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Background/Objectives: Bimodal stimulation (BS), which combines the use of a cochlear implant (CI) in one ear and a hearing aid (HA) in the opposite ear, is an established strategy to treat hearing loss by exploiting the unique capabilities of each device. CIs stimulate the auditory nerve by bypassing damaged hair cells, while HAs amplify sounds by requiring a functional hearing residual. The aim of this systematic review is to investigate the advantages and disadvantages of BS such as speech perception in noise. Methods: We examined clinical studies published from October 2020 to July 2024, following the PRISMA guidelines, focusing on the advantages and disadvantages of BS on speech perception in noise in adulthood. Results: BS in adult patients significantly improves speech perception in quiet and noisy environments, especially for those with increased residual hearing. Unilateral CIs and BS perform similarly in quiet conditions, but BS significantly improves speech discrimination in noisy environments if loudness between the two devices is appropriately balanced. Conclusions: Directional microphones and programming software are new technologies that succeed in reducing environmental noise and improving verbal perception outcomes, although their features in the literature are controversial. In addition, the individuals using BS may face temporal mismatches mainly due to differing device latencies, affecting sound localization. Compensating for these mismatches can enhance localization accuracy. However, modulated noise remains a significant obstacle to verbal perception in noise. Valuable assessment tools such as music tests provide further information on hearing performance and quality of life. More research is needed to define certain selection criteria.

Barrett’s esophagus (BE) represents a pre-cancerous condition that is characterized by the metaplastic conversion of the squamous esophageal epithelium to a columnar intestinal-like phenotype. BE is the consequence of chronic reflux disease and has a potential progression burden to esophageal adenocarcinoma (EAC). The pathogenesis of BE and EAC has been extensively studied but not completely understood, and it is based on two main hypotheses: “transdifferentiation” and “transcommitment”. Omics technologies, thanks to the potentiality of managing huge amounts of genetic and epigenetic data, sequencing the whole genome, have revolutionized the understanding of BE carcinogenesis, paving the way for biomarker development helpful in early diagnosis and risk progression assessment. Genomics and transcriptomics studies, implemented with the most advanced bioinformatics technologies, have brought to light many new risk loci and genomic alterations connected to BE and its progression to EAC, further exploring the complex pathogenesis of the disease. Early mutations of the TP53 gene, together with late aberrations of other oncosuppressor genes (SMAD4 or CKND2A), represent a genetic driving force behind BE. Genomic instability, nonetheless, is the central core of the disease. The implementation of transcriptomic and proteomic analysis, even at the single-cell level, has widened the horizons, complementing the genomic alterations with their transcriptional and translational bond. Increasing interest has been gathered around small circulating genetic traces (circulating-free DNA and micro-RNAs) with a potential role as blood biomarkers. Epigenetic alterations (such as hyper or hypo-methylation) play a meaningful role in esophageal carcinogenesis as well as the study of the tumor micro-environment, which has led to the development of novel immunological therapeutic options. Finally, the esophageal microbiome could be the protagonist to be investigated, deepening our understanding of the subtle association between the host microbiota and tumor development.

Zenker’s Diverticulum (ZD) is the most common hypopharyngeal diverticulum; however, it is often underdiagnosed. It results from the herniation of the mucosa and submucosa through Killian’s Triangle. Dysphagia is the primary symptom, occurring in 80–90% of cases. The primary goal of treatment is to transect the cricopharyngeal muscle (CM) and connect the ZD cavity to the esophageal lumen. Traditional treatments include surgical open transcervical diverticulectomy and CM septomyotomy, using rigid or flexible endoscopes. However, surgery is burdened by technical difficulties and not negligible rates of adverse events (AEs). For this reason, endoscopic techniques for ZD treatment have gained traction in recent years. Flexible endoscopic septum division (FESD), introduced nearly 20 years ago, involves a full-thickness incision of the diverticular septum. The advent of third-space endoscopy has led to the application of these techniques to ZD treatment as well. Zenker-POEM (Z-POEM) and, subsequently, Per Oral Endoscopic Septomyotomy (POES) have been developed. Hybrid techniques, such as Peroral Endoscopic Diverticulotomy (POED) and tunneling-free methods, represent additional ZD treatment options. This review outlines the armamentarium of ZD endoscopic management, summarizing the characteristics of these techniques, their benefits and limitations, and highlighting future research directions.

