelve cases were implanted using the cochleostomy approach, and the remaining 64 cases were implanted with the RW approach of electrode insertion. In the cochleostomy patients, the HP rate was 91.7% (11 of 12 patients), and in the RW patients, the HP rate was 92.2% (59 of 64 patients), as shown in None of the studies of the FLEX28/FLEXSOFT cases were based on prospective clinical trials.p-values > 0.05). At 4 month follow-up, 43.5% (107 from 246) of patients attained complete HP in the medium-length electrode group, while 36.8% (28 from 76) of patients attained complete HP in the longer electrode group . For complete HP comparisons at 12-month follow-up, the medium length vs. longer electrode groups showed no statistical difference (p = 0.11).None of the comparisons showed significant differences . The remaining comparisons were not significantly different . For age comparisons, complete HP at 12 months follow up for 28 mm insertion group, and the complete HP comparisons at 12 months follow up 20 mm vs 28 mm insertion we found quite remarkable difference in proportions, but still not significant .This systematic literature review (SR) shows high rates of stable HP for all flexible electrodes over time. The same applies to complete HP.These results can be achieved using standardized surgical techniques such as the avoidance of perilymph aspiration, clean surgery avoiding blood and bone dust entering the scala tympani or sticking to the electrode, slow electrode insertion to avoid intracochlear pressure peaks, slow drilling with diamond burrs on the cochlea, and systemic and topical corticosteroids , 31.Achieving HP in CI surgery seems to be closely associated with the development of dedicated atraumatic electrode arrays. Experimental data emphasizes that flexible electrodes are less traumatic than stiffer electrodes . The strThe first reports on EAS demonstrated lower HP rates because of the stiff electrodes used and the unrefined surgical techniques utilized at the time , 5. The No significant differences in the HP rates between medium and long electrodes were demonstrated. This also applies to complete HP rates at the two time points investigated.Although different consensus papers  advocateCalculating the effect of age resulted in a significant difference in favor of patients under 45 years of age. This confirmed earlier reports showing better HP in children and younger adults , 41–42.Initially, EAS with medium electrodes was advocated for partial deafness, which was defined as a hearing deterioration of less than 15 dB in the LF in the last 2 years. Usami et al. , 44 idenConcerning long-term results for EAS patients using medium-length electrodes, postoperative residual hearing declines over time, and the deterioration of residual hearing of the implanted ear is related to the rate of progression in the contralateral ear , 46. A cAs reported, patients with stable residual hearing can lose the residual hearing after CI surgery resulting in nonfunctional residual hearing levels.Using a shorter electrode array can leave the patient with insufficient electric stimulation. This depends on the individual cochlear size and occurs when an electrode array that does not reach the second turn of the cochlea or the apical bulb of the spiral ganglion is situated at 650–690° , 50. SubDifferent strategies can be used in the case of nonfunctional HL after HP surgery with short or medium-length electrode arrays.A possible approach is reimplantation. Fitzgerald et al.  reportedA second solution was first presented by Lenarz et al. , partialA third way was published by Yoshimura et al., who reported implantation of a longer electrode in patients with LF hearing, with the concept of deactivating the apical channels placed in the LF hearing initially until the LF hearing deteriorated over time . Polak eAlthough some trends were noticeable, the number of cases was too small to draw any final conclusion as to whether or not medium electrode insertions are different from longer electrode insertions regarding HP. Not all the studies reported their data in a similar way. Furthermore, many studies were retrospective, with low data quality. It is important to note that the results of the prospective studies did not differ from the retrospective studies, reporting comparable high HP rates. However, there were no prospective registered studies on 28-mm and 31.5-mm flexible electrodesThe lack of significant differences between the electrode lengths may be due to the following confounding aspects. First, the individual sizes of the cochlea were not taken into account. Due to the large cochlear size variation of up to 50%, the insertion angles will vary accordingly, despite using the same electrode length . SubsequIn addition, the Covid pandemic, with its effects on restriction on clinical studies, resulted in limiting the SR till 2020 .A differentiation between the RW approach and the extended RW approach could not be made and thus does not demonstrate the effect of the RW approach on HP. For future prospective studies, a distinction between the RW approach and the extended RW approach is necessary to identify a true difference between the RW approach and the other approaches by which the cochlea is accessed through various degrees of drilling and subsequent breach of the endosteal endoscalar lining.Medium flexible electrodes are well studied and approved for EAS surgery in the case of partial deafness. However, even though a high HP rate at 12 months is reported, patients may progressively lose their residual hearing over time and sometimes immediately after surgery, necessitating a switch from EAS to full electric stimulation. This leaves the patient without electric stimulation in the second cochlear turn, which means that there is no stimulation of around 25% of the spiral ganglion located within the second turn, which is an inefficient use of the CI.Conversely, this SR revealed a high HP rate with the long flexible electrodes, which was not statistically different from the HP outcomes with the medium flexible electrodes. Long flexible electrodes offer the advantage of providing electrical stimulation to the full spiral ganglion in case of future deterioration of the residual hearing.The data of this SR support the concept presented by the Japanese CI team of Usami SI , who proTherefore, longer flexible electrodes should be considered equally for EAS surgery. The authors advocate the use of these longer electrodes to reach the second cochlear turn, in particular when a stable hearing was not ascertained or uncertain in the next years.This SR reveals the necessity of prospective studies assessing HP surgery with deep 650° electrode insertions in patients with RH. These studies should distinguish between atraumatic and traumatic insertion approaches (RW vs. extended RW/cochleostomy) and factors in cochlear duct length measurements. Current studies report that new otosurgical planning software (Otoplan) is suitable for cochlear size calculations  and cochBoth medium-length and longer electrode arrays showed high hearing preservation rates. Considering the hearing deterioration over time, implanting a longer electrode at primary surgery should be considered, thus preventing the need for future reimplantation.