Mean Threshold Research Articles

Efficiency of resveratrol in the prevention and treatment of age-related hearing loss.

Age-related hearing loss (ARHL) is a major public health concern, which is characterized by gradual, progressive sensorineural hearing loss and deterioration of sound localization, with no effective treatment available to date. The aim of the present study was to evaluate the efficacy of resveratrol to prevent and treat ARHL. For this purpose, 32 male C57BL/6 mice were assigned to four groups: Early treatment, late treatment, control and sham control. The experiment lasted for 15 months. Treatment was started at three months of age in the early treatment group and at sixth months in the late treatment group. The auditory brainstem response test was performed once every three months. At the end of the study period, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, NF-κB, Bcl-2, Bcl-xL, Bax, Bcl-2 homologous antagonist/killer (Bak), caspase-3 and caspase-9 levels in the cochlear tissues of the animals were analyzed by reverse transcription-quantitative PCR. Hearing thresholds of the mice in the early treatment group were better than those in the other groups (P<0.001) at the end of the study. However, hearing levels in the late treatment group were not significantly different from those in the control groups (P>0.05), although mean thresholds were lower. The threshold shift in the early treatment group was significantly lower at all frequencies when compared with those in the control groups (P<0.001). The mRNA expression levels of pro-apoptotic genes Bax and Bak were lower (P<0.05), anti-apoptotic genes Bcl-2 and Bcl-xL were higher (P<0.05), NF-κB, COX-2 and iNOS as genes that have a role in inflammation and caspase-3 and caspase-9 as genes with a vital role in apoptosis were lower (P<0.05) in the early treatment group when compared with the late treatment and control groups. These results suggested that resveratrol is effective in the prevention of ARHL, particularly when started prior to the beginning of hearing loss.

Clinical performance of high-risk HPV testing on self-samples versus clinician samples in routine primary HPV screening in the Netherlands: An observational study.

BackgroundHigh-risk human papillomavirus (hrHPV) testing on self-collected samples has potential as a primary screening tool in cervical screening, but real-world evidence on its accuracy in hrHPV-based screening programmes is lacking.MethodsIn the Netherlands, women aged 30–60 years invited for cervical screening can choose between sampling at the clinician's office (Cervex Brush) or self-sampling at home (Evalyn Brush). HrHPV testing is performed using Roche Cobas 4800. We collected screening test results between January 2017 and March 2018 and histological follow-up until August 2019. The main outcome measures were mean cycle threshold (Ct) value, cervical intraepithelial neoplasia (CIN) grade 3 or cancer (CIN3+) and CIN grade 2 or worse (CIN2+).Findings30,808 women had a self-collected and 456,207 had a clinician-collected sample. In hrHPV-positive women with adequate cytology, Ct values were higher for self-collection than clinician-collection with a mean Ct difference of 1·25 (95% CI 0·98–1·52) in women without CIN2+, 2·73 (1·75–3·72) in CIN2 and 3·59 (3·03–4·15) in CIN3+. The relative sensitivity for detecting CIN3+ was 0·94 (0·90–0·97) for self-collection versus clinician-collection and the relative specificity was 1·02 (1·02–1·02).InterpretationThe clinical accuracy of hrHPV testing on a self-collected sample for detection of CIN3+ is high and supports its use as a primary screening test for all invited women. Because of the slightly lower sensitivity of hrHPV testing on a self-collected compared to a clinician-collected sample, an evaluation of the workflow procedure to optimise clinical performance seems warranted.FundingNational Institute for Public Health and the Environment (the Netherlands) and the European Commission.

Detection of Pathogens of Acute Febrile Illness Using Polymerase Chain Reaction from Dried Blood Spots.

ABSTRACT.Quantitative polymerase chain reaction (qPCR) of dried blood spots (DBS) for pathogen detection is a potentially convenient method for infectious disease diagnosis. This study tested 115 DBS samples paired with whole blood specimens of children and adolescent from Burkina Faso, Sudan, and Madagascar by qPCR for a wide range of pathogens, including protozoans, helminths, fungi, bacteria, and viruses. Plasmodium spp. was consistently detected from DBS but yielded a mean cycle threshold (Ct) 5.7 ± 1.6 higher than that from whole blood samples. A DBS qPCR Ct cutoff of 27 yielded 94.1% sensitivity and 95.1% specificity against the whole blood qPCR cutoff of 21 that has been previously suggested for malaria diagnosis. For other pathogens investigated, DBS testing yielded a sensitivity of only 8.5% but a specificity of 98.6% compared with whole blood qPCR. In sum, direct PCR of DBS had reasonable performance for Plasmodium but requires further investigation for the other pathogens assessed in this study.

