Profound Degree Research Articles

Efficacy of cochlear implantation in cochlear nerve deficiency children – A single center study

PurposesThe objective of this research was to interpret and analyze the imaging, audiological features and cochlear implantation outcomes in cochlear nerve deficiency children. Material and methodsRetrospective analysis. Results25 prelingual hearing loss children diagnosed cochlear nerve deficiency (CND), the age range from 1 to 15 (mean age, 5.04), underwent cochlear implantation at Ear Nose and Throat Hospital - Ho Chi Minh City (ENT hospital – HCMC) from 2016 to 2023. All children had sensorineural hearing loss (SNHL) from severe to profound degree. Magnetic resonance imaging (MRI) showed cochlear nerve hypoplasia in 76 % and cochlear nerve aplasia in 24 % of cases. Inner ear malformations were found in 52 % of cases. The mean Categories of Auditory Performance (CAP) score at 1 year after surgery was 4.8. At 6 months and 1 year after surgery, the mean CAP score of the aplasia group was significantly lower than that of the hypoplasia group (p < 0.05). ConclusionsIn cochlear nerve deficiency children, auditory perception and speech performance still improved after cochlear implantation. However, this progress was significantly limited in cochlear nerve aplasia group.

Auditory Electrophysiological Thresholds With Different Chirps and Their Correlation With Behavioral Thresholds in Hearing-Impaired Children.

Research focusing on changes in the clinical practice of audiological diagnosis has become increasingly necessary, particularly in pediatric audiology. The pursuit of accurate and reliable examinations has intensified given the importance of early detection and intervention in cases of childhood hearing loss. Thus, this study aims to investigate the correlation between electrophysiological auditory thresholds, as obtained through frequency-specific auditory brainstem responses with two distinct chirp stimuli (narrow-band CE-Chirp Level Specific and narrow-band iChirp), in children with hearing impairments. In addition, this research set out to correlate these thresholds with behavioral responses while simultaneously comparing the examination durations relative to the type of stimuli and the degree of hearing loss. A cohort of 20 children (aged 6 months to 12 years) with varying degrees of hearing impairment (ranging from mild to profound) were recruited. The participants underwent bilateral measurement of their electrophysiological thresholds via auditory brainstem responses across different frequencies (500, 1000, 2000, and 4000 Hz), and the timeframe for determining these thresholds was carefully recorded. Subsequently, behavioral thresholds were ascertained using pure-tone audiometry or visual reinforcement audiometry based on the child's age. The data collected was subsequently analyzed using Pearson and Spearman correlation coefficients. To compare examination times, the Student t test and the Kruskal-Wallis test were used. There was a pronounced correlation between the thresholds obtained through both narrow-band chirp stimuli. Moreover, a substantial correlation was found between electrophysiological and behavioral thresholds at 1000, 2000, and 4000 Hz, especially when compared with pure-tone audiometry. The mean differences between the electrophysiological and behavioral thresholds were below 6 dB nHL, and the exam duration was relatively consistent across both devices, averaging 47.63 (±19.41) min for the narrow-band CE-Chirp Level Specific and 52.42 (±26) min for the narrow-band iChirp. Notably, variations in exam duration did not relate to varying degrees of hearing loss when using the narrow-band CE-Chirp Level Specific. Nevertheless, the narrow-band iChirp indicated significantly shorter durations in instances of profound degree measurements, demonstrating a statistically significant difference. The narrow-band CE-Chirp Level Specific and narrow-band iChirp stimuli provided similar estimates of electrophysiological auditory thresholds in children with hearing impairments, giving accurate estimations of behavioral thresholds. The time it took to complete the assessment is comparable between both stimuli. For the narrow-band iChirp, the degree of hearing loss was shown to impact the testing time, and children with profound hearing loss underwent faster exams. Ultimately, this study exhibits significant clinical implications as it reveals that the narrow-band CE-Chirp Level Specific and narrow-band iChirp stimuli could be remarkably promising for clinically exploring electrophysiological thresholds in children with hearing impairments.

