Electrically evoked auditory brainstem responses in deaf children with cochlear nerve canal stenosis.

BACKGROUND: Deaf children with cochlear nerve canal stenosis (CNCs) are always considered poor candidates for cochlear implantation. OBJECTIVES: To investigate the function of the peripheral auditory pathway in deaf children with CNCs, as revealed by the electrically evoked auditory brainstem response (EABR), and postoperative cochlear implants (CIs) outcomes. MATERIALS AND METHODS: Thirteen children with CNCs and 13 children with no inner ear malformations (IEMs) who received CIs were recruited. The EABR evoked by electrical stimulation from the CI electrode was recorded. Postoperative CI outcomes were assessed using Categories of Auditory Performance (CAP) and Speech Intelligibility Rate (SIR). RESULTS: Compared with children with no IEMs, children with CNCs showed lower EABR extraction rates, higher thresholds, a longer wave V (eV) latency and lower CAP and SIR scores. The auditory and speech performance was positively correlated with the diameter of the cochlear nerve canal and the number of channels showing wave III (eIII) and eV in children with CNCs. CONCLUSIONS AND SIGNIFICANCE: The physiological function of the peripheral auditory pathway in children with CNCs is poorer than that in children with no IEMs. Postoperative auditory and speech abilities may depend on the severity of cochlear nerve malformation and auditory conduction function.

A pharynx-to-brain axis controls pharyngeal inflammation-induced anxiety.

Anxiety is a remarkably common condition among patients with pharyngitis, but the relationship between these disorders has received little research attention, and the underlying neural mechanisms remain unknown. Here, we show that the densely innervated pharynx transmits signals induced by pharyngeal inflammation to glossopharyngeal and vagal sensory neurons of the nodose/jugular/petrosal (NJP) superganglia in mice. Specifically, the NJP superganglia project to norepinephrinergic neurons in the nucleus of the solitary tract (NTSNE). These NTSNE neurons project to the ventral bed nucleus of the stria terminalis (vBNST) that induces anxiety-like behaviors in a murine model of pharyngeal inflammation. Inhibiting this pharynx→NJP→NTSNE→vBNST circuit can alleviate anxiety-like behaviors associated with pharyngeal inflammation. This study thus defines a pharynx-to-brain axis that mechanistically links pharyngeal inflammation and emotional response.

Downregulation of KCNMA1 in mice accelerates auditory hair cells senescence via ferroptosis.

KCNMA1 encodes the K+ potassium channel α-subunit that plays a significant role in the auditory system. Our previous studies indicated that KCNMA1 is associated with age-related hearing loss(AHL). However, the detailed mechanism of KCNMA1 involvement in auditory age-related degradation has not been fully clarified. Therefore, we explored the expression of KCNMA1 in the peripheral auditory of 2-month-old and 12-month-old mice by Western blotting and immunofluorescence. The results of animal experiments showed that KCNMA1 expression was decreased in 12-month-old mice compared with 2-month-old mice, whereas the ferroptosis level was increased. To verify the role of KCNMA1 in AHL, we downregulated KCNMA1 in HEI-OC1 cells by transfecting shRNA. After downregulation, the ferroptosis level was increased and the aging process was accelerated. Furthermore, the aging process was affected by the expression of ferroptosis. In conclusion, these results revealed that KCNMA1 is associated with the aging process in auditory hair cells by regulating ferroptosis, which deepens our understanding of age-related hearing loss.

Relationships between bilateral auditory brainstem activity and inter-implant interval in children with cochlear implants.

PURPOSE: To investigate the effect of the interval between bilateral cochlear implantation on the development of bilateral peripheral auditory pathways as revealed by the electrically evoked auditory brainstem response (EABR). METHODS: Fifty-eight children with profound bilateral sensorineural hearing loss were recruited. Among them, 33 children received sequential bilateral cochlear implants (CIs), and 25 children received simultaneous bilateral CIs. The bilateral EABRs evoked by electrical stimulation from the CI electrode were recorded on the day of second-side CI activation. RESULTS: The latencies of wave III (eIII) and wave V (eV) were significantly shorter on the first CI side than on the second CI side in children with sequential bilateral CIs but were similar between the two sides in children with simultaneous bilateral CIs. Furthermore, the latencies were prolonged from apical to basal channels along the cochlea in the two groups. In children with sequential CIs, the inter-implant interval was negatively correlated with the eV latency on the first CI side and was positively correlated with bilateral differences in the eIII and eV latencies. CONCLUSIONS: Unilateral CI use promotes the maturation of ipsilateral auditory conduction function. However, a longer inter-implant interval results in more unbalanced development of bilateral auditory brainstem pathways. Bilateral cochlear implantation with no or a short interval is recommended.

