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Biological and glucocorticoids treatment impair the medium-term immunogenicity to SARS-CoV-2 mRNA vaccines in autoimmune inflammatory rheumatic diseases

Eur J Med Res. 2024 Jan 5;29(1):28. doi: 10.1186/s40001-023-01620-7.

ABSTRACT

BACKGROUND: This study aims to assess the sustained immunological response to the SARS-CoV-2 vaccine in patients with autoimmune inflammatory rheumatic diseases (AIRD) undergoing different treatment regimens.

METHODS: We conducted a prospective observational study involving 157 AIRD patients without prior COVID-19 infection. Treatment regimens included non-treatment or glucocorticoid-only (not-treated/GCs), non-biological drugs, biological therapy, and JAK inhibitors. All participants completed the two-dose vaccine schedule, and 110 of them received an additional booster dose. Serum samples were collected approximately 3-6 months after the second and third vaccine doses to measure antibodies against the Spike protein (antiS-AB) and neutralizing antibodies (nAB) targeting six SARS-CoV-2 variants.

RESULTS: Following the third dose, all patients exhibited a significant increase in antiS-AB (FC = 15, p < 0.0001). Patients under biological therapy had lower titres compared to the non-biological (66% decrease, p = 0.038) and the not-treated/GCs group (62% decrease, p = 0.0132), with the latter persisting after the booster dose (86% decrease, p = 0.0027). GC use was associated with lower antiS-AB levels in the biological group (87% decrease, p = 0.0124), although not statistically significant after confounders adjustment. nABs showed the highest positivity rates for the wild-type strain before (50%) and after the booster dose (93%), while the Omicron variant exhibited the lowest rates (11% and 55%, respectively). All variants demonstrated similar positivity patterns and good concordance with antiS-AB (AUCs from 0.896 to 0.997).

CONCLUSIONS: The SARS-CoV-2 vaccine booster strategy effectively elicited a sustained antibody immune response in AIRD patients. However, patients under biological therapies exhibited a reduced response to the booster dose, particularly when combined with GCs.

PMID:38183092 | DOI:10.1186/s40001-023-01620-7

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Physical activity practiced at a young age is associated with a less severe subsequent clinical presentation in facioscapulohumeral muscular dystrophy

BMC Musculoskelet Disord. 2024 Jan 5;25(1):35. doi: 10.1186/s12891-023-07150-x.

ABSTRACT

BACKGROUND: In facioscapulohumeral muscular dystrophy (FSHD), it is not known whether physical activity (PA) practiced at young age is associated with the clinical presentation of disease. To assess this issue, we performed a retrospective cohort study concerning the previous practice of sports and, among them, those with medium-high cardiovascular commitment in clinically categorized carriers of a D4Z4 reduced allele (DRA).

METHODS: People aged between 18 and 60 were recruited as being DRA carriers. Subcategory (classical phenotype, A; incomplete phenotype, B; asymptomatic carriers, C; complex phenotype, D) and FSHD score, which measures muscle functional impairment, were assessed for all participants. Information on PAs was retrieved by using an online survey dealing with the practice of sports at a young age.

RESULTS: 368 participants were included in the study, average age 36.6 years (SD = 9.4), 47.6% male. The FSHD subcategory A was observed in 157 (42.7%) participants with average (± SD) FSHD score of 5.8 ± 3.0; the incomplete phenotype (category B) in 46 (12.5%) participants (average score 2.2 ± 1.7) and the D phenotype in 61 (16.6%, average score 6.5 ± 3.8). Asymptomatic carriers were 104 (subcategory C, 28.3%, score 0.0 ± 0.2). Time from symptoms onset was higher for patients with A (15.8 ± 11.1 years) and D phenotype (13.3 ± 11.9) than for patients with B phenotype (7.3 ± 9.0). The practice of sports was associated with lower FSHD score (-17%) in participants with A phenotype (MR = 0.83, 95% CI = 0.73-0.95, p = 0.007) and by 33% in participants with D phenotype (MR = 0.67, 95% CI = 0.51-0.89, p = 0.006). Conversely, no improvement was observed in participants with incomplete phenotype with mild severity (B).

CONCLUSIONS: PAs at a young age are associated with a lower clinical score in the adult A and D FSHD subcategories. These results corroborate the need to consider PAs at the young age as a fundamental indicator for the correct clinical stratification of the disease and its possible evolution.

PMID:38183077 | DOI:10.1186/s12891-023-07150-x

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The role of dairy consumption in the relationship between wealth and early life physical growth in India: evidence from multiple national surveys

BMC Public Health. 2024 Jan 5;24(1):96. doi: 10.1186/s12889-023-17520-8.

