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Nevin Manimala Statistics

Maintaining a National Acute Kidney Injury Risk Prediction Model to Support Local Quality Benchmarking

Circ Cardiovasc Qual Outcomes. 2022 Aug 12:101161CIRCOUTCOMES121008635. doi: 10.1161/CIRCOUTCOMES.121.008635. Online ahead of print.

ABSTRACT

BACKGROUND: The utility of quality dashboards to inform decision-making and improve clinical outcomes is tightly linked to the accuracy of the information they provide and, in turn, accuracy of underlying prediction models. Despite recognition of the need to update prediction models to maintain accuracy over time, there is limited guidance on updating strategies. We compare predefined and surveillance-based updating strategies applied to a model supporting quality evaluations among US veterans.

METHODS: We evaluated the performance of a US Department of Veterans Affairs-specific model for postcardiac catheterization acute kidney injury using routinely collected observational data over the 6 years following model development (n=90 295 procedures in 2013-2019). Predicted probabilities were generated from the original model, an annually retrained model, and a surveillance-based approach that monitored performance to inform the timing and method of updates. We evaluated how updating the national model impacted regional quality profiles. We compared observed-to-expected outcome ratios, where values above and below 1 indicated more and fewer adverse outcomes than expected, respectively.

RESULTS: The original model overpredicted risk at the national level (observed-to-expected outcome ratio, 0.75 [0.74-0.77]). Annual retraining updated the model 5×; surveillance-based updating retrained once and recalibrated twice. While both strategies improved performance, the surveillance-based approach provided superior calibration (observed-to-expected outcome ratio, 1.01 [0.99-1.03] versus 0.94 [0.92-0.96]). Overprediction by the original model led to optimistic quality assessments, incorrectly indicating most of the US Department of Veterans Affairs’ 18 regions observed fewer acute kidney injury events than predicted. Both updating strategies revealed 16 regions performed as expected and 2 regions increasingly underperformed, having more acute kidney injury events than predicted.

CONCLUSIONS: Miscalibrated clinical prediction models provide inaccurate pictures of performance across clinical units, and degrading calibration further complicates our understanding of quality. Updating strategies tailored to health system needs and capacity should be incorporated into model implementation plans to promote the utility and longevity of quality reporting tools.

PMID:35959674 | DOI:10.1161/CIRCOUTCOMES.121.008635

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Nevin Manimala Statistics

Understanding the reasons for refusal of polio vaccine by families in Quetta Block, Pakistan

East Mediterr Health J. 2022 Jul 31;28(7):498-505. doi: 10.26719/emhj.22.052.

ABSTRACT

BACKGROUND: Global polio eradication is a goal yet to be achieved in countries like Pakistan. In recent years, the Polio Eradication Initiative has been making steady progress with good campaign coverage and low numbers of polio cases. However, in 2019 Pakistan reported 146 cases compared to 12 in 2018. A major factor cited for this regression was a surge in vaccine refusals by parents and caretakers.

AIMS: To assess the reasons for the refusal of polio vaccination in Quetta Block, Balochistan.

METHODS: The study was conducted using data acquired from 2 polio vaccination campaigns over 3 months in 2019. The data were collected in Quetta Block, a highly endemic zone having continuous transmission of the polio virus over several years. The data were analysed using the statistical software, SPSS, version 20. We used descriptive statistics to demonstrate the characteristics of the study population. Categorical variables were measured as frequencies and percentages.

RESULTS: Refusal rates were almost 8.6% for the polio campaign of April and 8.1% for June 2019. Misconceptions about vaccines made up 56.4% of reasons for refusals, followed by religion 16%.

CONCLUSION: Misconceptions about the vaccine are the main driving force behind vaccine refusals in the study setting. Efficient strategies are required to address misconceptions in this red zone of poliovirus transmission in Balochistan.

PMID:35959665 | DOI:10.26719/emhj.22.052

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Nevin Manimala Statistics

Comprehensive two-dimensional gas chromatography with mass spectrometry: an advanced bioanalytical technique for clinical metabolomics studies

Analyst. 2022 Aug 12. doi: 10.1039/d2an00584k. Online ahead of print.