Correlational Analysis of Nasal Resistance and Acoustic Rhinometry Measurements With the Localization of Fungus Balls in the Paranasal Sinuses.

Objective: To investigate the reason for fungal balls (FBs) being localized in paranasal sinuses, we analyzed the clinical presentations of patients with FB rhinosinusitis (FBS). Methods: Clinical data, anatomical variation (ie, nasal septal deviation, concha bullosa, and Haller cell), as well as measurements of nasal resistance (NR), nasal cavity volume (NCV), and nasal cross-sectional area (NCA) using active anterior rhinomanometry and acoustic rhinometry were collected from FBS patients hospitalized in our hospital between January 2021 and December 2022. A retrospective analysis was conducted using IBM SPSS 19.0 to perform the Shapiro-Wilk test, t-test and logistic regression analysis. Results: A total of 95 FBS patients, including 33 male and 62 female patients, were included in this study. FBs in maxillary sinus were the most common (83, 87.4%), followed by sphenoid sinus (9, 9.5%). Logistic multivariate regression analysis revealed that a higher left-to-right NR ratio was associated with an increased likelihood of FBs being present in the left sinus [Odds ratios (OR) = 0.185; 95% CI, 0.061-0.558; P < .01]. When the ratio of the left-to-right second-minimum NCA was higher and the FB was more in the right sinus (OR = 3.194; 95% CI, 1.593-6.405; P = .001). Additionally, when the difference between left and right NCV was greater and FB occurred more commonly in the right sinus (OR = 1.435; 95% CI, 1.196-1.721; P < .001). Nonetheless, the presence of nasal septum deviation and concha bullosa did not significantly contribute to FB formation. Conclusions and significance: The differences in NR, NCA, and NCV between the affected and unaffected sides of nasal cavity are risk factors for the FB formation. To reduce FBS recurrence, it is important to focus on improving nasal ventilation during the surgical treatment.

Visceral adiposity in cirrhosis: Association with disease severity and impact of liver transplantation.

BACKGROUND: Changes in adipose tissue distribution in liver cirrhosis are poorly characterized and may affect clinical outcomes. METHODS: Adult liver transplant (LT) January 2008-August 2017 recipients with abdominal MRI within 6 months pre-LT were retrospectively assessed. Visceral adipose tissue, subcutaneous adipose tissue, and skeletal muscle area (cm2) were determined at L3. Visceral-to-subcutaneous adipose tissue ratio (VSR) was used to define relative adipose distribution, stratified by sex. Correlation was tested with Pearson. Body composition measures were compared by Child-Turcotte-Pugh (CTP) class, before and after LT, and evaluated as predictors of clinical outcomes. RESULTS: A total of 318 patients were studied. Mean age was 56 years, 33.64% were female, and 47.80% had CTP C cirrhosis. CTP C was associated with a 0.42-point increase in VSR compared with CTP A (95% CI = 0.13-0.71, p < 0.01), adjusting for age, sex, diabetes, and HCC. Among the 79 (24.84%) patients with repeat MRI 1-2 years after LT, VSR significantly improved from before LT (1.31 vs. 0.95, p < 0.01). In adjusted analysis, CTP C was associated with a 0.86-point decrease in post-LT VSR compared with pre-LT VSR (95% CI = -1.27 to -0.44, p < 0.01). Body mass index poorly correlated with VSR before and after LT. Elevated pre-LT VSR trended toward an association with a 7.17-point decrease in pre-LT glomerular filtration rate (95% CI = -14.35 to -0.02, p = 0.05), adjusting for CTP C, age, sex, diabetes, hypertension, pre-LT sarcopenia, and hepatocellular carcinoma. Elevated pre-LT VSR did not affect 3-year post-LT mortality (log-rank p = 0.24). CONCLUSIONS: Poorly represented by body mass index, visceral adiposity is increased in cirrhosis and is associated with CTP class. However, this adipose redistribution may be modifiable by LT.

The effect of cochlear size on electrically evoked auditory brainstem responses in deaf children.