A Systematic Review Examining the Approaches Used to Estimate Interindividual Differences in Trainability and Classify Individual Responses to Exercise Training.

Background: Many reports describe statistical approaches for estimating interindividual differences in trainability and classifying individuals as “responders” or “non-responders.” The extent to which studies in the exercise training literature have adopted these statistical approaches remains unclear.Objectives: This systematic review primarily sought to determine the extent to which studies in the exercise training literature have adopted sound statistical approaches for examining individual responses to exercise training. We also (1) investigated the existence of interindividual differences in trainability, and (2) tested the hypothesis that less conservative thresholds inflate response rates compared with thresholds that consider error and a smallest worthwhile change (SWC)/minimum clinically important difference (MCID).Methods: We searched six databases: AMED, CINAHL, EMBASE, Medline, PubMed, and SportDiscus. Our search spanned the aerobic, resistance, and clinical or rehabilitation training literature. Studies were included if they used human participants, employed standardized and supervised exercise training, and either: (1) stated that their exercise training intervention resulted in heterogenous responses, (2) statistically estimated interindividual differences in trainability, and/or (3) classified individual responses. We calculated effect sizes (ESIR) to examine the presence of interindividual differences in trainability. We also compared response rates (n = 614) across classification approaches that considered neither, one of, or both errors and an SWC or MCID. We then sorted response rates from studies that also reported mean changes and response thresholds (n = 435 response rates) into four quartiles to confirm our ancillary hypothesis that larger mean changes produce larger response rates.Results: Our search revealed 3,404 studies, and 149 were included in our systematic review. Few studies (n = 9) statistically estimated interindividual differences in trainability. The results from these few studies present a mixture of evidence for the presence of interindividual differences in trainability because several ESIR values lay above, below, or crossed zero. Zero-based thresholds and larger mean changes significantly (both p < 0.01) inflated response rates.Conclusion: Our findings provide evidence demonstrating why future studies should statistically estimate interindividual differences in trainability and consider error and an SWC or MCID when classifying individual responses to exercise training.Systematic Review Registration: [website], identifier [registration number].

Viral and Atypical Bacterial Detection in Young Nepalese Children Hospitalized with Severe Pneumonia.

ABSTRACTRespiratory viruses cause a substantial proportion of respiratory tract infections in children but are underrecognized as a cause of severe pneumonia hospitalization in low-income settings. We employed 22 real-time PCR assays and retrospectively reanalyzed 610 nasopharyngeal aspirate specimens from children aged 2 to 35 months with severe pneumonia (WHO definition) admitted to Kanti Childrens’ Hospital in Kathmandu, Nepal, from January 2006 through June 2008. Previously, ≥1 of 7 viruses had been detected by multiplex reverse transcription-PCR in 30% (188/627) of cases. Reanalyzing the stored specimens, we detected ≥1 pathogens, including 18 respiratory viruses and 3 atypical bacteria, in 98.7% (602/610) of cases. Rhinovirus (RV) and respiratory syncytial virus (RSV) were the most common, detected in 318 (52.1%) and 299 (49%) cases, respectively, followed by adenovirus (AdV) (10.6%), human metapneumovirus (hMPV) (9.7%), parainfluenza virus type 3 (8.4%), and enterovirus (7.7%). The remaining pathogens were each detected in less than 5%. Mycoplasma pneumoniae was most common among the atypical bacteria (3.7%). Codetections were observed in 53.3% of cases. Single-virus detection was more common for hMPV (46%) and RSV (41%) than for RV (22%) and AdV (6%). The mean cycle threshold value for detection of each pathogen tended to be lower in single-pathogen detections than in codetections. This finding was significant for RSV, RV, and AdV. RSV outbreaks occurred at the end of the monsoon or during winter. An expanded diagnostic PCR panel substantially increased the detection of respiratory viruses in young Nepalese children hospitalized with severe pneumonia.IMPORTANCE Respiratory viruses are an important cause of respiratory tract infections in children but are underrecognized as a cause of pneumonia hospitalization in low-income settings. Previously, we detected at least one of seven respiratory viruses by PCR in 30% of young Nepalese children hospitalized with severe pneumonia over a period of 36 months. Using updated PCR assays detecting 21 different viruses and atypical bacteria, we reanalyzed 610 stored upper-respiratory specimens from these children. Respiratory viruses were detected in nearly all children hospitalized for pneumonia. RSV and rhinovirus were the predominant pathogens detected. Detection of two or more pathogens was observed in more than 50% of the pneumonia cases. Single-virus detection was more common for human metapneumovirus and RSV than for rhinovirus and adenovirus. The concentration of virus was higher (low cycle threshold [CT] value) for single detected pathogens, hinting at a high viral load as a marker of clinical significance.

