Holm-Bonferroni Correction Research Articles

Tiktok as a Source of Education and Misinformation in Lichen Sclerosus.

The purpose of this study is to evaluate the content, delivery, and quality of medical information for vulvar lichen sclerosus on the social media platform TikTok. This is a descriptive, cross-sectional study. Using the third-party data scraping tool Apify, TikTok videos tagged with #lichensclerosus or "lichen sclerosus" were identified and sorted by view count. A sample of 100 videos was reviewed by 2 independent reviewers, excluding those not discussing lichen sclerosus. Videos were assessed using a coding document, the Patient Educational Materials Assessment Tool, and the DISCERN instrument. Interrater reliability was measured, and statistical analyses included Fleiss' kappa, intraclass correlation coefficient, t tests, and Wilcoxon rank sum test with Holm-Bonferroni correction. Content creators included patients (46%), health care professionals (30%), and others. Topics focused on clinical disease (52%) and treatment (48%). Evidence-based medicine was discussed in 71.7% of treatment-related videos, while 51.7% included nonevidence-based approaches, with a neutral or positive sentiment. Videos discussing topical steroids often had negative sentiments. Quality assessment revealed 61% of videos were understandable, 27% actionable, and 46% contained misinformation. Videos by health care professionals had less misinformation and higher quality scores compared to patient-generated content. Commercially biased videos were more understandable but contained more misinformation. TikTok serves as a significant platform for sharing information on lichen sclerosus, but nearly half of the content contains misinformation. Health care professionals need to engage in social media to provide accurate information and counteract misinformation. Enhanced collaboration with patient advocates and careful resource sharing can improve the quality and reliability of medical information available online.

Beyond nest size: the clinicopathological spectrum of large nested melanocytic tumours and the value of comparative genomic hybridisation and messenger RNA expression analysis

Large nested melanomas (LNMs) are a rare subtype of naevoid melanoma consisting of large junctional melanocytic nests that are more common in older individuals and/or associated with sun damage. However, the presence of large melanocytic nests alone does not lead to a diagnosis of malignancy, ​as they can also be found in melanocytic naevi. LNMs are challenging because they lack most classic histological features of malignancy and require thorough clinicopathological evaluation. This ambiguity calls for a critical reassessment of the current diagnostic criteria for the subclassification of benign or malignant within the spectrum of large nested melanocytic tumours (LNMTs). Eighteen LNMTs and six special-site melanocytic naevi (SSMNs) ​were studied using different approaches: clinical features, dermoscopy, histopathology, immunohistochemistry, array comparative genomic hybridisation (aCGH) and messenger RNA (mRNA) sequencing analysis, with the aim of identifying novel and reproducible criteria for the recognition of LNMs.Careful clinicopathological evaluation of the 18 LNMTs led to the diagnosis of seven LNMs and 11 large nested melanocytic naevi (LNMNs). Lentiginous spread and nest bridging were significantly associated with LNMs after Holm–Bonferroni correction. Asymmetry, largest nest size, poor lateral demarcation, the number of colours and dermoscopic structures, and preferentially expressed antigen in melanoma (PRAME) immunostaining were more common in LNMs but did not reach statistical significance. Four of seven LNMs and nine of 11 LNMNs lacked the BRAF V600E mutation. Regarding aCGH, no LNMN or SSMN cases had ≥3 copy number variations (CNVs), in contrast to 50% of LNM cases. Importantly, LNM and LNMN could be distinguished by differential mRNA expression of nine genes. Our study demonstrates that there is a spectrum of LNMTs and that the clinicopathological diagnosis of LNM, for which we support the term ‘late-onset nested naevoid melanomas’, can be significantly strengthened by the presence of lentiginous pattern, nest bridging, gene CNV and differential mRNA expression.

Alterations in Gray Matter Structural Networks in Amnestic Mild Cognitive Impairment: A Source-Based Morphometry Study.

Amnestic mild cognitive impairment (aMCI), considered as the prodromal stage of Alzheimer's disease, is characterized by isolated memory impairment and cerebral gray matter volume (GMV) alterations. Previous structural MRI studies in aMCI have been mainly based on univariate statistics using voxel-based morphometry. We investigated structural network differences between aMCI patients and cognitively normal older adults by using source-based morphometry, a multivariate approach that considers the relationship between voxels of various parts of the brain. Ninety-one aMCI patients and 80 cognitively normal controls underwent structural MRI and neuropsychological assessment. Spatially independent components (ICs) that covaried between participants were estimated and a multivariate analysis of covariance was performed with ICs as dependent variables, diagnosis as independent variable, and age, sex, education level, and site as covariates. aMCI patients exhibited reduced GMV in the precentral, temporo-cerebellar, frontal, and temporal network, and increased GMV in the left superior parietal network compared to controls (pFWER < 0.05, Holm-Bonferroni correction). Moreover, we found that diagnosis, more specifically aMCI, moderated the positive relationship between occipital network and Mini-Mental State Examination scores (pFWER < 0.05, Holm-Bonferroni correction). Our results showed GMV alterations in temporo-fronto-parieto-cerebellar networks in aMCI, extending previous results obtained with univariate approaches.