Abstract Background Individuals with thiamine-responsive megaloblastic anemia (TRMA) mainly manifest macrocytic anemia, sensorineural deafness, ocular complications, and nonautoimmune diabetes. Macrocytic anemia and diabetes may be responsive to high-dosage thiamine treatment, in contrast to sensorineural deafness. Little is known about the efficacy of thiamine treatment on ocular manifestations. Cases presentation Our objective is to report data from four Italian TRMA patients: in Cases 1, 2 and 3, the diagnosis of TRMA was made at 9, 14 and 27 months. In 3 out of 4 subjects, thiamine therapy allowed both normalization of hyperglycemia, with consequent insulin suspension, and macrocytic anemia. In all Cases, thiamine therapy did not resolve the clinical manifestation of deafness. In Cases 2 and 3, follow-up showed no blindness, unlike Case 4, in which treatment was started for megaloblastic anemia at age 7 but was increased to high doses only at age 25, when the genetic diagnosis of TRMA was performed. Conclusions Early institution of high-dose thiamine supplementation seems to prevent the development of retinal changes and optic atrophy in TRMA patients. The spectrum of clinical manifestations is broad, and it is important to describe known Cases to gain a better understanding of this rare disease.

IntroductionSensorineural hearing loss (SNHL) has been suggested to be possibly related to congenital toxoplasmosis (CT), although its prevalence varies from 0% to 26%. This variance appears to be dependent especially on early timing of treatment. However, the available data are based on outdated studies conducted on small groups of patients that lack homogeneity. Therefore, to establish evidence-based guidelines for audiologic monitoring in CT, we conducted a comprehensive evaluation of a large case series over a long period of time.Patients and methodsThis is a single-center, retrospective cohort that enrolled all infants and children who were exposed in utero to Toxoplasma gondii and/or congenitally infected between September 1980 and December 2022. They underwent standard serial audiological evaluations to detect possible SNHL at an early stage. The first evaluation was performed during the initial assessment to define the onset of congenital toxoplasmosis, with another evaluation conducted at least at 12 months of life.ResultsWe collected data from 1,712 patients, and 183 (10.7%) were diagnosed with CT. Among these cases, 78 children (42.6%) presented with symptomatic CT at the onset, exhibiting ocular findings (21.1%), clinical cerebral manifestations (6.1%), and/or abnormal findings on neuroimaging (35.5%). Therapy was administrated at the onset in 164 patients (89.6%) with 115 of them starting treatment prior to 2.5 months of age (0–388, median 32.00 ± 92.352 days of life). Only one patient presented with SNHL at the onset, but this was apparently unrelated to CT. The median number of audiological assessments was 2.2 ± 1.543 (2–10). No patients developed any grade of delayed hearing loss, both in treated and untreated groups. The median age at last audiological evaluation was 2.3 ± 2.18 years (1–8), although the median follow-up period was 12.4 years (±6.3), ranging from 1 to 27 years.ConclusionsBased on these data, it appears that SNHL may be less frequent in CT than previously assumed. We recommend conducting an audiological assessment at the onset (within the first 2.5 months of life) to comprehensively define the type of CT onset, and then conducting another evaluation within 9 months of life.