ABSTRACT

The detection of human-derived metabolites as potential diagnostic biomarkers of genetic disorders, metabolic diseases, systemic diseases, and infectious diseases has been much studied in recent years, especially as technical capabilities improve, and statistical procedures are increasingly able to tease critical chemical attributes from complex data sets. Given the complex distribution of human biological matrices, the characterization and/or identification of these chemical entities is technically challenging, and is often confounded by incomplete chromatographic resolution or insufficient discriminatory power of the mass spectrometry (MS) domain. Recently, comprehensive two-dimensional gas chromatography (GC×GC) has evolved into a mature higher separation order technique that offers unprecedented resolving power, which in turn can greatly advantage clinical metabolomics studies via the expansion of metabolite coverage. In this contribution, the current state of knowledge in the development of GC×GC coupled to MS as a high-resolution bioanalytical technique for the analysis of clinical metabolites is reviewed. Selected recent applications (years 2012 to 2021) that emphasize improved GC×GC-MS strategies for clinical human metabolites’ detection, identification, and quantitative analysis are described. In addition, we share our perspectives on current challenges and potential future directions of GC×GC in clinical applications.

PMID:35959641 | DOI:10.1039/d2an00584k

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Nevin Manimala Statistics

Predicting the anticancer activity of 2-alkoxycarbonylallyl esters against MDA-MB-231 breast cancer – QSAR, Machine Learning and Molecular Docking

Curr Drug Discov Technol. 2022 Aug 11. doi: 10.2174/1570163819666220811094019. Online ahead of print.

ABSTRACT

BACKGROUND: The continuous increase in mortality of breast cancer and other forms of cancer due to the failure of current drugs, resistance, and associated side effects calls for the development of novel and potent drug candidates.

METHODS: In this study, we used the QSAR and extreme learning machine models in predicting the bioactivities of some 2-alkoxycarbonylallyl esters as potentials drug candidates against MDA-MB-231 breast cancer. The lead candidates were docked at the active site of a carbonic anhydrase target.

RESULTS: The QSAR model of choice satisfied the recommended values and was statistically significant. The R2pred (0.6572) was credence to the predictability of the model. The extreme learning machine ELM-Sig model showed excellent performance superiority over other models against MDA-MB-231 breast cancer. Compound 22 with a docking score of 4.67 kcal mol-1 displayed better inhibition of the carbonic anhydrase protein, interacting through its carbonyl bonds.

CONCLUSION: The extreme learning machine’s ELM-Sig model showed excellent performance superiority over other models and should be exploited in the search for novel anticancer drugs.

PMID:35959613 | DOI:10.2174/1570163819666220811094019

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Nevin Manimala Statistics

Mechanical analysis of the impact of the morphology of the iris and ciliary body on the central vault after posterior chamber phakic intraocular lens implantation

Zhonghua Yan Ke Za Zhi. 2022 Aug 11;58(8):615-623. doi: 10.3760/cma.j.cn112142-20220214-00060.

ABSTRACT

Objective: To investigate the impact of the iris and ciliary body morphology on the central vault after phakic posterior chamber intraocular lens (pIOL) implantation. Methods: This research was based on the retrospective analysis of 123 patients (123 eyes) who underwent pIOL implantation in the Department of Ophthalmology, Affiliated Hospital of Qingdao University between June 2018 and June 2020. The anterior segment structure was observed with an ultrasound biomicroscope before surgery, and all morphological parameters of the iris and ciliary body were measured manually using the ImageJ software, including iris span (IS), iris convexity (IC), iris-ciliary body contact distance (ICCD) and iris-lens contact distance (ILCD). The ICCD was divided into Q1, Q2 and Q3 groups according to the equidistant distance of 0.36 mm. The lens thickness was measured with the IOLMaster. The horizontal corneal diameter and anterior chamber depth were measured using the Pentacam. The central vaults were measured by optical coherence tomography at 1 week, 3 months and 1 year after surgery. The relationships between vault values and preoperative parameters of the anterior segment were evaluated using the Pearson correlation analysis, Spearman correlation analysis, and multiple linear regression. The repeated measures ANOVA was applied to identify changes of vault values over time. Results: The mean values of the vaults at 1 week, 3 months and 1 year after surgery were (723±265) μm, (642±255) μm and (613±280) μm, respectively. The difference among them was statistically significant (F=50.143, P<0.001). The vaults continued to decline within 1 year after pIOL implantation, and the total decline was (122±86) μm. The vaults declined by (69±98) μm from postoperative 1 week to 3 months and by (52±54) μm from postoperative 3 months to 1 year. The regression formula showed that the pIOL size and ILCD were positively related with the vault, while the LT, IS and IC were negatively related with the vault at 1 week postoperatively (adjusted R²=0.404, P<0.001). The pIOL size and ILCD were positively related with the vault, while the IS and IC were negatively related with the vault at 3 months postoperatively (adjusted R²=0.342, P<0.001). The pIOL size was positively related with the vault, while the IS and IC were negatively related with the vault at 1 year postoperatively (adjusted R²=0.661, P<0.001). The vault values were higher in group Q3 compared to group Q1 at every timepoint, and the vault value was higher in group Q2 compared to Q1 at 1 year postoperatively. Conclusions: In the early postoperative period, eyes with a larger pIOL, shorter iris span, longer contact distance between the iris and ciliary body, and longer contact distance between the iris and lens were associated with a higher rate of excessive vaults. Meanwhile, eyes with a thicker lens and larger iris reverse convexity were more likely to obtain insufficient vaults. Within one year after surgery, the pIOL size, IS, IC and ICCD continued to impact on the vault. The ICCD, ILCD and IC can reflect the posterior chamber volume and change the haptic location and force, thus affecting the vault.