3D electro-anatomical mapping to guide conduction system pacing in complex cardiac anatomies

Abstract Background Conduction System Pacing (CSP) includes both His Bundle Pacing (HBP) and Left Bundle Branch Pacing (LBBP). It guarantees physiological cardiac activation and it is essential to avoid pacing-induced dyssynchrony. Markedly dilated atria, up-grading to CRT, and congenital cardiopathies still represent complex anatomical scenarios in which the available tools could often result inadequate and graved by suboptimal results. Objective To evaluate the feasibility and effectiveness of 3D electro-anatomical mapping (EAM) to guide CSP (both HBP and LBBP) in patients with characteristics that allows “a priori” classification as complex anatomical scenario with low probability of success using only fluoroscopic guidance and available tools. Left atrium area &amp;gt;40 cm2; post-PICM up-grading and congenital heart disease were considered signs of anatomical complexity. Methods and results The study includes 25 patients (19 males, mean age 76–11 years; mean baseline EF 34.2–12.6%; 17 BBB; 5 post-PICM up-grading), candidates for CSP. 16 and 9 were respectively implanted with PM and ICD (13/12 dual/three-chamber devices). CARTO system was used in 6 ptss and EnsiteTM Precision in 19. EAM involved reconstruction of the right atrium and sub-tricuspid septum with the use of a decapolar catheter. Several “tags” have been placed on the His signals, in order to reconstruct the “His Cloud” and distinguish within it the proximal, medium, and distal area (Fig. 1). The sub-tricuspid septum was always reconstructed so that intra-procedurally operator could easily move from HBP to LBBP based on electrical parameters or paced QRS morphology. The mapping catheter was removed after the mapping phase and replaced with the pacing lead. Both exposed fixed screw 3830 leads and standard stylet-driven leads were used. HBP was achieved in 10 pts and LBBP in 13 pts. Three failures were resolved by CS lead implant. The time spend for His cloud mapping was 18±7 min. The mean threshold was 1.1±0.5 V; sensing 11.6±9.3 mV and impedance 786±339 ohm. Baseline QRS 155±19 ms and paced QRS 119±7 ms. In cases of LBBP we were also able to measure on the EAM map the depth of the catheter within the septum, resulting in 11.5±3.1 mm and the distance of the initial screw site from the His of 26.5±10.3 mm. Conclusions The electro-anatomical mapping allows the accurate reconstruction of “His cloud” by properly distinguishing proximal, middle, distal His. The sub-tricuspid zone of the interventricular septum is also reconstructed in high definition, so that intra-procedurally it is possible to easily move from HBP to LBBP and vice-versa based on the electrical parameters and paced QRS morphology. This method appears safe and effective even in complex cardiac anatomies possibly saving time and fluoroscopy use. The tags on the His cloud and sub-tricuspid septum can satisfactorily guide lead placement with high reproducibly. Funding Acknowledgement Type of funding sources: None. Figure 1. 3D-EAM used to guide HBP implant

Detection of Kras Gene in Colorectal Cancer Patients through Liquid Biopsy: A Cost-effective Method.

To detect the Kras gene through liquid biopsy, a less invasive technique in diagnosed colorectal cancer patients. Cross-sectional study. Department of Oncology, Dr. Ziauddin Hospital and Bait-us-Sukoon Cancer Hospital, Karachi, from 2019 to 2020. Circulating tumor DNA (ctDNA) in colorectal cancer patients was extracted through magnetic bead technique using MagMAX cell free DNA kit (Thermofisher, Uk). The frequency of Kras gene was quantified using a real-time polymerase chain reaction (RT-PCR) assay (qPCR). ANOVA and Chi-square tests were utilised for statistical analysis. Mean threshold cycle (CT) of Kras gene showed significantly higher expression 15.6 ± 1.82 (p=0.001) in stage IV CRC cases compared to early stages (19.53 ± 18.223.7 ± 2.9 and 19.8 ± 2.69 of stage 1, 2 and 3, respectively. Similarly, ΔCT mean of Kras gene at stage IV showed significantly higher expression of 2.48 ± 1.40 (0.048), compared to 2.39 ± 0.6, 3.12 ± 0.68 and 3.15 ± 0.41 of stage 1, 2 and 3, respectively. Males (n=40, 55%) showed significant association (p=0.001) with CRC compared to females (n=33, 45%). Categorisation of tumor types within different age groups revealed that colon cancer was more frequent (n=11, 15.1%) in the 41-50 age group, while rectal cancer was more frequent (n= 11, 15.1%) in the 41-50 age group, while rectal cancer was more in the 51-60 age group (n=11, 15.1%). Kras gene was detected with significantly increased levels in plasma of CRC patients at advanced stages. This confirms that liquid biopsy can be used to detect Kras gene in ctDNA of CRC patients through a magnetic bead based technique. Key Words: Liquid biopsy, Circulating tumor DNA, KRAS, Colorectal cancer, Real-time polymerase chain reaction.

