Healthy Control Population Research Articles

Long-term antibody responses to COVAXIN and COVISHIELD vaccines in rheumatoid arthritis patients and healthy control population – A cross-sectional study

ABSTRACT Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and damage in the joints. It often requires treatment with disease-modifying antirheumatic drugs (DMARDs) to manage symptoms and prevent progression. The study investigates the long-term antibody responses to COVAXIN and COVISHIELD vaccines in RA patients. Methodology: This cross-sectional study (IEC approval no: AlIMS/BBN/IEC/AUG/2021/60-R dated Sept 05, 2022, and Ref No: 799/U/IEC/ESICMC/F490/09/2022 dated Oct 31, 2022) enrolled 103 diagnosed RA patients receiving DMARDs and 183 healthy controls. The participants who completed 1 year after the second dose of vaccination were included, and detailed information on demographic, medical, and vaccination were collected. Laboratory investigations included complete blood count, inflammatory markers, and antispike antibody levels. Statistical analyses assessed differences between COVAXIN and COVISHIELD subgroups, considering DMARDs usage and disease duration. Results: Among RA patients, both COVAXIN and COVISHIELD groups exhibited low disease activity. No significant (P > 0.05) differences were found in IL-6, CRP, or antispike antibody levels between COVAXIN and COVISHIELD subgroups in RA patients and healthy controls. Notably, 89% of female RA patients received COVISHIELD. Co-morbidities, including hypothyroidism (44%), were prevalent in COVISHIELD-received RA patients. Antibody concentration varied significantly among DMARDs usage groups in COVAXIN-vaccinated RA patients, with a notable difference between three-drug and HCQ-alone regimens. However, no such difference was observed in the COVISHIELD group. Disease duration did not significantly impact antispike antibody concentration in either of the vaccination group. Conclusion: RA patients had a decreased antibody response, 1 year after receiving the second dose of the COVID-19 vaccine. Nonetheless, there was no discernible difference in the antispike antibody concentration between the COVISHIELD and COVAXIN vaccination groups. Additionally, immunosuppressive medications significantly impact serological responses to these vaccines.

Thinning of central foveal thickness in the retina of patients with schizophrenia.

The neural retina shares a common embryonic origin with the brain and yields pathological changes like that in the brain in various neuropsychiatric disorders, including schizophrenia. Non-invasive examination by optical coherence tomography (OCT) revealed retinal structure abnormalities in patients with schizophrenia. This study investigated retina structures in 29 patients with schizophrenia and 25 healthy controls in a Chinese Han ethnic population with spectral domain OCT. Measurements of central foveal thickness (CFT) as well as other retinal structures in macular and peripapillary subregions were performed. Associations between OCT parameters and clinical features, including severity of positive and negative symptoms, disease duration and antipsychotic dosage were analyzed. With controlling for age and sex, patients showed significantly thinner CFT, thinner central macular thickness, and thinner total retinal thickness in subregions of the central, inner superior, inner temporal, and inner nasal macula of both eyes, thinner ganglion cell complex in a subregion of the left eye, as well as larger cup volume in the peripapillary region of the right eye. In addition, CFT also negatively correlated with severity of negative symptoms. These findings suggest that CFT has the potential to be a disease biomarker of schizophrenia.

Perturbed Microbial Ecology in Neuromyelitis Optica Spectrum Disorder: Evidence from the Gut Microbiome and Fecal Metabolome