Sensorineural Hearing Loss and Cochleovestibular Malformations in Children in Côte d’Ivoire

Objective: to find the distribution of various malformations and to report the clinical features of commonly encountered IEMs in our practice. Methods: This was a retrospective cross-sectional study, over a period of 14 months (January 2019 to March 2020), in the ENT departments of University Hospitals and the Mother and Child Hospital in Bingerville. All patients, aged up 15 years with computed tomography and/or MRI available, who had a cochleovestibular malformation and sensorineural or predominantly sensorineural mixed hearing loss confirmed were included. Results: The prevalence of sensorineural hearing loss related to cochleovestibular malformations was 3.75% (6 cases out of 160 patients). Patients ranged in age from 2 to 14 years. The diagnosis was made before the age of 3.5 years in 5/6 cases. The sex ratio was 1. Language delay was noted in 5/6 cases. No contributing risk factors were identified. All patients had profound and bilateral hearing loss. Associated malformations were present in 2/6 cases. The most common abnormalities were semicircular canal hypoplasia, internal auditory canal abnormalities and cochlear malformations. There was an association between sensorineural hearing loss linked to malformation and the profound degree of hearing loss. Conclusion: Sensorineural deafness linked to cochleovestibular malformations in children appears to be uncommon. However, they are associated with a risk of profound sensorineural hearing loss. It is therefore important, in the face of any sensorineural hearing loss in the child, to systematically carry out an imaging assessment, even in our low income’s countries.

LOGISTICS OF TRANSPORT SERVICES FOR PEOPLE WITH DISABILITIES IN POLAND- CASE STUDY

This study embarks on a profound investigation into the experiences and challenges confronted by individuals with disabilities. It emphasizes their interactions with architectural structures and their engagement with assisting technologies. Based on a meticulously curated survey, the study reveals that the educational background of respondents is diverse, with secondary education emerging as the most prevalent. A significant segment of the sample, 48%, is identified with a profound degree of disability (I disability group), underscoring the need to address their unique challenges. Key findings highlight a range of architectural barriers, with stairs lacking alternative access methods as the primary impediment. This highlights the urgency for urban planning and infrastructural updates tailored for inclusivity. The frequency of outdoor activities, predominantly daily, provides insights into mobility patterns and potential challenges faced. On the technological front, the survey reveals a disparity in the adoption and satisfaction levels with assisting technologies. Only a small minority use these tools daily, with a significant segment expressing inadequacy or partial alignment with their needs. Interestingly, a pronounced affinity towards these technologies is observed among highereducated individuals, suggesting potential links between education and technological engagement. Furthermore, the study explores the intricacies of architectural barriers in residential areas. Larger cities, for instance, present unique challenges, such as the lack of appropriate voice signaling. Such insights advocate for location-specific interventions. This research provides a comprehensive understanding of the diverse challenges faced by individuals with disabilities in Poland. By integrating these insights, the study emphasizes the need for holistic and targeted solutions, laying the foundation for creating an inclusive and accessible societal environment. This paper also aims to explore the logistics of transport services for people with disabilities in Poland, focusing on their availability, accessibility, cost, regulations, and the awareness and education surrounding these services. By examining these factors, this paper seeks to identify the challenges faced by people with disabilities when using transport services in Poland and suggests measures to enhance the logistics of these services.

Cladribine and Cyclophosphamide Lymphodepletion Prior to Axicabtagene Ciloleucel in Relapsed or Refractory Large B-Cell Lymphoma

