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Darpan Radheshyam Thakare,1,2,&ast; Kritika Singh,1,&ast; Tooba Qamar,1 Deeksha Singh,1 Sandeep Balakrishnan,1 Upendra Rathore,1 Neeraj Jain,3 Manish Ora,4 Durga Prasanna Misra1 1Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, India; 2Department of Clinical Immunology and Rheumatology, King George Medical University (KGMU), Lucknow, Uttar Pradesh, India; 3Department of Radiodiagnosis, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, India; 4Department of Nuclear Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, India&ast;These authors contributed equally to this workCorrespondence: Durga Prasanna Misra, Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, 226014, Uttar Pradesh, India, Email durgapmisra@gmail.com; dpmisra@sgpgi.ac.inPurpose: Existing biomarkers including C-reactive protein (CRP) do not adequately distinguish active and inactive TAK. We compared serum p-glycoprotein (p-gp)/Multidrug Resistance Protein 1 (MDR1), monomeric CRP (mCRP), CRP, and mCRP:CRP ratio in Takayasu arteritis (TAK) and healthy controls and their relationship with disease activity.Patients and Methods: Serum p-gp mCRP (ELISA) and CRP (nephelometry) were compared between consecutive adults with TAK (> 18 years) enrolled from a prospective cohort (n = 92) and healthy controls (n = 29), and between active vs inactive TAK (n = 46 each). In a subset of active immunosuppressive-naïve TAK (n = 29), correlation was assessed between serum p-gp and p-gp expression on circulating T helper lymphocyte populations: overall (CD4+), Th17 (CD4+IL-17+), Th17.1 (CD4+IL-17+IFN-γ+) lymphocytes [normalized to Tregs (CD4+CD25+FoxP3+)]. Changes in serum p-gp, mCRP, CRP, and mCRP:CRP were compared before and after immunosuppression (n = 29). Data was represented using median (Q1-Q3). Receiver operating characteristics (ROC) curves were generated for TAK vs controls, and active vs inactive TAK with serum p-gp, mCRP, CRP, and mCRP:CRP. Multivariable-adjusted linear regression was used to predict active disease with serum p-gp, mCRP, CRP, or mCRP:CRP.Results: Serum p-gp (11.19 vs 8.05 ng/mL), mCRP (1.61 vs 1.25 μg/L), and CRP (5.40 vs 2.1 mg/L) were elevated in TAK vs controls (p < 0.05 for all). CRP was higher and mCRP:CRP ratio was lower in active vs inactive TAK (p < 0.001). ROC curves identified moderate prediction for active disease with CRP and inactive disease with serum p-gp (area under ROC curve 0.705 and 0.392, respectively). Multivariable-adjusted linear regression confirmed association of CRP with active disease (p = 0.009) and serum p-gp with inactive disease (p = 0.041). In treatment-naïve TAK, serum p-gp negatively correlated with p-gp+Th17.1 lymphocytes (Spearman’s rho=− 0.39, p = 0.046). CRP and serum p-gp were significantly lowered following immunosuppressive therapy in treatment-naïve TAK (p < 0.05).Conclusion: Serum p-gp and mCRP are elevated in TAK. Serum p-gp is associated with inactive disease.Keywords: Takayasu arteritis, MDR1 protein, C-reactive protein, large vessel vasculitis, aortoarteritis, disease activity

Gaurav Pande,1 Manjunath Hatti,1 Mohit Kumar Rai,2 Praveer Rai,1 Kamlesh Kumar,1 Krishna VP,1 Abhimanyu Nehra,1 Sudeep Kumar,3 Smarak Ranjan Rout,3 Sourav Kumar Mishra,3 Dinesh Kumar,4 Umesh Kumar,4 Prabhaker Mishra,5 Abdul Majeed,1 Vivek Anand Saraswat,1,&ast; Kritika Singh,2 Harshit Singh,2 Durga Prasanna Misra,2 Vikas Agarwal2,&ast; 1Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India; 2Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India; 3Cardiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India; 4Department of Advanced Spectroscopy and Imaging, Center of Biomedical Research, Lucknow, India; 5Biostatistics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India&ast;These authors contributed equally to this workCorrespondence: Vikas Agarwal, Unit III, Clinical Immunology and Rheumatology, SGPGIMS, Raebareli Road, Lucknow, India, Tel +918004904390, Fax +91522268812, Email vikasagr@yahoo.comBackground and Aims: Acute-on-chronic liver failure (ACLF) with increasing organ failure is associated with poor outcomes. Severely deranged systemic hemodynamics and decreased effective arterial blood volume contribute to tissue damage and organ failure. Response-guided therapy with albumin, vasoconstrictors, and furosemide may help overcome effective hypovolemia, improve diuresis and impact survival.Methods: In the observation cohort, 230 patients with ACLF (CANONIC criteria) with ascites (≥Grade II) and ACLF ≥Grade I were enrolled. A total of 136 patients (GROUP I) received response-guided (urine sodium > 80mmol/day) slow albumin-furosemide infusion ± terlipressin (SAFI ± T), while 94 patients (GROUP II) received standard medical therapy. Twenty-eight-day survival, ascites mobilization (nil or grade 1), and adverse events were noted. In another mechanistic cohort (n = 40), laboratory evidences for improvement in various pathophysiological alterations; gut permeability, endotoxemia, cytokine storm, neutrophil dysfunction, and hemodynamic alterations following SAFI ± T/Noradrenaline (NAdr) were evaluated.Results: Age, gender, CLIF-C-ACLF, SOFA and MELD scores, ACLF grades and urine sodium were not different between the two groups in the observation cohort. Ascites was mobilized in 102/136 in GROUP I (SAFI ± T) and 23/94 in GROUP II (p < 0.05). Twenty-eight-day survival was significantly higher in GROUP I = 103/136 (75.7%) vs GROUP II = 50/94 (53.2%), (P = < 0.001). All those who were unable to reach urine sodium > 80 mmol/day died. Four patients in GROUP I developed scrotal gangrene. In the mechanistic cohort, 72% of patients survived with significant improvement in gut permeability, endotoxemia, serum cytokines, neutrophil dysfunction, and hemodynamic alterations.Conclusion: Ascitic fluid mobilization by response-guided SAFI ± T/NAdr therapy improves survival by improving splanchnic and systemic hemodynamics, decreasing gut congestion, gut permeability, and endotoxemia, improving neutrophil functions, and reducing pro-inflammatory cytokines in circulation.Graphical Abstract: Keywords: urine sodium, hemodynamics, renal artery resistive index, cytokines, neutrophil extracellular traps

Kritika Singh,1,* Upendra Rathore,1,* Mohit Kumar Rai,1 Manas R Behera,2 Neeraj Jain,3 Manish Ora,4 Dharmendra Bhadauria,2 Supriya Sharma,5 Gaurav Pande,6 Sanjay Gambhir,4 Alok Nath,7 Sudeep Kumar,8 Aman Sharma,9 Vikas Agarwal,1 Durga Prasanna Misra1 1Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, 226014, India; 2Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, 226014, India; 3Department of Radiodiagnosis, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, 226014, India; 4Department of Nuclear Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, 226014, India; 5Department of Surgical Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, 226014, India; 6Department of Medical Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, 226014, India; 7Department of Pulmonary Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, 226014, India; 8Department of Cardiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, Uttar Pradesh, 226014, India; 9Clinical Immunology and Rheumatology Services, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India*These authors contributed equally to this workCorrespondence: Durga Prasanna Misra, Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, 226014, India, Tel +91 5222495273, Fax + 91 522-2668812, Email DurgapMisra@gmail.comPurpose: We evaluated T helper lymphocyte profile, including novel Th17 subsets Th17.1 (secrete IFN-γ, associate with corticosteroid resistance) and PD1+Th17 (secrete TGF-β 1, implicated in fibrosis), and related cytokines in peripheral blood of Takayasu arteritis (TAK).Materials and Methods: We evaluated circulating Th1, Th2, Th17, Th17.1, PD1+CD4+ T lymphocytes, PD1+Th17, and Treg lymphocytes, inflammatory (IFN-γ, IL-4, IL-6, IL-17A, IL-23, IL-1β, TNF-α) and regulatory (IL-10, TGF-β 1) cytokines in peripheral blood of TAK (n = 57; median age 35 (interquartile range 26– 45) years; 40 females) in a cross-sectional design. We studied inflammatory and regulatory cytokines in culture supernatant of peripheral blood mononuclear cells (PBMCs) from TAK following stimulation with anti-CD3/anti-CD28 and their modulation by tacrolimus (immunosuppressive) with/without tadalafil (anti-fibrotic). Furthermore, we followed up immunosuppressive-naïve active TAK (n = 16) and compared T helper lymphocyte populations and cytokines before and after immunosuppressive therapy. Healthy controls (HC, n = 21) and sarcoidosis (disease control, n = 11) were compared against TAK.Results: TAK had higher Th17, Th17.1 and PD1+Th17 lymphocytes than HC (p < 0.001), and higher PD1+CD4+ T lymphocytes than sarcoidosis (p < 0.001). Th17 lymphocytes associated with active TAK after multivariable-adjusted logistic regression (p = 0.008). TAK had greater cytokine secretion from PBMCs (IFN-γ, IL-17A, IL-10 versus HC; IL-6, TNF-α, IL-1β versus HC or sarcoidosis) (p < 0.05). In-vitro, PBMCs from TAK showed reduced secretion of all inflammatory cytokines with tacrolimus, with synergistic reduction in IL-17A, IL-6, IL-1β and IL-10 following addition of tadalafil to tacrolimus. Serial follow-up of immunosuppressive-naïve TAK (n = 16) showed reduction in serum IL-6 and TGF-β 1 (p < 0.05) and IL-6 in culture supernatant (p < 0.05) following immunosuppressive therapy.Conclusion: Novel Th17 sub-populations (Th17.1 and PD1+Th17) are elevated in TAK. Th17 lymphocytes associate with active TAK. In-vitro experiments on cultured PBMCs suggest promise for further evaluation of a combination of immunosuppressive tacrolimus with anti-fibrotic tadalafil (or other anti-fibrotic therapies) in clinical trials of TAK.Keywords: arteritis, aortic arch syndromes, PD-1 protein, drug resistance, corticosteroid, fibrosis

Rutviz Rajendra Mistry,1 Pallavi Patro,2 Vikas Agarwal,1 Durga Prasanna Misra1 1Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, India; 2Department of Pharmacology, Sriram Chandra Bhanja (SCB) Medical College, Cuttack, India Abstract: In this narrative review, we overview the recent literature on enthesitis-related arthritis (ERA). For the purpose of our review, we searched Scopus for recent articles on this subject from 2013 onward, including some classic older articles for perspective. ERA is a juvenile idiopathic arthritis (JIA) subtype more common in males, associated in a majority with human leucocyte antigen B27. Such children generally present with asymmetric oligoarthritis or polyarthritis, predominantly of lower limb joints, associated with enthesitis or sacroiliitis. While diagnosis remains clinical, ultrasound is being increasingly used to detect subclinical enthesitis and for guiding entheseal site injections. Spine MRI can help detect sacroiliitis, inflammatory spinal changes, and pelvic sites of enthesitis in such patients. The recent juvenile spondyloarthropathy disease activity index recognizes the key clinical features of ERA, viz enthesitis and inflammatory back pain, which other disease activity indices used in JIA did not include. Management includes NSAIDs with physical therapy. Conventional disease-modifying agents like sulfasalazine and methotrexate may be used to minimize duration of NSAID use and in those with high inflammatory burden. In patients refractory to these drugs, biologics such as antitumor necrosis factor alpha agents have proven useful, based on evidences from randomized controlled trials and retrospective registry analyses. Factors predicting a poorer outcome in such children include hip or ankle involvement or restricted spinal mobility. Considering that children with ERA have overall poorer long-term outcomes than other subtypes of JIA, there is a need to further optimize therapeutic strategies for such patients. Keywords: enthesitis-related arthritis, juvenile spondyloarthropathy, diagnosis, management, exercise, anti-TNF

Objective: An evaluation of fetal and infant mortality review (FIMR) programs nationwide was conducted to characterize their unique role in improving the system of perinatal health care. The aim of this paper is to examine intermediate outcomes of the FIMR, in particular the development and implementation of recommendations produced by the FIMRs and the conduct of essential MCH services by the FIMRs.Methods: We report on 74 FIMRs whose communities were selected for the nationwide evaluation and for whom we had data from the FIMR director or comparable respondent. We focus on the recommendations of the FIMRs and the essential maternal and child health (MCH) services conducted by the FIMRs as intermediate outcomes (or outputs) and then examine how selected characteristics of the FIMR may influence these.Results: FIMRs developed recommendations on a broad range of topics but there were some areas for which nearly all programs had developed recommendations. The FIMRs relied primarily on strategies related to programs and practices, with few FIMRs reporting attention to policy-oriented approaches. Implementation of recommendations was high. Factors that influenced likelihood of implementing recommendations and conduct of essential MCH services included structure of the FIMR and training received by FIMR directors and staff.Conclusions: The focus of FIMR recommendations and the likelihood of implementation vary across FIMRs as does the conduct of essential MCH services. FIMR team structure and training of the director and staff are important areas to consider in efforts to maximize the impact of FIMR. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the association of the presence of a fetal and infant mortality review (FIMR) program, other perinatal systems initiative (PSI), or both in a community with the performance of essential maternal and child health (MCH) services by local health departments (LHDs).Methods: Data were obtained from telephone interviews with professionals from LHDs across the United States. Logistic regression was used to estimate the odds of a LHD conducting each essential MCH service in communities with and without FIMR programs or with and without PSIs, adjusted for geographic area.Results: Of the 193 communities in the sample, 41 had only a FIMR program, 36 had only a PSI, 47 had both programs, and 69 had neither. The presence of a FIMR was related to greater performance of essential MCH services in LHDs in six areas: data assessment and analysis; client services and access; quality assurance and improvement; community partnerships and mobilization; policy development; and enhancement of capacity of the health care work force. Similar findings were noted for the same broad essential services for PSIs. The comparisons of LHDs in FIMR and non-FIMR communities, however, showed greater involvement of communities with a FIMR program in essential MCH services related to data collection and quality assurance than were found for comparisons of LHDs in communities with and without a PSI. The presence of a PSI was uniquely associated with conducting needs assessments for pregnant women and infants, participation in coalitions for infants, promoting access for uninsured women to private providers and involving local officials and agencies in health plans for both populations. When both programs were present, LHDs had a greater odds of engaging in essential MCH services related to assessment and monitoring of the health of the population, reporting on progress in meeting the health needs of pregnant women and infants, and presenting data to local political officials than when either program alone was in the community.Conclusions: Local health departments in communities with FIMR programs or PSIs appear to be more likely to conduct essential MCH services in the community. Some of these relations are unique to FIMR, particularly for data collection and quality assurance services, and some are unique to PSIs, for example those that involve interaction with other community agencies or groups. Performance of the essential MCH services also appears to be enhanced when both a FIMR program and a PSI are present in the community. [ABSTRACT FROM AUTHOR]