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) is a central nervous system inflammatory demyelinating immune-mediated ailment, which is influenced by genetic, epigenetic, and environmental elements. The escalating incidence of NMOSD in recent years implies alterations in environmental risk factors. Recent research has established a correlation between gut microbiomes and the development of NMOSD. MethodsMetagenomic shotgun sequencing and gas chromatography-mass spectrometry (GC-MS) were employed to assess alterations of the structure and function in the fecal microbiome, as well as levels of short-chain fatty acids (SCFAs) in fecal and blood samples, among individuals with neuromyelitis optica spectrum disorder (NMOSD) during the acute phase (n=25), the remission phase (n=11), and a group of healthy controls (HCs) (n = 24). We further explored the correlation between gut microbiota and the pathogenesis of NMOSD through fecal microbiota transplantation (FMT). The gut microbiome from human donors diagnosed with NMOSD or HCs was transplanted into germ-free mice, followed by an analysis of the alterations in the structure and functionality of the transplanted mice's gut microbiome. Additionally, the impact of microbiome transfer on the immunity and spinal cord of germ-free mice was assessed through various techniques, including ELISA, flow cytometry, western blot, histopathology, and transcriptome sequencing. Results(1) At the taxonomic levels of genus and species, there were significant differences in the α-diversity of the microbiome between HCs and NMOSD patients in the acute phase, with NMOSD patients having higher species diversity. (2) In the acute phase, the gut microbiota of NMOSD patients was characterized by Ruminococcaceae_unclassified, Campylobacter, Parabacteroides, Lactobacillus, Akkermansia, Streptococcus oralis, Clostridium leptum, Clostridium asparagiforme, Firmicutes bacterium CAG 238, and Lactobacillus fermentum. (3) The relative abundances of Coprobacter, Turicimonas, Gemmiger, Enterobacter, Roseburia sp.CAG 471, Veillonella tobetsuensis, Proteobacteria bacterium CAG 139, Ruminococcus bicirculans, Lactococcus lactis, Flavonifractor plautii, and Streptococcus cristatus were notably lower in patients experiencing remission compared to NMOSD patients in the acute phase, On the other hand, the relative abundances of Flavonifractor (P = 0.049) and Clostridium aldenense (P = 0.049) were significantly higher. Following medication, the gut microbiome distribution in NMOSD patients during remission closely resembled that of healthy controls (HCs). (4) Compared with HCs, acetate levels in the feces of patients with NMOSD in the acute phase were significantly lower. (5) In addition, we transplanted feces from NMOSD patients into germ-free mice and revealed a significant increase in the levels of IL-6, IL-17A, and IL-23 in the blood of mice belonging to the NMOSD fecal transplantation (NFMT) group. Additionally, the IL-10 level exhibited a significant reduction. Moreover, the proportion of Th17 cells displayed a significant increase, while the proportion of Treg cells exhibited a significant decrease in the spleens of NFMT mice. ConclusionPatients in the acute phase of neuromyelitis optica spectrum disorder (NMOSD) exhibited imbalances in their gut microbiota and a deficiency in short-chain fatty acids (SCFAs). Following drug treatment, the composition of intestinal microbes in NMOSD patients during the remission phase closely resembled that of the healthy control population. The FMT experiment provided evidence of the significant association between intestinal flora and the pathogenesis of NMOSD. Consequently, investigating gut microbiota and identifying novel microbial markers hold promise for the diagnosis and treatment of NMOSD patients.

Microstomia is associated with functional impairment and is a poor prognostic factor in systemic sclerosis – a single center observational study with survival analysis

BackgroundObjectives were to assess the mouth opening ability (MOA) among patients with systemic sclerosis (SSc) in comparison to a healthy control population. The impact of microstomia (decrease in any of the MOA parameters) on physical performance and long-term survival was also investigated.MethodsInterincisal (ID), interlabial (LD), the intercommissural distances at both opened mouth and closed mouth (OW, CW) and the oral area (OA) and circumference (OC) all were assessed in 131 SSc patients. Microstomia was defined based on the oral aperture values of a healthy control group (n = 63) with similar median age and sex distribution. Tests evaluating functional performance were performed. Survival analysis by univariate and multivariate Cox regression analysis was performed.ResultsMicrostomia was present in 56.5% of the entire SSc cohort. Patients with microstomia had higher number of contractures compared to those with preserved oral aperture parameters (median 10 vs. 7, p < 0.01). LD, OA and OC correlated negatively with the number of joint contractures, both in the entire SSc cohort and separately in the diffuse (dcSSc) and limited cutaneous subsets (lcSSc), (rho: between − 0.267 and − 0.516, p < 0.05). Reduced ID was associated with worse Health Assessment Questionnaire Disability Index (HAQ-DI) only in dcSSc while reduced LD was linked to increased HAQ-DI scores in both SSc subsets. Decreased OA upon enrollment was associated with an increased risk in mortality by multivariate Cox regression analysis (HR: 2.74; 95% CI, 1.15–6.53).ConclusionsMicrostomia was associated with joint damage, and higher overall disability based on HAQ-DI. Interlabial distance was a beneficial, convenient measurable parameter to characterize oral aperture. Oral area was an independent poor prognostic factor regarding long-term survival.

Metal Punch vs. Drill for Rotator Cuff Anchor Socket Creation; Cadaveric and Clinical Comparisons

