Tag: nevin manimala

Ann Rheum Dis. 2023 Nov 2:ard-2023-224732. doi: 10.1136/ard-2023-224732. Online ahead of print.

ABSTRACT

OBJECTIVE: Relapsing polychondritis (RP) is a systemic inflammatory disease of unknown aetiology. The objective of this study was to examine the contribution of rare genetic variations to RP.

METHODS: We performed a case-control exome-wide rare variant association analysis that included 66 unrelated European American cases with RP and 2923 healthy controls (HC). Gene-level collapsing analysis was performed using Firth’s logistics regression. Exploratory pathway analysis was performed using three different methods: Gene Set Enrichment Analysis, sequence kernel association test and higher criticism test. Plasma DCBLD2 levels were measured in patients with RP and HC using ELISA.

RESULTS: In the collapsing analysis, RP was associated with a significantly higher burden of ultra-rare damaging variants in the DCBLD2 gene (7.6% vs 0.1%, unadjusted OR=79.8, p=2.93×10^-7). Plasma DCBLD2 protein levels were significantly higher in RP than in HC (median 4.06 ng/µL vs 0.05 ng/µL, p<0.001). The pathway analysis revealed a statistically significant enrichment of genes in the tumour necrosis factor signalling pathway driven by rare damaging variants in RELB, RELA and REL using higher criticism test weighted by eigenvector centrality.

CONCLUSIONS: This study identified specific rare variants in the DCBLD2 gene as a putative genetic risk factor for RP. These findings should be validated in additional patients with RP and supported by future functional experiments.

PMID:37918895 | DOI:10.1136/ard-2023-224732

Ann Rheum Dis. 2023 Nov 2:ard-2023-224623. doi: 10.1136/ard-2023-224623. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare the long-term efficacy and safety of azathioprine (AZA), 18-month fixed-schedule rituximab (RTX), 18-month tailored RTX and 36-month RTX in preventing relapses in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis who achieved a complete remission after induction therapy. Patients treated with 36-month RTX received either a fixed or a tailored regimen for the first 18 months and a fixed regimen for the last 18 months (36-month fixed/fixed RTX and 36-month tailored/fixed RTX, respectively).

METHODS: The Maintenance of Remission using Rituximab in Systemic ANCA-associated Vasculitis (MAINRITSAN) trials sequentially compared: 18-month fixed-schedule RTX versus AZA (MAINRITSAN); 18-month fixed-schedule RTX versus 18-month tailored-RTX (MAINRITSAN2); and extended therapy to 36 months with four additional RTX infusions after MAINRITSAN2 versus placebo (MAINRITSAN3). Patients were then followed prospectively through month 84 and their data were pooled to analyse relapses and adverse events. The primary endpoint was relapse-free survival at month 84.

RESULTS: 277 patients were enrolled and divided in 5 groups: AZA (n=58), 18-month fixed-schedule RTX (n=97), 18-month tailored-RTX (n=40), 36-month tailored/fixed RTX (n=42), 36-month fixed/fixed RTX (n=41). After adjustment for prognostic factors, 18-month fixed-schedule RTX was superior to AZA in preventing major relapses at month 84 (HR 0.38, 95% CI 0.20 to 0.71). The 18-month tailored-RTX regimen was associated with an increased risk of major relapse compared with fixed-schedule regimen (HR 2.92, 95% CI 1.43 to 5.96). The risk of major relapse was similar between 36-month fixed/fixed and 18-month fixed-RTX (HR 0.69, 95% CI 0.38 to 1.25).

CONCLUSIONS: According to these results, it appears that the 84-month remission rate is higher with an 18-month fixed RTX regimen compared with AZA and 18-month tailored RTX. Also, extending RTX to 36 months does not appear to reduce the long-term relapse rate compared with the 18-month fixed RTX regimen. However, as this study was underpowered to make this comparison, further prospective studies are needed to determine the potential long-term benefits of extending treatment in these patients.

PMID:37918894 | DOI:10.1136/ard-2023-224623

Ann Rheum Dis. 2023 Nov 2:ard-2023-224501. doi: 10.1136/ard-2023-224501. Online ahead of print.