Objectives: While the goals of fetal and infant mortality review (FIMR) programs and other perinatal systems initiatives (PSI) are similar, our knowledge of the processes they use to meet their goals is limited. This article compares a nationwide sample of FIMR programs and PSIs with regard to their roles and involvement in performance of eight essential maternal and child health services (EMCHS) as part of a national evaluation of FIMR.Methods: The evaluation was a cross-sectional observational study in which geographic units were sampled based on the presence or absence of a FIMR or other PSI using FIMRs as the sampling frame of reference. Telephone interviews were conducted with 74 FIMR and 62 PSI directors in the sampled communities.Results: Both programs performed several of the essential MCH services. FIMRs were significantly more likely to be located in a local health department than were PSIs. The results of multiple logistic regression analyses indicate that the performance of the essential MCH services by the programs was increased when both a FIMR and a PSI were in the community. FIMR programs alone had reduced odds of performing several essential MCH services than did PSIs alone. The findings also indicate that performance of some essential MCH services was reduced for FIMR programs and PSIs located in a local health department.Conclusions: Comparisons between FIMR and other PSIs suggest that both programs are currently engaged in diverse efforts to attain their goal of improving the health and health care delivery system for pregnant women, infants, and their families. FIMR programs appear to be more circumscribed in their activities than PSIs, but the presence of both programs in a community appears to enhance the programs' performance of the essential MCH services. [ABSTRACT FROM AUTHOR]

Symmetric inflammatory polyarthritis is the most prominent manifestation of rheumatoid arthritis (RA). However, RA can practically affect any organ system, whether hematologic, neurological, cardiac, lung, skin, eyes, or kidneys. Systemic involvement in RA can be severe when there is interstitial lung disease, scleritis, amyloidosis, pure red cell aplasia, or myelodysplasia. Cardiovascular disease is the leading cause of death in patients with RA with a similar cardiovascular risk to that with diabetes mellitus. Patients with RA are at an increased risk of infections or osteoporosis, largely due to treatment-related etiologies. Rheumatoid vasculitis is a devastating long-term complication of RA which is fortunately becoming rarer over time due to better disease activity control. While the risk of mortality overall seems to be reducing over time, the excess mortality risk with RA compared with the general population persists. Fibromyalgia, anxiety, depression, fatigue, and physical inactivity remain important comorbidities associated with RA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The ACR in 2021 and the EULAR in 2022 published recommendations for management of ANCA-associated vasculitis. Given the differences in the demographic, clinical profiles, and the socio-economic realities between various countries, there is a need for development of guidelines for the management of AAV for less economically developed regions of the world., Methods: These guidelines were made following the GRADE methodology. After the systematic literature review, recommendations were formulated and opinion was sought from the 18-member expert panel consisting of 17 clinicians and one patient representative., Results: Twenty recommendations were formulated. We recommend ANCA testing by ELISA over IIF. For remission induction in active GPA or MPA, we recommend use of intravenous cyclophosphamide or rituximab in combination with glucocorticoids. We conditionally recommend the use of reduced dose glucocorticoids over standard dose glucocorticoids for remission induction in active GPA or MPA. For remission maintenance in patients with GPA or MPA, we recommend the use of rituximab over azathioprine for at least 48 months from diagnosis. We conditionally recommend the use of plasma exchange in patients with severe renal vasculitis. For remission induction in EGPA, we recommend use of cyclophosphamide or rituximab in severe disease and mepolizumab or azathioprine or methotrexate or mycophenolate mofetil in non-severe disease., Conclusions: These are the first ever Indian recommendations for the management of AAV. Despite our effort to formulate these recommendations based on high quality evidence, some recommendations were still based on low quality evidence but with high rate of agreement among expert panel members., Competing Interests: Declaration of competing interest Nil., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To examine associations among experiences of racial discrimination, perceived stress, and birth satisfaction and to test if perceived stress mediates the relationship between racial discrimination and birth satisfaction among Black women in the postpartum period., Design: Secondary analysis of data from the Biosocial Impact on Black Births study., Setting: A postpartum unit of a large hospital in Central Florida., Participants: Black women (N = 154) in the postpartum period., Methods: Participants completed the lifetime Experiences of Discrimination scale, Perceived Stress Scale and Birth Satisfaction Scale-Revised between 24 hours and 23 days after birth. We calculated descriptive statistics and Spearman's ρ correlation coefficients to evaluate associations among variables. We used multiple linear regression to evaluate perceived stress as a mediator between racial discrimination and birth satisfaction., Results: Racial discrimination had a positive association with perceived stress (β = 2.445, p = .03), and perceived stress had a negative association with birth satisfaction (β = -0.221, p = .02). Racial discrimination had no significant direct effect on birth satisfaction (β = -0.091, p = .94); therefore, perceived stress did not mediate the relationship., Conclusion: More experiences of discrimination over the life span were associated with higher levels of perceived stress. Participants who reported higher levels of perceived stress reported lower levels of birth satisfaction. Our study adds to the body of knowledge regarding associations between racial discrimination and perceived stress and perceived stress and birth satisfaction., Competing Interests: Conflict of Interest The authors report no conflicts of interest or relevant financial relationships., (Copyright © 2024 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.)