BackgroundArthroscopic rotator cuff repair has been shown to decrease pain and increase function of certain rotator cuff tears. One potential source of pain is the technique used for bone tunnel creation in the humerus prior to suture anchor placement. This study compared the standard metal punch method to a continuous drilling method for tunnel creation prior to subsequent suture anchor placement. Our hypothesis was that the use of a drill would result in less bony trauma and therefore superior resolution of postoperative pain following rotator cuff repair. MethodsTunnels were created for six cadaveric (age: 50.83±3.25; male n=3; female n=3) shoulder humeri using a 4-anchor construct to mimic transosseous equivalent rotator cuff repair. Following suture fixation, μCT scans were performed for evaluation of peri-tunnel bone architecture. A tensile force was applied to the anchor through the suture material at a constant displacement rate of 1mm/s until ultimate failure of the construct. All statistical analyses were performed using SPSS (version 25; IBM, Armonk, NY, USA), and significance was set at p≤0.05. A total of 43 subjects between 18 and 80 years old were randomized into the study, with 22 in the drill group and 21 in the punch group. Following surgery, the first 5 patients in each cohort underwent MRI at the 2-week postoperative visit. Pain and other patient reported measures (PROMs) were assessed at all standard of care postoperative visits. Patient demographics and PROMs were assessed for significance within the groups using repeated ANOVA and unpaired t-test. A P-value of <0.05 was set for significance. ResultsPreclinical - There were no statistically significant differences (p>0.05) between punched and drilled anchors with respect to peri-socket bone architecture and material properties. Clinical – There were no statistically significant differences (p>0.05) between punch and drill cohorts for assessments of pain, function, or bone marrow lesion size. However, the punch cohort reported statistically significant and clinically meaningful reductions in pain scores at 2 weeks, 6 weeks, 3 months, and 6 months compared to preoperative scores (p<0.02), whereas the drill cohort reported statistically significant and clinically meaningful reductions in pain scores at 6 weeks, 3 months, and 6 months after surgery (p <0.05). Similarly, the punch cohort reported statistically significant reductions in PROMIS pain interference scores, which were within 1 standard deviation of the healthy adult control population, at 2 weeks, 6 weeks, 3 months, and 6 months compared to preoperative scores (p <0.05), whereas the drill cohort did not report statistically significant improvements in PROMIS PI scores until 3 months postoperatively and were not within 1 standard deviation of the healthy adult control population until 6 months after surgery. ConclusionPreclinical and clinical data suggest that it is reasonable to utilize either a punch or drill socket-creation method for suture anchor placement in arthroscopic rotator cuff repair, while considering the potential for earlier pain relief associated with the punch method.

Polysaccharide, Conjugate, and mRNA-based Vaccines are Immunogenic in Patients with Netherton Syndrome

BackgroundNetherton syndrome (NS) is a rare, severe genetic skin disorder, currently classified as an inborn error of immunity (IEI) due to previously reported immune dysregulation. We recently reported the results of an immunological evaluation showing no evidence for a relevant B- and/or T-cell mediated immunodeficiency, but immune responses after vaccination were not evaluated in that study. Therefore, we evaluated immune responses to three vaccine platforms in adult NS patients to further investigate the presence of a clinically relevant B- and/or T-cell immunodeficiency.MethodsVaccination responses in eight adult NS patients were assessed in a cross-sectional study performed between January and August 2022. Clinical patient data were retrospectively retrieved from electronic patient files. Immune responses to a polysaccharide Streptococcus pneumoniae vaccine (PPV23) and conjugate Haemophilus influenzae type b vaccine (ActHiB) were measured. SARS-CoV-2-specific (functional) antibody and T-cell responses following booster vaccination with an mRNA-based COVID-19 vaccine were compared to controls.ResultsNone of the included patients suffered from recurrent and/or severe infections that could be attributed to a B- and/or T-cell immunodeficiency. ActHiB induced immune responses were normal in 7/7 NS patients. PPV23 induced responses were absent in 1/7, diminished in 2/7, and normal in 4/7 patients. Levels of SARS-CoV-2-specific binding and neutralizing antibodies after mRNA-based COVID-19 booster vaccination in NS patients were comparable to controls. SARS-CoV-2-specific CD4 + T-cell responses were detectable in all NS patients. In contrast, SARS-CoV-2-specific CD8 + T-cell responses were detectable in only 2/6 NS patients. T-cell responses to a positive control antigen pool were comparable to controls.ConclusionsVaccine-induced immune responses were detectable after polysaccharide, conjugate and mRNA-based vaccination in our cohort of NS patients. A spectrum of responsiveness to vaccine challenges was found, with the ranges of vaccine responses overlapping those demonstrated in healthy control populations.

Impact of HHIP gene polymorphisms on phenotypes, serum IL-17 and IL-18 in COPD patients of the Chinese Han population

BackgroundGenetic factors, including the Hedgehog Interacting Protein (HHIP) gene, play a crucial role in Chronic Obstructive Pulmonary Disease (COPD) susceptibility. This study examines the association between HHIP gene polymorphisms and COPD susceptibility, phenotypes, and serum IL-17 and IL-18 levels in a Han Chinese population.MethodsA case-control study was conducted with 300 COPD patients and 300 healthy controls in Chinese Han population. Participants underwent genotyping for HHIP gene polymorphisms, pulmonary function tests, and quantitative CT scans. DNA samples were sequenced using a custom chip targeting the HHIP gene. Serum IL-17 and IL-18 levels were measured by enzyme-linked immunosorbent assay. Associations between SNPs, COPD susceptibility, and phenotypes were analyzed using logistic and multiple linear regression models, adjusting for confounders.ResultsOur study identified the rs11100865 polymorphism in the HHIP gene as significantly associated with COPD susceptibility (OR 2.479, 95% CI 1.527–4.024, P = 2.39E-04) after screening 114 SNPs through rigorous quality control. Stratified analyses further indicated this association was particularly in individuals aged 60 or older. Serum levels of IL-17 and IL-18 were significantly elevated in COPD patients compared to controls, with rs11100865 showing a notable association with IL-18 levels (B = 49.654, SE = 19.627, P = 0.012). However, no significant associations were observed between rs11100865 and serum IL-17 levels, COPD-related imaging parameters, or clinical phenotypes.ConclusionThis study identified a significant association between HHIP gene polymorphisms and COPD susceptibility in a Han Chinese population, with connections to inflammation, but found no significant associations between this SNP and COPD-related imaging or clinical phenotypes.Trial registrationwww.chictr.org.cn ID: ChiCTR2300071579 2023-05-18.