ABSTRACT

OBJECTIVES: Investigating the association between different definitions of axial involvement and syndesmophytes development over 2 years in patients with psoriatic arthritis (PsA).

METHODS: Patients from a prospective multicentre cohort (Belgian Epidemiological Psoriatic Arthritis Study) involving 17 Belgian rheumatology practices were recruited between December 2012 and July 2014 and included when fulfilling the Classification Criteria for Psoriatic Arthritis. Axial involvement included six clinical and two radiographic oriented definitions.Two calibrated central readers evaluated radiographic damage by assessing the modified Stoke Ankylosing Spondylitis Spinal Score and modified New York criteria. New syndesmophytes after 2 years were described conditional on axial involvement at baseline. Logistic regression analyses were used to investigate the association between syndesmophyte development and axial involvement. All definitions of axial involvement were evaluated separately.

RESULTS: From 150 patients, a 2-year follow-up of spinal radiographs was obtained. There are 11 patients with new syndesmophytes after 2 years. For the clinical definitions of axial involvement ‘global assessment’, ‘detailed assessment’, ‘back pain (BP)’ and ‘inflammatory BP (IBP)’ the probabilities of developing syndesmophytes ranged between 0.06 and 0.08 and were similar for the presence or absence of the definition. When including elevated C reactive protein (CRP) to the definitions the probability of developing syndesmophytes over 2 years increased two times for CBP and seven times for IBP.With radiographic axial involvement a similar trend was seen; radiographic sacroiliitis as definition showed a probability three times higher. When combined with elevated CRP there would be a 14 times higher chance to develop syndesmophytes in 2 years. The ORs varied from 0.83 to 13.80, though none of them were statistically significant.

CONCLUSIONS: The likelihood of syndesmophyte formation in PsA is low. The probability of developing syndesmophytes is much higher when axial involvement is determined radiographically rather than clinically, particularly in the context of high CRP.

PMID:37918893 | DOI:10.1136/ard-2023-224501

Z Geburtshilfe Neonatol. 2023 Nov 2. doi: 10.1055/a-2180-7302. Online ahead of print.

ABSTRACT

INTRODUCTION: Pregnant women and their offspring represented a vulnerable patient collective during the Covid-19 pandemic. Beyond the direct effect of SARS-CoV-2 via vertical transmission, an indirect impact on the fetus can occur through placental lesions deteriorating placental villous function. We performed a histopathological analysis of placentas of parturients with SARS-CoV-2 compared to healthy controls.

METHODS AND MATERIALS: Between February 2022 and July 2022 we conducted a prospective case-control study analyzing placental specimens of parturients with SARS-CoV-2 infection compared to specimens of placentas of healthy controls. Patient history, Covid-19-specific symptoms, and obstetric outcomes were recorded. Statistical analysis was performed.

RESULTS: During the observation period 71 patients were included with a gestational age 37 1/7-41 5/7 weeks. Thirty-six patients presented with SARS-CoV-2 infection. The control group consisted of 35 patients and showed no placental abnormalities. Among SARS-CoV-2-positive parturients, 66.7% of placentas of the case group showed histopathological abnormalities classified as vascular or inflammatory abnormalities. 22.2% of placentas showed acute ischemic infarction areas. 8.3% of placentas showed subchorionic layered thrombi. There was one case of severe acute subchorionitis. SARS-CoV-2 increased the risk of placental lesions significantly (OR 3.000, CI 1.890-4.762, p=0.0001). Placental lesions had no significant impact on perinatal acidosis (OR 0.455, CI 0.044-4.667, p=0.498) or number of cesarean sections (OR 2.314, CI 0.717-7.473, p=0.156).

CONCLUSION: SARS-CoV-2 infection during labor and delivery increased the risk of adverse outcomes. Histopathological analysis indicated that the placenta as a maternal-fetal interface was affected by SARS-CoV-2, leading to systemic vasculopathy and inflammation.

PMID:37918832 | DOI:10.1055/a-2180-7302

Metabolism. 2023 Oct 31:155715. doi: 10.1016/j.metabol.2023.155715. Online ahead of print.