Development of an extension of the OMERACT Summary of Measurement Properties table to capture equity considerations: SOMP-Equity

ObjectiveTo develop an equity extension of the OMERACT Summary of Measurement Properties (SOMP) Table, SOMP Equity to describe whether a patient reported outcome measure (PROM) works well among patients of diverse languages and cultures, education levels, and other population characteristics. MethodsWe used the PROGRESS-Plus framework to categorize equity characteristics assessed in trials of PROM. PROGRESS refers to Place of residence, Race/ethnicity/culture/language, Occupation, Gender/sex, Religion, Education, Socioeconomic status, and Social Capital, while the ‘plus’ captures additional characteristics, such as age. We pilot tested our SOMP Equity Extension using the Health Assessment Questionnaire (HAQ) as a prototypical PROM. ResultsThe SOMP Equity Extension retains the same columns as the original OMERACT SOMP (domain match, feasibility, construct validity, test-retest reliability, longitudinal construct validity, clinical trial discrimination, thresholds of meaning) but uses the PROGRESS-Plus characteristics as rows. We found several examples of studies of the HAQ which had assessed one or more PROGRESS-Plus characteristics. ConclusionsThe most commonly reported equity considerations were related to language. OMERACT Equity virtual meeting participants were polled and they indicated that the SOMP Equity Extension is useful for highlighting and tracking equity considerations for OMERACT Core Outcome Measurement Instruments.

Deep Features for Training Support Vector Machines.

Features play a crucial role in computer vision. Initially designed to detect salient elements by means of handcrafted algorithms, features now are often learned using different layers in convolutional neural networks (CNNs). This paper develops a generic computer vision system based on features extracted from trained CNNs. Multiple learned features are combined into a single structure to work on different image classification tasks. The proposed system was derived by testing several approaches for extracting features from the inner layers of CNNs and using them as inputs to support vector machines that are then combined by sum rule. Several dimensionality reduction techniques were tested for reducing the high dimensionality of the inner layers so that they can work with SVMs. The empirically derived generic vision system based on applying a discrete cosine transform (DCT) separately to each channel is shown to significantly boost the performance of standard CNNs across a large and diverse collection of image data sets. In addition, an ensemble of different topologies taking the same DCT approach and combined with global mean thresholding pooling obtained state-of-the-art results on a benchmark image virus data set.

Patient preferences for gene therapy in haemophilia: Results from the PAVING threshold technique survey.

ObjectivesThe aim of the Patient preferences to Assess Value IN Gene therapies (PAVING) study was to investigate trade‐offs that adult Belgian people with haemophilia (PWH) A and B are willing to make when choosing between prophylactic factor replacement therapy (PFRT) and gene therapy.MethodsThe threshold technique was used to quantify the minimum acceptable benefit (MAB) of a switch from PFRT to gene therapy in terms of ‘Annual bleeding rate’ (ABR), ‘Chance to stop prophylaxis’ (STOP), and ‘Quality of life’ (QOL). The design was supported by stakeholder involvement and included an educational tool on gene therapy. Threshold intervals were analysed using interval regression models in Stata 16.ResultsA total of 117 PWH completed the survey. Mean thresholds were identified for all benefits, but substantial preference heterogeneity was observed; especially for the STOP thresholds, where the distribution of preferences was bimodal. Time spent on the educational tool and residence were found to impact MAB thresholds. The most accepted (88% of PWH) gene therapy profile investigated in this study comprised of zero bleeds per year (vs. six for PFRT), 90% chance to stop prophylaxis, no impact on QoL, and 10 years of follow‐up on side effects (vs. 30 for PFRT).ConclusionsResults from this study proved the value of educating patients on novel treatments. Moreover, preference heterogeneity for novel treatments was confirmed in this study. In gene therapy decision‐making, preference heterogeneity and the impact of patient education on acceptance should be considered.

Outcome measurement instrument selection for lung physiology in systemic sclerosis associated interstitial lung disease: A systematic review using the OMERACT filter 2.1 process