Introduction : Chemotherapy-based lymphodepletion (LD) with fludarabine and cyclophosphamide (Flu/Cy) is a standard preparatory step for chimeric antigen T-cell (CAR T) therapy and its importance for optimal CAR T expansion and efficacy is well-established. An international Flu shortage required our center and others to utilize alternative agents for LD or risk interruption in patient therapy. When unable to utilize Flu as part of the LD regimen for patients with relapsed/refractory large B-cell lymphoma (RR LBCL) that required CD19-directed CAR T as a standard of care therapy, our center adopted a standard operating procedure to substitute Flu with Cladribine (Clad), an alternate purine analogue with similar chemical structure, as part of Clad/Cy LD prior to axicabtagene ciloleucel (axi-cel). Here we report outcomes in these patients. Methods : We performed a retrospective, single-center analysis of consecutive RR LBCL patients who received Clad/Cy LD prior to axi-cel at Moffitt Cancer Center between 8/2022 and 1/2023, and compared outcomes to a historical cohort, consisting of 144 Flu/Cy axi-cel LBCL patients treated between 11/2017 and 2/2021. The Clad/Cy LD regimen, given as standard care, maintained Cy at 500 mg/m 2 and substituted Flu 30 mg/m 2 with Clad 5 mg/m 2/day with both agents given on Days -5, -4, and -3. For efficacy we compared best overall response (BOR) at 90 days and progression-free survival (PFS) comparing the two LD regimens. For safety we compared the rates of cytokine release syndrome (CRS) and neurotoxicity as graded by ASTCT criteria. We also performed correlative analyses exploring absolute lymphocyte count (ALC) kinetics, axi-cel expansion by quantitative PCR, and changes in the cytokine milieu as assessed by the enzyme-linked immunosorbent Ella™ system (Bio-Techne, Oxford, UK) at serial time points following infusion. Results : 23 patients received Clad/Cy LD followed by axi-cel for R/R DLBCL. Baseline characteristics of the study cohort based on LD are shown in the Table. Compared to the historical cohort, Clad/Cy patients received axi-cel after fewer lines of treatment (median 2 [range, 1-3] vs 2 [range, 1-7]; Rank-Sum test p&amp;lt;0.01) and had a greater proportion of relapsed (not refractory) disease (52% vs 22%, p&amp;lt;0.01). The 90-day BOR did not differ between the Clad/Cy and Flu/Cy groups (79% vs 84%; P=0.54) with a similar distribution of complete (22% vs 24%) and partial responders (57% vs 60%). With a median follow-up of 4.6 (95% CI, 3.2-6.2) months for Clad/Cy and 24.2 (95% CI, 21.5-25.8) months for Flu/Cy cohorts, PFS was similar (Figure 1B, Log-Rank p=0.84). Rates of CRS grade ≥ 2 were higher in the Clad/Cy cohort (70% vs 44%; p=0.02), but no CRS grade ≥ 3 was observed in the Clad/Cy compared to 13 (9%) of Flu/Cy patients, including three grade 5 events. Neurotoxicity ≥ grade 2 (44% vs 43%; p=0.77) and peak C-reactive protein levels (15 vs Flu/Cy 12; p=0.3) did not differ for the Clad/Cy and Flu/Cy cohorts. Both regimens had comparable peak axi-cel copy numbers (Clad/Cy 7.9 × 10 6 vs Flu/Cy 5.1 × 10 6 copies/µg). Clad/Cy resulted in a predictable decrease in the ALC from Day -5 to Day 0, but a less profound degree of lymphopenia on Day 0 (0.04 vs 0.02; p&amp;lt;0.01) with ALC 0 achieved later (Day +2 [IQR, +1 to +4] vs Day +1 [IQR, -1 to +2] for Flu/Cy). The median magnitude of change of cytokine levels (Delta = Day -5 - Day 0 concentration) differed between Clad/Cy and Flu/Cy for all tested analytes except IL-6 (3.4 vs 4.6 pg/mL for Flu/Cy; p=0.29). Clad/Cy resulted in greater increases in IL-2 (0.5 vs 0.2 for Flu/Cy; p=0.01) and GM-CSF (2.0 vs 0.9 for Flu/Cy; p=0.03), whereas Flu/Cy had higher IL-15 (31.4 vs 16.8 for Clad/Cy; p&amp;lt;0.01). Interestingly, IFN-γ tended to increase in Clad/Cy and to decrease in Flu/Cy (1.2 vs 0.0; p=0.01). Conclusions : Clad/Cy LD is feasible for axi-cel conditioning in the treatment of RR LBCL. Although it resulted in less profound LD on the day of CAR T infusion, a later ALC nadir, and a different cytokine milieu compared to Flu/Cy, it was associated with similar peak axi-cel expansion and, at short term follow-up, there appears to be similar initial efficacy and toxicity. Future analyses focusing on response durability and long-term toxicities such as infections and post-CAR T cytopenias are warranted.

Autosomal Dominant Non-Syndromic Hearing Loss (DFNA): A Comprehensive Narrative Review.

Autosomal dominant non-syndromic hearing loss (HL) typically occurs when only one dominant allele within the disease gene is sufficient to express the phenotype. Therefore, most patients diagnosed with autosomal dominant non-syndromic HL have a hearing-impaired parent, although de novo mutations should be considered in all cases of negative family history. To date, more than 50 genes and 80 loci have been identified for autosomal dominant non-syndromic HL. DFNA22 (MYO6 gene), DFNA8/12 (TECTA gene), DFNA20/26 (ACTG1 gene), DFNA6/14/38 (WFS1 gene), DFNA15 (POU4F3 gene), DFNA2A (KCNQ4 gene), and DFNA10 (EYA4 gene) are some of the most common forms of autosomal dominant non-syndromic HL. The characteristics of autosomal dominant non-syndromic HL are heterogenous. However, in most cases, HL tends to be bilateral, post-lingual in onset (childhood to early adulthood), high-frequency (sloping audiometric configuration), progressive, and variable in severity (mild to profound degree). DFNA1 (DIAPH1 gene) and DFNA6/14/38 (WFS1 gene) are the most common forms of autosomal dominant non-syndromic HL affecting low frequencies, while DFNA16 (unknown gene) is characterized by fluctuating HL. A long audiological follow-up is of paramount importance to identify hearing threshold deteriorations early and ensure prompt treatment with hearing aids or cochlear implants.