ABSTRACT

BACKGROUND: Computed tomography (CT) imaging is widely used for diagnosing and determining the severity of coronavirus disease 2019 (COVID-19). Chest CT imaging can be used to calculate the epicardial adipose tissue (EAT) and upper abdominal visceral adipose tissue (Abd-VAT) areas. The EAT is the main source of inflammatory cytokines involved in chest inflammatory diseases; thus, the EAT area might be a more useful severity predictor than the Abd-VAT area for COVID-19. However, to the best of our knowledge, there are no large-scale reports that sufficiently consider this issue. In addition, there are no reports on the characteristics of patients with normal body mass index (BMI) and high adipose tissue.

AIM: The purpose of this study was to analyze whether the EAT area, among various adipose tissues, was the most associated factor with COVID-19 severity. Using a multicenter COVID-19 patient database, we analyzed the associations of chest subcutaneous, chest visceral, abdominal subcutaneous, and Abd-VAT areas with COVID-19 outcomes. In addition, the clinical significance of central obesity, commonly disregarded by BMI, was examined.

METHODS: This retrospective cohort study evaluated patients with COVID-19 aged ≥18 years In Japan. Data including from chest CT images collected between February 2020 and October 2022 in four hospitals of the Japan COVID-19 Task Force were analyzed. Patient characteristics and COVID-19 severity were compared according to the adipose tissue areas (chest and abdominal subcutaneous adipose tissue [Chest-SAT and Abd-SAT], EAT, and Abd-VAT) calculated from chest CT images.

RESULTS: We included 1077 patients in the analysis. Patients with risk factors of severe COVID-19 such as old age, male sex, and comorbidities had significantly higher areas of EAT and Abd-VAT. High EAT area but not high Abd-VAT area was significantly associated with COVID-19 severity (adjusted odds ratio (aOR): 2.66, 95 % confidence interval [CI]: 1.19-5.93). There was no strong correlation between BMI and VAT. Patients with high VAT area accounted for 40.7 % of the non-obesity population (BMI < 25 kg/m²). High EAT area was also significantly associated with COVID-19 severity in the non-obesity population (aOR: 2.50, 95 % CI: 1.17-5.34).

CONCLUSIONS: Our study indicated that VAT is significantly associated with COVID-19 severity and that EAT is the best potential predictor for risk stratification in COVID-19 among adipose tissue areas. Body composition assessment using EAT is an appropriate marker for identifying obesity patients overlooked by BMI. Considering the next pandemic of the global health crisis, our findings open new avenues for implementing appropriate body composition assessments based on CT imaging.

PMID:37918794 | DOI:10.1016/j.metabol.2023.155715

Environ Pollut. 2023 Oct 31:122795. doi: 10.1016/j.envpol.2023.122795. Online ahead of print.

ABSTRACT

With growing concerns regarding the ecological and human risks of organic micropollutants (OMPs) in water, much effort has been devoted worldwide to establishing quality standards and compiling candidate and watch lists. Although bank filtration is recognized as an efficient natural water treatment in the removal of contaminants such as OMPs, the increase in exploitation requires continuous assessment of removal efficiency. This review aims to provide a critical overview of BF reports on more than a hundred priority substances (PSs) and compounds of emerging concern (CECs) listed in the relevant European Union regulations. Field- and lab-scale studies analyzing the removal efficiency and its variance of individual OMPs and biological indicators using BF and the main influencing factors and their interactions, shortcomings, and future challenges are discussed in this review. The removal efficiency of EU-relevant contaminants by BF has been comprehensively investigated for only a few pollutants listed in the environmental EU regulations: pharmaceutically active compounds, (e.g., the anti-inflammatory drug diclofenac, some antibiotics (e.g., sulfamethoxazole and trimethoprim)), a few pesticides (e.g., atrazine), and faecal indicators such as Escherichia coli. In many cases, the measured concentrations of PSs and CECs have not been published numerically, which hinders comprehensive statistical analysis. Although BF is one of the most cost-effective and efficient water treatments, present field and lab studies have demonstrated the diversity of site-specific factors affecting its efficiency. Even in the case of substances known to be removed by BF, the efficiency rates can vary with environmental and anthropogenic factors (e.g., hydrogeological parameters and the contamination level of infiltrating water) and abstraction well parameters (e.g., the depth, distance, and pumping volume). The published removal rate variations and influencing factors often reflect the research design (field or lab-scale), which can lead to ambiguities.