ObjectiveThe Outcome Measures in Rheumatology (OMERACT) is a research organization focused on improving health care outcomes for patients with autoimmune and musculoskeletal diseases. The Connective Tissue Disease-Interstitial Lung Disease (CTD-ILD) Working Group on Lung Physiology is a group within OMERACT charged with identifying outcome measures that should be implemented in studies of patients with CTD-ILD. The OMERACT Filter 2.1 is an evidence-based algorithm used to identify outcome measures that are truthful, feasible, and able to discriminate between groups of interest. Our objective was to summate evidence (published literature, key opinion leader input, patient perspectives) that would influence the CTD-ILD Working Group's vote to accept or reject the use of two measures of lung physiology, the forced vital capacity (FVC) and the diffusion capacity of carbon monoxide (DLco) for use in randomized controlled trials (RTCs) and longitudinal observational studies (LOSs) involving patients with systemic sclerosis associated ILD (SSc-ILD). MethodsPatient Research Partners (those afflicted with SSc-ILD) and the CTD-ILD Working Group on Lung Physiology were polled to assess their opinion on the FVC and DLco in terms of feasibility; the CTD-ILD Working Group was also queried on these instruments’ face and content validity. We then conducted a systematic literature review to identify articles in the SSc-ILD population that assessed the following measurement properties of FVC and DLco: (1) construct validity, (2) test-retest reliability, (3) longitudinal construct validity, (4) clinical trial discrimination/sensitivity to detect change in clinical trials, and (5) thresholds of meaning. Results were summarized in a Summary of Measurement Properties (SOMP) table for each instrument. OMERACT CTD-ILD Working Group members discussed and voted on the strength of evidence supporting these two instruments and voted to endorse, provisionally endorse, or not endorse either instrument. ResultsForty Patient Research Partners reported these two measures are feasible (are not an unnecessary burden or represent an infeasible longitudinal assessment of their disease). A majority of the 18 CTD-ILD Working Group members voted that both the FVC and DLco are feasible and have face and content validity. The systematic literature review returned 1,447 non-duplicated articles, of which 177 met eligibility for full text review. Forty-eight studies (13 RCTs, 35 LOSs) were included in the qualitative analysis. The FVC SOMP table revealed high quality, consistent data with evidence of good performance for all five measurement properties, suggesting requisite published evidence to proceed with endorsement. The DLco SOMP table showed a lack of data to support test-retest reliability and inadequate evidence to support clinical trial discrimination. There was unanimous agreement (15 [100%]) among voting CTD-ILD Working Group members to endorse the FVC as an instrument for lung physiology in RCTs and LOSs in SSc-ILD. Based on currently available evidence, DLco did not meet the OMERACT criteria and is not recommended for use in RCTs to represent lung physiology of SSc-ILD. The OMERACT Technical Advisory Group agreed with these decisions. ConclusionThe OMERACT Filter 2.1 was successfully applied to the domain of lung physiology in patients with SSc-ILD. The FVC was endorsed for use in RCTs and LOSs based on the Working Group's vote; DLco was not endorsed.

13. The diagnostic utility of biomarkers: spinal instability or underlying infection

<h3>BACKGROUND CONTEXT</h3> Surgical site infection is a devastating complication of surgery that increases morbidity for patients undergoing spinal surgery. However, diagnosis in some cases remains challenging often requiring a trip to the operating room to obtain cultures. Current literature has provided evidence that preoperative blood markers are diagnostic of infection in patients undergoing hip arthroplasty and total knee replacement, but there has been limited investigation on biomarker diagnostic utility in patients undergoing spinal surgery. <h3>PURPOSE</h3> To identify the diagnostic utility of laboratory markers to diagnose postoperative spinal infection. <h3>STUDY DESIGN/SETTING</h3> Retrospective case-control analysis <h3>PATIENT SAMPLE</h3> Patients having undergone prior spine surgery with a confirmed positive intraoperative culture during revision for presumed infection. An additional aseptic cohort was established with patients undergoing revision surgery for reasons other than infection. <h3>OUTCOME MEASURES</h3> White blood cell (WBC), erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), mean platelet volume (MPV), platelet number, MPV/platelet ratio, diagnostic sensitivity, specificity and threshold values for the diagnosis of spinal infection. <h3>METHODS</h3> A retrospective review was conducted at a single center academic hospital. Patients undergoing spinal fusion with a diagnosis of surgical site infection (SSI) from the dates of 2013 to 2019 were identified. In the aseptic cohort, any individual that had overt signs of infection or had infection within one year of revision procedure was excluded. Patients with a history of cancer, trauma, autoimmune disease on suppressive therapy, or noncompliance with medical therapy were excluded. WBC, ESR, CRP, MPV, MPV/Platelet ratio and demographic data was compared between groups and an AUC analysis was performed to determine threshold values. <h3>RESULTS</h3> A total of 418 patients were included, 224 in the aseptic cohort and 194 in the infection cohort. In terms of baseline demographics, there were significant differences between the cohorts in BMI, CCI, and ASA (p<0.05). BMI in the infection cohort was found to be greater than the aseptic cohort with a mean value of 33.7 vs 30.9 respectively. CCI and ASA was also elevated in the infections cohort as compared to the aseptic cohort with mean values of 3.84 for CCI and 2.90 for ASA as compared to 1.08 and 2.45 in the aseptic cohort. Significant differences were found between the cohorts with respect to MPV/platelet ratios, platelet number, MPV, CRP, ESR and WBC (p<0.01). Platelet ratio, platelet number, CRP, ESR and WBC were all greater in the infection group as compared to the aseptic group (platelet ratio 36.1 vs 24.7, platelet number 347 vs 249, CRP 9.99 vs 4.81, ESR 76.6 vs 46.5, WBC 9.87 vs 7.82 p<0.01) These differences were used to determine predictive cutoffs. The most sensitive markers for predicting postoperative infection were platelet number (cutoff 284 AUC 0.751; sensitivity 0.662) and ESR (cutoff 40.00 AUC 0.715; sensitivity 0.838). The most specific markers for predicting postoperative infection were platelet ratio (cutoff 31.02 AUC 0.758; specificity 0.842) and platelet count (cutoff 284.00 AUC 0.715; specificity 0.804). <h3>CONCLUSIONS</h3> This study concluded that preoperative platelet number and ESR are best used as screening measures, while MPV/platelet ratio and count are useful confirmatory markers. Further analysis will allow for a more depth investigation into optimal combination of biomarkers to result in the greatest diagnostic utility, but this initial report serves as evidence that preoperative biomarker collection may be a valuable tool to confirm the diagnosis in suspected postoperative surgical site infections. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