Adherence to integrated management of childhood illness (IMCI) guidelines by community health workers in Kano State, Nigeria through use of a clinical decision support (CDS) platform

BackgroundThe World Health Organization (WHO) Integrated Management of Childhood Illness (IMCI) guidelines established in 1992 to decrease preventable under-five child morbidity and mortality, was adopted by Nigeria in 1997. Over 20 years later, while under-five child mortality remains high, less than 25% of first level facilities have trained 60% of community health workers (CHW) who care for sick children with IMCI. This study investigated the impact in CHWs overall adherence to IMCI guidelines, particularly for critical danger signs, as well as usability and feasible following the implementation of THINKMD’s IMCI-based digital clinical decision support (CDS) platform.MethodsAdherence to IMCI guidelines was assessed by observational and digital data acquisition of key IMCI clinical data points by 28 CHWs, prior, during, and post CDS platform implementation. Change in IMCI adherence was determined for individual CHW and for the cohort by analyzing the number of IMCI data points acquired by each CHW per clinical evaluation. Consistency of adherence was also calculated by averaging the percentage of total evaluations each data point was observed. Usability and acceptability surveys were administered following use of the CDS platform.ResultsTHINKMD CDS platform implementation notably enhanced the CHWs’ ability to capture key IMCI clinical data elements. We observed a significant increase in the mean percentage of data points captured between the baseline period and during the CDS technology implementation (T-test, t = -31.399, p < 0.016, Holm-Bonferroni correction, two-sided), with the mean values going from 30.7% to 72.4%. Notably, even after the completion of the technology implementation phase, the mean percentage of IMCI elements captured by CHWs remained significantly elevated compared to the baseline, with a 26.72 percentage point increase (from 30.7% to 57.4%, T-test, t = -15.779, p < 0.05, Holm-Bonferroni correction, two-sided). Usability and feasibility of the platform was high. CHWs reported that the CDS platform was easy to learn and use (93%) and enabled them to identify sick children (100%).ConclusionThese results demonstrate that utilization of a digital clinical decision support tool such as THINKMD’s IMCI based CDS platform can significantly increase CHW adherence to IMCI guidelines over paper-based utilization, increase clinical quality and capacity, and improve identification of key danger signs for under-five children while being highly accepted and adopted.

EEG correlates to perceived urgency elicited by vibration stimulation of the upper body

Conveying information effectively while minimizing user distraction is critical to human–computer interaction. As the proliferation of audio–visual communication pushes human information processing capabilities to the limit, researchers are turning their attention to haptic interfaces. Haptic feedback has the potential to create a desirable sense of urgency that allows users to selectively focus on events/tasks or process presented information with minimal distraction or annoyance. There is a growing interest in understanding the neural mechanisms associated with haptic stimulation. In this study, we aim to investigate the EEG correlates associated with the perceived urgency elicited by vibration stimuli on the upper body using a haptic vest. A total of 31 participants enrolled in this experiment and were exposed to three conditions: no vibration pattern (NVP), urgent vibration pattern (UVP), and very urgent vibration pattern (VUVP). Through self-reporting, participants confirmed that the vibration patterns elicited significantly different levels of perceived urgency (Friedman test, Holm–Bonferroni correction, p < 0.01). Furthermore, neural analysis revealed that the power spectral density of the delta, theta, and alpha frequency bands in the middle central area (C1, Cz, and C2) significantly increased for the UVP and VUVP conditions as compared to the NVP condition (One-way ANOVA test, Holm–Bonferroni correction, p < 0.01). While the perceptual experience of haptic-induced urgency is well studied with self-reporting and behavioral evidence, this is the first effort to evaluate the neural correlates to haptic-induced urgency using EEG. Further research is warranted to identify unique correlates to the cognitive processes associated with urgency from sensory feedback correlates.

Perivascular Adipose Tissue Density and Stenosis Plaque Degree in Lower Limb Peripheral Arteries in CT

Background: Perivascular adipose tissue (PVAT) attenuation has emerged as a novel biomarker for identifying high-risk arterial plaques due to its association with inflammation. Recognizing the systemic nature of atherosclerosis and its link with major cardiovascular events in coronary disease, this study evaluated PVAT attenuation in the peripheral arteries using CT imaging to expand the understanding of its diagnostic and prognostic potential. Methods: a retrospective analysis of 53 consecutive patients who underwent CT angiography, examining PVAT density across five primary peripheral arterial segments. A 5 mm region of interest adjacent to the vascular wall was analyzed by two blinded readers, with reproducibility coefficients calculated to determine the reliability of the measurements. For the statistical analyses, mean values were derived from these measurements. The patients were stratified into four groups based on the degree of arterial stenosis: &lt;25%, 25–50%, 50–70%, and &gt;70%. PVAT density comparisons between these groups were performed using the Kruskal–Wallis test and the pairwise Mann–Whitney U test with Holm–Bonferroni correction for multiple comparisons. Results: the Kruskal–Wallis test revealed statistically significant disparities in PVAT density across the categorically differentiated stenosis groups (p &lt; 0.001), indicating an association between PVAT density and arterial stenosis severity. This association was especially pronounced in the external iliac, common femoral, superficial femoral, and popliteal arteries, where the p-values were consistently below 0.05. Subsequent pairwise analyses utilizing the Mann–Whitney U test with Holm–Bonferroni correction affirmed these findings, in particular for the external iliac, common femoral, superficial femoral and popliteal arteries (p &lt; 0.05). Conclusions: our findings reinforce the correlation between increased PVAT density and the degree of arterial stenosis, supporting the clinical value of PVAT as a non-invasive biomarker for cardiovascular risk stratification and potentially guiding therapeutic interventions.

Aberration correction by polynomial approximation for synthetic aperture ultrasound imaging