Objectives: To investigate the relationship between auditory pathway function and cochlear size in deaf children with a radiologically normal inner ear or Mondini malformation. Methods: Thirty-five deaf children without inner ear malformations (IEMs) and forty cases with Mondini malformation were included in this study. The electrically evoked auditory brainstem responses (EABRs) evoked by electrical stimulation at the round window niche (RWN) and round window membrane (RWM) were recorded during cochlear implantation (CI) surgery. The anatomical parameters of the cochlea were assessed by high-resolution computed tomography and OTOPLAN 3-D construction software. Correlations between EABRs and cochlear sizes were analyzed. Results: The EABR thresholds and/or latencies were negatively correlated with the basal cochlear diameter, cochlear width and/or cochlear duct length in both patients without IEMs and those with Mondini malformation. Conclusion: The physiological function of the peripheral auditory system depends on the anatomical structure of the cochlea to an extent. A larger cochlear size appears to be associated with better auditory conduction function. Our findings may be beneficial to selection of the proper electrode type and prediction of postoperative auditory rehabilitation. Level of Evidence: Level 4.

Consideration of the Clinical Diagnosis of Allergic Fungal Sinusitis: A Single-Center Retrospective Study.

INTRODUCTION: Allergic fungal rhinosinusitis (AFRS) is characterized by refractory and high recurrence rate. Improper treatment may lead to repeated recurrence and even serious complications, including vision loss, blindness, and intracranial complications. However, AFRS is easy to be misdiagnosed clinically. OBJECTIVE: To ensure early diagnosis, the clinical presentations of patients with AFRS were studied. METHODS: Data from patients with sinusitis hospitalized in the First Affiliated Hospital of the University of Science and Technology of China (USTC) from January 2015 to October 2022 were collected. The patients were divided into three groups; group A patients with AFRS, group B patients suspected of AFRS, and group C patients with fungus ball sinusitis (FBS).We retrospectively analyzed the data using IBM SPSS 19.0 to perform the chi-square test and one-way ANOVA test. RESULTS: In total, 35 cases of AFRS, 91 cases of suspected AFRS, and 661 cases of FBS were rediagnosed. Compared with FBS patients, AFRS patients were younger, the total IgE, the percentage of eosinophils and basophils in peripheral blood were higher, and the proportion of patients with allergic rhinitis, asthma or hypo olfactory was higher. It had a higher recurrence rate. These results were also observed in the comparison between suspected AFRS patients and FBS patients, but no significant difference was found in the comparison between suspected AFRS patients and suspected AFRS patients. CONCLUSIONS AND SIGNIFICANCE: AFRS may be misdiagnosed due to the low detection of fungi. To ensure early diagnosis, we recommend that patients with clinical, radiological, and laboratory features similar to those of AFRS but without evidence of fungal staining be treated according to the treatment criteria of AFRS.

Electrically Evoked Auditory Brainstem Responses in Children Fitted with Hearing Aids Prior to Cochlear Implantation.

This study investigates the effect of hearing aid use on the peripheral auditory pathways in children with sensorineural hearing loss prior to cochlear implantation, as revealed by the electrically evoked auditory brainstem response (EABR). Forty children with hearing aids were recruited. Half of them had normal inner ear structures and the other half had inner ear malformations (IEMs). The EABR was evoked by electrically stimulating the round window niche (RWN) and round window membrane (RWM) during the cochlear implantation operation. The onset age of hearing aid use was significantly correlated with the peak latencies, but not amplitudes, of the wave III (eIII) and wave V (eV). Higher EABR thresholds were found for RWN stimulation than for RWM stimulation and in the children with IEMs than in those without IEMs. Our study provides neurophysiological evidence that earlier use of hearing aids may ameliorate physiological functions of the peripheral auditory pathway in children with and without IEMs. The EABR evoked by the electrical stimulation at RWM is more sensitive compared with that at RWN for evaluating functions of the auditory conduction pathway.

Evidence for predictions established by phantom sound.