Background and Aims: Perianal fistula represents one of the most disabling manifestations of Crohn′s disease (CD) due to complete destruction of the affected mucosa, which is replaced by granulation tissue and associated with changes in tissue organization. To date, the molecular mechanisms underlying perianal fistula formation are not well defined. Here, we dissected the tissue changes in the fistula area and addressed whether a dysregulation of extracellular matrix (ECM) homeostasis can support fistula formation. Methods: Surgical specimens from perianal fistula tissue and the surrounding region of fistulizing CD were analyzed histologically and by RNA sequencing. Genes significantly modulated were validated by real-time polymerase chain reaction, Western blot, and immunofluorescence assays. The effect of the protein product of TNF-stimulated gene-6 (TSG-6) on cell morphology, phenotype, and ECM organization was investigated with endogenous lentivirus-induced overexpression of TSG-6 in Caco-2 cells and with exogenous addition of recombinant human TSG-6 protein to primary fibroblasts from region surrounding fistula. Proliferative and migratory assays were performed. Results: A markedly different organization of ECM was found across fistula and surrounding fistula regions with an increased expression of integrins and matrix metalloproteinases and hyaluronan (HA) staining in the fistula, associated with increased newly synthesized collagen fibers and mechanosensitive proteins. Among dysregulated genes associated with ECM, TNFAI6 (gene encoding for TSG-6) was as significantly upregulated in the fistula compared with area surrounding fistula, where it promoted the pathological formation of complexes between heavy chains from inter-alpha-inhibitor and HA responsible for the formation of a crosslinked ECM. There was a positive correlation between TNFAI6 expression and expression of mechanosensitive genes in fistula tissue. The overexpression of TSG-6 in Caco-2 cells promoted migration, epithelial–mesenchymal transition, transcription factor SNAI1, and HA synthase (HAs) levels, while in fibroblasts, isolated from the area surrounding the fistula, it promoted an activated phenotype. Moreover, the enrichment of an HA scaffold with recombinant human TSG-6 protein promoted collagen release and increase of SNAI1, ITGA4, ITGA42B, and PTK2B genes, the latter being involved in the transduction of responses to mechanical stimuli. Conclusions: By mediating changes in the ECM organization, TSG-6 triggers the epithelial–mesenchymal transition transcription factor SNAI1 through the activation of mechanosensitive proteins. These data point to regulators of ECM as new potential targets for the treatment of CD perianal fistula.

Abstract Tumor‐associated macrophages (TAMs) have a unique favorable effect on the prognosis of colorectal cancer (CRC), although their association with stage‐specific outcomes remains unclear. We assessed the densities of CD68+ and CD163+ TAMs at the invasive front of resected CRC stage III CRC from 236 patients, 165 of whom received post‐surgical FOLFOX treatment, and their relationship with disease‐free survival (DFS). Associations between macrophage mRNAs and clinical outcome were investigated in silico in 59 stage III CRC and FOLFOX‐treated patients from The Cancer Genome Atlas (TCGA). Biological interactions of SW480 and HT29 cells and macrophages with FOLFOX were tested in co‐culture models. Low TAM densities were associated with shorter DFS among patients receiving FOLFOX (CD68+, p = 0.0001; CD163+, p = 0.0008) but not among those who were untreated. By multivariate Cox analysis, only low TAM (CD68+, p = 0.001; CD163+, p = 0.002) and nodal status (CD68+, p = 0.009; CD163+, p = 0.007) maintained an independent predictive value. In the TCGA cohort, high CD68 mRNA levels were associated with better outcome (p = 0.02). Macrophages enhanced FOLFOX cytotoxicity on CRC cells (p

Endoscopic ultrasound (EUS)-guided interventions have revolutionized the management of malignant biliary obstruction (MBO) and gastric outlet obstruction (GOO), providing minimally invasive alternatives with improved outcomes. These procedures have significantly reduced the need for high-risk surgical interventions or percutaneous alternatives and have provided effective palliative care for patients with advanced gastrointestinal and bilio-pancreatic malignancies. EUS-guided biliary drainage (EUS-BD) techniques, including hepaticogastrostomy (EUS-HGS), choledochoduodenostomy (EUS-CDS), and antegrade stenting (EUS-AS), offer high technical and clinical success rates, with a good safety profile particularly when Endoscopic Retrograde Cholangiopancreatography (ERCP) is not feasible. EUS-HGS, which allows biliary drainage by trans-gastric route, is primarily used for proximal stenosis or in case of surgically altered anatomy; EUS-CDS with Lumen-Apposing Metal Stent (LAMS) for distal MBO (dMBO), EUS-AS as an alternative of EUS-HGS in the bridge-to-surgery scenario or when retrograde access is not possible and EUS-guided gallbladder drainage (EUS-GBD) with LAMS in case of dMBO with cystic duct patent without dilation of common bile duct (CDB). EUS-guided gastroenterostomy (EUS-GE) has already established its role as an effective alternative to surgical GE and enteral self-expandable metal stent, providing relief from GOO with fewer complications and faster recovery times. However, we do not yet have strong evidence on how to combine the different EUS-guided drainage techniques with EUS-GE in the setting of double obstruction. This comprehensive review aims to synthesize growing evidence on this topic by randomized controlled trials, cohort studies, and case series not only to summarize the efficacy, safety, and technical aspects of these procedures but also to propose a treatment algorithm based essentially on the anatomy and stage of the neoplasm to guide clinical decision-making, incorporating the principles of personalized medicine. This review also highlights the transformative impact of EUS-guided interventions on the treatment landscape for MBO and GOO. These techniques offer safer and more effective options than traditional approaches, with the potential for widespread clinical adoption. Further research is needed to refine these procedures, expand their applications, and improve patient care and quality of life. [ABSTRACT FROM AUTHOR]