ABSTRACT

INTRODUCTION: Prevalence of undernutrition continues to be high in India and low household wealth is consistently associated with undernutrition. This association could be modified through improved dietary intake, including dairy consumption in young children. The beneficial effect of dairy on child growth has not been explored at a national level in India. The present analyses aimed to evaluate the direct and indirect (modifying association of household level per adult female equivalent milk and milk product consumption) associations between household wealth index on height for age (HAZ) and weight for age (WAZ) in 6-59 months old Indian children using data from of nationally representative surveys.

METHODS: Two triangulated datasets of two rounds of National Family Health Survey, (NFHS-3 and 4) and food expenditure (National Sample Survey, NSS61 and 68) surveys, were produced by statistical matching of households using Non-Iterative Bayesian Approach to Statistical Matching technique. A Directed Acyclic Graph was constructed to map the pathways in the relationship of household wealth with HAZ and WAZ based on literature. The direct association of wealth index and its indirect association through per adult female equivalent dairy consumption on HAZ and WAZ were estimated using separate path models for each round of the surveys.

RESULTS: Wealth index was directly associated with HAZ and WAZ in both the rounds, but the association decreased from NFHS-3 (βHAZ: 0.145; 95% CI: 0.129, 0.16) to NFHS-4 (βHAZ: 0.102; 95%CI: 0.093, 0.11). Adult female equivalent milk intake (increase of 10gm/day) was associated with higher HAZ (β_NFHS-3=0.001;95% CI: 0, 0.002; β_NFHS-4=0.002;95% CI: 0.002, 0.003) but had no association with WAZ. The indirect association of wealth with HAZ through dairy consumption was 2-fold higher in NFHS-4 compared to NFHS-3.

CONCLUSIONS: The analysis of triangulated survey data shows that household level per- adult female equivalent dairy consumption positively modified the association between wealth index and HAZ, suggesting that regular inclusion of milk and milk products in the diets of children from households across all wealth quintiles could improve linear growth in this population.

PMID:38183073 | DOI:10.1186/s12889-023-17520-8

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A comparative study of the CT effective dose in whole-body 18F-FDG PET/CT for arm-raised position and arm-lowered position

Radiography (Lond). 2024 Jan 4;30(1):416-421. doi: 10.1016/j.radi.2023.12.012. Online ahead of print.

ABSTRACT

INTRODUCTION: This study aimed to investigate and compare the effective dose (ED) delivered by computed tomography (CT) in whole-body positron emission tomography/CT (WB-PET/CT) scans between patients positioned with their arms-raised and those with their arms-lowered during the scan on a large population.

METHODS: The retrospective study involved 785 oncology patients who underwent WB-PET/CT scans with 18F-FDG between January and June 2019. Exclusion criteria were applied, resulting in a final analysis of data from 732 adult patients. All of the patients were measured height and weight, and the ED from CT in WB-PET/CT was estimated using the dose length product value and a conversion factor. Statistical analyses were conducted to explore relationships between factors and the ED. Linear regression analysis was performed to investigate connections between weight and ED, and height and ED. Multiple linear regression was used to predict ED based on sex, weight, and arm position.

RESULTS: The arm-lowered group had a higher ED than the arm-raised group, and the median dose was 1.1 times higher in the arm-lowered group. The difference in ED between the two groups was found to be greater with higher body weight. Arm-position (β = 0.460), sex (β = -0.190), and weight (β = 0.057) were significant predictors of ED.

CONCLUSION: This study demonstrated that arm position, sex, and weight were significant factors influencing the ED from CT scans in WB-PET/CT.

IMPLICATIONS FOR PRACTICE: The research underscores the importance of considering these factors when evaluating radiation exposure in clinical practice, particularly for patients undergoing WB-CT imaging. These findings contribute to a better understanding of the radiation dosimetry associated with different patient positions during WB-PET/CT scans.

PMID:38181465 | DOI:10.1016/j.radi.2023.12.012

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A longitudinal analysis of the impact of the local tobacco retail availability and neighbourhood deprivation on male smoking behaviours in Shanghai, China

Health Place. 2024 Jan 4;85:103171. doi: 10.1016/j.healthplace.2023.103171. Online ahead of print.