Sensitizations to pollen differ between Central European and Sub-Saharan African atopic dermatitis patients

Summary Background Atopic dermatitis (AD) is often associated with allergic comorbidities, such as allergic asthma or allergic rhinoconjunctivitis (ARC). Sensitizations to pollen can directly impact AD, as patients can experience exacerbation during pollen season. This study aims to gain more insights into the pollen sensitization patterns of AD patients in Central Europe compared with sub-Saharan Africa (SSA). Methods We performed a case–control study involving a total of 90 participants: 20 AD patients and 10 healthy controls (HC) each from Switzerland (CH), Tanzania (TZ), and Madagascar (MD). We collected clinical data and serum samples and performed a multiplex IgE test (ALEX2 Allergy Explorer, MacroArray Diagnostics, Vienna, Austria). Results The prevalence of ARC and asthma in AD patients was similar in all countries (ARC: 60% TZ, 70% CH, 75% MD; asthma: 25% TZ, 30% CH, 20% MD). Total IgE levels were significantly higher in both SSA HC populations compared with the Swiss HC. The analysis of specific IgE levels revealed major differences in sensitization patterns between Africa and Europe, especially regarding grass pollen allergens. Swiss AD patients were sensitized to various grass pollen such as Bahia grass, Bermuda grass, common reed, perennial ryegrass, rye, and timothy grass. However, these allergens were irrelevant in the SSA population: no AD patient or HC subject was sensitized to the tested grass pollen. Conclusion The considerably different sensitization patterns between European and SSA AD patients warrant the development of allergy testing and desensitization therapies tailored to the African setting. Therefore, there is a need to characterize local pollen types and counts.

6437 Analysis of 17-OH-Progesterone (17OHP) and Androstenedione (A4) Profiles To Rationalise Biochemical Monitoring Of CAH Patients

Abstract Disclosure: N.R. Lawrence: None. N.P. Krone: None. J.F. Dawson: None. Z. Lang: None. W. Arlt: Advisory Board Member; Self; Diurnal. A. Brac de la Perriere: Research Investigator; Self; Diurnal. A.L. Hirschberg: Research Investigator; Self; Diurnal. A. Juul: Research Investigator; Self; Diurnal. D.P. Merke: Research Investigator; Self; Diurnal. J.D. Newell-Price: Research Investigator; Self; Diurnal. A. Prete: Research Investigator; Self; Diurnal. A.E. Taylor: None. A. Rees: Research Investigator; Self; Diurnal. N. Reisch: Research Investigator; Self; Diurnal. M. Stikkelbroeck: Research Investigator; Self; Diurnal. P.A. Touraine: Research Investigator; Self; Diurnal. G. Collins: None. R.J. Ross: Consulting Fee; Self; Diurnal. Background: There is no consensus on how to monitor biochemical control of CAH as excess ACTH overnight is common on standard therapy. Modified-release hydrocortisone (MRHC) gives potential for improved disease control and the need to understand this impact on disease monitoring.Aim: To define the relationship between 17OHP and A4, in healthy controls and CAH patients. Methods: Analysis of 24-hour 2-hourly 17OHP and A4 endocrine profiles in patients randomised to either standard treatment or MRHC (n=122, mean age 36.3 (SD 11.6) years, 78 female, 44 male) and a population of healthy controls (n=20, age 30.0 (12.3), 13 male, 7 female). Markers were regressed, cross correlated and assessed by Bayesian Change Point analysis using R. Results: Regressing the natural logarithms of 17OHP on A4, Bayesian multiple change point analysis converged on a stable changepoint equivalent to 17OHP of 4.5 nmol/L 149 ng/dl (95%, CI:4.2 to 4.7 nmol/L, Rhat &amp;lt; 1.008). Below the 17OHP change point A4 is proportionally lower than above, with no evidence of difference between sexes or steroid preparation. The relationship between 17OHP and A4 was different for healthy subjects, who for similar levels of A4 have lower levels of 17OHP than CAH patients in nmol/L (ng/dl): A4 of 1 (29) and 10 (286) associated with 17OHP 1.5 (50) and 8.8 (291) in healthy subjects’ vs 3.3 (109) and 71.2 (2353) in CAH patients, respectively. There was no consistent rhythm in either marker in healthy patients, shown by an autocorrelation function (ACF) that falls quickly to zero. ACF approaches zero more quickly in CAH patients on MRHC than those on standard therapy who more commonly exhibit a diurnal rhythm with an 0700hrs peak. There was no lag between markers, with cross-correlation function plots symmetrical. Conclusions: The relationship between 17OHP and A4 is different in CAH than healthy controls. In CAH, high A4 suggests poor control but a low A4 may still be associated with a raised 17OHP. In CAH patients, 17OHP concentrations within the healthy subject range are associated with A4 below levels seen in healthy subjects. When elevated in CAH patients, A4 and 17OHP rise and fall together with no lag; thus, A4 does not give more information on control over time. On MRHC the biomarkers show a reduced diurnal rhythm; therefore, individual measurements taken in clinic are more likely to reflect the daily average than measurements taken when on standard therapy. Presentation: 6/1/2024