PMID:35959606 | DOI:10.3760/cma.j.cn112142-20220214-00060

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Nevin Manimala Statistics

Therapeutic effect of amniotic membrane-fibrin sealant cement on severe ocular surface alkali burn in rabbits

Zhonghua Yan Ke Za Zhi. 2022 Aug 11;58(8):606-614. doi: 10.3760/cma.j.cn112142-20220310-00103.

ABSTRACT

Objective To prepare a biologically active amniotic membrane powder and explore its preservation conditions, and to evaluate the efficacy of the amniotic membrane (AM)-fibrin sealant (FS) cement made from the amniotic powder on the rabbit severe ocular surface alkali burn model. Methods Experimental research. Fresh AM was air-dried, cooled with liquid nitrogen, ground into amniotic powder and sterilized by radiation. The expression of transformed growth factor, nerve growth factor receptor (NGFR), hepatocyte growth factor (HGF), epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) after preparation and 10, 20 and 30 days after storage at room temperature, 4 ℃ and -20 ℃ was tested and compared with that in the fresh AM. The AM-FS cement containing different concentrations of amniotic powder and no amniotic powder was diluted. Rabbit corneal epithelial cells were cultured for 72 hours. The effects of different concentrations of amniotic powder on epithelial cell growth were observed by light microscopy, and the amniotic powder concentration with the largest absorbance value at 450 nm was selected for subsequent animal experiments. Thirty-two right eyes of 32 rabbits as the severe ocular surface alkali burn model were divided using the random counting method into the AM-FS cement group, fresh AM transplantation group, FS group and antibiotic control group (8 rabbits each group) and given different interventions. After weekly observation of corneal repair, hematoxylin and eosin staining, immunohistochemical staining of monocyte chemotaxis protein 1 (MCP-1)and vascular endothelial growth factor (VEGF) were performed and detected by light microscopy at 28 days. The logFC values of the growth factor or receptor expression difference ratio were corrected by BH; the data were analyzed by t-test and analysis of variance. Results: The expression of TGF in the amniotic membrane powder compared with the fresh amniotic membrane group (logFC=-0.11), and the expression of NGFR (HGF, EGF, bFGF) was higher than that of the fresh amniotic membrane group (logFC=-2.07, 0.72, 0.46, 2.62; P<0.05); the expression of HGF, bFGF and EGF in amniotic membrane powder stored for 10 days and 20 days were no lower than fresh amniotic membrane; at 30 days, the expression of growth factors or receptors except HGF and bFGF were decreased, and HGF, bFGF and EGF were no less than 4 ℃ and -20 ℃.The maximum A value was obtained for 0.25 mg/ml of the amniotic membrane powder after 72 hours of the CEC culture 0.98±0.05. The corneal recovery was better in the AM-FS and fresh amniotic membrane transplant groups, with corneal turbidity scores of 3.75±0.46 and 3.50±0.46, respectively, on 28 days, lower than antibiotics (4.29±0.45) (t=2.480, 3.629; P=0.019, 0.001). The corneal neovascular area in the antibiotic control group was compared with the other three groups (t=4.040, 4.339, 2.820; all P<0.001); the corneal neovascular area in the AM-FS group was (9.88±0.20) and (18.96±0.18) mm2 at 7 and 28 days. The corneal neovascularization area at 7 and 28 days in the fresh AM group [(9.54±0.22) and (18.08±0.96) mm2] was smaller than the AM-FS group (t=3.085, 3.017, P=0.005, 0.005). Despite the tiny statistical difference (0.34, 0.88), there was no clinical difference. Hematoxylin and eosin staining showed corneal structures were intact in the AM-FS and fresh AM groups, the epithelial arrangement became normal, and the corneal healing was superior to the FS and antibiotic control groups. Immunohistochemistry showed that the positive expression of VEGF in the fresh AM group was weaker than that in the remaining three groups. MCP-1 was expressed to a similar extent in the AM-FS and fresh AM groups. Conclusions: The active cytokine had high expression and stable properties at room temperature. The AM-FS cement containing 0.25 mg/ml amniotic powder can promote the repair of corneal epithelium, reduce inflammatory reaction and corneal neovascularization after alkali burning in rabbit eyes.