ABSTRACT

Some evidence from Western high-income countries suggests local tobacco retail availability and neighbourhood deprivation may influence smoking behaviours. However, this assertion has not been considered in China, where 44% of males continue to smoke. Data were analysed from Chinese males (n = 2054) who participated in Waves 3-5 (2009-2015) of the International Tobacco Control (ITC) China Survey by linking information on tobacco retail availability (estimated through population weighted Kernel Density of tobacco retailers in 2019) and neighbourhood deprivation (calculated as a composite score derived from the 2010 Chinese census) across Shanghai. Generalised Estimating Equation models were fitted to examine the impacts of local tobacco availability and neighbourhood deprivation on smoking behaviours (current smoking versus current non-smoking, quitting versus current smoking, longer durations of smoking abstinence versus current smoking) using the longitudinal data. Examining the impacts separately, participants living in neighbourhoods with greater availability and higher levels of deprivation were less likely to maintain longer durations of smoking abstinence in both unadjusted and adjusted models. Neighbourhood deprivation, but not availability, was found to be associated with higher odds of being a current smoker. Examining the impacts jointly, neighbourhood deprivation was still positively associated with current smoking and negatively associated with longer durations of smoking abstinence, but the negative association between availability and longer durations of smoking abstinence disappeared. The findings offer some evidence that greater tobacco retail availability and deprivation are obstacles on prolonged smoking cessation among males in Shanghai, China. Policymakers should consider small-area level place-based restrictions in China, such as reducing the availability of tobacco, as part of a comprehensive tobacco control strategy aimed at addressing the high prevalence of smoking.

PMID:38181462 | DOI:10.1016/j.healthplace.2023.103171

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Intra-rater and inter-rater reliability of 3D facial measurements

Appl Ergon. 2024 Jan 4;116:104218. doi: 10.1016/j.apergo.2023.104218. Online ahead of print.

ABSTRACT

Three-dimensional (3D) body scanning technology has applications for obtaining anthropometric data in human-centered and product development fields. The reliability of 3D measurements gathered from 3D scans must be assessed to understand the degree to which this technology is appropriate for use in place of manual anthropometric methods. The intra- and inter-rater reliabilities of 3D facial measurements were assessed among four novice raters using 3D landmarking. Intraclass correlation coefficient (ICC) statistics were calculated for the 3D measurement data collected in three phases to assess baseline reliabilities and improvements in reliabilities as the result of additional training and experience. Based on the results of this study, the researchers found that the collection of 3D measurement data, by multiple raters and using 3D landmarking methods, yielded a high percentage of ICC statistics in the good to excellent (>0.75 ICC) reliability range. Rater training and experience were important considerations in improving intra- and inter-rater reliabilities.

PMID:38181456 | DOI:10.1016/j.apergo.2023.104218

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Autologous bone marrow mononuclear cells to treat severe traumatic brain injury in children

Brain. 2024 Jan 5:awae005. doi: 10.1093/brain/awae005. Online ahead of print.

ABSTRACT

Autologous bone marrow mononuclear cells (BMMNCs) infused after severe traumatic brain injury have shown promise for treating the injury. We evaluated their impact in children, particularly their hypothesized ability to preserve the blood-brain barrier and diminish neuroinflammation, leading to structural central nervous system preservation with improved outcomes. We performed a randomized, double-blind, placebo-sham-controlled Bayesian dose-escalation clinical trial at 2 children’s hospitals in Houston, TX and Phoenix, AZ, USA (NCT01851083). Patients 5-17 years of age with severe traumatic brain injury (Glasgow Coma Scale ≤ 8) were randomized to BMMNC or placebo (3:2). Bone marrow harvest, cell isolation, and infusion were completed by 48 hours post-injury. Bayesian continuous reassessment method was used with cohorts of size 3 in the BMMNC group to choose the safest between 2 doses. Primary endpoints were quantitative brain volumes using magnetic resonance imaging and microstructural integrity of the corpus callosum (CC; diffusivity and edema measurements) at 6 months and 12 months. Long-term functional outcomes and ventilator days, intracranial pressure monitoring days, intensive care unit days, and therapeutic intensity measures were compared between groups. Forty-seven patients were randomized, with 37 completing 1-year follow-up (23 BMMNC, 14 placebo). BMMNC treatment was associated with an almost 3-day (23%) reduction in ventilator days, 1-day (16%) reduction in intracranial pressure monitoring, and 3-day (14%) reduction in intensive care unit (ICU) days. White matter volume at 1 year in the BMMNC group was significantly preserved compared to placebo (decrease of 19891 vs 40491, respectively; mean difference of -20600, 95% CI: -35868 to -5332; P = 0.01), and the number of CC streamlines was reduced more in placebo than BMMNC, supporting evidence of preserved CC connectivity in the treated groups (-431 streamlines placebo vs. -37 streamlines BMMNC; mean difference of -394, 95% CI: -803 to 15; P = 0.055), but this did not reach statistical significance due to high variability. We conclude that autologous BMMNC infusion in children within 48 hours after severe traumatic brain injury is safe and feasible. Our data show that BMMNC infusion led to 1) shorter intensive care duration and decreased ICU intensity; 2) white matter structural preservation; and 3) enhanced CC connectivity and improved microstructural metrics.

PMID:38181433 | DOI:10.1093/brain/awae005

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Epigenetic control of adamantinomatous craniopharyngiomas

J Clin Endocrinol Metab. 2024 Jan 5:dgae006. doi: 10.1210/clinem/dgae006. Online ahead of print.