Background: An early hearing detection and intervention program (EHDI) is the first step for the habilitation of children with permanent hearing impairment (PHI). Actually, early intervention programs have increasingly shifted toward family involvement, emphasizing that the child’s family should take an active role in the habilitation process. Therefore, familiar empowerment is the best way to improve a child’s emerging abilities. The aim of this study was to investigate parental self-efficacy beliefs and involvement as well as the language skills of deaf or hard of hearing DHH children who were habilitated with hearing aids and followed using the T.A.T.A web app (NeonaTal Assisted TelerehAbilitation), an example of asynchronous telepractice. Methods: The study describes the early stages of the habilitation program of 15 PHI children followed through the T.A.T.A. web app, which empowers families through a weekly questionnaire submitted during the first 270 to 360 days of their child’s life, for 14 weeks. The family involvement rate scale (FIRS) was used to evaluate parental compliance, and all children received in-person visits at the beginning and at the end of the training period. Results: The children showed greater auditory perceptual skills at the end of the training period on the basis of both the Infant Listening Progress Profile (ILiP) score and the Categories of Auditory Performance (CAP) and FIRS scales. In other words, the auditory skills improved with age as well as with parental participation. Conclusions: The T.A.T.A. web app promotes a proactive management and a tailored habilitation through an active familiar involvement, easily achieved in clinical routine and in emergency settings without additional costs.

Simple Summary: Delayed gastric conduit emptying (DGCE) is a common complication of esophageal surgery. The current study compares three endoscopic procedures—Intra-Pyloric Injection of Botulinum Toxin (IPBT), Pneumatic Balloon Dilation (PBD), and a combination of both in the same session (BTPD)—to determine which approach is the most effective in DGCE treatment. By analyzing data from 64 patients endoscopically treated, results showed that the combination approach (BTPD) was associated with a higher rate of symptom resolution. BTPD allowed patients to resume eating and be discharged more quickly. These findings suggest that BTPD may be the most effective treatment for DGCE, offering better patient outcomes and potentially guiding future treatment strategies. Background/Objectives: Delayed gastric conduit emptying (DGCE) occurs in 15–39% of patients who undergo esophagectomy. Intra-Pyloric Injection of Botulinum Toxin (IPBT), Pneumatic Balloon Dilation (PBD), and the same session combination (BTPD) represent the main endoscopic procedures, but comparative data are currently unavailable. Methods: We retrospectively analyzed prospectively collected data on all consecutive patients with DGCE treated endoscopically with IPBT, PBD, or BTPD. ISDE Diagnostic Criteria were used for DGCE diagnosis and classification. A Gastric Outlet Obstruction Score was used for clinical staging. All patients undergoing IPBT received 100 UI of toxin, while those undergoing PBD were dilated up to 20 mm. Clinical success (CS) was defined as the resolution of symptoms/resumption of feeding at discharge or expanding dietary intake at any rate. Recurrence was defined as symptom relapse after more than 15 days of well-being requiring endoscopic/surgical intervention. Results: A total of 64 patients (81.2% male, 90.6% Ivor-Lewis esophagectomy, 77.4% adenocarcinoma) with a median age of 62 years (IQR 55–70) were enrolled: 18 (28.1%) in the IPBT group, 24 (37.5%) in the PBD group, and 22 (34.4%) in the BTPD group. No statistically significant differences were found in the baseline characteristics, surgical techniques, and median follow-up among the three groups. BTPD showed a higher CS rate (100%) compared to the PD and BTPD groups (p = 0.02), and a Kaplan–Meier analysis with a log–rank test revealed that the BTPD group was associated both with a significatively shorter mean time to refeed of 1.16 days (95% CI 0.8–1.5; p = 0.001) and a shorter median time to discharge of one day (95% CI 1–3; p = 0.0001). Conclusions: Endoscopic management of DGCE remains challenging. Waiting for further strong evidence, BTPD can offer patients a higher clinical efficacy rate and a shorter time to refeed and be discharged. [ABSTRACT FROM AUTHOR]