To look for the spectrum of infections and the factors predisposing to infection in patients with systemic sclerosis (SSc). In this retrospective study, demographic, clinical features, details of infections, immunosuppressive therapy, and outcomes of patients with SSc attending clinics at department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India from 1990 to 2022 were captured. Multivariable-adjusted logistic regression was applied to identify independent predictors of infection. Data of 880 patients, mean age 35.5 ± 12 years, and female: male ratio 7.7:1, were analyzed. One hundred and fifty-three patients had at least 1 infection with a total of 233 infectious episodes. Infections were most common in lung followed by skin and soft tissue. Tuberculosis was diagnosed in 45 patients (29.4%). Klebsiella was the commonest non-tubercular organism in lung and Escherichia coli in urinary tract infections. In comparison to matched control group, patients with infection had a greater number of admissions due to active disease, odds ratio (OR) 6.27 (CI 3.23-12.18), were receiving immunosuppressive medication OR, 5.05 (CI 2.55-10.00), and had more digital ulcers OR, 2.53 (CI 1.17-5.45). Patients who had infection had more likelihood for death OR, 13.63 (CI 4.75 -39.18). Tuberculosis is the commonest infection and lung remains the major site of infection in patients with SSc. Number of hospital admissions, digital ulcers and immunosuppressive therapy are predictors of serious infection in patients with SSc. Patients with infections had more likelihood of death., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Preterm birth (PTB; <37 weeks completed gestation) is a devastating problem affecting over 13 million live births worldwide. In the U.S., African Americans experience significantly higher rates of PTB compared to non-Hispanic Whites. PTB disparities have been linked to social determinants of health (e.g., socioeconomic status, discrimination). However, the biological underpinnings related to these associations are unclear. DNA methylation (DNAm) is subject to environmental influences, and DNAm modifications are known to affect gene expression. Using a multi-omic approach, we examined differences in combined DNA methylation (DNAm) and messenger RNA (mRNA) transcriptomic data from 20 pregnant African American women (12 PTB; 8 term birth) early in pregnancy (8-18 weeks gestation). We found that the HLA- DQB2 gene was both differentially methylated (cg12296550; p = .02) and differentially expressed ( p = .014; log2FC = 2.5) between women with PTB and term birth. Gene expression analysis showed HLA- DQB2 and HLA- DRB4 ( p = .028; log2FC = -3.6) were the two most highly expressed genes. HLA-DQB2 expressed higher in PTB and HLA- DRB4 expressed higher in term birth. However, no genes remained significant ( p < .05) after Bonferroni correction. HLA- DRB4 and AKR1C1 were identified as a potential biomarkers in dimensionality reduction models and are also important to immune function and allogenic breakdown. Altered gene expression may lead to inflammatory imbalances or allogenic intolerance resulting in PTB. This study provides proof-of-concept evidence for the feasibility and importance of future multi-omics studies with larger populations to further explore the genes and pathways identified here., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Chronic placental inflammation is a routinely diagnosed group of placental lesions that reflect immunologic dysfunction of the mother, fetus, or both., Methods: Complete placental pathology examinations were performed for all term births at New York Presbyterian- Brooklyn Methodist Hospital from January 2010-August 2016. Diagnoses were blinded except to gestational age. CPI lesions were marked as chronic choriodeciduitis, decidual plasma cells, chronic inflammation of basal plate with anchoring villitis, and chronic villitis., Results: In this cohort of term pregnancies, 257 (11.6 %) males and 218 (9.8 %) females had ≥1 CPI lesions. Chronic villitis was the most common (319 or 14 %), with chronic choriodeciduitis, decidual plasma cells, and chronic inflammation of basal plate with anchoring villitis in 94 (4 %), 69 (3 %) and 170 (8 %), respectively. In males, chronic villitis was associated with lower gestational adjusted birthweight and had no association with placental weight. In females, chronic villitis was associated with lower gestational adjusted birthweight, but the effect became nonsignificant after adjustment for placental weight., Discussion: In summary, CPI lesions' incidence and association with birth weight vary by sex. Chronic villitis is associated with lower birthweight in females; this effect is completely mediated by placental weight. Chronic villitis showed a weak direct association of chronic villitis in males, but no association with lower placental weight in males. We suggest that differences between our results and previous publications reflect effects of sampling bias., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Carolyn Salafia reports financial support was provided by National Institute of Environmental Health Sciences. The grant ID # is ES029281. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The impacts of prenatal maternal affective symptoms on the placental structure are not well-established. Employing Geographic Information System (GIS) spatial autocorrelation, Moran's I, can help characterize placental thickness uniformity/variability and evaluate the impacts of maternal distress on placental topography., Methods: This study (N = 126) utilized cohort data on prenatal maternal affective symptoms and placental 2D and 3D morphology. Prenatal maternal depression, stress, anxiety and sleep quality were scored for each trimester using the Edinburgh Postnatal Depression Scale (EPDS), Stressful Life Event Scale (SLE), Penn State Worry Questionnaire (PSWQ), and Pittsburgh Sleep Quality Index (PSQI), respectively. Placental shape was divided into Voronoi cells and thickness variability among these cells was computed using Moran's I for 4-nearest neighbors and neighbors within a 10 cm radius. Sex-stratified Spearman correlations and linear regression were used to study associations between mean placental thickness, placental GIS variables, placental weight and the average score of each maternal variable., Results: For mothers carrying boys, poor sleep was associated with higher mean thickness (r = 0.308,p = 0.035) and lower placental thickness uniformity (r = -0.36,p = 0.012). Lower placental weight (r = 0.395,p = 0.003), higher maternal depression (r = -0.318,p = 0.019) and worry/anxiety (r = -0.362,p = 0.007) were associated with lower placental thickness uniformity for mothers carrying girls., Limitations: The study is exploratory and not all GIS models were developed. Excluding high-risk pregnancies prevented investigating pregnancy complications related hypotheses. A larger sample size is needed for greater confidence for clinical application., Conclusions: Placental topography can be studied using GIS theory and has shown that prenatal maternal affective symptoms and sleep have sex-specific associations with placental thickness., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: Chronic inflammation promotes cardiovascular risk in rheumatoid arthritis (RA). Biological disease-modifying antirheumatic drugs (bDMARDs) improve disease activity and cardiovascular disease outcomes. We explored whether bDMARDs influence the impact of disease activity and inflammatory markers on long-term cardiovascular risk in RA., Methods: We studied 4370 participants without cardiovascular disease in a 10-country observational cohort of patients with RA. Endpoints were (1) major adverse cardiovascular events (MACE) encompassing myocardial infarction, stroke and cardiovascular death; and (2) any ischaemic cardiovascular events (iCVE) including MACE plus revascularisation, angina, transient ischaemic attack and peripheral arterial disease., Results: Over 26 534 patient-years, 239 MACE and 362 iCVE occurred. The interaction between 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) and bDMARD use was significant for MACE (p=0.017), suggesting the effect of DAS28-CRP on MACE risk differed among bDMARD users (n=515) and non-users (n=3855). DAS28-CRP (per unit increase) is associated with MACE risk in bDMARD non-users (HR 1.21 (95% CI 1.07 to 1.37)) but not users (HR 0.69 (95% CI 0.40 to 1.20)). The interaction between CRP (per log unit increase) and bDMARD use was also significant for MACE (p=0.011). CRP associated with MACE risk in bDMARD non-users (HR 1.16 (95% CI 1.04 to 1.30)), but not users (HR 0.65 (95% CI 0.36 to 1.17)). No interaction was observed between bDMARD use and DAS28-CRP (p=0.167) or CRP (p=0.237) for iCVE risk., Conclusions: RA activity and inflammatory markers associated with risk of MACE in bDMARD non-users but not users suggesting the possibility of biological-specific benefits locally on arterial wall independently of effects on systemic inflammation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Black women in the United States report moderate to high levels of perceived stress during pregnancy. Though lower levels of involvement and support from father of the baby (FOB) and higher levels of conflict have been associated with higher levels of maternal perceived stress, it is not clear how Black pregnant women experience the mother-father relationship and its influence on perceived stress., Purpose: To examine and describe the mother-father relationship and its role in experiences of perceived stress from the perspective of Black pregnant women., Methods: Using a convergent, mixed methods approach with ideal-type analysis, we conducted a