Predictions, the bridge between the internal and external worlds, are established by prior experience and updated by sensory stimuli. Responses to omitted but unexpected stimuli, known as omission responses, can break the one-to-one mapping of stimulus-response and can expose predictions established by the preceding stimulus built up. While research into exogenous predictions (driven by external stimuli) is often reported, that into endogenous predictions (driven by internal percepts) is rarely available in the literature. Here, we report evidence for endogenous predictions established by the Zwicker tone illusion, a phantom pure-tone-like auditory percept following notch noises. We found that MMN, P300, and theta oscillations could be recorded using an omission paradigm in subjects who can perceive Zwicker tone illusions, but could not in those who cannot. The MMN and P300 responses relied on attention, but theta oscillations did not. In-depth analysis shows that an increase in single-trial theta power, including total and induced theta, with the endogenous prediction, is lateralized to the left frontal brain areas. Our study depicts that the brain automatically analyzes internal perception, progressively establishes predictions and yields prediction errors in the left frontal region when a violation occurs.

Brain hemispheres with right temporal lobe damage swap dominance in early auditory processing of lexical tones.

Labor division of the two brain hemispheres refers to the dominant processing of input information on one side of the brain. At an early stage, or a preattentive stage, the right brain hemisphere is shown to dominate the auditory processing of tones, including lexical tones. However, little is known about the influence of brain damage on the labor division of the brain hemispheres for the auditory processing of linguistic tones. Here, we demonstrate swapped dominance of brain hemispheres at the preattentive stage of auditory processing of Chinese lexical tones after a stroke in the right temporal lobe (RTL). In this study, we frequently presented lexical tones to a group of patients with a stroke in the RTL and infrequently varied the tones to create an auditory contrast. The contrast evoked a mismatch negativity response, which indexes auditory processing at the preattentive stage. In the participants with a stroke in the RTL, the mismatch negativity response was lateralized to the left side, in contrast to the right lateralization pattern in the control participants. The swapped dominance of brain hemispheres indicates that the RTL is a core area for early-stage auditory tonal processing. Our study indicates the necessity of rehabilitating tonal processing functions for tonal language speakers who suffer an RTL injury.

Event-Related Potential Evidence for Involuntary Consciousness During Implicit Memory Retrieval.

Classical notion claims that a memory is implicit if has nothing to do with consciousness during the information retrieval from storage, or is otherwise explicit. Here, we demonstrate event-related potential evidence for involuntary consciousness during implicit memory retrieval. We designed a passive oddball paradigm for retrieval of implicit memory in which an auditory stream of Shepard tones with musical pitch interval contrasts were delivered to the subjects. These contrasts evoked a mismatch negativity response, which is an event-related potential and a neural marker of implicit memory, in the subjects with long-term musical training, but not in the subjects without. Notably, this response was followed by a salient P3 component which implies involvement of involuntary consciousness in the implicit memory retrieval. Finally, source analysis of the P3 revealed moving dipoles from the frontal lobe to the insula, a brain region closely related to conscious attention. Our study presents a case of involvement of involuntary consciousness in the implicit memory retrieval and suggests a potential challenge to the classical definition of implicit memory.

Electrically evoked auditory brainstem responses in deaf patients with Mondini malformation during cochlear implantation.

PURPOSE: To investigate the auditory pathway functions in deaf patients with Mondini malformation using the electrically evoked auditory brainstem response (EABR) during cochlear implantation (CI). METHODS: A total of 58 patients with severe to profound sensorineural hearing loss (SNHL) were included in this study. Of these patients, 27 cases had Mondini malformation and 31 control cases had no inner ear malformations (IEMs). Intraoperative EABRs evoked by electrical stimulation at the round window niche (RWN) and round window membrane (RWM) were recorded. RESULTS: Patients with Mondini malformation showed significantly lower EABR extraction rates than those with no IEMs did. However, for patients who showed EABRs, no significant difference in EABR thresholds, wave III (eIII) latencies, wave V (eV) latencies or eIII-eV latency intervals was found between two groups. CONCLUSION: The physiological functions of the peripheral auditory system in patients with Mondini malformation may divide into opposite extremes, as revealed by a robust EABR and the absence of the EABR, respectively. The auditory conduction function should be objectively and individually evaluated for patients with Mondini malformation by the EABR.

Characteristics of electrically evoked auditory brainstem response in children with large vestibular aqueduct syndrome after cochlear implantation.