Zenker's Diverticulum (ZD) is the most common hypopharyngeal diverticulum; however, it is often underdiagnosed. It results from the herniation of the mucosa and submucosa through Killian's Triangle. Dysphagia is the primary symptom, occurring in 80–90% of cases. The primary goal of treatment is to transect the cricopharyngeal muscle (CM) and connect the ZD cavity to the esophageal lumen. Traditional treatments include surgical open transcervical diverticulectomy and CM septomyotomy, using rigid or flexible endoscopes. However, surgery is burdened by technical difficulties and not negligible rates of adverse events (AEs). For this reason, endoscopic techniques for ZD treatment have gained traction in recent years. Flexible endoscopic septum division (FESD), introduced nearly 20 years ago, involves a full-thickness incision of the diverticular septum. The advent of third-space endoscopy has led to the application of these techniques to ZD treatment as well. Zenker-POEM (Z-POEM) and, subsequently, Per Oral Endoscopic Septomyotomy (POES) have been developed. Hybrid techniques, such as Peroral Endoscopic Diverticulotomy (POED) and tunneling-free methods, represent additional ZD treatment options. This review outlines the armamentarium of ZD endoscopic management, summarizing the characteristics of these techniques, their benefits and limitations, and highlighting future research directions. [ABSTRACT FROM AUTHOR]

Background/Objectives: Bimodal stimulation (BS), which combines the use of a cochlear implant (CI) in one ear and a hearing aid (HA) in the opposite ear, is an established strategy to treat hearing loss by exploiting the unique capabilities of each device. CIs stimulate the auditory nerve by bypassing damaged hair cells, while HAs amplify sounds by requiring a functional hearing residual. The aim of this systematic review is to investigate the advantages and disadvantages of BS such as speech perception in noise. Methods: We examined clinical studies published from October 2020 to July 2024, following the PRISMA guidelines, focusing on the advantages and disadvantages of BS on speech perception in noise in adulthood. Results: BS in adult patients significantly improves speech perception in quiet and noisy environments, especially for those with increased residual hearing. Unilateral CIs and BS perform similarly in quiet conditions, but BS significantly improves speech discrimination in noisy environments if loudness between the two devices is appropriately balanced. Conclusions: Directional microphones and programming software are new technologies that succeed in reducing environmental noise and improving verbal perception outcomes, although their features in the literature are controversial. In addition, the individuals using BS may face temporal mismatches mainly due to differing device latencies, affecting sound localization. Compensating for these mismatches can enhance localization accuracy. However, modulated noise remains a significant obstacle to verbal perception in noise. Valuable assessment tools such as music tests provide further information on hearing performance and quality of life. More research is needed to define certain selection criteria. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to compare, in users of bimodal cochlear implants, the performance obtained using their own hearing aids (adjusted with the standard NAL-NL1 fitting formula) with the performance using the Phonak Naìda Link Ultra Power hearing aid adjusted with both NAL-NL1 and a new bimodal system (Adaptive Phonak Digital Bimodal (APDB)) developed by Advanced Bionics and Phonak Corporations. Methods: Eleven bimodal users (Naìda CI Q70 + contralateral hearing aid) were enrolled in our study. The users’ own hearing aids were replaced with the Phonak Naìda Link Ultra Power and fitted following the new formula. Speech intelligibility was assessed in quiet and noisy conditions, and comparisons were made with the results obtained with the users’ previous hearing aids and with the Naída Link hearing aids fitted with the NAL-NL1 generic prescription formula. Results: Using Phonak Naìda Link Ultra Power hearing aids with the Adaptive Phonak Digital Bimodal fitting formula, performance was significantly better than that with the users’ own rehabilitation systems, especially in challenging hearing situations for all analyzed subjects. Conclusions: Speech intelligibility tests in quiet settings did not reveal a significant difference in performance between the new fitting formula and NAL-NL1 fittings (using the Naída Link hearing aids), whereas the performance difference between the two fittings was very significant in noisy test conditions.