Long survivors after radical cystectomy versus healthy population: propensity score matched analysis of health-related quality of life.

To investigate Health Related Quality of Life (HRQoL) features of long survivors after radical cystectomy (RC) compared to healthy population (HP) control. Patients with cT2-4/N0/M0 or Bacillus Calmette-Guérine (BCG) failure high-grade non-muscle-invasive bladder cancer (NMIBC) undergoing RC and ileal Orthotopic Neobladder (iON) from 2010 to 2015 were enrolled in "BCa cohort". Patients aged ≥ 18 yrs old, with no previous diagnosis of BCa or any genitourinary cancer disease were included from General Practitioner outpatients and enrolled in "HP cohort". A 1:1 propensity score matched (PSM) analysis was performed, and HRQoL outcomes were collected according to European Organization for Research and Treatment of Cancer (EORTC), and generic (QLQ-C30) questionnaires. A total of 401 patients were enrolled in the study, 99 and 302 in BCa and HP cohorts, respectively. After applying 1:1 PSM analysis 67 patients were included for each group. Analysis of self-reported HRQoL outcomes described a better HRQoL in BCa cohort. Particularly, in the long run patients receiving RC and iON significantly experienced higher global health-status/QoL (p < 0.001), emotional (p = 0.003) and cognitive functioning (p < 0.001) than HP cohort, providing a significantly lower impairment in terms of fatigue (p = 0.004), pain (p = 0.004), dyspnea (p = 0.02) and insomnia (p = 0.005). Long survivors after RC and iON seems to have a major awareness of self-reported HRQoL compared to HP control group.

A COMPARATIVE ANALYSIS OF LUMBAR INTERVERTEBRAL MOTION BETWEEN LOW BACK PAIN SUBGROUPS AND HEALTHY CONTROLS USING QUANTITATIVE FLUOROSCOPY

Study purpose and backgroundKinematic variables have been identified as potential biomarkers for low back pain patients; however, an in-depth comparison between chronic (n=22), acute (n=15), and healthy controls (n=136) has not been done. This retrospective data analysis compared intervertebral lumbar motion parameters, angular range of motion, translation, maximum disc height, motion share inequality (MSI) and variability (MSV), and laxity, between these groups.Methods and resultsKinematic parameters were determined using video tracking techniques utilising quantitative fluoroscopy (QF), during both weight-bearing and recumbent controlled sagittal bending tasks. Data was analysed for normality, and appropriate statistical tests were applied to determine differences between groups. There were no significant differences between the groups for age, height, weight and sex. Whilst few differences were found between acute and healthy groups, differences were shown between both chronic and healthy, and acute and chronic groups for all six parameters. Of particular note were examples of differences in the motion share parameters between the acute and chronic populations, with an increased MSI in the chronic group during recumbent flexion, and MSV during recumbent extension, and inversely an increase in MSV in the acute group during weight-bearing flexion.ConclusionAnalysis of intervertebral lumbar motion provides valuable insights into kinematic differences between chronic, acute, and healthy control populations. These findings suggest that there is variation between the groups which is knowledge that may benefit management strategies. Further exploration of the time varying data is warranted to explore how such differences may relate to the motion share inequalities and variability shown.Conflicts of InterestNo conflicts of interestSources of FundingNo funding obtained

Relationship between Oral Lichen Planus and Cardiovascular Disease of Atherosclerotic Origin: Systematic Review and Meta-Analysis.

Background/Objectives: Oral lichen planus (OLP) is a chronic inflammatory autoimmune disease of the oral mucosa that affects between 0.5% and 2% of the general population. In the last decade, several studies have associated cardiovascular diseases (CVDs) with some inflammatory skin diseases such as oral lichen planus, demonstrating the presence of dyslipidemia in these pathologies. The objective of this work is to review whether patients with OLP show higher dyslipidemia and CRP levels compared to a healthy control population without OLP. Methods: Searches were carried out in Medline, Scopus, and Cochrane. The studies had to perform a histopathological diagnosis for OLP and the patients could not take any medication to treat this disorder. Non-lichenoid reactions were included. Results: After an initial search that provided us with 254 papers, this number was reduced to 10 articles after a detailed evaluation. All of them were case-control studies that compared the presence of analytical cardiovascular risk factors in patients affected by OLP and in healthy subjects. Conclusions: There is no scientific evidence of the possible association between OLP and CVDs. The only association we can prove is the one between OPL and CVD risk factors, especially those related to the lipid profile. More studies are needed in order to evaluate this relationship in patients diagnosed with CVDs.