AbstractBackgroundPreviously, there has been some work in the field of optical imaging on phase compensation by employing Legendre polynomials as an expansion of the phase function, and this seems to be an appealing unstudied area in the field of ultrasound imaging.PurposeThe paper is devoted to solving one of the problems of enhancing the authenticity of diagnostics data obtained in ultrasound visualization systems and presents a novel approach to aberration correction, which ensures a reliable eliminating of phase distortions. The novelty of the proposed approach consists in the use of the decomposition of the wave front by Legendre polynomials to approximate aberrations of the phase front of ultrasonic waves propagating through distorting layers.MethodsThe phase aberrations are corrected using a single sector probe that captures echoes in synthetic aperture mode. The proposed method approximates the changes in the wave front by means of the Legendre polynomials. The performance was investigated by placing a 13‐mm‐wide ultrasonic probe with 64 elements operating at 2 MHz on the surface of a commercial quality control phantom ATS Model 539 through a distorting layer. The following metrics were measured: peak value, root mean square (RMS), full width at half maximum (FWHM), contrast‐to‐noise ratio (CNR). During the experiments, three different aberrators were used interchangeably as distorting layers, two of which were made of photopolymer resin with RMS values of 39 and 97 ns and a speed of sound close to that of a human temporal bone tissue, and the third was an ex vivo human temporal bone with the RMS value of 44 ns. To test the correction, three regions inside the phantom were examined. Two‐sided nonparametric Wilcoxon rank‐sum test was used for assessing the statistical significance. The significance level for this study was set at α ≤ 0.05. To counteract the problem of multiple comparisons, the p‐values were adjusted by the Holm–Bonferroni correction method.ResultsThe statistically significant results have demonstrated the possibility of increasing peak intensity value up to 3.08 times, reducing the RMS width and FWHM of the intensity angular distribution down to 60% and 82%, respectively, and increasing CNR up to 2.12 times by using the proposed phase distortion correction method, compared with the case without correction. The results show that the method can be used as an effective aberration correction technique for all tested regions inside the phantom and distorting layers. Its usage allowed correcting up to 97% of the aberrations caused by the ex vivo temporal bone model.ConclusionThe results show that the usage of the proposed method for aberration correction can successfully increase the intensity and reduce the angular width of the ultrasound wave scattered by the point targets inside the phantoms. The method works with different distorting layers and is capable of correcting phase aberrations in multiple sections of the sonogram. The limitation of the proposed method consists in the fact that it requires the use of aperture synthesis and access to raw radiofrequency data, which restricts its application in common scanners.

Image quality and metal artifact reduction in total hip arthroplasty CT: deep learning-based algorithm versus virtual monoenergetic imaging and orthopedic metal artifact reduction

BackgroundTo compare image quality, metal artifacts, and diagnostic confidence of conventional computed tomography (CT) images of unilateral total hip arthroplasty patients (THA) with deep learning-based metal artifact reduction (DL-MAR) to conventional CT and 130-keV monoenergetic images with and without orthopedic metal artifact reduction (O-MAR).MethodsConventional CT and 130-keV monoenergetic images with and without O-MAR and DL-MAR images of 28 unilateral THA patients were reconstructed. Image quality, metal artifacts, and diagnostic confidence in bone, pelvic organs, and soft tissue adjacent to the prosthesis were jointly scored by two experienced musculoskeletal radiologists. Contrast-to-noise ratios (CNR) between bladder and fat and muscle and fat were measured. Wilcoxon signed-rank tests with Holm-Bonferroni correction were used.ResultsSignificantly higher image quality, higher diagnostic confidence, and less severe metal artifacts were observed on DL-MAR and images with O-MAR compared to images without O-MAR (p < 0.001 for all comparisons). Higher image quality, higher diagnostic confidence for bone and soft tissue adjacent to the prosthesis, and less severe metal artifacts were observed on DL-MAR when compared to conventional images and 130-keV monoenergetic images with O-MAR (p ≤ 0.014). CNRs were higher for DL-MAR and images with O-MAR compared to images without O-MAR (p < 0.001). Higher CNRs were observed on DL-MAR images compared to conventional images and 130-keV monoenergetic images with O-MAR (p ≤ 0.010).ConclusionsDL-MAR showed higher image quality, diagnostic confidence, and superior metal artifact reduction compared to conventional CT images and 130-keV monoenergetic images with and without O-MAR in unilateral THA patients.Relevance statementDL-MAR resulted into improved image quality, stronger reduction of metal artifacts, and improved diagnostic confidence compared to conventional and virtual monoenergetic images with and without metal artifact reduction, bringing DL-based metal artifact reduction closer to clinical application.Key points• Metal artifacts introduced by total hip arthroplasty hamper radiologic assessment on CT.• A deep-learning algorithm (DL-MAR) was compared to dual-layer CT images with O-MAR.• DL-MAR showed best image quality and diagnostic confidence.• Highest contrast-to-noise ratios were observed on the DL-MAR images.Graphical

Refining first-line treatment decision in RAS wildtype (RAS-WT) metastatic colorectal cancer (mCRC) by combining clinical biomarkers: Results of the randomized phase 3 trial FIRE-3 (AIO KRK0306).

13 Background: Optimal patient selection for first-line treatment targeting epithelial growth factor receptor (EGFR) in RAS-WT mCRC is based on primary tumor sidedness (PTS) with anti-EGFR being the preferred option for patients with left-sided mCRC (LC). Right-sided mCRCs (RC) are preferentially treated in combination with bevacizumab targeting vascular endothelial growth factor (VEGF). Here, improvement in patient selection was evaluated by combining clinical biomarkers beyond PTS using the randomized phase III trial FIRE-3. Methods: FIRE-3 evaluated first-line FOLFIRI (folinic acid, fluorouracil and irinotecan) plus cetuximab (FOLFIRI/Cet) versus FOLFIRI plus bevacizumab (FOLFIRI/Bev) in patients with RAS-WT mCRC. Besides PTS, further clinical biomarkers were evaluated in pairwise combinations using Cox regression models and model-based recursive partitioning with Weibull models to predict treatment benefit of either treatment arm regarding overall survival (OS): age, sex, liver-limited disease status (LLD) and baseline carcinoembryonic antigen serum level (CEA). The resulting P-values of second-order interactions were adjusted using Holm-Bonferroni correction. The model with the best test statistics and P-value was chosen for further evaluations. Results: In 400 patients with RAS-WT mCRC, a model combining PTS and LLD status best predicted treatment outcome of either treatment arm (c-index = 0.603, p=0.005). Here, a significant survival benefit of FOLFIRI/Cet over FOLFIRI/Bev was evident in patients with LC/non-LLD (HR 0.62, p=0.02) compared to LC/LLD (HR 0.83, p=0.40). In patients with RC, FOLFIRI/Bev was significantly associated with increased OS compared to FOLFIRI/Cet when patients suffered from non-LLD (HR 2.09, p=0.010). However, patients with RC/LLD rather had a benefit from FOLFIRI/Cet compared to FOLFIRI/Bev (HR 0.59, p=0.218). Conclusions: Combining clinical biomarkers PTS and LLD status might improve optimal patient selection for targeted first-line treatment in RAS-WT mCRC. Validation in further data sets is warranted. Clinical trial information: NCT00433927 .