BACKGROUND: The vestibular aqueduct (VA) width may affect the auditory conduction pathway of large vestibular aqueduct syndrome (LVAS) children. OBJECTIVE: Analyzing the electrically evoked auditory brainstem response (EABR) after cochlear implantation (CI) in severe to profound sensorineural hearing loss (SNHL) children with LVAS. MATERIALS AND METHODS: Fifty-four children with SNHL who received CI were selected, including 21 children with LVAS and 33 children without inner ear malformations (IEMs). The VA width was measured in LVAS children. The post-operative EABRs were recorded in all children. RESULTS: For the LVAS group, the VA width was positively correlated with wave III (eIII) latency of EABR at the No. 2 electrode (E2), E5, E8, and E11, the VA width was positively correlated with wave V (eV) latency of EABR at E2, E5, E8, and E11. Only the eV latency of E2 showed a significant difference between the two groups. CONCLUSION AND SIGNIFICANCE: SNHL children with LVAS and no IEMs have similar conduction of the auditory pathway. In the LVAS group, the conduction of the auditory pathway becomes better with the decrease of VA width. Rational use of post-operative EABRs and the measurement of anatomical parameters can effectively assess the development of part auditory pathways in LVAS children, which may be helpful in predicting post-operative speech and hearing recovery.

Auditory Sensory Gating in Children With Cochlear Implants: A P50-N100-P200 Study.

Background: While a cochlear implant (CI) can restore access to audibility in deaf children, implanted children may still have difficulty in concentrating. Previous studies have revealed a close relationship between sensory gating and attention. However, whether CI children have deficient auditory sensory gating remains unclear. Methods: To address this issue, we measured the event-related potentials (ERPs), including P50, N100, and P200, evoked by paired tone bursts (S1 and S2) in CI children and normal-hearing (NH) controls. Suppressed amplitudes for S2 compared with S1 in these three ERPs reflected sensory gating during early and later phases, respectively. A Swanson, Nolan, and Pelham IV (SNAP-IV) scale was performed to assess the attentional performance. Results: Significant amplitude differences between S1 and S2 in N100 and P200 were observed in both NH and CI children, indicating the presence of sensory gating in the two groups. However, the P50 suppression was only found in NH children and not in CI children. Furthermore, the duration of deafness was significantly positively correlated with the score of inattention in CI children. Conclusion: Auditory sensory gating can develop but is deficient during the early phase in CI children. Long-term auditory deprivation has a negative effect on sensory gating and attentional performance.

Caffeine Induces Autophagy and Apoptosis in Auditory Hair Cells via the SGK1/HIF-1α Pathway.

Caffeine is being increasingly used in daily life, such as in drinks, cosmetics, and medicine. Caffeine is known as a mild stimulant of the central nervous system, which is also closely related to neurologic disease. However, it is unknown whether caffeine causes hearing loss, and there is great interest in determining the effect of caffeine in cochlear hair cells. First, we explored the difference in auditory brainstem response (ABR), organ of Corti, stria vascularis, and spiral ganglion neurons between the control and caffeine-treated groups of C57BL/6 mice. RNA sequencing was conducted to profile mRNA expression differences in the cochlea of control and caffeine-treated mice. A CCK-8 assay was used to evaluate the approximate concentration of caffeine. Flow cytometry, TUNEL assay, immunocytochemistry, qRT-PCR, and Western blotting were performed to detect the effects of SGK1 in HEI-OC1 cells and basilar membranes. In vivo research showed that 120 mg/ kg caffeine injection caused hearing loss by damaging the organ of Corti, stria vascularis, and spiral ganglion neurons. RNA-seq results suggested that SGK1 might play a vital role in ototoxicity. To confirm our observations in vitro, we used the HEI-OC1 cell line, a cochlear hair cell-like cell line, to investigate the role of caffeine in hearing loss. The results of flow cytometry, TUNEL assay, immunocytochemistry, qRT-PCR, and Western blotting showed that caffeine caused autophagy and apoptosis via SGK1 pathway. We verified the interaction between SGK1 and HIF-1α by co-IP. To confirm the role of SGK1 and HIF-1α, GSK650394 was used as an inhibitor of SGK1 and CoCl2 was used as an inducer of HIF-1α. Western blot analysis suggested that GSK650394 and CoCl2 relieved the caffeine-induced apoptosis and autophagy. Together, these results indicated that caffeine induces autophagy and apoptosis in auditory hair cells via the SGK1/HIF-1α pathway, suggesting that caffeine may cause hearing loss. Additionally, our findings provided new insights into ototoxic drugs, demonstrating that SGK1 and its downstream pathways may be potential therapeutic targets for hearing research at the molecular level.