Discriminant diagnostic validity of paediatric bipolar disorder screening tests: A systematic review and meta-analysis.

Bipolar disorders (BD) are among the most significantly impairing of childhood and adolescent psychiatric disorders. Although BD symptoms may begin in adolescence, they are frequently not diagnosed until adulthood, and accordingly BD scales could aid diagnostic assessment in paediatric populations. This review aims to synthesis the evidence for the accuracy of BD symptom index tests for discriminating BD from non-BD (other diagnoses or healthy controls) in paediatric population. Additionally, several theoretically relevant moderators of diagnostic accuracy were evaluated. A systematic search across three databases were conducted from 1980 to 2022, augmented by grey literature database searches, citation chaining and contacting authors. Data from eligible studies were synthesized using meta-analysis. A multilevel model was fitted to account for nested effect sizes, with 31 potential moderators examined in univariate and multivariate models. Twenty-Eight studies were eligible, yielding 115 effect sizes for analysis. Meta-analytic modelling indicated BD symptom index tests have a high diagnostic accuracy (g = 1.300; 95% CI: 0.982 - 1.619; p < .001) in paediatric population. Accuracy was relative to the type of comparison group, index test content, index test informant and index test's scale or subscale. Screening tests based on mania content, caregiver report and non-healthy comparison groups have clinical utility in identifying paediatric BD. Other informant-and-content combination may not accurately identify paediatric BD. Unlike healthy controls, tests derived from studies using non-healthy comparison groups, represent BD symptom non-specificity and BD symptom overlap with other disorders, providing external validity and clinical utility.

The Influence of Epilepsy on Oral Health Outcomes: A Retrospective Study in South Indian Adults.

Introduction Epilepsy, a chronic neurological disorder marked by recurrent seizures, affects approximately 50 million people worldwidewith a higher prevalence in developing countries. This condition challenges motor skills and coordination, leading to poor oral health maintenance. The study aimed to evaluate the effect of epilepsy on oral health outcomes in adults by contrasting South Indian epileptics with healthy controls. The primary objective was to assess the prevalence of oral health issues in patients with epilepsy compared to healthy individuals and to analyze the types andfrequency of dental procedures required inepileptic patients compared to healthy controls in the South Indian population. Materials and methods A retrospective study was conducted in the Department of Oral Medicine and Radiology, Saveetha Dental College and Hospitals, Chennai, India. Approved by the Institutional Human Ethical Committee (Registration ID: IHEC/SDC/OMED-2202/23/106), the study involved105 epileptic patients and 105 healthy controls from records between January 2021 and December 2023. Both male and female patients within the age limit of 18-55 years were included. Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 29.0 (Released 2022; IBM Corp., Armonk, New York, United States). Results The study involved 210 participants with an equal gender distribution. Valproate was the most common medication used by 39% of epileptic patients. Gingival hyperplasia was significantly more prevalent in the epileptic group (24%). The epileptic group also required more dental procedures, with 32% of teeth needing restoration, 20% root canal treatment, and 20% extraction, compared to 12%, 11%, and 5%, respectively, in the control group. Conclusion Epileptic patients exhibit poorer oral health outcomes, including higher rates of gingival hyperplasia and a greater need for dental procedures compared to healthy controls. These findings highlight the necessity for targeted dental care and regular monitoring for individuals with epilepsy to improve their oral health and overall quality of life.

Prospective longitudinal cohort study of quantitative muscle magnetic resonance imaging in a healthy control population.

Quantitative muscle magnetic resonance imaging (qMRI) is a valuable methodology for assessing muscular injuries and neuromuscular disorders. Notably, muscle diffusion tensor imaging (DTI) gives insights into muscle microstructural and macrostructural characteristics. However, the long-term reproducibility and robustness of these measurements remain relatively unexplored. The purpose of this prospective longitudinal cohort study was to assess the long-term robustness and range of variation of qMRI parameters, especially DTI metrics, in the lower extremity muscles of healthy controls under real-life conditions. Twelve volunteers (seven females, age 44.1 ± 12.1 years, body mass index 23.3 ± 2.0 kg/m2) underwent five leg muscle MRI sessions every 20 ± 4 weeks over a total period of 1.5 years. A multiecho gradient-echo Dixon-based sequence, a multiecho spin-echo T2-mapping sequence, and a spin-echo echo planar imaging diffusion-weighted sequence were acquired bilaterally with a Philips 3-T Achieva MR System using a 16-channel torso coil. Fifteen leg muscles were segmented in both lower extremities. qMRI parameters, including fat fraction (FF), water T2 relaxation time, and the diffusion metrics fractional anisotropy (FA) and mean diffusivity (MD), were evaluated. Coefficients of variance (wsCV) and intraclass correlation coefficients (ICCs) were calculated to assess the reproducibility of qMRI parameters. The standard error of measurement (SEM) and the minimal detectable change (MDC) were calculated to determine the range of variation. All tests were applied to all muscles and, subsequently, to each muscle separately. wsCV showed good reproducibility (≤ 10%) for all qMRI parameters in all muscles. The ICCs revealed excellent agreement between time points (FF = 0.980, water T2 = 0.941, FA = 0.952, MD = 0.948). Random measurement errors assessed by SEM and the MDC were low (< 12%). In conclusion, in this study, we showed that qMRI parameters in healthy volunteers living normal lives are stable over 18 months, thereby defining a benchmark for the expected range of variation over time.