Abstract #1402115: A Case of Starvation Ketoacidosis in Pregnancy Secondary to Perforated Appendicitis

Starvation ketoacidosis in pregnant patients is a rare but life-threatening condition. There are few case reports in the literature of starvation ketoacidosis of pregnancy with no consensus on treatment. We present a case of starvation ketoacidosis in pregnancy that was successfully treated with dextrose and insulin infusion. A 35-year-old pregnant woman with a history of prior gestational diabetes diagnosed in a previous but not current pregnancy presented at 33 weeks of gestation with severe abdominal and poor oral intake for 3 days prior to admission. On evaluation, the patient was found to have a perforated appendix with peritonitis and was taken to the operating room for open laparotomy. During surgery, she was noted to have an anion gap metabolic acidosis. Arterial blood gas revealed pH of 7.06 (range 7.35-7.45), pCO2 of 43mmHg (range 32-35 mmHg), pO2 of 120 mmHg (range 83-108 mmHg), and bicarbonate of 12 mmol/L (range 22-26 mmol/L). Further blood work demonstrated serum bicarbonate of 14 mmol/L (range 21-30 mmol/L), and an anion gap of 18 (4-16). Beta-hydroxybutyrate was elevated at 58.5 mg/dL (range 0-3 mg/dL), with serum glucose of 134 mg/dL (range 70-99 mg/dL) and normal lactate of 1.3 mmol/L (range 0.5-2.2 mmol/L). Urinalysis demonstrated 2+ ketones (range negative). She was started on a dextrose 5% infusion with insulin infusion at a fixed rate to overcome any inherent insulin resistance and suppress lipolysis. Metabolic parameters were corrected in 12 hours and the patient was extubated in 24 hours. At 48 hours, insulin and dextrose infusions were discontinued. She then underwent cesarian section 1.5 weeks later due to development of pelvic abscess requiring surgical intervention. She delivered a healthy baby girl. Women in late pregnancy are at increased risk for ketosis during even brief periods of fasting. This is due to increased relative insulin resistance and enhanced lipolysis, a protective mechanism to ensure adequate glucose supply to the growing fetus. Prompt recognition of ketosis and timely management are essential to prevent profound acidosis and avoid maternal-fetal mortality. Although there is no consensus on management of starvation ketoacidosis in pregnancy, most case reports suggest carbohydrate administration is the cornerstone of treatment, although insulin administration can be considered if there is concern for marginal insulin reserve or there is treatment failure with carbohydrate administration alone. In our case, given the profound degree of acidosis, simultaneous administration of carbohydrate and insulin was pursued with rapid resolution of the patient’s metabolic derangements.

Intercession of Ionic regulation and ATPase activity induced by propiconazole in Fish

Triazole fungicides are being widely utilized globally in the present agribusiness, however in different volumes. Although improvement is important for crops, there are severe environmental, health and safety issues associated with aquatic living biomes that integrate people and creatures. Various antagonistic effects on durability, growth and organic structures are affected by pesticides and their processing. In order to present the biosafety and toxicological highlights of poisons by hazard assessment considerations using various creature models and fish organisms, a few inspection efforts have been made. In general, propiconazole is utilized among a few fungicides in farming and families and the detailed convergences of this pesticide are terrible in different water bodies such as waterways and streams, soil and even in rainwater. As in need, PCZ is reflected for hazard appraisal studies to consider profound and diverse degree of toxicological impacts subject to portion, presentation time and course. The PCZ constancy in nature is acting as a severe hazard to people as another non-target earthly and amphibian life form. Thus, the poisonous impacts of fungicides with unusual reference to PCZ on fish, the mode of toxicity concerns on the general wellbeing and harmful effects on individuals are methodically surveyed. The data are given on their appropriate control and counteraction plans. The motivation behind this distribution was subsequently to investigate the various poisonous effects of introduction of triazole. In addition, it incorporates ATPase action and ionic guideline to layout activities for surveying the degree of accurate existence of harmful effects of PCZ poisonousness of freshwater.