PMID:35959605 | DOI:10.3760/cma.j.cn112142-20220310-00103

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Nevin Manimala Statistics

Susceptibility of drug-resistant staphylococci isolated from different parts of the ocular anterior segment to common ophthalmic antibiotics

Zhonghua Yan Ke Za Zhi. 2022 Aug 11;58(8):598-605. doi: 10.3760/cma.j.cn112142-20220119-00023.

ABSTRACT

Objectie To investigate the susceptibility of drug-resistant staphylococci isolated from different parts of the anterior segment to levofloxacin, tobramycin, cefazolin sodium, fusidic acid and clindamycin. Methods: Experimental Study. A total of 67 patients with anterior segment infection (33 cases of conjunctivitis, 6 cases of bacterial keratitis, 7 cases of blepharitis, 9 cases of neonatal dacryocystitis, 9 cases of neonatal dacryocystitis, 1 case of adult dacryocystitis and 11 cases of other infectious eye diseases) were collected from the conjunctival sac, cornea, eyelid margin and lacrimal sac. Minimum inhibitory concentration (MIC) determination of methicillin-resistant Staphylococcus (MRS) strains and β-lactamase-producing (β-Lac) strains by a micro-liquid-based method, according to the M100 standard of the American Institute for Clinical and Laboratory Standardization Susceptibility and resistance determinations were made. Data were statistically analyzed using Chi-square or Fisher’s exact test. Results: Thirty-five MRS, 30 β-Lac and 2 β-Lac MRS isolates were identified from 67 multidrug-resistant Staphylococcus . There were 3, 9, 4, and 19 MRS isolates isolated from the lacrimal sac, cornea, eyelid margin and conjunctival sac, accounting for 3/4, 9/12, 4/8, 19/43 (44.2%) of the isolated sites respectively. There were 1, 3, 3, and 23 β-Lac isolates, accounting for 1/4, 3/12, 3/8 and 23/43 (53.5%) of the isolated sites, respectively. The highest proportion of β-Lac isolates isolated from patients with a diagnosis of conjunctivitis was 17 (25.3%) from the conjunctival sac. Among the MRS strains isolated from the cornea and lacrimal sac, 5 (7.5%) and 3 (4.5%) were from patients diagnosed with bacterial keratitis and neonatal tear, respectively. The number of MRS strains and β-Lac isolates isolated from patients with a diagnosis of blepharitis were both 3 (4.5%) from the lid margin.Among the strains isolated from the eyelid margin and the conjunctival sac, drug-resistant Staphylococcus epidermidis was the main strain, the drug-resistant Staphylococcus aureus was the major isolates in lacrimal sac and cornea. Among the 35 MRS isoaltes, 25, 24, 12, 12, and 11 were sensitive to cefazolin sodium, fusidic acid, levofloxacin, clindamycin and tobramycin, and the sensitivity rates were 71.4%, 68.6%, 34.3%, 34.3% and 31.4%, the difference was statistically significant (χ2=22.756, P<0.001), The sensitivity rates of levofloxacin, tobramycin, cefazolin sodium, fusidic acid and clindamycin against MRS isolates from the anterior segment were both statistically significant differences (χ2=18.493, 11.594, 8.906, 9.841, 16.059; all P<0.05). The susceptibility rates of MRS isolates against five antibiotics was statistically significant differences (χ2=33.080, P<0.001). Among the 30 β-Lac isolates, 27, 22, 19, 16, and 8 were sensitive to cefazolin sodium, fusidic acid, levofloxacin, tobramycin and clindamycin, and the sensitivity rates were 90.0 % , 73.3%, 63.3%, 53.3% and 26.7%, the difference was statistically significant (χ2=28.280, P<0.001). The sensitivity rates of five antibiotics against β-Lac isolates from the anterior segment were both statistically significant differences (χ2=50.971, 24.543, 48.147, 44.899, 18.676; all P<0.001). The susceptibility rates of β-Lac isolates against five antibiotics was statistically significant differences (χ2=23.383, P<0.001). The sensitivity of cefazolin sodium and fusidic acid against β-Lac isolates were higher than MRS isolates. Conclusions: Cefazolin sodium and fusidic acid may be the best choice for the treatment of drug-resistant Staphylococcus isolated from anterior conjunctival sac, cornea, eyelid margin and lacrimal sac, especially for β-Lac-producing drug-resistant Staphylococcus infection.