#1141 Chronic kidney disease in inflammatory bowel disease: systematic review and meta-analysis

Abstract Background and Aims Chronic kidney disease (CKD) is defined by a reduction in kidney function (estimated glomerular filtration rate &amp;lt; 60 mL/min/1.73 m2) and/or damage markers that are present for at least three months, regardless of the underlying aetiology. Case reports and cohort studies suggest that inflammatory bowel disease (IBD is associated with CKD. The extent and magnitude of a potential association between IBD and CKD is currently unknown. Method A comprehensive search was conducted in EMBASE, MEDLINE, Web of Science, the Cochrane database, and SCOPUS. Two separate reviewers were involved in the process of article selection and evaluation. In studies where a comparison between an IBD population and a non-IBD control population was available, odds ratios were calculated to quantify the association. To derive an overall estimate of the effect, the Mantel–Haenszel test was employed, utilising a random effect model. This systematic was registered with Prospero. Results Fifty-four articles were included in the review (Table 1). Eight articles compared an IBD population with a healthy control population and were included in the meta-analysis, although with high heterogeneity (I2 88%). An increased risk of CKD in the IBD population was observed, with an overall odds ratio of 1.59 (95% CI 1.31-1.93) (Fig. 1). Importantly, this effect was independent of 5-aminosalicylic acid use. Data on other therapies was sparse, except for known nephrotoxic medication like tacrolimus and cyclosporine. Interestingly, several studies reported a decreasing relative risk with increasing age, potentially reflecting an increased baseline risk in this ageing population. Conclusion The existing evidence on CKD in IBD was systematically reviewed, including all human epidemiological studies. An increased CKD prevalence in IBD was found; independent of medication. Hence, we suggest regular measurements of kidney function for all patients with IBD, irrespective of the therapeutic regimen. Measurements should include determination of the baseline creatinine, albumin/creatinine ratio and urinary sediment. For patients having a normal baseline function, we would recommend annual follow-up. A more systematic research approach regarding CKD and IBD is warranted

Alterations of the Ganglion Cell Complex in Age-Related Macular Degeneration: An Amish Eye Study Analysis

To compare the ganglion cell complex (GCC) thickness in eyes with age-related macular degeneration (AMD) vs healthy controls in an elderly Amish population. Prospective cross-sectional study. This is a post hoc analysis of the family-based prospective study of Amish subjects. Study subjects underwent imaging with the Cirrus HD-OCT (Carl Zeiss Meditec Inc) using a macular cube protocol of 512 × 128 scans (128 horizontal B-scans, each comprising 512 A-scans) over a 6 mm × 6 mm region centered on the fovea. The ganglion cell analysis algorithm calculated the GCC thickness by segmenting the outer boundaries of the retinal nerve fiber layer (RNFL) and inner plexiform layer (IPL) in all B-scans of the volume, with the region between these boundaries representing the combined thickness of the ganglion cell layer (GCL) and the IPL. A number of parameters were used to evaluate the GCC thickness: the average GCC thickness, minimum (lowest GCC thickness at a single meridian crossing the elliptical annulus), and sectoral (within each of 6 sectoral areas: superior, superotemporal, superonasal, inferior, inferonasal, and inferotemporal). The stage of AMD was graded on color fundus photographs in accordance with the Beckman Initiative for Macular Research classification system. Of 1339 subjects enrolled in the Amish eye study, a total of 1294 eyes of 1294 subjects had all required imaging studies of sufficient quality and were included in the final analysis. Of these, 798 (62%) were female. Following age adjustment, the average GCC thickness was significantly (P < .001) thinner in AMD subjects (73.71 ± SD; 13.77 µm) compared to normals (77.97 ± 10.42 µm). An independent t test showed that the early AMD (75.03 ± 12.45 µm) and late AMD (61.64 ± 21.18 µm) groups (among which eyes with geographic atrophy [GA] had the lowest thickness, of 58.10 ± 20.27 µm) had a statistically significant lower GCC thickness compared to eyes without AMD. There was no significant differences in average GCC thickness between early AMD and intermediate AMD (76.36 ± 9.25 µm) eyes. The GCC thickness in AMD eyes is reduced compared to normal eyes; however, the relationship is complex, with the greatest reduction in late AMD eyes (particularly eyes with GA) but no difference between early and intermediate AMD eyes.