Effect of malleostapedotomy procedure on 17 cases of congenital middle ear malformation

Objective: To conclude the clinical features and the postoperative efficacy of congenital middle ear malformation treated with Malleostapedotomy (MS), and to explore the security and effectiveness of MS surgery. Methods: The clinical data of 17 patients (18 ears) with congenital middle ear malformation undergoing MS procedure were analyzed. There were 10 males (11 ears) and 7 females (7 ears), aged from 7 to 48 years. The imaging examination, pure-tone audiometry, intraoperative findings and postoperative hearing improvement of these patients were analyzed and summarized, and software SPSS23.0 was used for statistical analysis. Rusults All the 17 patients (18 ears) presented with hearing loss since childhood on the affected sides. Preoperative high resolution CT (HRCT) of the temporal bone revealed definite malformations in 9 ears (6 ears with incus long process dysplasia and 3 ears with anterior and posterior crus dysplasia). Before surgery, the mean bone conductive hearing threshold at 500, 1 000, 2 000 and 4 000 Hz was (15.6±10.2) dB HL, the mean air conductive hearing threshold was (60.6±9.7) dB HL, and the mean air-bone gap was (45.0±8.9) dB. During the surgery, all 18 ears were found to be accompanied by absence or hypoplasia of incus long process. 12 ears had stapes fixation, 6 ears had oval window atresia. All patients were treated with MS procedure by using Piston. The patients were followed up for 3 months to 1 year. The mean bone conductive hearing threshold was (14.7±8.8) dB HL. The mean air conductive hearing threshold was (37.7±11.6) dB HL, and the mean air-bone gap was (23.0±8.0) dB. There were statistically significant differences in the mean air conductive hearing threshold and mean air-bone gap before and after surgery (P<0.05). While there were no statistically significant differences in the mean bone conductive hearing threshold before and after surgery (P=0.550). Conclusions: MS procedure is safe and reliable in patients with congenital middle ear malformation of incus long process dysplasia, stapes fixation or oval window atresia. HRCT is useful in evaluating the major deformity of ossicular chain and facial nerve deformity. However, it is not enough to evaluate the joint of incus-stapes and oval window atresia. MS surgery in middle ear malformation requires advanced surgical experience and skills. The hearing improvement can be significant, even though some air-bone gap after surgery exist.

The effect of coronavirus disease 2019 on the hearing system.

This study aimed to evaluate different auditory regions with audiological tests, based on the presumption that there may be damage to the structures in the hearing system after coronavirus disease 2019. Twenty individuals with no history of coronavirus disease 2019 and 27 individuals diagnosed with coronavirus disease 2019 were compared. Pure tone, speech and extended high-frequency audiometry, acoustic immitansmetry, transient evoked and distortion product otoacoustic emissions testing, and auditory brainstem response testing were conducted. The pure tone audiometry and extended high-frequency mean threshold values were higher in the coronavirus disease 2019 group. The transient evoked otoacoustic emissions signal-to-noise ratios were bilaterally lower at 4 kHz in individuals with a coronavirus disease 2019 history. In the auditory brainstem response test, only the interpeak latencies of waves III-V were significantly different between groups. Coronavirus disease 2019 may cause damage to the hearing system. Patients should be followed up in the long term with advanced audiological evaluation methods in order to determine the extent and level of damage.