Multifactorial Risk Reduction with Nutrition and Exercise Intervention: A Case Report and Review of Mechanisms

The practice of cardiology by recent guidelines 1 includes assessment and management of cardiovascular risk with lifestyle first, followed by medications when lifestyle changes do not produce sufficient results or high risk is present. However, in clinical practice, the assessment of diet and exercise followed by meaningful intervention in these areas are not often emphasized by physicians, and implementation by patients is often lessthan optimal. In this case, there was a dramatic improvement in cardiovascular risk factors, including a profound degree of weight loss, along with a fall in systolic pressure, serum triglycerides, low-density lipoprotein cholesterol (LDL-C) and total cholesterol, possibly driven by the improvement in the microbiome induced by the patient’s exercise and dietary change to a whole food, plant-based diet. These remarkable changes represent an unusual response in terms of the degree, but not the direction, of improvement with exercise and a plant-based diet. The patient’s prospects of sustained weight loss and lifelong lower cardiovascular risk appear to be best with his adopted lifestyle changes, particularly the whole food, plant-based diet.

Heavy prenatal alcohol exposure and overall morbidities: a Danish nationwide cohort study from 1996 to 2018

Heavy prenatal alcohol exposure is harmful and can lead to fetal alcohol spectrum disorders. A systematic review and meta-analysis identified 428 comorbidities in individuals with fetal alcohol spectrum disorders, and reported pooled prevalence estimates. We aimed to investigate overall risk of morbidities in heavy prenatal alcohol-exposed children by estimating risk of the identified comorbidities, and previously unidentified diseases and health-related problems. Our Danish nationwide register-based cohort study included all singleton births. Individuals were followed up to age 18 years, between 1996 and 2018. Stillbirths and children of immigrants were not included in the study, and births of women who migrated within 1 year before or during pregnancy were also excluded due to loss to follow-up. Data on health and education were extracted from the Danish Medical Birth Register, the Danish National Patient Registry, the Danish National Prescription Registry, the Danish Civil Registration System, and the Population Education Register. We estimated crude and standardised risk differences of hospital diagnoses. Heavy prenatal alcohol exposure was defined by hospital contacts with alcohol-attributable diagnoses given to the mother or her child, or by maternal redeemed prescriptions for drugs to treat alcohol dependence 1 year before or during pregnancy. Of 1 407 689 identified singleton births, 219 186 were excluded for reasons including they were born to immigrants, lost to follow-up, or were stillbirths. Of the remaining 1 188 503 children, 4799 (0·4%) had heavy prenatal alcohol exposure and 1 183 704 (99·6%) were classified as non-alcohol-exposed births. 578 179 (48·6%) babies were female and 610 324 (51·4%) were male. We found 234 of 428 previously identified comorbidities in individuals with fetal alcohol spectrum disorder, of which 29 conditions had a standardised risk difference of at least 0·5%, predominantly related to brain function, behavioural disorders, infections, and neonatal conditions. The four highest standardised risk differences were found for low birthweight (4·70% [95% CI 3·70-5·71]), small for gestational age (4·63% [3·72-5·55]), delayed milestone (3·81% [2·99-4·64]), and other preterm infants (2·69% [1·71-3·68]). Of previously unidentified diseases and health-related problems, 32 of 719 had a standardised risk difference of at least 1·0%, mainly related to brain function, some injuries, substance-related conditions, and childhood adversities. Heavy prenatal alcohol exposure is associated with an overall increased risk of child morbidities and previously unrecognised alcohol-related health problems. Prenatal alcohol exposure is a key public health issue with a potential negative impact on child and adolescent health. This study urges for renewed efforts and substantiates the profound degree to which pre-conceptional care is mandatory. The Obel Family Foundation, The Health Foundation, TrygFonden, Aase and Ejnar Danielsens Foundation, The North Denmark Region Health Science and Research Foundation, Holms Memorial Foundation, Dagmar Marshalls Foundation, the A.P. Møller Foundation, King Christian X Foundation, Torben and Alice Frimodts Foundation, the Axel and Eva Kastrup-Nielsens Foundation, and the A.V. Lykfeldts Foundation.

Hearing outcomes in children with congenital cytomegalovirus infection: From management controversies to lack of parents' knowledge.