PMID:37918769 | DOI:10.1016/j.envpol.2023.122795

Sci Total Environ. 2023 Oct 31:168120. doi: 10.1016/j.scitotenv.2023.168120. Online ahead of print.

ABSTRACT

The chemical composition of river waters represents an important matter of investigation to understand environment modifications in response to climate changes and global warming. Prolonged dry periods, heavy flood events, degradation of the lands and ice thawing, modify the chemical composition of river waters influencing the drivers governing the complex dynamics of river catchments where everything comes together. In this framework, Compositional Data Analysis (CoDA) offers methods in which the complex structure of the river water composition and the interrelationships among the various components are put into the proper context for their statistical analysis. In this research, we propose a new CoDA approach combining the robust Mahalanobis distance (D) calculus of ilr-transformed chemical variables and the perturbation difference, both with respect to a pristine compositional benchmark. The aim was to trace the change in the chemical composition of the Eastern Siberian River Chemistry Database where degradation of the permafrost for global warming produces important effects on natural waters. The findings indicate complex multiplicative laws and feedback mechanisms governing solutes in Eastern Siberian rivers, with high values of D found where permafrost is more discontinuous. Perturbations clearly discriminate chemical components more resilient to stresses induced by global changes (Ca²⁺, Mg²⁺ and HCO₃^–) from those whose variability is not maintained under control (Cl^–, Na⁺, SO₄^2-). These outcomes open up a new scenario in searching for spatiotemporal resilience metrics to reveal rivers response to environmental changes.

PMID:37918739 | DOI:10.1016/j.scitotenv.2023.168120

J AAPOS. 2023 Oct 31:S1091-8531(23)00226-4. doi: 10.1016/j.jaapos.2023.08.015. Online ahead of print.

ABSTRACT

BACKGROUND: Psychosocial metrics associated with self-reported blindness or visual impairment for adolescents in the National Survey of Drug Use and Health (NSDUH) have not been fully characterized. This retrospective cohort analysis of the latest NSDUH aimed to determine novel characteristics associated with self-reported visual loss among adolescents in the United States.

METHODS: Data from the NSDUH2020, a publicly available, federally validated database, were analyzed. Self-reported severe visual impairment or blindness was defined as being truly blind or having serious difficulty seeing even when wearing corrective lenses (s-rSVI). Inclusion criteria were all cases of s-rSVI in adolescents aged 12-17 years. NSDUH weights were used to accommodate complex survey design, nonresponse rates, and population variance. Weighted percentages, asymptotic two-sided Rao-Scott χ² analyses, and multivariable binary logistic regression were performed. Statistical significance was considered reached at P < 0.05.

RESULTS: A total of 5,667 adolescents aged 12-17 years were surveyed, and s-rSVI occurred in 236 cases (weighted percentage, 3.48%). Within our final risk model, characteristics associated with enhanced odds of s-rSVI based on multivariable logistic regression analysis were female sex, Asian and Latino race/ethnicity (relative to non-Hispanic White), and self-reported serious difficulty hearing and concentrating (all P < 0.05).

CONCLUSIONS: This national retrospective cohort analysis highlights risk factors associated with s-rSVI for adolescents within the 2020 NSDUH. Clinicians and policymakers should consider at-risk demographics for s-rSVI during development and enhancement of screening programs, population health initiatives, and healthcare policy issues.

PMID:37918705 | DOI:10.1016/j.jaapos.2023.08.015

Orthop Traumatol Surg Res. 2023 Oct 31:103745. doi: 10.1016/j.otsr.2023.103745. Online ahead of print.

ABSTRACT

BACKGROUND: Glenoid Bone Loss (GBL) calculation in patients with shoulder instability has a wide variability in methods and their reliability. The purpose of this study was to describe and validate a new semi-automated software developed to improve GBL calculation using a 3D imaging modeling (IODA-shoulder) and to compare the method to the PICO area method.