Round window versus conventional bony cochleostomy technique in pediatric cochlear implantation; A Randomized controlled double blinded trial.

&lt;p&gt;&lt;strong&gt;Background:&lt;/strong&gt; Objective of the study was to investigate the outcomes of cochlear implantation when done via two different techniques namely, the round window or the bony cochleostomy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods:&lt;/strong&gt; A single-center, double-blinded randomized controlled trial including forty prelingual, bilateral severe to profoundly deaf children less than six years from the year 2014 to 2016 in a tertiary referral center in India were randomly allocated to round window and bony cochleostomy group. Our primary outcome measures were intraoperative neural response telemetry levels, behavioral threshold (t) and comfortable (c) loudness levels. The secondary subjective outcomes were measured via the category of auditory performance (CAP) and the meaningful auditory integration scale (MAIS) score. The cases were followed up for 9 months.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results:&lt;/strong&gt; Intra-operative, electrically evoked compound action potentials (ECAP) showed comparable mean thresholds for both the techniques except intermediate electrodes (p~0.04) showed lower values for the round window. Similarly, a lower threshold (p~0.03) and comfortable mean current levels (p~0.03) were noticed for the round window group at 6 months post-implantation. Secondary speech perception outcome scores measured via category of auditory performance (CAP) and MAIS score were comparable. &lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; The round window insertion technique has physiological benefit as compared to the bony cochleostomy as evidenced by better stimulation levels in the intermediate electrodes and lower mean threshold and comfortable levels in the round window with more beneficial peri-modiolar position of electrode arrays. However, comparable speech perception outcomes revealed no clinical benefit in the cochlear implant performance depending on the technique of electrode insertion. &lt;/p&gt;

Structural and functional findings in patients with moderate diabetic retinopathy

PurposeTo evaluate structural and functional ocular changes in patients with type 2 diabetes mellitus (DM2) and moderate diabetic retinopathy (DR) without apparent diabetic macular edema (DME) assessed by optical coherence tomography (OCT) and microperimetry.MethodsThis was a single-center cross-sectional descriptive study for which 75 healthy controls and 48 DM2 patients with moderate DR were included after applying exclusion criteria (one eye per patient was included). All eyes underwent a complete ophthalmic examination (axial length, macular imaging with swept-source OCT, and MAIA microperimetry). Macular thicknesses, ganglion cell complex (GCC) thicknesses, and central retinal sensitivity were compared between groups, and the relationships between the OCT and microperimetry parameters were evaluated.ResultsMacular thickness was similar in both groups (242.17 ± 35.0 in the DM2 group vs 260.64 ± 73.9 in the control group). There was a diminution in the parafoveal area thickness in the DM2 group in the GCC complex. Retinal sensitivity was reduced in all sectors in the DM2 group. The central global value was 24.01 ± 5.7 in the DM2 group and 27.31 ± 2.7 in the control group (p < 0.001). Macular integrity was 80.89 ± 26.4 vs 64.70 ± 28.3 (p < 0.001) and total mean threshold was 23.90 ± 4.9 vs 26.48 ± 2.6 (p < 0.001) in the DM2 and control group, respectively. Moderate correlations were detected between the central sector of MAIA microperimetry and retina total central thickness (− 0.347; p = 0.0035). Age, visual acuity, and hemoglobin A1c levels also correlated with retinal sensitivity.ConclusionMacular GCC thickness and central retinal sensitivity were reduced in patients with moderate DR without DME, suggesting the presence of macular neurodegeneration.

Temporal processing, spectral processing, and speech perception in noise abilities among individuals with chronic kidney disease undergoing hemodialysis

Background In the literature, the effect of chronic kidney disease on the peripheral auditory system has been well documented. But studies investigating the effect of chronic kidney disease on speech perception and auditory processing abilities are limited. Aims/objectives The present study investigated the effect of chronic kidney disease on different auditory processing tasks and speech perception in noise among adults. Material and methods A total of 28 adults participated in the study. Group 1 included 14 individuals with chronic kidney disease undergoing hemodialysis, and Group 2 included 14 individuals with no known kidney complications. Amplitude modulation detection threshold, gap detection threshold, spectral ripple discrimination threshold, and speech recognition threshold in noise were measured. Independent samples t-test was carried out to investigate whether mean thresholds are significantly different between groups. Results Results showed poorer gap detection threshold, amplitude modulation detection threshold, spectral ripple discrimination threshold, and speech recognition threshold in noise among individuals with chronic kidney disease compared to individuals with no known kidney complications. Conclusions The present study showed poorer auditory processing and speech perception abilities in individuals with chronic kidney disease.

Local Cisplatin Delivery in Mouse Reliably Models Sensorineural Ototoxicity Without Systemic Adverse Effects.