IntroductionSeveral studies and meta-analyses suggested the role of vitamin D 25OH in preventing severe forms of coronavirus disease 2019 (COVID-19). However, the evidence on the clinical benefits of vitamin D 25OH adequacy in patients hospitalized for COVID-19 remain conflicting and speculative. We aimed to investigate the association between vitamin D 25OH serum levels and mortality in hospitalized patients with moderate to severe COVID-19.MethodThis prospective observational multicentre study included 361 consecutive patients with moderate to severe COVID-19 admitted to the Italian hospitals involved in the NUTRI-COVID19 trial from March to August 2020. For each patient, serum vitamin D 25OH levels were assessed 48 h since admission and classified as deficient (

Permanent childhood hearing impairment (PCHI) represents the most frequent sensory pathology at birth. PCHI has a relevant psychological impact on the life of both the affected children and their families. Thus, the aim of this work is to explore the degree of parental distress felt by mothers of a deaf or hard-of-hearing child, to determine if this stress is associated with variables related to the children’s health (e.g., the severity of hearing loss, presence of other conditions, difficulty with treatment options, difficulty with rehabilitation) or family characteristics such as socio-economic and educational status. The study used the Parenting Stress Index–Short Form (PSI-SF) questionnaire administered to mothers. The results were analyzed in relation to variables such as parents’ education level, number of children, severity of hearing loss, presence of other chronic conditions, presence of cognitive delay, familiarity with hearing loss, time of diagnosis, use of prosthetics, and start in a rehabilitation program. The data indicate a correlation between maternal stress levels and low-educational levels, as well as the presence of congenital infections and cognitive delay. These results highlight the need for a comprehensive physical and psychological approach for hearing-impaired children, as stress factors can affect the adherence to effective rehabilitation.

Background and Objectives: Midlife hearing loss (HL) has been considered as a major modifiable risk factor for a later-life progression to dementia. Our aim was to detect a link between precocious sensorineural hearing loss (SNHL) and mild cognitive impairment (MCI) and their association to putative risk factors for a common pathology. Materials and methods: In this study, a retrospective case-control study was carried out. A total of 112 patients were enrolled as following: 81 patients with bilateral SNHL and 31 subjects with normal hearing, whose ages ranged from 50 to 65 years. Both groups performed pure tone audiometry, a tinnitus handicap inventory (THI), Mini-Mental State examination (MMSE), and the Montreal Cognitive Assessment (MoCA), Hospital Anxiety and Depression Scale (HADS-A and HADS-D). Results: The mean age was 58 ± 5.2 in SNHL patients and 53.2 ± 4.8 in the control group. The mean pure tone average in the SNHL group was 40.2 ± 18.7 dB HL on the right side and 41.2 ± 17.2 dB HL on the left side, while in the control group it was 12.5 ± 2.8 dB HL on right side and 12.4 ± 3.1 dB HL on left side. About 64% of patients with SNHL exhibited comorbidities, and the most common condition was hypertension. Altered MoCA test scores were significantly related to the pure tone averages in patients with SNHL compared to the control group (p = 0.0004), while the differences in the HADS-A and HADS-D were not significant. Furthermore, a significant correlation was observed in SNHL patients between an altered MoCA test and hypercholesterolemia (p = 0.043). Conclusions: Hearing impairment and screening tests to detect MCI should be considered in the midlife in order to carry out strategies to prevent the progression to dementia. Hypertension and hypercholesterolemia are two risk factors in the development of endothelial dysfunction, oxidative stress, and vascular inflammation, and may represent the common pathology linking the inner ear and brain damage.

Background: Currently, the novel coronavirus (SARS-CoV-2) causes an acute respiratory illness named COVID-19 and is a controversial risk factor for hearing loss (HL). Herein, we aim to describe the associated symptoms and to evaluate hearing function in the COVID-19 pediatric population. Methods: A retrospective cross-sectional observational study was carried out on 37 children who contracted COVID-19 infection with no previous audio-vestibular disorders. Clinical data on the infections were collected, and an audiological assessment of all affected children was performed by using different diagnostic protocols according to their age. Results: Fever, upper respiratory and gastrointestinal manifestations were common presentations of infection. Audiological function was normal in 30 (81.08%) children, while 7 children showed an increased hearing threshold: 6 (16.21%) had transient conductive hearing loss (CHL) due to middle ear effusion and normalized at the follow-up and 1 had sensorineural hearing loss (SNHL). A single child was affected by bilateral SNHL (2.7%); however, he underwent a complete audiological work-up leading to a diagnosis of genetic HL due to a MYO6 gene mutation which is causative of progressive or late onset SNHL. Conclusions: HL needs to be considered among the manifestations of COVID-19 in children, nevertheless, we found cases of transient CHL. The onset of HL during or following COVID-19 infection does not eliminate the indication for maintaining audiological surveillance and audiological work-ups, including genetic diagnosis, to avoid the risk of mistaking other causes of HL.