Electrically evoked auditory brainstem responses to electrical stimulation at round window membrane in congenitally deaf children at different ages.

OBJECTIVES: To investigate the usefulness of measuring the electrically evoked auditory brainstem responses (eABRs) to electrical stimulation at the round window niche (RWN) and round window membrane (RWM) and the effect of deafness duration on functions of the auditory pathway to the level of the brainstem. METHODS: According to the age at cochlear implantation (CI), 99 children with profound sensorineural hearing loss were divided into four groups: ≤12 months (group A), 13-36 months (group B), 37-60 months (group C) and >60 months (group D). The eABRs were evoked by electrical stimulation at RWN and RWM during the operation of CI. RESULTS: The higher eABR extraction rate and lower threshold for RWM stimulation was found than those for RWN stimulation. The eⅢ latencies and eⅢ-eⅤ latency intervals for RWM stimulation were similar among four groups. However, children with earlier CI (group A) showed a significantly shorter eⅤ latency than others. CONCLUSION: The eABR evoked by the electrical stimulation at RWM is more stable and sensitive compared with that at RWN for evaluating functions of the auditory conduction pathway. Development in the upper brainstem pathway may be more vulnerable to long-term deafness as revealed by the eⅤ latency.

Deficient sensory and cognitive processing in children with cochlear implants: An event-related potential study.

Compared with children having normal hearing (NH), those with cochlear implants (CIs) perform poorly in spoken language comprehension which involves both low-level acoustic encoding and higher-level cognitive processing. Here, we performed an electroencephalography study to portray this brain dynamics of speech perception in CI children. We presented a Mandarin Chinese monosyllable or four-syllable idiom to CI and NH children, and infrequently varied its lexical tone to form a novel monosyllable or pseudo-idiom in an oddball paradigm. The tone contrast embedded in the monosyllables evoked similar mismatch negativities (MMNs) in CI and NH children at an early stage (~200 ms). However, the amplitude of the MMN evoked by the tone contrast in the idiom context was significantly lower in CI children than in NH children. Furthermore, robust late discriminative negativity (LDN) at a late stage (~500 ms) was found only in NH children, but not in CI children. The MMN and LDN findings indicate deficits of low-level acoustic encoding in a complex context (such as an idiom) and higher-level cognitive processing in CI children, respectively. Both deficient sensory and cognitive processing may contribute to the speech perception difficulties in CI children.

Uncontrolled Confounders May Lead to False or Overvalued Radiomics Signature: A Proof of Concept Using Survival Analysis in a Multicenter Cohort of Kidney Cancer.

PURPOSE: We aimed to explore potential confounders of prognostic radiomics signature predicting survival outcomes in clear cell renal cell carcinoma (ccRCC) patients and demonstrate how to control for them. MATERIALS AND METHODS: Preoperative contrast enhanced abdominal CT scan of ccRCC patients along with pathological grade/stage, gene mutation status, and survival outcomes were retrieved from The Cancer Imaging Archive (TCIA)/The Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) database, a publicly available dataset. A semi-automatic segmentation method was applied to segment ccRCC tumors, and 1,160 radiomics features were extracted from each segmented tumor on the CT images. Non-parametric principal component decomposition (PCD) and unsupervised hierarchical clustering were applied to build the radiomics signature models. The factors confounding the radiomics signature were investigated and controlled sequentially. Kaplan-Meier curves and Cox regression analyses were performed to test the association between radiomics signatures and survival outcomes. RESULTS: 183 patients of TCGA-KIRC cohort with available imaging, pathological, and clinical outcomes were included in this study. All 1,160 radiomics features were included in the first radiomics signature. Three additional radiomics signatures were then modelled in successive steps removing redundant radiomics features first, removing radiomics features biased by CT slice thickness second, and removing radiomics features dependent on tumor size third. The final radiomics signature model was the most parsimonious, unbiased by CT slice thickness, and independent of tumor size. This final radiomics signature stratified the cohort into radiomics phenotypes that are different by cancer-specific and recurrence-free survival; HR (95% CI) = 3.0 (1.5-5.7), p <0.05 and HR (95% CI) = 6.6 (3.1-14.1), p <0.05, respectively. CONCLUSION: Radiomics signature can be confounded by multiple factors, including feature redundancy, image acquisition parameters like slice thickness, and tumor size. Attention to and proper control for these potential confounders are necessary for a reliable and clinically valuable radiomics signature.