secondary analysis of data among 60 Black pregnant women enrolled in the Biosocial Impact on Black Births study. Women completed online self-report questionnaires and participated in a semi-structured interview by telephone., Results: Participants who reported more conflict with FOB also reported higher levels of perceived stress (ρ(47) = .431, P= .002). Themes (importance, communication, support, conflict, satisfaction, and stress) emerged from the data. Five distinct mother-father relationship typologies were identified following an ideal-type analysis of the combined dataset: Cared For; Managing Expectations; Just Friends, For the Kids; It's Complicated; and Can't be Bothered., Conclusions: These findings are an innovative exemplar of ideal-type analysis and provide a deeper understanding of the nuance and dynamics within the mother-father relationship and how it influences perceived stress among Black pregnant women., Implications: Clinicians must recognize the significance of the mother-father relationship and, when appropriate, encourage paternal involvement or intervene if there is conflict during pregnancy., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Systemic lupus erythematosus (SLE) is characterised by increased cardiovascular morbidity and mortality risk. We aimed to examine the prevalence of traditional cardiovascular risk factors and their control in an international survey of patients with systemic lupus erythematosus., Methods: In this multicentre, cross-sectional study, cardiovascular risk factor data from medical files of adult patients (aged ≥18) with SLE followed between Jan 1, 2015, and Jan 1, 2020, were collected from 24 countries, across five continents. We assessed the prevalence and target attainment of cardiovascular risk factors and examined potential differences by country income level and antiphospholipid syndrome coexistence. We used the Systemic Coronary Risk Evaluation algorithm for cardiovascular risk estimation, and the European Society of Cardiology guidelines for assessing cardiovascular risk factor target attainment. People with lived experience were not involved in the research or writing process., Findings: 3401 patients with SLE were included in the study. The median age was 43·0 years (IQR 33-54), 3047 (89·7%) of 3396 patients were women, 349 (10.3%) were men, and 1629 (48·1%) of 3390 were White. 556 (20·7%) of 2681 patients had concomitant antiphospholipid syndrome. We found a high cardiovascular risk factor prevalence (hypertension 1210 [35·6%] of 3398 patients, obesity 751 [23·7%] of 3169 patients, and hyperlipidaemia 650 [19·8%] of 3279 patients), and suboptimal control of modifiable cardiovascular risk factors (blood pressure [target of <130/80 mm Hg], BMI, and lipids) in the entire SLE group. Higher prevalence of cardiovascular risk factors but a better blood pressure (target of <130/80 mm Hg; 54·9% [1170 of 2132 patients] vs 46·8% [519 of 1109 patients]; p<0·0001), and lipid control (75·0% [895 of 1194 patients] vs 51·4% [386 of 751 patients], p<0·0001 for high-density lipoprotein [HDL]; 66·4% [769 of 1158 patients] vs 60·8% [453 of 745 patients], p=0·013 for non-HDL; 80·9% [1017 of 1257 patients] vs 61·4% [486 of 792 patients], p<0·0001 for triglycerides]) was observed in patients from high-income versus those from middle-income countries. Patients with SLE with antiphospholipid syndrome had a higher prevalence of modifiable cardiovascular risk factors, and significantly lower attainment of BMI and lipid targets (for low-density lipoprotein and non-HDL) than patients with SLE without antiphospholipid syndrome., Interpretation: High prevalence and inadequate cardiovascular risk factor control were observed in a large multicentre and multiethnic SLE cohort, especially among patients from middle-income compared with high-income countries and among those with coexistent antiphospholipid syndrome. Increased awareness of cardiovascular disease risk in SLE, especially in the above subgroups, is urgently warranted., Funding: None., Competing Interests: Declaration of interests AGS has received speaker fees from Merck and Schering-Plough, Bristol Myers Squibb, UCB, Pfizer, Novartis, Lilly and Women's College Hospital, Toronto, ON, Canada. AMK has received speaker fees from Boehringer Ingelheim and Sanofi; has participated on advisory boards for Pfizer, Gilead, and Boehringer Ingelheim; and has received congress sponsorship from Pfizer, Celgene, UCB, Mylan, and Roche. GJP-E has received grants from Janssen; consulting fees from GSK, AstraZeneca, Janssen, Novartis, and Bago; speakers fees from GSK, Werfen, Janssen, AstraZeneca, and Novartis; support for attending meetings and travel from GSK, AstraZeneca, and Boehringer Ingelheim; and for participation on a data safety monitoring board or advisory board from RemeGen, AstraZeneca, and Janssen. GAK has received consulting fees from Janssen and Scipher; and for participation on a data safety monitoring board or advisory board from Janssen. MFU-G has received grant support from Janssen and Pfizer; has been a speaker for GSK and AstraZeneca; and has been a member of advisory boards for AstraZeneca and Ferrer. NC-C has received grants from Roche and UCB. EH has received consulting fees and meeting fees from Johnson & Johnson, Boehringer Ingelheim, Bayer, GSK, Roche-Chugai, and Sanofi-Genzyme; speaking fees from Johnson & Johnson, GSK, and Roche-Chugai; and research funding from Commonwealth Serum Laboratories Behring, GSK, Roche-Chugai, and Johnson & Johnson. NP has received grants from Gilead Sciences Hellas and the European Centre for Disease Prevention and Control. OAM has received speaker's fees or payment for advisory boards from AbbVie, APSEN, AstraZeneca, Boehringer Ingelheim, Celltrion, GSK, and Janssen. MS has received research grants and consulting fees, and has participated as a speaker for: AbbVie, Bristol Myers Squibb, GSK, Janssen, Lilly, Pfizer, Roche, and AstraZeneca. ACSM has received speaker fees from GSK and AstraZeneca. All other authors and SURF-SLE and APS Collaborators declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Purpose: The purpose of this study among pregnant and postpartum Black women was twofold: (1) to compare levels of perceived stress, depressive symptoms, social support, and neighborhood disorder and crime before the pandemic vs during the pandemic; and (2) to examine the association of perceived stress, depressive symptoms, and social support with neighborhood disorder and crime at both time points., Methods: This was a prospective study as part of the Biosocial Impact on Black Births, a longitudinal study that examined the role of maternal factors on preterm birth among Black women. A sample of 143 women were included who responded to survey questions during pregnancy prior to the pandemic and again after birth, during the pandemic. Women completed the COVID survey between May 21, 2020, and January 28, 2021., Results: The levels of perceived stress (70.75 and 76.28, respectively, P < .01) and social support (17.01 and 18.78, respectively, P < .01) were lower during the pandemic than prior to the pandemic. Social support, perceived stress, and depressive symptoms were significantly correlated with the pre-pandemic measures of perceived neighborhood disorder and crime. Perceived stress and depressive symptoms were also significantly correlated with pandemic measures of perceived neighborhood., Conclusion: Women reported lower levels of perceived stress during the pandemic than prior to the pandemic, but neighborhood characteristics were consistently associated with perceived stress and depressive symptoms both prior to and during the pandemic. Further exploration is warranted to better understand these relationships., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The cardiovascular disease (CVD) risk is elevated by 1.5 times among South Asians with rheumatological conditions like rheumatoid arthritis (RA) in the UK. However, there is a dearth of culturally sensitive educational interventions tailored to this population. We have culturally adapted an existing cognitive behavioural patient education intervention, originally designed for predominantly White populations, to address this gap., Methods: The adaptation process followed the Ecological Validity Model, comprising four phases: stage-setting and expert consultations, preliminary content adaptation, iterative content adaptation with patient partners, and finalisation with patient partners and feedback. The Theoretical Domains Framework (TDF) was employed to evaluate the relevance, acceptability, and cultural adaptation of the existing intervention. Seven South Asian Patient Experts with RA were interviewed, and their input aided in developing new content for the culturally sensitive intervention., Results: The intervention was successfully adapted to suit South Asians. Cultural adaptation involved reviewing elements of the existing intervention, including language tone, content, and metaphors. Moreover, by incorporating behaviour change techniques, the content was designed to enhance understanding of RA, CVD risk associated with RA, and promote a healthy lifestyle. The newly developed educational intervention addressed topics such as community resistance, perspectives on health and culture, societal pressure, and opportunities for change. Key messages were visually illustrated through pictorial diagrams in a twenty-five-minute online resource., Conclusion: The first culturally adapted CVD intervention targeting South Asian individuals with RA, particularly those who are non-English-speaking, is now accessible free of charge at www.nras.org.uk/apnijung nationally and internationally., (© 2024 The Mediterranean Journal of Rheumatology (MJR).)