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 (Italy) (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 (p < 0.001), NICU (p < 0.001), craniofacial anomalies (p < 0.001), low birth weight (p = 0.04) and HIV (p = 0.03) were confirmed as risk factors. 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.

Abstract Objectives Tinnitus is a common symptom largely impactful on quality of life, especially in the elderly. Our aim was to evaluate the efficacy of self‐administered screening tests to correlate the severity of subjective perception of tinnitus with emotional disorders and the overall cognitive status. Methods Patients aged ≥ 55 years with chronic tinnitus were recruited and submitted to a complete audiological evaluation; Tinnitus Handicap inventory (THI); Hospital Anxiety and Depression Scale (HADS‐A and HADS‐D) and Mini‐Mental State Examination (MMSE). Demographic and audiological features of patients with and without cognitive impairment (MMSE score cut‐off of 24/30) were analyzed in order to reveal the relationship among tinnitus, emotional disorders, and cognitive dysfunction. Results 102 patients were recruited (mean age: 70.4 ± 9.6). THI score was directly related to HADS‐A score (r = .63) HADS‐D score (r = .66), whereas there was no relationship between tinnitus severity and MMSE (r = .13). CI and n‐CI groups did not differ in the characteristics of tinnitus (p > .05), however, hearing threshold (p = .049) and anxious depressive traits measured with HADS‐A (p = .044) and HADS‐D (p = .016) were significantly higher in the group with cognitive impairment. Furthermore, age ≥ 75 years (p = .002, OR = 13.8), female sex (p = .032; OR = 6.5), severe hearing loss (p = .036; OR = 2.3), and anxiety (p = .029; OR = 9.2) resulted risk factors for CI. Therefore, in CI group MMSE score was inversely related to age (r = −.84). Conclusions Cognitive impairment and psychiatric discomfort should be considered in tinnitus patients, related to increasing age, female sex, and severe hearing loss. Thus, self‐administered questionnaires can be useful in addressing clinical approach.

Background and Aim: Cytomegalovirus (CMV) is the main cause of congenital infection in developed countries leading to deafness but the burden of sensorineural hearing loss (SNHL) in asymptomatic children remains incompletely characterized. Aim of this study was to evaluate the long-term audiological outcome in this group of patients.Methods: Consecutive neonates with congenital CMV infection were followed from 2002 to 2018. Patients were considered asymptomatic if free from any clinical and instrumental impairment at referral and underwent serial clinical exams, audiological evaluations and CMV-PCR determinations.Results: A cohort of 258 children was analyzed and the disease onset was asymptomatic in 125 (48%) infants. Among these, we studied 102 patients with a follow-up longer than 1 year and a median observation period of 2.8 years (range: 1–10.3 years). No patient developed a stable delayed SNHL but only 14 (14%) presented a variable hearing impairment, seven of which bilateral. The unstable SNHL was mild in 12 infants and moderate in two. Patients with fluctuating SNHL had significantly higher urine viral load (p 0.002) and more often positive viremia (p 0.015) than babies with stable normal hearing.Conclusions: CMV infected, asymptomatic neonates have a low risk of transient SNHL later in infancy. Positive viremia and high urine viral load at onset are significant risk factors for delayed fluctuating SNHL. These data are relevant for an appropriate follow up plan of these patients.

Background: Individuals with thiamine-responsive megaloblastic anemia (TRMA) mainly manifest macrocytic anemia, sensorineural deafness, ocular complications, and nonautoimmune diabetes. Macrocytic anemia and diabetes may be responsive to high-dosage thiamine treatment, in contrast to sensorineural deafness. Little is known about the efficacy of thiamine treatment on ocular manifestations. Cases presentation: Our objective is to report data from four Italian TRMA patients: in Cases 1, 2 and 3, the diagnosis of TRMA was made at 9, 14 and 27 months. In 3 out of 4 subjects, thiamine therapy allowed both normalization of hyperglycemia, with consequent insulin suspension, and macrocytic anemia. In all Cases, thiamine therapy did not resolve the clinical manifestation of deafness. In Cases 2 and 3, follow-up showed no blindness, unlike Case 4, in which treatment was started for megaloblastic anemia at age 7 but was increased to high doses only at age 25, when the genetic diagnosis of TRMA was performed. Conclusions: Early institution of high-dose thiamine supplementation seems to prevent the development of retinal changes and optic atrophy in TRMA patients. The spectrum of clinical manifestations is broad, and it is important to describe known Cases to gain a better understanding of this rare disease. [ABSTRACT FROM AUTHOR]