Cisplatin is a lifesaving chemotherapeutic drug with marked ototoxic adverse effects. Cisplatin-induced hearing loss affects a significant part of cancer-surviving patients and is an unmet clinical need with important socioeconomic consequences. Unfortunately, in current preclinical animal models of cisplatin ototoxicity, which are mainly based on systemic delivery, important morbidity is observed, leading to premature death. This methodology not only raises obvious animal welfare concerns but also increases the number of animals used in ototoxicity studies to compensate for dropouts related to early death. To overcome these important limitations, we developed a local delivery model based on the application of a cisplatin solution directly into the otic bulla through a retroauricular approach. The local delivery model reliably induced significant hearing loss with a mean threshold shift ranging from 10 to 30 dB, strongly affecting the high frequencies (22 and 32 kHz). Importantly, mice did not show visible stress or distress indicators and no significant morbidity in comparison with a traditional systemic delivery control group of mice injected intraperitoneally with 10 mg/kg cisplatin, where significant weight loss >10% in all treated animals (without any recovery) led to premature abortion of experiments on day 3. Mass spectrometry confirmed the absence of relevant systemic uptake after local delivery, with platinum accumulation restricted to the cochlea, whereas important platinum concentrations were detected in the liver and kidney of the systemic cisplatin group. A clear correlation between the cochlear platinum concentration and the auditory threshold shift was observed. Immunohistochemistry revealed statistically significant loss of outer hair cells in the basal and apical turns of the cochlea and an important and statistically significant loss of auditory neurons and synapses in all cochlear regions. In conclusion, local cisplatin delivery induces robust hearing loss with minimal morbidity, thereby offering a reliable rodent model for human cisplatin ototoxicity, reducing the number of animals required and showing improved animal welfare compared with traditional systemic models.

Does respiratory variation in inferior vena cava diameter predict fluid responsiveness in adult patients? A systematic review and meta-analysis of diagnostic accuracy studies

Objectives: To systematically review the diagnostic utility of the respiratory variation of the inferior vena cava diameter measured using ultrasonography for predicting fluid responsiveness in adult patients and compare the three commonly used equations, inferior vena cava distensibility, inferior vena cava collapsibility and inferior vena cava variability. Methods: We searched PubMed, Scopus, Web of Science and Cochrane library, and included studies investigating the diagnostic accuracy of the respiratory variation of the inferior vena cava measured using ultrasonography compared to a reference standard for measuring cardiac output after a fluid challenge for fluid responsiveness, and stratified participants as fluid responsive or not. We included studies conducted in the emergency department or intensive care unit. We excluded studies on paediatric, prehospital, cancer, pregnant, dialysis patients or healthy volunteers. Results: We retrieved 270 records and excluded 171 because of irrelevance, patient population or publication type. We screened the abstracts of 99 studies and then the full texts of 42 studies. Overall, 21 studies with 1321 patients were included, of whom 689 (52%) were fluid responsive. The mean threshold value for positive inferior vena cava distensibility, inferior vena cava collapsibility and inferior vena cava variability was 17%, 35% and 12%, respectively. The heterogeneity between studies was high. Bivariate diagnostic random-effects meta-analysis was used to calculate the summary receiver operating characteristics curves. The overall accuracy, sensitivity and specificity of respiratory variation of the inferior vena cava diameter were 0.85, 0.72 and 0.81, respectively. The accuracy of inferior vena cava distensibility and inferior vena cava collapsibility was similar. The diagnostic utility of respiratory variation of the inferior vena cava diameter was lower but not statistically significant in mechanically ventilated patients compared with spontaneous breathing for predicting fluid responsiveness. Conclusion: The respiratory variation of the inferior vena cava diameter has moderate diagnostic utility for predicting fluid responsiveness independent of the equation used.

The Development of Spondee Word in Garhwali Language

Background: Garhwali is spoken by people in Uttarkashi, Chamoli, Tehri Garhwal, Pauri Garhwal, Dehradun, Rudraprayag, and Haridwar districts of Uttarakhand, India. Aims and Objectives: The present study focused on the development of spondee words in Garhwali language. Materials and Methods: The final spondee word list included 50 words. A total of 30 adults were participated in the present study. The test started with obtaining thresholds of AC and BC between the frequencies 250 and 8 KHz of the individual. Results: The mean pure tone average for frequencies 500 Hz, 1 KHz, 2 KHz, and 4 KHz was 10.46 dBHL, then the spondee word list was presented at the level of 20 dBSL. The speech recognition threshold (SRT) mean threshold was 11 dBHL. Conclusion: This study provided evidence on the quality of being especially suitable for paired words for testing SRT in Garhwali people. This test material can be used in selecting appropriate rehabilitative options and also to measure the efficacy of different rehabilitative devices.