Objective: To describe the incidence, risk factors, and outcomes associated with serious infections in patients with Takayasu arteritis (TA)., Methods: Serious infections, defined as infections resulting in hospitalization or death or unusual infections like tuberculosis, were identified from a cohort of patients with TA. Corticosteroid and disease-modifying antirheumatic drug (DMARD) use at the time of serious infection was noted. Demographic characteristics, clinical presentation, angiography, and disease activity at presentation, and the use of DMARDs during follow-up were compared between patients with TA with or without serious infections. Mortality in patients with TA who developed serious infections was compared to those who did not using hazard ratios (HR; with 95% CI)., Results: Of 238 patients with TA, 38 (16%) had developed serious infections (50 episodes, multiple episodes in 8; 3 episodes resulted in death). Among the 38 initial episodes, 11/38 occurred in those not on corticosteroids and 14/38 in those not on DMARDs. Pneumonia (n = 19) was the most common infection, followed by tuberculosis (n = 12). Patients with TA who developed serious infections vs those who did not had higher disease activity at presentation (active disease 97.4% vs 69.5%, mean Indian Takayasu Arteritis Activity Score 2010 12.7 (SD 7.3) vs 10.2 (SD 7.0), mean Disease Extent Index in Takayasu Arteritis 11.2 (SD 6.1) vs 8.8 (SD 6.1) and were more frequently initiated on corticosteroids or DMARDs. HRs calculated using exponential parametric regression survival-time model revealed increased mortality rate in patients with TA who developed serious infections (HR 5.52, 95% CI 1.75-17.39)., Conclusion: Serious infections, which occurred in the absence of immunosuppressive treatment in approximately one-fifth of patients with TA, were associated with increased mortality in patients with TA.

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

A subset of Takayasu arteritis (TAK) has onset in the pediatric age group (≤18 years). The differences in mortality between pediatric-onset and adult-onset TAK are unclear. Therefore, we undertook a systematic review with meta-analysis to compare mortality risk in pediatric-onset with adult-onset TAK. Scopus, Pubmed (MEDLINE and Pubmed Central), recent conference abstracts, clinicaltrials.gov, and the Cochrane database were searched up to August 2023 for relevant studies. Five studies (all of moderate or high quality on the Newcastle Ottawa scale) were identified which had compared mortality between 151 pediatric-onset and 499 adult-onset TAK. Pediatric-onset TAK was associated with a significantly higher risk of death than adult-onset TAK (pooled risk ratio 2.27, 95% confidence interval 1.05 - 4.85, I 2 =0%). Cardiovascular disease and infections were the major causes of death in both pediatric-onset and adult-onset TAK. Sub-group analyses identified a greater mortality risk with pediatric-onset TAK in retrospective (but not prospective) studies and in studies of high quality (but not in those of moderate quality). Meta-regression did not reveal a significant influence of differences in sex distribution or age or the proportions of patients with pediatric-onset or adult-onset TAK on the pooled mortality risk. An increased mortality risk with pediatric-onset TAK on meta-analysis is consistent with more frequent severe organ manifestations of pediatric-onset TAK (heart failure, renal failure) when compared with adult-onset TAK. Future studies should systematically evaluate differences in the pathogenesis between pediatric-onset and adult-onset to understand the reasons for such observed differences in the mortality risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: A subset of Takayasu's arteritis (TAK) begins in the paediatric age group (≤18 years). Differences in prognosis between paediatric-onset and adult-onset TAK are unclear. We compared the differences in the presentation and survival between paediatric-onset and adult-onset TAK in our cohort of TAK., Methods: From a retrospective cohort of TAK, clinical presentation, angiographic features, treatments received, disease activity, and survival were compared between paediatric-onset and adult-onset TAK. Multivariable-adjusted logistic regression models were used to compute adjusted odds ratio (aOR) with 95% confidence intervals (95%CI) for paediatric-onset vs. adult-onset TAK. Hazard ratios (HR, with 95%CI) for mortality with paediatric-onset vs adult-onset TAK (crude, adjusted for prognostic covariates or differences in presentation) and propensity score-matched survival analyses were estimated., Results: Among 56 paediatric-onset and 135 adult-onset TAK, chest pain (aOR 3.21, 95%CI 1.06-9.74), heart failure (aOR 3.16, 95%CI 1.05-9.53), headache (aOR 2.60, 95%CI 1.01-6.74), ascending aorta (aOR 3.02, 95%CI 1.04-8.80) and left renal artery involvement (aOR 2.45, 95%CI 1.04-5.80) were more frequent in paediatric-onset TAK. Despite similar longitudinal patterns of disease activity and glucocorticoid or disease-modifying antirheumatic drug (DMARD) use, mortality was higher for paediatric-onset TAK (HR, unadjusted 6.13, 95%CI 1.51-24.91; adjusted for prognostic covariates gender, diagnostic delay, baseline disease activity, number of conventional and biologic/targeted synthetic DMARDs used, 4.97, 95%CI 1.20-20.58; adjusted for differences between groups 5.54, 95%CI 1.22-25.09; after propensity-score matching for prognostic covariates, 54 pairs, log-rank p-value 0.026)., Conclusions: Considering the greater mortality risk, greater vigilance is required while managing paediatric-onset TAK.