Congenital cytomegalovirus (cCMV) is the leading nongenetic cause of sensorineural hearing loss (HL). However, there are no universally accepted approaches to diagnosis, follow-up and treatment. The aim of this study was to evaluate the main characteristics of cCMV-infected children, focusing on their management and long-term hearing outcomes. This retrospective study included all children with cCMV infection who were referred to a third-level referral audiologic center for a 6-year hearing follow-up. The main information collected from the medical records included gestational age, birth weight, trimester of maternal seroconversion, hearing status at birth and after 6 years, hearing fluctuations, treatment with oral valganciclovir (within the first month of life and for 6 months), use of hearing devices, presence of speech-language delay, motor delay, cognitive delay and balance disorders, awareness of cCMV among parents, and parents' engagement in behaviors that could increase the risk of CMV infection during pregnancy. A total of 141 children with cCMV infection (72 males and 69 females; mean gestational age: 37+3 weeks; mean birth weight: 2893g) were assessed. Overall, 48 children (34.0%) had a diagnosis of speech-language delay, 32 (22.7%) of sensorineural HL (59.4% bilaterally; 50% of profound degree), 18 (12.8%) of motor delay, 16 (11.3%) of balance disorders, and 6 (4.3%) of cognitive delay. Among children with HL, 8 (25.0%) were fitted with hearing aids (5 unilaterally and 3 bilaterally), and 5 (15.6%) had undergone cochlear implantation (1 unilaterally and 4 bilaterally), while a bimodal hearing solution was adopted for 2 (6.3%) patients. Compared to children with asymptomatic cCMV infection, symptomatic children had a higher prevalence of neurological and auditory sequelae (P<0.01) and bilateral (P=0.003) and severe-to-profound HL (P=0.004). Overall, 23 children (16.3%) received oral valganciclovir, and only one of them experienced hearing deterioration. Only 14.9% of mothers and 5% of fathers were aware that cCMV could cause progressive or late-onset HL, and 87.9% of parents (248/282) had engaged in behaviors that increased the risk of CMV infection during pregnancy. This study confirmed the importance of performing a long audiological follow-up in children diagnosed with cCMV infection due to the possible late-onset, progressive and fluctuating nature of HL. Moreover, the study highlighted many current controversies in preventive (poor prenatal education), diagnostic (routine maternal serological screening) and therapeutic (valganciclovir administered to asymptomatic children) approaches to cCMV infection. More efforts should be made to improve prevention strategies and raise awareness of cCMV infection risks among the population.

Characteristics of patients with sudden onset sensorineural hearing loss: observational study

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Sudden sensorineural hearing loss (SNHL) is considered as acute onset hearing disturbance characterized by hearing loss of greater than 30 decibels.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; This retrospective research included data from 83 hospitalized patients (92 ears) and was conducted in a regional multidisciplinary children's medical centre between January 2014 and December 2019. We performed examinations of the eardrum as well as cranial nerves.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; Among the 92 ears with SNHL, 8 ears (8.7%) in age group of 2-18 years, 33 ears (35.9%) in the group of 19-30 years, 30 (32.6%) and 21 ears (22.8%) represented the age groups of 31-65 and those aged over 65 years respectively. Hearing loss in 5 ears (5,4%) was rated as light, in 7 ears (7.6%) as moderate, in 14 ears (15.2%) as severe, and 66 ears (71.7%) out of the 92 had profound degree of hearing loss. Early treatment of SNHL was positive predictive factor for recovery (OR=2.54, 95% CI 1.09-5.91, p=0.03). The presence of tinnitus was also strongly linked with better recovery outcomes while not significantly associated (OR=2.59, 95% CI 0.91-7.37, p=0.07).&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; In the course of our research, we found that 11.9% of patients made a full recovery, while the total recovery rate was 42.3%. Positive prognostic markers for hearing recovery were early treatment and a strong trend was observed with the presence of tinnitus.&lt;/p&gt;

Progression of Contralateral Hearing Loss in Patients with Unilateral Ear Involvement: A Scoping Review

Background:Progression of contralateral hearing loss following otologic and neuro-otologic surgeries is a distressing and rare complication. The aim of this study was to systematically review the suspected etiologies and audiological findings in adults who experienced contralateral hearing loss.Methods:PubMed/MEDLINE, PsycINFO, CINAHL, ISI Web of Science, Cochrane Library, EMBASE, and Scopus databases were searched for this scoping review. The current review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. No limits were placed on language or year of publication.Results:Of a total of 46 studies, 43 studies met the inclusion criteria reporting contralateral hearing loss. The included studies were classified into 3 different categories: contralateral hearing loss after skull base surgeries (n = 21), contralateral hearing loss after middle ear surgeries (n = 17), and contralateral hearing loss after traumatic lesions (n = 5). The cerebrospinal fluid leakage and drill-generated noise were reported as the most reported etiology of contralateral hearing loss following skull base and middle ear surgeries, respectively. The onset of contralateral hearing loss varied from immediately to 18 months after surgery. The severity of contralateral hearing loss varied from a slight to a profound degree of hearing loss.Conclusion:Our results highlighted that contralateral hearing loss should be considered following the skull base and middle ear surgeries. Furthermore, this rare complication should be noticed after traumatic lesions.