PMID:35959604 | DOI:10.3760/cma.j.cn112142-20220119-00023

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Evaluation of two biomechanical stiffness indexes in the diagnosis of eratoconus and their changes after corneal collagen cross-linking surgery

Zhonghua Yan Ke Za Zhi. 2022 Aug 11;58(8):584-591. doi: 10.3760/cma.j.cn112142-20211027-00507.

ABSTRACT

Objective: To evaluate the diagnostic efficacy of stress-strain index (SSI) for different stages or degrees of keratoconus and changes of SSI and stiffness parameter A1 (SPA1) after corneal collagen cross-linking (CXL) surgery. Methods: Cross-sectional study and retrospective case series study. Ninety-four patients (113 eyes) diagnosed as clinical keratoconus (CKC) in Qingdao Eye Hospital from July 2019 to August 2021 were enrolled in the CKC group, including 69 males and 25 females, aged (20.82±4.53) years, and further divided into subgroups of mild (35 patients, 36 eyes), moderate (36 patients, 40 eyes) and severe (33 patients, 37 eyes) CKC. Fifty-six unaffected eyes of monocular keratoconus patients were enrolled in the subclinical keratoconus (SKC) group. Ninety-one healthy subjects (91 eyes) were recruited as the control group. All subjects were examined by Pentacam topography and Corvis ST measurements to obtain mean keratometry, maximal keratometry, deformation amplitude (DA) ratio at 2 mm, integrated radius (IR), Ambrósio’s relational thickness to the horizontal profile, corneal central thickness, SPA1 and SSI for comparison. Forty-eight CKC patients (65 eyes) underwent CXL surgery, and the above parameters were recorded before and 3, 6 and 12 months after operation. Data were analyzed by the ANOVA test, Kruskal-Wallis H test, paired sample test, receiver operating characteristic curves and Pearson correlation. Results: The value of SPA1 in the SKC group accounted for 85.53% (87.92±12.38 vs. 102.79±11.74; t=-6.614, P<0.001) compared with the control group, but the value of SSI had no difference in the two groups (t=0.105, P=0.916). The value of SPA1 in the CKC group accounted for 52.87% (54.35±14.70 vs. 102.79±11.74; t=25.985, P<0.001) compared with the control group. The value of SSI in the CKC group accounted for 67.96% (0.70±0.14 vs. 1.03±0.14; t=-15.305, P<0.001) compared with the control group. The more severe the disease was, the smaller the SPA1 and SSI values were 64.27±12.12, 55.22±12.23, 43.75±12.33; 0.78±0.14, 0.71±0.11, 0.61±0.09, and there were significant statistical differences among groups (mild vs. moderate, mild vs. severe, moderate vs. severe; SPA1: t=3.257, -7.249, -4.159; all P<0.001. SSI: t=2.383, 5.065, 2.798; P=0.018,<0.001,=0.006). Receiver operating characteristic analysis showed that SPA1 had good diagnostic efficiency for subclinical patients [area under curve (AUC)=0.802], while the SSI had no diagnostic value (P=0.802). SPA1 had better diagnostic efficiency than the SSI for keratoconus in different stages, especially in the mild CKC and SKC groups (AUC: 0.914 vs. 0.847). The SSI had a significant positive correlation with SPA1 and a significant negative correlation with DA ratio and IR in the control, SKC and CKC groups (r=0.278, 0.368, 0.550; r=-0.346, -0.462, -0.547; r=-0.612, -0.591, -0.718; P<0.01). For patients who received CXL, maximal keratometry decreased significantly at 6 and 12 months postoperatively (t=4.029, 3.633; all P<0.001), whereas SPA1 increased significantly (t=-3.960, -4.500; all P<0.001). However, the SSI only increased significantly at 3 months (t=-2.577, P=0.012) and returned to the preoperative level at 6 and 12 months postoperatively, with no statistical difference compared with the preoperative level (t=-0.544, -0.257; P=0.589, 0.798). Conclusions: While there was no significant change in the SSI of SKC, the SSI of CKC decreased, and the more severe the disease was, the smaller the value was. The SSI was significantly and consistently correlated with DA ratio, IR and SPA1. The SSI compared with SPA1 had a lower degree of identification in different stages and degrees of keratoconus. The consistency of SPA1 with clinical effects after CXL surgery was higher than that of the SSI parameter.