Recall of Autobiographical Memories Following Odor vs Verbal Cues Among Adults With Major Depressive Disorder

Major depressive disorder (MDD) is associated with deficits in autobiographical memory (AM) recall, which is thought to stem from disruptions in effortful recall. Understanding whether these deficits are mitigated when recall is stimulated more directly, such as by odor cues, could inform therapeutic interventions for MDD. To evaluate whether deficits in specific AM recall in MDD are mitigated when odor cues vs word cues are used to prompt memory. This cross-sectional study assessed recall of specific AMs in response to both odor cues and word cues (in a randomized, counterbalanced order) in a repeated measures design. Data were collected between September 2021 and November 2022. The study took place at the University of Pittsburgh School of Medicine in Pennsylvania and included adults with a primary diagnosis of MDD, according to the Mini International Neuropsychiatric Interview. Data were analyzed from January to June 2023. The primary outcome measure was the percentage of specific AMs recalled in response to odor-cued memories vs word-cued memories. Additional outcome measures included ratings of arousal, vividness, repetition, and recall response time for odor-cued memories vs word-cued memories. Thirty-two adults (mean [SD] age, 30.0 [10.1] years; 26 [81.3%] female; 6 [18.8%] male) with a primary diagnosis of MDD completed the study. Participants recalled more specific AMs for odor cues than word cues (mean [SD], 68.4% [20.4%] vs 52.1% [23.3%]; Cohen d, 0.78; P < .001). Additionally, odor-cued recall was rated more arousing (mean [SD], 3.0 [0.8] vs 2.6 [0.7]; Cohen d, 1.28; P < .001) and vivid (mean [SD], 3.3 [0.7] vs 3.0 [0.7]; Cohen d, 0.67; P < .001), and was slower than word-cued recall (mean [SD], 14.5 [3.6] vs 8.9 [3.4] seconds; Cohen d, 1.18; P < .001). When compared with the population mean for word cues in healthy controls (80%), participants recalled fewer specific memories in response to words (Cohen d, 1.18; P < .001), supporting the presence of overgenerality. Notably, the percentage of specific memories recalled in response to odor cues did not differ from the healthy control population mean (Cohen d, 0.26; P = .15). In this cross-sectional study, adults with MDD recalled more specific AMs in response to odor cues compared with word cues. This study suggests that AM deficits may only be observed when verbal cues are used and provides a potential new method for increasing specific AM recall in patients with MDD.

Functional evaluation of a novel fibreglass-reinforced polyamide custom dynamic AFO for foot drop patients: A pilot study

BackgroundAnkle-foot orthoses (AFOs) are orthopaedic devices often prescribed to treat foot drop. For patients who are not satisfied with off-the-shelf solutions, custom AFOs personalized to the patient's lower limb anatomy are required. Dynamic AFOs provide stability while allowing for physiological ankle mobility in the stance phase of walking. Research questionCan a morphology-based dynamic custom AFO made of fiberglass-reinforced polyamide restore a quasi-normal gait pattern and improve comfort in patients with foot drop? MethodsIn this pilot study, the legs and feet of ten foot drop patients (age=64.9 ± 11.4 years; BMI=26.2 ± 2.1 kg/m2) were scanned using a Kinect-based 3D scanner. A custom AFO was designed and produced for each patient using a fiberglass-reinforced polyamide through selective laser sintering. To assess kinematics, skin markers were placed on relevant bony landmarks according to a validated protocol. Each patient was instructed to walk at a self-selected comfortable speed under three conditions: wearing the custom AFO, wearing an off-the-shelf orthosis (Codivilla spring), and without any AFO (shod condition). Muscle activation in the tibialis anterior, gastrocnemius, rectus femoris and biceps femoris muscles in both legs was recorded using wireless sEMG sensors. The comfort and of each AFO was evaluated using a Visual Analogue Scale. ResultsThe custom AFO resulted in significant increase of stride length and walking speed compared to the shod condition. Except for the hip joint, which exhibited greater maximum flexion and reduced range of motion, the kinematic parameters of all other joints were similar to those observed in a healthy control population. Furthermore, the custom AFO received significantly higher comfort scores compared to the Codivilla spring. SignificanceThis study has provided evidence supporting the effectiveness of custom orthotic solutions in restoring lower limb kinematics and improving the perceived comfort in foot drop patients compared to off-the-shelf solutions.

Erratum: An integrated analysis of fecal microbiome and metabolomic features distinguish non-cirrhotic NASH from healthy control populations.

Erratum: An integrated analysis of fecal microbiome and metabolomic features distinguish non-cirrhotic NASH from healthy control populations.