Abstract 6162: Histone deacetylase inhibitor modulates T cell recruitment to metastatic pancreatic neuroendocrine tumors by CCR5 regulation

Abstract Pancreatic neuroendocrine tumors (PNETS) represent the second most common pancreatic neoplasm with surgical resection serving as the mainstay of treatment for localized PNETs (lPNETs) &amp;gt; 2 cm in size; however, therapeutic options for managing metastatic PNETs (mPNETs) remain limited. Recently, immunotherapy with checkpoint inhibitors has emerged as effective therapy across a range of malignancies but has shown limited efficacy in PNET patients partly due to what has been reported as a “cold” tumor microenvironment (TME). Here, we aimed to characterize the TME among both localized and mPNETs and identify mechanisms to increase tumor immunogenicity and T cell recruitment among these patients. We analyzed tumor-infiltrating and peripheral T cells from patients with lPNETs and mPNETs by flow cytometry and found higher expression of CD69+ (activation), CCR5+ (recruitment), and PD1+ (exhaustion) in T cells isolated from TME compared to peripheral blood. Further, we identified a more profound degree of CD3+ and CD8+ T cell infiltration among mPNETs compared to lPNETs by immunohistochemistry analysis, suggesting that mPNETs are at least moderately enriched with activated T cells. RNA-sequencing performed on 22 sporadic, well-differentiated primary PNETs revealed distinct transcriptional signatures dependent upon metastatic potential. These divergent transcriptomes were analyzed by an L1000 computational algorithm, which classifies landmark gene signatures perturbed by drug treatments. We identified the histone deacetylase inhibitor vorinostat as the drug most likely to perturb the PNET gene signature. A KEGG pathway analysis revealed that these vorinostat-target genes were commonly involved in both Th1, Th2, and Th17 cell differentiation and in the NF-κB pathway. Vorinostat treatment of patient-derived mPNET resulted in increased T cell migration towards metastatic tumors across a semi-permeable membrane; cotreatment with a competitive CCR5 antagonist abrogated this effect. In addition, vorinostat treatment of BON-1 and QGP-1, two PNET cell lines, elevated both NF-κB activity and CCR5 expression, with induction reduced following inhibition of NF-κB nuclear localization. Our study demonstrates that T cell recruitment toward mPNET tissue is dependent upon CCR5 expression. These results reveal that PNET TME is regulatable by vorinostat and opens an avenue of potential sensitization to immune checkpoint blockade among patients with PNETs. Citation Format: Jacques A. Greenberg, Jessica N. Limberg, Akanksha Verma, David Kim, Maureen D. Moore, Timothy M. Ullmann, Jessica W. Thiesmeyer, Zachary Loewenstein, Kevin J. Chen, Caitlin E. Egan, Dessislava I. Stefanova, Rohan Bareja, Rasa Zarnegar, Brendan M. Finnerty, Theresa Scognamiglio, Olivier Elemento, Thomas J. Fahey, Irene M. Min. Histone deacetylase inhibitor modulates T cell recruitment to metastatic pancreatic neuroendocrine tumors by CCR5 regulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6162.

Well Diving is Not Well for Hearing: Sudden Sensory Neural Hearing Loss-A Case Report

Background: Sudden sensory neural hearing loss can be caused by many factors. It may range from minimal to profound degree of hearing loss. Barotrauma is a type of ear damage caused by pressure difference between the atmosphere and the inner ear. This may result in permanent sensory neural hearing loss. Objective: The aim of the study was to use behavioral and electrophysiological assessments to analyze the hearing of a patient who experienced sudden hearing loss following a dive in well. Case Report: A 31 year old male adult who reported sudden hearing loss following a dive in the well was evaluated. Hearing assessment was done. Pure tone audiometry revealed bilateral profound hearing loss. Immittance audiometry showed ‘A’ type tympanogram in both ears and acoustic reflexes absent in both ears. In ABR click stimulus test, no responses were observed till 105dBnHL in both ears. DPOAE’s were also absent in both ears. Vestibular assessments (subjective and objective) were also done. Conclusion: The current case study verifies the importance of audiological assessment for divers and importance of safety measures to be taken.

Reading Philosophy, Writing Poetry: Intertextual Modes of Making Meaning in Early Medieval China

Reading Philosophy, Writing Poetry: Intertextual Modes of Making Meaning in Early Medieval China

The enduring effect of early life adversities on health trajectories

In this issue of The Lancet Public Health, Naja Rod and colleagues report on their national cohort study of over half a million young Danes (aged 0–15 years) who had more than 3·8 million hospital treatment episodes.1 The findings generated from this major epidemiological investigation show the profound degree to which early life adversities detrimentally affect health outcomes among children, adolescents, and young adults.1 This investigation overcomes some of the limitations of previously published studies, such as those that investigated a single early life adversity indicator that might not have a causal influence on subsequent health risks.