PMID:35959602 | DOI:10.3760/cma.j.cn112142-20211027-00507

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Nevin Manimala Statistics

Application and development of voice analysis and endoscopic technology combined with artificial intelligence in the diagnosis and treatment of throat disease

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2022 Aug;36(8):647-650. doi: 10.13201/j.issn.2096-7993.2022.08.017.

ABSTRACT

In the diagnosis and treatment of throat disease, the application and development of combining voice analysis or endoscopic technology with artificial intelligence has developed rapidly. This paper reviews the history and principles of the combination of voice analysis or endoscopic technology with artificial intelligence, summarizes its status of application and development, and sums up its advantages that lie in the strong learning and interpretation ability, amazing speed and tolerance, and stable replication and expansion. The key to restrict its development is the uncertainty in the process of machine learning, the error caused by small samples, and the ethical philosophical thinking. Future development direction should be that the surgeons in otolaryngology head and neck department on the basis of excellent professional knowledge, learn related knowledge of epidemiology, classic statistics, strengthen the exchanges and cooperation with machine learning developers. Eventually, advanced science and technology can be truly used in clinical practice to maximize the benefit of the majority of patients.

PMID:35959588 | DOI:10.13201/j.issn.2096-7993.2022.08.017

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Nevin Manimala Statistics

The application value of video head impulse test, caloric test and dizziness handicap inventory in the diagnosis of acoustic neuroma

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2022 Aug;36(8):613-616. doi: 10.13201/j.issn.2096-7993.2022.08.009.

ABSTRACT

Objective:To explore the application value of video head impulse test(vHIT), caloric test(CT) and the dizziness handicap inventory(DHI) in the diagnosis of acoustic neuroma(AN), to analyze the correlation between vHIT and CT, and to determine the correlationsof tumor size, vHIT, CT and DHI score. Methods:The clinical data of 24 patients with AN who underwent surgery in our department from January 2019 to January 2022 were analyzed retrospectively, including craniocerebral MRI, vHIT, caloric test and DHI score. All the data were statistically analyzed by GraphPadPrism9.0. Results:There was a significant negative correlation between the UW value of CT and the vestibular eye reflex gain of vHIT(P<0.01, r=-0.62). The tumor size was significantly correlated with the increase of UW value of CT(P<0.01, r=0.69), and with the decrease of vestibulo-ocular reflex gain of vHIT(P<0.01, r=-0.53). The average Dizziness Handicap Inventory score was 8.9±16.2, which was not correlated with tumor size(P>0.05). Conclusion:Both vHIT and CT can effectively evaluate the vestibular function of patients with AN(and they are complementary), and they are related to the size of the tumor and have certain value in the diagnosis of acoustic neuroma.

PMID:35959580 | DOI:10.13201/j.issn.2096-7993.2022.08.009