Ophthalmic and Systemic Factors of Acute Nonarteritic Anterior Ischemic Optic Neuropathy in the Quark207 Treatment Trial

PurposeWe describe the baseline ophthalmic and cardiovascular (CV) risk factors, reported as associated with NAION, across countries, race and sex for the Quark207 treatment trial for acute NAION. DesignProspective randomized control clinical trial ParticipantsAdults age 50-80 years old with acute NAION recruited from 80 sites across 8 countries, 191 of whom were controls.Main measuresOphthalmic features of NAION and CV risk factors MethodsWe evaluated demographics, clinical and ophthalmological data including best-corrected visual acuity (BCVA) and average visual field total deviation (TD) in affected eyes and cup:disc ratio in fellow eyes at enrollment. We report the prevalence (median and interquartile Q1, Q3) of ophthalmic features and CV risk factors, stratified by country, race, and sex. We corrected for multiple comparisons using Dunn’s test with Bonferroni correction for continuous variables and Chi-square testing with Holm-Bonferroni correction for categorical variables. ResultsThe study enrolled 500 males and 229 females, median age 60 and 61 (p=0.027) years, respectively. Participants were predominantly White (570) and Asian (149). The study eye BCVA was 71 (53, 84) characters (approximately logMAR score 0.4), and the TD for stimulus III was -16.5 dB (-22.2, -12.6) and -15.7 dB (-20.8, -10.9) for stimulus V. The vertical and horizontal cup:disc ratio was 0.1 (0.1, 0.3) for unaffected fellow eyes. The prevalence of CV risk factors varied among countries. The most notable differences were in the baseline comorbidities and ophthalmological features, which differed between the Asian and White races. Males and females differed with respect to a few clinically meaningful features. ConclusionsThe CV risk factors in our NAION cohort varied among the seven countries, race and sex but were not typically more prevalent than previously reported in the general population. Ophthalmic features, typical of NAION, were generally consistent across countries, race and sex, except for worse BCVA and TD in China. Men have a frequency of NAION twice women. Having a small cup:disc ratio in the fellow eye was the most prevalent and consistent risk factor across all demographics. This study suggests that other factors, not yet identified, may contribute to the development of NAION.

Neural correlates of thermal stimulation during active touch.

Thermal feedback technologies have been explored in human-computer interaction to provide secondary information and enhance the overall user experience. Unlike fast-response haptic modalities such as vibration and force feedback, the human brain's processes associated with thermal feedback are not fully understood. In this study, we utilize electroencephalography (EEG) brain imaging to systematically examine the neural correlates associated with a wide range of thermal stimuli, including 9, 15, 32, and 42°C, during active touch at the fingertip. A custom experimental setup is developed to provide thermal stimulation at the desirable temperature levels. A total of 30 participants are recruited to experience the four levels of thermal stimulation by actively touching a thermal stimulation unit with the index finger while recording brain activities via EEG. Time-frequency analysis and power spectral density (PSD) of the EEG data are utilized to analyze the delta, theta, alpha, beta, and gamma frequency bands. The results show that the delta, theta, and alpha PSDs of 9 and 15°C stimuli are significantly higher than the PSDs of 32 and 42°C in the right frontal area during the early stage of the stimulation, from 282 ms up to 1,108 ms (One-way ANOVA test, Holm-Bonferroni correction, p < 0.05). No significant differences in PSDs are found between 9 and 15°C thermal stimuli or between 32 and 42°C thermal stimuli. The findings of this study inform the development of thermal feedback system in human-computer interaction.

P153: The CIMA-Q and CompAS cohort studies on factors associated with Alzheimer's disease (AD): Exploring sociodemographic, health and neuropsychological profile of Subjective Cognitive Decline (SCD) participants from two culturally differentiated samples.