Delayed Speech Dengan dan Tanpa Gangguan Pendengaran pada Anak Usia 6 Bulan sampai 3 Tahun di Jala Puspa RSPAL Dr. Ramelan Surabaya Periode 2017-2020

Late or untreated delayed speech can be a risk for social, emotional, behavioral and cognitive problems in adulthood. Delayed speech is associated with hearing loss, mental retardation, autism spectrum disorder (OSD), bilingualism, and lack of psychosocial stimuli. Objectives: To determine the prevalence of delayed speech with and without hearing loss in children aged six months until three years. Methods: This study used 872 medical records of delayed speech children aged six months until three years with and without hearing loss in 2017 until 2020 period at Jala Puspa RSPAL Dr. Ramelan, Surabaya. The presence or absence of hearing loss was examined using Brainstem Evoked Response Audiometry (BERA), and the degree of hearing loss was examined using Auditory Steady-State Response (ASSR) test. Results: From a total of 872 medical records data studied, 558 (64.0%) were males and 314 (36.0%) were females. The majority (44.8%) of delayed speech children were from the two-year age group. There were 565 (64.8%) delayed speech children with hearing loss and 307 (35.2%) without hearing loss. Of those with hearing loss, 48.0% showed a profound degree. There was an increase in delayed speech children without hearing loss compared to those with hearing loss, from 1:2.04 in 2017 to 1:1.12 in 2020. Conclusion: There was an increase in delayed speech children without hearing loss compared to those with hearing loss.Keywords: ASSR, BERA, delayed speech, hearing loss

Determine the Frequency of Sensorineural Deafness in Children with Cerebral Palsy

Aim: To determine the frequency of sensorineural deafness in child with cerebral palsy. Study Design: Descriptive/cross-sectional Place and Duration of Study: Department of Neurology, Chandka Medical College Hospital, Larkana from 1st October 2020 to 31st March 2021. Methodology: One hundred and seventy patients of both genders age between 1-14 years were enrolled. Children diagnosed as having cerebral palsy and fulfilling the inclusion criteria was included. Hearing assessment was done with audiometry and degree of hearing loss was recorded in both ears in the form of mild, moderate, severe and profound degree of hearing loss. Results: Most of the patients 90 (52.94%) were between 1-5 years old followed by 51(30%) patients between 5-10 years with mean age of 4.8±7.8 years. 115 (67.65%) cases were males and 55 (32.35%) females. 54 (31.8%) cases had microcephaly and116 (68.2) cases had normal head circumference. Among 170 cases of cerebral palsy 48 (28.23%) cases had hearing loss and 122 (71.77%) of patients of CP had no hearing deficit. Among 48 cases of CP with hearing loss 15 (31.25%) cases had mild, 14 (29.17) cases had moderate, 10 (20.83%) had severe and 11 (22.92%) cases had profound hearing loss. Conclusion: The frequency of sensorineural deficit is high and significantly associated with cerebral palsy patients. Keywords: Degree of hearing loss, Sensorineural hearing loss, Cerebral palsy

Clinical features and prognostic factors of pediatric idiopathic sudden hearing loss from moderate to profound degree

BackgroundThe pediatric idiopathic sudden sensorineural hearing loss (PISSNHL) is not rare in the clinics, however, the prognostic factors of PISSNHL are still unclear. ObjectivesTo investigate the clinical and audiologic characteristics associated with prognosis in PISSNHL. Material and methodsClinical and audiological characteristics and possible prognostic factors were retrospectively evaluated in 76 PISSNHL patients aged less than 19 years. ResultsHearing loss was moderate in nine patients, severe in 21 patients, profound in 46 patients. Among five types of audiogram, 3.9% were classified as ascending, 11.8% as descending, 25.0% as flat, 55.3% as profound, and 3.9% as concave. The recovery rate according to Siegel's criteria was 55.3%. There was no significant difference between the recovery group and the poor recovery group in terms of age, sex, laterality of hearing loss, the onset of treatment, and accompanying symptoms (p > 0.05). The initial hearing levels and the audiogram type were significantly different in the two groups (p < 0.001) according to univariate analysis, while only the initial hearing level was significantly different (p = 0.046) according to multivariate analysis. Conclusions and significancePrognosis of PISSNHL was mainly related to initial hearing at onset. An initial hearing level greater than 80 dB was a poor prognostic factor.