With more than 466 million people affected, hearing loss represents the most common sensory pathology worldwide. Despite its widespread occurrence, much remains to be explored, particularly concerning the intricate pathogenic mechanisms underlying its diverse phenotypes. In this context, metabolomics emerges as a promising approach. Indeed, lying downstream from molecular biology's central dogma, the metabolome reflects both genetic traits and environmental influences. Furthermore, its dynamic nature facilitates well-defined changes during disease states, making metabolomic analysis a unique lens into the mechanisms underpinning various hearing impairment forms. Hence, these investigations may pave the way for improved diagnostic strategies, personalized interventions and targeted treatments, ultimately enhancing the clinical management of affected individuals. In this comprehensive review, we discuss findings from 20 original articles, including human and animal studies. Existing literature highlights specific metabolic changes associated with hearing loss and ototoxicity of certain compounds. Nevertheless, numerous critical issues have emerged from the study of the current state of the art, with the lack of standardization of methods, significant heterogeneity in the studies and often small sample sizes being the main limiting factors for the reliability of these findings. Therefore, these results should serve as a stepping stone for future research aimed at addressing the aforementioned challenges. [ABSTRACT FROM AUTHOR]

Tumor-associated macrophages (TAMs) play a role in tumor development and progression. We hypothesized that abundance of TAMs might modify efficacy of 5-fluorouracil chemotherapy in colorectal cancer. We measured the density of CD68+ TAMs at the invasive front of primary tumor of colorectal carcinoma (PT-TAMs; n = 208), at available matched metastatic lymph node (LN-TAMs; n = 149), and in an independent set of primary colorectal cancers (PT-TAMs, n = 111). The hazard ratios for disease-free survival were computed by Cox proportional-hazards model. In exploratory analysis, the interaction between TAMs and 5-fluorouracil adjuvant therapy was significant (PT-TAMs, p = 0.02; LN-TAMs, p = 0.005). High TAMs were independently associated with better disease-free survival only in 5-fluorouracil-treated patients (PT-TAMs, HR 0.23; 95%CI, 0.08–0.65; p = 0.005; LN-TAMs, HR 0.13; 95%CI, 0.04–0.43; p = 0.001). The independent predictive value of PT-TAMs was replicated in the external set (HR, 0.14; 95%CI 0.02–1.00; p = 0.05). In an in vitro experiment, 5-fluorouracil and macrophages showed a synergistic effect and increased colorectal cancer cell death. High densities of TAMs, particularly in metastatic lymph-nodes, identify stage III colorectal cancer patients benefitting from 5-fluorouracil adjuvant therapy.

Crohn’s disease (CD) is a chronic inflammatory condition that can affect different portions of the gastrointestinal tract. Lymphatic drainage was demonstrated to be dysfunctional in CD pathogenesis, ultimately causing the failure of the resolution of intestinal inflammation. To investigate the molecular mechanisms underlying these dysfunctions, we isolated human intestinal lymphatic endothelial cells (HILECs) from surgical specimens of patients undergoing resection for complicated CD (CD HILEC) and from a disease-free margin of surgical specimens of patients undergoing resection for cancer (healthy HILEC). Both cell types underwent transcriptomic profiling, and their barrier functionality was tested using a transwell-based co-culture system between HILEC and lamina propria mononuclear cells (LPMCs). Results showed CD HILEC displayed a peculiar transcriptomic signature that highlighted mTOR signaling as an orchestrator of leukocyte trafficking through the lymphatic barrier of CD patients. Moreover, we demonstrated that LPMC transmigration through the lymphatic endothelium of patients with CD depends on the capability of mTOR to trigger interleukin 20 receptor subunit α (IL20RA)-mediated intracellular signaling. Conclusively, our study suggests that leukocyte trafficking through the intestinal lymphatic microvasculature can be controlled by modulating IL20RA, thus leading to the resolution of chronic inflammation in patients with CD.