Objective:To explore commonalities and differences in the sociodemographic, health, and neuropsychological characteristics of participants with SCD recruited in two culturally differentiated cohort studies, namely CIMA-Q (Canada; Bellevile et al., 2019) and CompAS (Spain; Juncos et al., 2012).Methods:Older adults with subjective cognitive complaints of the CompAS (N=251; 68.92% women; Control: 30.3%; SCD: 25.9%; MCI: 28.7%) and the CIMA-Q (N=179; 71.5% women; Control:16.1%; SCD: 36.8%; MCI:28.6%) were recruited, respectively, from primary care centers and memory clinics, excluding patients with dementia and other neurological or psychiatric disturbances. Cognitive complaints were assessed considering coincident items of the QAM and MFE questionnaires. Cut-off points for the 5%ile were calculated independently in both samples and according to this, participants were classified as SCD or controls (CompAS: N= 141; CIMA-Q: N=161) considering complaints relevance at baseline (Pereiro et al., 2021). Participants underwent neuropsychological assessment. Participants diagnosed as Mild Cognitive Impairment (MCI) were excluded from the analysis. Between cohort-studies and inter-group (control, SCD) differences were tested in the sociodemographic, health and neuropsychological measures considered. The Holm-Bonferroni correction was applied to reduce the probability of type I error (p&lt;.003).Results:Identical cut-off points for 5%ile were obtained in both samples though SCD prevalence was slightly higher in CIMA-Q. For both samples, equivalence between Control and SCD participants in sociodemographic, health, functionality, and neuropsychological measures was observed. Only complaints and depressive symptomatology was significantly higher in SCD participants than in controls in both CompAS and CIMA-Q studies.Participants of the CIMA-Q, Controls and SCD, showed significantly higher age, cognitive reserve proxies, comorbidity, and better attentional performance than the CompAS participants (see Table 1). CompAS participants, Controls and SCD, showed more neuropsychiatric symptomatology than CIMA-Q participants (see Table 1).Conclusions:Control and SCD participants showed equivalence on sociodemographic, health, functional, and neuropsychological measures in both studies. However, significant between-sample differences in the two groups, particularly in SCD participants, were observed in sociodemographic, health, cognitive reserve, behavioral and attentional measures. Identification of these factors are critical to analyze the transcultural validity of cognitive complaints in predicting progression to AD.Table 1Between group (control, SCD) and Between study (CIMA-Q, CompAS) differences in sociodemographic, health, and cognitive measuresCIMA-QCompASBetween-studies differencesBetween-group differencesBetween-group differencesControlSCDSociodemographicsAgeNSNSCIMA-Q&gt;CompAS; F(1,124)=22.78; p&lt;.001CIMA-Q&gt;CompAS; F(1,172)=36.97; p&lt;.001GenderNSNSNSNSSchooling (years)NSNSNSCIMA-Q&gt;CompAS; F(1,172)=20.74; p&lt;.001Prof. qualificationNSNSCIMA-Q&gt;CompAS; χ24=18.18; p=001CIMA-Q&gt;CompAS; χ24=33.95; p&lt;001Cognitive reserve (quartiles)NSNSCIMA-Q&gt;CompAS; χ23=13.57; p=004CIMA-Q&gt;CompAS;χ23==42.56; p&lt;001Memory familiar antecedentsNSNSNSCIMA-Q&gt;CompAS; χ21==15.03; p&lt;001NeuropsychologySubjective complaints*SCD&gt;Control; F(1,119)=147.17, p&lt;.001)SCD&gt;Control; F(1,177)=192.87, p&lt;.001NSNSCharlson Index*SCD&gt;Control; F(1,115)=5.29, p=.023NSCIMA-Q&gt;CompAS; F(1,123)=394.96; p&lt;.001CIMA-Q&gt;CompAS; F(1,168)=335.98; p&lt;.001General cognitionNS (MoCA)NS (CAMCOG-R)----GDS-15*SCD&gt;Control; F(1,119)=8.60, p=.004SCD&gt;Control; F(1,176)=11.97, p&lt;.001NSNSTMT-A (secs.)*NSNSNSNSTMT-B (secs.)*NSNSCompAS&gt;CIMA-Q; F(1,118)=12.56; p&lt;.001CompAS&gt;CIMA-Q; F(1,163)=21.74; p&lt;.001Verbal fluencyNSNSNSNSSemantic fluencyNSNSNSNSBoston testNSNSNSNSNPI-QNSNSCompAS&gt;CIMA-Q; F(1,119)=16.68; p&lt;.001CompAS&gt; CIMA-Q; F(1,162)=24.46; p&lt;.001Immediate recall (RAVL test)NSNSNSNSShort delay (RAVL test)NSNSNSNSLong delay(RAVL test)NSNSNSNSIntrusions (RAVL test)NSNSNSNSIAVD*NSNSNSNSNote: *On these measures, higher scores denote worse cognition or health condition. TMT: Trail Making Test (A and B forms); NPI-Q: Neuropsychiatric Inventory-Questionnaire; RAVL: Rey Auditory Verbal Learning; IAVD: Instrumental Activity of Daily Living.

A Novel Scoring System Using Geriatric Nutritional Risk Index, C-Reactive Protein, and Disease Status Predicts Survival after Second Allogeneic Stem Cell Transplantation

Introduction: Second allogeneic stem cell transplantation (SCT2) is generally associated with poorer overall survival (OS) and non-relapse mortality (NRM) than first SCT (SCT1). However, some patients survive long after SCT2, and the number of SCT2 cases increases yearly. Thus, a prognostic stratification system is required to select optimally eligible patients for SCT2. We have previously shown that the geriatric nutritional risk index (GNRI) predicts OS and NRM for SCT2 (Ann Haematol. 2020;99:1655). In this study, using a multicenter database, we aimed to validate the importance of the GNRI and establish a scoring system that can more accurately stratify the prognosis after SCT2. Methods: We retrospectively analyzed patients with hematopoietic malignancies who underwent SCT2 between 2004 and 2020 at transplant centers of the Kanto Study Group for Cell Therapy (KSGCT), using the KSGCT database. The primary endpoint was 3-year OS. The secondary endpoints were disease-free survival (DFS), NRM, and cumulative incidence of relapse (CIR). The GNRI was defined as 1.489×albumin(g/L) + 41.7×(weight/ideal weight) (Am J Clin Nutr. 2005;82:777). We chose a GNRI cutoff value of 92.0 according to our previous report. We defined acute leukemia and malignant lymphoma in the first or second complete remission, CML in the 1st or 2nd chronic phase, and MDS with refractory anemia as standard risk, and other malignant diseases as high risk. Results: Among 722 patients who underwent SCT2, we were able to calculate the GNRI and perform a detailed analysis for 376. The median patient age was 44 years (range: 16-69). The underlying diseases were AML (n=207, 55.1%), ALL/LBL (n=107, 28.5%), MDS (n=33, 8.8%), CML (n=11, 2.9%), and other (n=18, 4.8%). The median follow-up period for survivors was 1375 days (range: 223-4213). Three years after SCT2, the OS, DFS, NRM, and CIR were 26.6%, 21.7%, 40.4%, and 37.9%, respectively. Based on previous research, we divided patients into two groups: low GNRI ( ≤92) (n=162, 43.1%) and high GNRI (&amp;gt;92) (n=214, 56.9%). In the low GNRI group, OS was better, NRM was lower, and CIR was comparable to that in the high GNRI group (3y-OS 36.0% vs. 14.3%, p&amp;lt;0.001; 3y-NRM 29.5% vs. 55.2%, p&amp;lt;0.001; 3y-CIR 33.4% vs. 41.3%, p=0.146). Through univariate analysis and stepwise multivariate regressions on the dependent variables for OS, low GNRI (hazard ratio [HR] 1.39, 95%CI 1.05-1.85, p=0.024), high C-reactive protein (CRP) (&amp;gt;0.5 mg/dl; HR 1.96, 95%CI 1.16-2.63, p&amp;lt;0.001), and disease status at SCT2 (HR 1.54, 95%CI 1.16-2.04, p=0.003) were associated with poor OS. Likewise, low GNRI (HR 1.71, 95%CI 1.18-2.47, p=0.0045), high CRP (HR 1.69, 95%CI 1.20-2.38, p=0.0029), high HCT-CI (≥3) (HR 1.58, 95%CI 1.12-2.23, p=0.0092) were unfavorable factors for NRM, while the shorter interval from SCT1 to SCT2 (HR 1.53, 95%CI 1.10-2.13 p=0.011) and high-risk disease status at SCT2 (HR 1.62, 95%CI 1.16-2.27, p=0.0046) were associated with high CIR. To predict OS after SCT2, we developed a scoring system consisting of three factors: low GNRI, high CRP level, and high-risk disease status. As the HRs for OS were comparable, a score of 1 was assigned to each factor. OS at 3 years was 50.7%, 29.5%, and 11.1% for patients with low (score 0, n=89), intermediate (score 1, n=106), and high (scores 2 and 3, n=174), respectively (p&amp;lt;0.001, Fig 1). Differences between groups were revealed using the Holm-Bonferroni correction. Conclusion: Low GNRI, high CRP level, and high-risk disease status were significantly associated with inferior OS after SCT2. The scoring system with these factors stratified the entire cohort into three risk groups including low risk with over 50% OS, and high risk with a very limited chance of survival.