Background  Increased mortality rates among coronavirus disease 2019 (COVID-19) positive patients admitted to intensive care units (ICUs) highlight a compelling need to establish predictive criteria for ICU admissions. The aim of our study was to identify criteria for recognizing patients with COVID-19 at elevated risk for ICU admission. Methods  We identified patients who tested positive for COVID-19 and were hospitalized between March and May 2020. Patients' data were manually abstracted through review of electronic medical records. An ICU admission prediction model was derived from a random sample of half the patients using multivariable logistic regression. The model was validated with the remaining half of the patients using c-statistic. Results  We identified 1,094 patients; 204 (18.6%) were admitted to the ICU. Correlates of ICU admission were age, body mass index (BMI), quick Sequential Organ Failure Assessment (qSOFA) score, arterial oxygen saturation to fraction of inspired oxygen ratio, platelet count, and white blood cell count. The c-statistic in the derivation subset (0.798, 95% confidence interval [CI]: 0.748, 0.848) and the validation subset (0.764, 95% CI: 0.706, 0.822) showed excellent comparability. At 22% predicted probability for ICU admission, the derivation subset estimated sensitivity was 0.721, (95% CI: 0.637, 0.804) and specificity was 0.763, (95% CI: 0.722, 0.804). Our pilot predictive model identified the combination of age, BMI, qSOFA score, and oxygenation status as significant predictors for ICU admission. Conclusion  ICU admission among patients with COVID-19 can be predicted by age, BMI, level of hypoxia, and severity of illness., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Background: We analyzed differences in presentation and survival of Takayasu arteritis (TAK) with or without renal artery involvement (RAI) from a large monocentric cohort of patients with TAK., Methods: Clinical and angiographic features were compared between TAK with versus without RAI, with bilateral versus unilateral RAI, and with bilateral RAI versus without RAI using multivariable-adjusted logistic regression. Inter-group differences in survival were analyzed [hazard ratios (HR) with 95% confidence intervals (95%CI)] adjusted for gender, age at disease onset, diagnostic delay, baseline disease activity, and significant clinical/angiographic inter-group differences after multivariable-adjustment/propensity score matching (PSM)., Results: Of 215 TAK, 117(54.42%) had RAI [66(56.41%) bilateral]. TAK with RAI or with bilateral RAI had earlier disease onset than without RAI (p < 0.001). Chronic renal failure (CRF) was exclusively seen in TAK with RAI. TAK with RAI (vs without RAI) had more frequent hypertension (p = 0.001), heart failure (p = 0.047), abdominal aorta (p = 0.001) or superior mesenteric artery involvement (p = 0.018). TAK with bilateral RAI (vs unilateral RAI) more often had hypertension (p = 0.011) and blurring of vision (p = 0.049). TAK with bilateral RAI (vs without RAI) more frequently had hypertension (p = 0.002), heart failure (p = 0.036), abdominal aorta (p < 0.001), superior mesenteric artery (p = 0.002), or left subclavian artery involvement (p = 0.041). Despite higher morbidity (hypertension, CRF), mortality risk was not increased with RAI vs without RAI (HR 2.32, 95%CI 0.61-8.78), with bilateral RAI vs unilateral RAI (HR 2.65, 95%CI 0.52-13.42) or without RAI (HR 3.16, 95%CI 0.79-12.70) even after multivariable adjustment or PSM., Conclusion: RAI is associated with increased morbidity (CRF, hypertension, heart failure) but does not adversely affect survival in TAK. Key Points •Renal artery involvement in TAK is associated with chronic renal failure. •TAK with renal artery involvement more often have heart failure and hypertension. •Bilateral renal artery involvement (compared with unilateral) is more often associated with hypertension and visual symptoms. •Renal artery involvement is not associated with an increased risk of mortality in TAK., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Objectives: To compare the presentation, angiographic features, evolution, and prognosis of prepulseless Takayasu arteritis (TAK) with TAK with pulse loss., Methods: Pre-pulseless TAK (defined as without pulse loss in the upper limbs, lower limb, carotid, or subclavian arteries) were identified from a cohort of TAK. Demographic characteristics, clinical features, angiographic involvement, baseline and longitudinal patterns of disease activity, medication use, and mortality rates were compared between pre-pulseless TAK and TAK with pulse loss. Adjusted odds ratios (aOR, with 95%CI) for categorical variables between pre-pulseless TAK and TAK with pulse loss were computed using multivariable-adjusted logistic regression models. Time-to-event data was compared using hazard ratios (HR) with 95%CI., Results: Compared with TAK with pulse loss, pre-pulseless TAK (91/238, 38.24%) more frequently had deranged renal function (aOR 4.43, 95%CI 1.58-12.37) and Hata's type IV disease (aOR 8.02, 95%CI 2.61-24.65), and less often had pulse or blood pressure asymmetry (aOR 0.34, 95%CI 0.18-0.63), limb claudication (aOR for upper limb 0.38, 95%CI 0.18-0.82, for lower limb 0.28, 95%CI 0.12-0.68), right subclavian (aOR 0.45, 95%CI 0.23-0.90) or left carotid artery involvement (aOR 0.42, 95%CI 0.21-0.84). Only two patients with pre-pulseless TAK developed pulse loss on follow-up. Despite fewer pre-pulseless TAK having active disease at presentation, similar proportions of patients in both groups had active disease on follow-up. Survival was similar in both groups (HR for mortality 0.41, 95%CI 0.09-1.90)., Conclusion: Pulse loss on follow-up is uncommon in those with prepulseless TAK. Pre-pulseless TAK is associated with similar long-term outcomes to TAK with pulse loss., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Mediterranean Journal of Rheumatology (MJR).)

Background: Preterm birth rates are consistently higher in African American (AA) pregnancies compared to White pregnancies in the United States. Neighborhood racial composition, experiences of racial discrimination, and systemic inflammation are factors that have been associated with preterm birth and other adverse pregnancy outcomes that may account for these disparities. Here, we investigated whether perceived neighborhood racial composition and experiences of discrimination were predictive of cytokine levels during pregnancy among AA individuals., Methods: 545 AA individuals completed surveys and had blood samples collected at prenatal clinics in the Midwest at three timepoints (8-18,19-29, and 30-36 weeks gestation) throughout pregnancy. Pro-inflammatory [interferon (IFN)-γ, interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, macrophage migration inhibitory factor (MIF)] and anti-inflammatory cytokines (IL-10) were quantified. Multivariate and multilevel models were used to examine associations of perceived neighborhood racial composition and experiences of racial discrimination with cytokine levels, controlling for relevant covariates., Results: Perceived neighborhood racial composition was significantly associated with MIF at 30-36 weeks gestation in multivariate regression (p < 0.001). Living in neighborhoods with more compared to fewer White people was predictive of higher levels of MIF (b = 0.599, SE = 0.12, p < 0.001). Experiences of discrimination were also associated with higher levels of MIF (β = 0.141, SE = 0.07, p = 0.036). Neither predictor was associated with other cytokines. Follow-up analyses revealed that neighborhood racial composition was also predictive of higher MIF levels at 8-18 weeks gestation (p = 0.02) and at 19-29 weeks gestation (p = 0.04)., Conclusions: Living in neighborhoods with more White individuals and having more lifetime experiences of racial discrimination were positively related to levels of the pro-inflammatory cytokine, MIF, among pregnant AA individuals. MIF's known positive relationships with chronic stress and preterm birth suggest that these elevations in MIF may have negative health consequences. Future studies should explore whether MIF serves as a pathway between neighborhood racial composition or experiences of racial discrimination and preterm birth risk among AA individuals., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Inc.)