ABSTRACT

INTRODUCTION: Studies addressing the methylation pattern in adamantinomatous craniopharyngioma (ACP) are lacking.

OBJECTIVE: To identify methylation signatures in ACPs regarding clinical presentation and outcome.

METHODS: Clinical and pathology data were collected from 35 ACP patients (54% male; 18.1 years [2-68]). CTNNB1 mutations and methylation profile (MethylationEPIC/Array-Illumina) were analyzed in tumoral DNA. Unsupervised machine learning analysis of this comprehensive methylome sample was achieved using hierarchical clustering and multi-dimensional scaling. Statistical associations between clusters and clinical features were achieved using Fisher’s test and global biological process interpretations were aided by Gene Ontology enrichment analyses.

RESULTS: Two clusters were revealed consistently by all unsupervised methods (ACP-1: n = 18; ACP-2: n = 17) with strong bootstrap statistical support. ACP-2 was enriched by CTNNB1 mutations (100% vs 56%, P = 0.0006), hypomethylated in CpG Island (CGI), non-CGI sites, and globally (P < 0.001), and associated with greater tumor size (24.1 vs 9.5cm3, P = 0.04). Enrichment analysis highlighted pathways on signaling transduction, transmembrane receptor, development of anatomical structures, cell-adhesion, cytoskeleton organization, and cytokine binding, and also cell-type specific biological processes as regulation of oligodendrocytes, keratinocyte, and epithelial cells differentiation.

CONCLUSION: Two clusters of ACP patients were consistently revealed by unsupervised machine learning methods, being one of them significantly hypomethylated, enriched by CTNNB1 mutated ACPs, and associated with increased tumor size. Enrichment analysis reinforced pathways involved in tumor proliferation and in cell-specific tumoral microenvironment.

PMID:38181427 | DOI:10.1210/clinem/dgae006

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Hyperspectral Mapping of Human Primary and Stem Cells at Cell-Matrix Interfaces

ACS Appl Mater Interfaces. 2024 Jan 5. doi: 10.1021/acsami.3c17113. Online ahead of print.

ABSTRACT

Extracellular matrices interface with cells to promote cell growth and tissue development. Given this critical role, matrix mimetics are introduced to enable biomedical materials ranging from tissue engineering scaffolds and tumor models to organoids for drug screening and implant surface coatings. Traditional microscopy methods are used to evaluate such materials in their ability to support exploitable cell responses, which are expressed in changes in cell proliferation rates and morphology. However, the physical imaging methods do not capture the chemistry of cells at cell-matrix interfaces. Herein, we report hyperspectral imaging to map the chemistry of human primary and embryonic stem cells grown on matrix materials, both native and artificial. We provide the statistical analysis of changes in lipid and protein content of the cells obtained from infrared spectral maps to conclude matrix morphologies as a major determinant of biochemical cell responses. The study demonstrates an effective methodology for evaluating bespoke matrix materials directly at cell-matrix interfaces.

PMID:38181419 | DOI:10.1021/acsami.3c17113

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Novel Left Ventricular Unloading Strategies in Patients on Peripheral Venoarterial Extracorporeal Membrane Oxygenation Support

ASAIO J. 2024 Jan 5. doi: 10.1097/MAT.0000000000002136. Online ahead of print.

ABSTRACT

The purpose of this study was to evaluate left ventricular (LV) unloading strategies in patients supported with peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO). A retrospective review was conducted of all consecutive patients requiring VA-ECMO support for any indication, who underwent novel LV unloading strategies with either direct left atrial venoarterial (LAVA) cannulation or pulmonary artery venoarterial (PAVA) venting, in comparison to Impella and intra-aortic balloon pump (IABP). The primary outcome was successful bridge to transplant, LV assist device, or myocardial recovery. Forty-six patients (63% male, mean age 52.8 ± 17.6 years) were included. Fourteen patients (30%) underwent novel unloading with either LAVA or PAVA, 11 patients (24%) underwent IABP placement, and 21 patients (46%) underwent Impella insertion. In the novel LV unloading cohort, 10 patients (71%) survived to hospital discharge. Four patients (29%) were weaned from ECMO and eight patients (57%) underwent cardiac transplantation. Although a trend favoring cannula-based unloading for the primary outcome was noted, the cohort was too small for statistical significance (79% LAVA/PAVA, 57% Impella, 45% IABP; p = 0.21). However, probability of survival was greater in the LAVA/PAVA cohort compared to Impella and IABP (p < 0.05). Thus, we demonstrate the efficacy of LA and PA cannulation as an alternative LV unloading strategy for patients supported with peripheral VA-ECMO.

PMID:38181416 | DOI:10.1097/MAT.0000000000002136