Comparison of prevalence and mental health problems across symptom frequency of self-reported symptoms of binge-eating disorder in a community sample of adolescents.

Binge-eating disorder (BED) and subthreshold BED (SBED) are prevalent in adults and associated with mental health problems including depression, non-suicidal self-injury, lower quality of life, and suicidality. There is solid evidence that binge-eating behaviors are also prevalent in adolescence, but knowledge about mental health in community adolescents with BED of different frequency thresholds is more limited. We aimed to investigate the prevalence and mental health problems associated with SBED of low frequency and/or limited duration compared with BED in a Danish community sample of adolescents. We included 2509 adolescents who completed the online survey of the 16-17-year follow-up of the Copenhagen Child Cohort (CCC2000), including items on BED symptoms approximating the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, and items on mental health and quality of life. The 1-year prevalence of SBED was 2.7% (95% confidence interval [CI]: 2.0%-3.3%) with a male:female ratio of 1:3.7; comparable to previous findings on BED in the same sample. SBED was also comparable to BED concerning cross-sectional associations with overall mental health problems, lower health-related quality of life, depressive symptoms, and suicidal ideation, whereas no associations were seen with non-suicidal self-injury after Holm-Bonferroni correction. In both groups, thoughts and behaviors concerning food and weight interfered significantly with daily life. SBED and BED were equally prevalent in this adolescent community sample, and similarly associated with indicators of poor mental health. The findings indicate that community adolescents reporting symptoms approximating clinical criteria of BED need intervention irrespectively of symptom frequency or duration. This study adds knowledge to the field by comparing BED of low frequency and/or limited duration ("subthreshold BED," SBED) with full-syndrome BED in adolescents and showing that SBED in adolescence is both prevalent and associated with poor mental health to a similar extent as that of BED. Findings indicate that self-reported symptoms according to clinical criteria of SBED and BED alike constitute a public health problem and point to youngsters in need of intervention.

Association of human epidermal growth factor receptor 2 expression with 21-gene recurrence score and survival among patients with estrogen receptor–positive breast cancer.

563 Background: Trastuzumab-deruxtecan was recently shown to improve survival for metastatic human epidermal growth factor receptor 2 (HER2)-low breast cancer. HER2-negative breast cancer has been redefined as a group of heterogeneous entities. However, HER2-low status is not considered as a prognostic factor among patients with nonmetastatic breast cancer, and the role of HER2 expression levels in the setting of 21-gene recurrence score (RS) remains unclear. We performed an observational cohort study using a national oncology database to evaluate the association of HER2 expression levels with RS and survival among patients with estrogen receptor (ER)-positive breast cancer. Methods: The National Cancer Database was queried for women diagnosed between 2006 and 2018 with ER-positive, pT1-3N0-1aM0 breast cancer who received surgery followed by adjuvant endocrine therapy with or without chemotherapy. HER2 expression levels were stratified by 3 groups: HER2-0 (immunohistochemistry [IHC] 0), HER2-1 (IHC +1), and HER2-2 (IHC +2 and in situ hybridization [ISH] negative). Logistic and Cox multivariable analysis (MVA) were used to identify factors associated with high RS (26 or higher) and overall survival (OS), respectively. Interaction term was analyzed to evaluate any heterogeneous associations in survival outcomes between HER2 levels and RS. Subgroup analysis was performed by repeating Cox MVA stratified by RS. Holm-Bonferroni correction was used to adjust for multiple comparisons, with p value less than 0.05 considered as statistically significant. Results: Among 108,973 women, 31,738 (29.1%), 52,839 (48.5%), and 24,396 (22.4%) patients had HER2-0, HER2-1, and HER2-2, respectively. Logistic MVA showed that, compared to HER2-0, HER2-2 was associated with higher RS (adjusted odds ratio [aOR] 1.09, 95% confidence interval 1.04-1.15, p &lt; 0.001), but HER2-1 was not (aOR 0.96, 95% CI 0.91-1.00, p = 0.05). Cox MVA showed that both HER2-1 (adjusted hazards ratio [aHR] 1.03, 95% CI 0.97-1.10, p = 0.34) and HER2-2 (aHR 1.06, 95% CI 0.98-1.14, p = 0.14) were not associated with OS. There was an interaction between HER2 expression levels and RS (interaction p = 0.03). Among those with RS &lt; 26, compared to HER2-0, HER2-2 was associated with worse OS (aHR 1.10, 95% CI 1.01-1.20, p = 0.02), but HER2-1 was not (aHR 1.04, 95% CI 0.97-1.12, p = 0.24). Among those with RS 26 or higher, both HER2-1 (aHR 1.00, 95% CI 0.88-1.13, p = 0.98) and HER2-2 (aHR 0.94, 95% CI 0.82-1.09, p = 0.41) were not associated with OS. Conclusions: To our knowledge, this is the largest study using nationwide oncology database to suggest that, when compared to HER2-0, HER2-2 was associated with higher RS and poor survival among patients with RS &lt; 26. Further studies would be warranted to evaluate the role of HER2 expression levels for risk stratification to tailor interventions.