PATIENTS AND METHODS: A semi-automated software to assess GBL was preliminary developed and validated on 7 fresh frozen specimens (scapulae with handmade glenoid defect), using water displacement method. Afterwards, the software was retrospectively deployed in 20 patients affected by recurrent shoulder dislocation. Inclusion criteria were: unilateral dislocation, minimum 2 dislocation episodes. Exclusion criteria were bone reconstruction of the glenoid, failed shoulder stabilization, bilateral dislocation, shoulder arthritis. Three-dimensional computed tomography images of bilateral shoulder were retrieved for each patient. Two methods to determine GBL were compared. The PICO surface area method and the new IODA method. We assessed the intra and inter-rater reliability of the two methods with the Intraclass Correlation Coefficient (ICC), the Bland-Alman analysis, and Lin’s concordance correlation coefficient (CCC).

RESULTS: we did not find a statistically significant difference between the mean volumes calculated with PICO and IODA methods, respectively 914 vs 815 mm³, p=0.155. The analysis carried out by using the traditional PICO method showed a lower concordance rate among four observers than the higher concordance found using IODA method, regardless of the size and the location of the defect. The ICC agreement with PICO was significantly lower than with IODA (0.76 vs. 0.97). We found a poor CCC with PICO (from 0.65 to 0.81) and a substantial one with IODA (from 0.96 to 0.98).

DISCUSSION: The intra and inter-rater reliability using IODA method is significantly better than PICO method. The assessment of GBL using IODA method is time saving, avoiding significant inter and intra observer variation, mainly due to individual skill and experience in the method.

LEVEL OF EVIDENCE: IV, Experimental study.

PMID:37918692 | DOI:10.1016/j.otsr.2023.103745

J Nutr. 2023 Oct 31:S0022-3166(23)72678-3. doi: 10.1016/j.tjnut.2023.10.024. Online ahead of print.

ABSTRACT

BACKGROUND: Nutrimetabolomics allows for the comprehensive analysis of foods and human biospecimens to identify biomarkers of intake and begin to probe their associations with health. Salmon contains hundreds of compounds which may provide cardiometabolic benefits.

OBJECTIVE: We used untargeted metabolomics to identify salmon food-specific compounds (FSCs) and their predicted metabolites that were found in plasma after a salmon-containing Mediterranean-style (MED) diet intervention. Associations between changes in salmon FSCs and changes in cardiometabolic health indicators (CHIs) were also explored.

METHODS: For this secondary analysis of a randomized, crossover, controlled feeding trial, 41 participants consumed MED diets with two servings of salmon per week for two five-week periods. CHIs were assessed and fasting plasma was collected pre- and post-intervention. Plasma, salmon, and 99 MED foods were analyzed using liquid chromatography mass spectrometry-based metabolomics. Compounds were characterized as salmon FSCs if detected in all salmon replicates but none of the other foods. Metabolites of salmon FSCs were predicted using machine learning. For salmon FSCs and metabolites found in plasma, linear mixed-effect models were used to assess change from pre- to post-intervention and associations with changes in CHIs.

RESULTS: Relative to the other 99 MED foods, there were 508 salmon FSCs with 237 unique metabolites. A total of 143 salmon FSCs and 106 metabolites were detected in plasma. Forty-eight salmon FSCs and 30 metabolites increased after the intervention (FDR<0.05). Increases in two annotated salmon FSCs and two metabolites were associated with improvements CHIs, including total cholesterol, LDL cholesterol, triglycerides, and Apolipoprotein B.

CONCLUSIONS: A data-driven nutrimetabolomics strategy identified salmon FSCs and their predicted metabolites that were detectable in plasma and changed after consumption of a salmon-containing MED diet. Findings support this approach for discovery of compounds in foods that may serve, upon further validation, as biomarkers or act as bioactive components influential to health.

CLINICAL TRIAL REGISTRY NUMBER: NCT02573129 (original Mediterranean-style diet intervention); NCT05500976 (ongoing clinical trial).

PMID:37918675 | DOI:10.1016/j.tjnut.2023.10.024