0961 Applying Fractal Analysis Towards the Understanding of Long-COVID-Induced Insomnia

Abstract Introduction As part of the recent international COVID Sleep Study-II, long COVID syndrome was found to be associated with chronic insomnia. However, an article submitted for publication out of the Hôpital Hôtel-Dieu found no significant difference between long-COVID-related insomnia and standard insomnia with respect to routine polysomnographic (PSG) parameters. In light of these findings, we seek to better understand the difference between long COVID insomnia and standard chronic insomnia by conducting a fractal analysis of the raw PSG signals of our subjects. Methods 15 long COVID patients with complaints of chronic insomnia were included as subjects, as well as 34 matched controls without long COVID who had similar complaints of chronic insomnia. All participants underwent one night of polysomnographic recording. We perform our analysis on movements of the abdomen (as an approximation of deep breathing quality) and on EEG waves, considering that shortness of breath and cognitive dysfunction are commonly associated with long COVID. Building upon an existing repertoire of medical research using the fractal dimension (FD) of patients’ signal data to differentiate pathologic and physiologic processes, we make use of Detrended Fluctuation Analysis (DFA) to calculate the FD of the abdomen (FDA) and of an aggregated EEG wave (FDE) for each patient. Results We find a decrease in the FDA (p=0.036) and increase in the FDE (p=0.012) of long COVID insomniacs with respect to those of our control group. These results are shown to be significant after applying a Holm-Bonferroni correction for multiple hypotheses. Conclusion Despite our small data sample, an in-depth analysis of PSG signals shows significant differences in the fractal nature of long-COVID-related insomnia with respect to standard chronic insomnia. Our results furthermore match our expectations, given that related research outside of the COVID domain indicates a decrease in the FD of muscle movements and an increase in the FD of EEG waves in unhealthy individuals. Further research could employ more participants in order to extend our results to other data channels outside of EEG signals and the abdomen. Support (if any)

Body shape and performance on the US Army Combat Fitness Test: Insights from a 3D body image scanner.

To identify relationships between body shape, body composition, sex and performance on the new US Army Combat Fitness Test (ACFT). Two hundred and thirty-nine United States Military Academy cadets took the ACFT between February and April of 2021. The cadets were imaged with a Styku 3D scanner that measured circumferences at 20 locations on the body. A correlation analysis was conducted between body site measurements and ACFT event performance and evaluated using Pearson correlation coefficients and p-values. A k-means cluster analysis was performed over the circumference data and ACFT performance were evaluated between clusters using t-tests with a Holm-Bonferroni correction. The cluster analysis resulted in 5 groups: 1. "V" shaped males, 2. larger males, 3. inverted "V" shaped males and females, 4. "V" shaped smaller males and females, and 5. smallest males and females. ACFT performance was the highest in Clusters 1 and 2 on all events except the 2-mile run. Clusters 3 and 4 had no statistically significant differences in performance but both clusters performed better than Cluster 5. The association between ACFT performance and body shape is more detailed and informative than considering performance solely by sex (males and females). These associations may provide novel ways to design training programs from baseline shape measurements.

In-shoe plantar pressure depends on walking speed and type of weight-bearing activity in people with diabetes at high risk of foot ulceration

BackgroundIn evaluating therapeutic footwear, in-shoe plantar pressure is usually obtained during mid-gait steps at self-selected walking speed in a laboratory setting. However, this may not accurately represent plantar pressures or indicate the cumulative stress experienced in daily life. We investigated the effects of walking speed and different weight-bearing activities on in-shoe plantar pressure in people with diabetes at high risk of ulceration. MethodsIn a cross-sectional study including 30 participants we compared in-shoe plantar pressures between three standardized walking speeds (0.8, 0.6 and 0.4 m/s) and between walking at self-selected speed and eight other weight-bearing activities (3 components of the Timed Up and Go test, accelerating, decelerating, stair ascending and descending, and standing). Mean forefoot regional peak plantar pressure and pressure-time integral were statistically assessed per foot using linear mixed models (α < 0.05) with Holm-Bonferroni correction. FindingsWith increasing walking speed, peak pressures increased and pressure-time integrals decreased (P ≤ 0.014). Peak pressures during standing, decelerating, stair ascending and Timed Up and Go test were lower (P ≤ 0.001), and with other activities not different to walking at self-selected speed. Pressure-time integrals during stair ascending and descending were higher (P ≤ 0.001), during standing lower (P ≤ 0.009), and with other activities not different to walking at self-selected speed. InterpretationIn-shoe plantar pressure depends on walking speed and type of weight-bearing activity. Only measuring pressures to evaluate footwear at self-selected walking speed in a laboratory setting may not accurately represent the stress on the foot in daily life of the high-risk patient; a more comprehensive assessment is suggested.

Association of whole blood mRNA expression and overall survival (OS) in metastatic castrate resistant prostate cancer (mCRPC).

201 Background: Previous studies have evaluated peripheral whole blood mRNA to identify prognostic biomarkers in metastatic prostate cancer, with no consistent genes of prognostic significance between studies and sample collection done at various points of therapy. We aim to identify the prognostic value of 20 previously identified genes in patients mCRPC from a prospective clinical trial. Methods: Between June 2013 and August 2015, whole blood was prospectively collected in PAXgene RNA tubes from 92 men with mCRPC (NCT01953640). Gene expression from samples with RIN &gt; 4.0 were quantified using a customized NanoString CodeSet of 20 candidate genes (C1QA, MCM2, STOM, GABARAPL2, R10K3, HMBS, TFDP1, CDKN1A, ITGAL, TMCC2, TERF2IP, MMP9, SNCA, TIMP1, SLC4A1, SELENBP1, TMEM66, SEMA4D, PROS1, CD22). The raw data from the nCounter Analysis system were normalized to the positive controls and log2 transformed. Univariable Cox proportional hazards models were performed on each target gene sufficiently above negative control (5 times the maximum value of the negative control) to evaluate associations with overall survival (OS). For each gene we considered a linear, quadratic, or categorical model with quantile cutpoints. Categorical models with cutpoints at the 25th percentile for the genes CD22, GABARAPL2, R10K3, and STOM were used as there was a nonlinear relationship between gene expression and death hazard. The remaining genes were modeled with a linear model. Findings were considered statistically significant based on p-values adjusted using the Holm-Bonferroni correction. Results: 18/20 genes were identified and passed quality control (QC) measures, which excluded C1QA and MCM2. 72/92 men had an evaluable pretreatment specimen that passed QC. The median age was 72 years. The study cohort was evenly balanced in terms of Gleason score ( &lt; = 7 v. &gt; 7) and 60% had high volume disease. The median follow-up time was 5.73 years (IQR: 5.39, 6.49) and 58 patients had died. Of the 18 genes evaluated, STOM (Stomatin) [hazard ratio (HR) 3.00, adjusted p = 0.007] and GABARAPL2 (GABA Type A Receptor Associated Protein Like 2) [HR 2.62, adjusted p = 0.033] were significantly associated with overall survival in univariate analysis. In multivariate analysis, after adjusting for volume of metastatic disease and Gleason score, STOM [HR 2.89, adjusted p = 0.014] was significantly associated with overall survival. Conclusions: Elevated whole blood mRNA expression of STOM is adversely associated with OS in mCRPC. Further studies investigating elucidating the molecular significance of STOM in mCRPC are planned. Clinical trial information: NCT01953640 .

Flavoprotein fluorescence elevation is a marker of mitochondrial oxidative stress in patients with retinal disease.

Recent studies of glaucoma, age-related macular degeneration, and diabetic retinopathy have demonstrated that flavoprotein fluorescence (FPF) can be utilized non-invasively as an indicator of mitochondrial oxidative stress in the retina. However, a comprehensive assessment of the validity and reliability of FPF in differentiating between healthy and diseased eyes across multiple disease states is lacking. Here, we evaluate the sensitivity and specificity of FPF in discriminating between healthy and diseased eyes in four leading causes of visual impairment worldwide, one of which has not been previously evaluated using FPF. We also evaluate the association between FPF and visual acuity. A total of 88 eyes [21 eyes of 21 unaffected controls, 20 eyes from 20 retinal vein occlusion (RVO) patients, 20 eyes from 20 diabetic retinopathy (DR) patients, 17 eyes from 17 chronic exudative age-related macular degeneration (exudative AMD) patients, and 10 eyes from 10 central serous retinopathy (CSR) patients] were included in the present cross-sectional observational study. Eyes were imaged non-invasively using a specially configured fundus camera OcuMet Beacon® (OcuSciences, Ann Arbor, MI). The macula was illuminated using a narrow bandwidth blue light (455 - 470 nm) and fluorescence was recorded using a narrow notch filter to match the peak emission of flavoproteins from 520 to 540 nm. AUROC analysis was used to determine the sensitivity of FPF in discriminating between diseased eyes and healthy eyes. Nonparametric Kruskal-Wallis Tests with post-hoc Mann Whitney U tests with the Holm-Bonferroni correction were performed to assess differences in FPF intensity, FPF heterogeneity, and best corrected visual acuity (BCVA) between the five groups. Spearman rank correlation coefficients were calculated to assess the relationship between FPF and BCVA. AUROC analysis indicated that FPF intensity is highly sensitive for detecting disease, particularly for exudative AMD subjects (0.989; 95% CI = 0.963 - 1.000, p=3.0 x 107). A significant difference was detected between the FPF intensity, FPF heterogeneity, and BCVA in all four disease states compared to unaffected controls (Kruskal-Wallis Tests, p = 1.06 x 10-8, p = 0.002, p = 5.54 x 10-8, respectively). Compared to healthy controls, FPF intensity values were significantly higher in RVO, DR, exudative AMD, and CSR (p < 0.001, p < 0.001, p < 0.001, and p = 0.001, respectively). Spearman rank correlation coefficient between FPF intensity and BCVA was ρ = 0.595 (p = 9.62 x 10-10). Despite variations in structural retinal findings, FPF was found to be highly sensitive for detecting retinal disease. Significant FPF elevation were seen in all four disease states, with the exudative AMD patients exhibiting the highest FPF values compared to DR, CSR, and RVO subjects. This is consistent with the hypothesis that there is elevated oxidative stress in all of these conditions as previously demonstrated by blood studies. FPF intensity is moderately correlated with the late-in disease-marker BCVA, which suggests that the degree of FPF elevation can be used as a metabolic indicator of disease severity.