Background: Pulmonary sarcoidosis (SAR) and tuberculosis (TB) are two granulomatous lung-diseases and often pose a diagnostic challenge to a treating physicians., Objective: The present study aims to explore the diagnostic potential of NMR based serum metabolomics approach to differentiate SAR from TB., Materials and Method: The blood samples were obtained from three study groups: SAR (N = 35), TB (N = 28) and healthy normal subjects (NC, N = 56) and their serum metabolic profiles were measured using 1D 1 H CPMG (Carr-Purcell-Meiboom-Gill) NMR spectra recorded at 800 MHz NMR spectrometer. The quantitative metabolic profiles were compared employing a combination of univariate and multivariate statistical analysis methods and evaluated for their diagnostic potential using receiver operating characteristic (ROC) curve analysis., Results: Compared to SAR, the sera of TB patients were characterized by (a) elevated levels of lactate, acetate, 3-hydroxybutyrate (3HB), glutamate and succinate (b) decreased levels of glucose, citrate, pyruvate, glutamine, and several lipid and membrane metabolites (such as very-low/low density lipoproteins (VLDL/LDL), polyunsaturated fatty acids, etc.)., Conclusion: The metabolic disturbances not only found to be well in concordance with various previous reports, these further demonstrated very high sensitivity and specificity to distinguish SAR from TB patients suggesting serum metabolomics analysis can serve as surrogate method in the diagnosis and clinical management of SAR., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: To analyze the risk, causes, and predictors of mortality in Takayasu arteritis (TAK)., Methods: Survival was assessed in a cohort of patients with TAK using Kaplan-Meier curves. Age- and sex-standardized mortality ratio (SMR = observed: expected deaths) for TAK were calculated by applying age- and sex-specific mortality rates for the local population to calculate expected deaths. Hazard ratios (HR with 95%CI) for predictors of mortality based on demographic characteristics, presenting features, baseline angiographic involvement, disease activity, number of immunosuppressive medications used, procedures related to TAK, and any serious infection were calculated using Cox regression or exponential parametric regression models., Results: Among 224 patients with TAK (159 females, mean follow-up duration 44.36 months), survival at 1, 2, 5, and 10 years was 97.34%, 96.05%, 93.93%, and 89.23%, respectively. Twelve deaths were observed, most of which were due to cardiovascular disease (heart failure, myocardial infarction, stroke). Mortality risk was significantly higher with TAK (SMR 17.29, 95%CI 8.95-30.11) than the general population. Earlier age at disease onset (HR 0.90, 95%CI 0.83-0.98; or pediatric-onset vs adult-onset disease, HR 5.51, 95%CI 1.57-19.32), higher disease activity scores (ITAS2010: HR 1.15, 95%CI 1.05-1.25, DEI.TAK: HR 1.18, 95%CI 1.08-1.29), any serious infections (HR 5.43, 95%CI 1.72-17.12), heart failure (HR 7.83, 95%CI 2.17-28.16), or coeliac trunk involvement at baseline (HR 4.01, 95%CI 1.26-12.75) were associated with elevated mortality risk., Conclusion: Patients with TAK had an elevated risk of mortality as compared with the general population. Cardiovascular disease was the leading cause of death in TAK., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: To describe the characteristics of participants in the Fathers Matter study for a better understanding of fathers of the baby who engage in pregnancy research involving primarily Black couples and their relationships with their partners., Study Design and Methods: The Fathers Matter Study uses a prospective design, identifying father-mother dyads during pregnancy and following them until birth as part of the Biosocial Impacts on Black Births Study. Participants completed prenatal and postpartum questionnaires., Results: Our analyses are based on 111 fathers. Nearly all ( n = 101, 91.1%) of fathers identified as Black and 51.4% ( n = 57) had a high school diploma, graduate equivalency diploma, or higher. About half ( n = 57, 51.4%) reported annual incomes of $10,000 or less. Most reported that relationships with the mother were very close both before ( n = 100, 89.9%) and during ( n = 85, 76.6%) pregnancy. However, substantial variability was found in relationship satisfaction, involvement in the pregnancy, financial support provided, and scales of conflict and support., Clinical Implications: We found homogeneity in sociodemographic and basic relationship measures. Complex measures of the father-mother relationships demonstrated considerable variability. Data from fathers may identify their contributions to successful birth outcomes. Understanding relationships between fathers and mothers could identify risk or protective characteristics to be addressed at the family or community levels., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Black women report higher levels of depressive symptoms during pregnancy than white women. A supportive relationship with the father of the baby may be protective and decrease depressive symptoms., Objective: We sought to examine the association between mother-father relationship and depressive symptoms among pregnant black women., Methods: Using a cross-sectional design, we conducted a secondary data analysis from a subsample of 405 pregnant black women who participated in the Biosocial Impact on Black Births study, a prospective cohort study. Participants completed questionnaires at 19- to 29-week gestation, including 6 measures of their relationship with the father of the baby: (1) contact, (2) involvement, (3) overall relationship, (4) change in relationship from prior to pregnancy to during pregnancy, (5) support, and (6) conflict. Latent class analysis was used to identify and classify the relationship construct. The Center for Epidemiologic Studies-Depression (CES-D) scale was used, with scores ≥23 considered high levels of depressive symptoms. Data were analyzed with logistic regression., Results: Following adjustment for maternal sociodemographic characteristics, comorbid conditions, and health behaviors, women in a conflictual relationship had higher odds of having depressive symptom scores ≥23 (adjusted odds ratio: 3.50, 95% confidence interval: 2.00, 6.12) than those having no relationship (adjusted odds ratio: 2.81, 95% confidence interval: 1.43, 5.52), when compared with those with a good relationship., Conclusions: These findings suggest that having either a conflictual or no relationship with the father of the baby during pregnancy increases the odds for higher maternal depressive symptoms (CES-D scores ≥ 23) among pregnant black women., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The challenges associated with diagnosing and treating cardiovascular disease (CVD)/Stroke in Rheumatoid arthritis (RA) arise from the delayed onset of symptoms. Existing clinical risk scores are inadequate in predicting cardiac events, and conventional risk factors alone do not accurately classify many individuals at risk. Several CVD biomarkers consider the multiple pathways involved in the development of atherosclerosis, which is the primary cause of CVD/Stroke in RA. To enhance the accuracy of CVD/Stroke risk assessment in the RA framework, a proposed approach involves combining genomic-based biomarkers (GBBM) derived from plasma and/or serum samples with innovative non-invasive radiomic-based biomarkers (RBBM), such as measurements of synovial fluid, plaque area, and plaque burden. This review presents two hypotheses: (i) RBBM and GBBM biomarkers exhibit a significant correlation and can precisely detect the severity of CVD/Stroke in RA patients. (ii) Artificial Intelligence (AI)-based preventive, precision, and personalized (aiP 3 ) CVD/Stroke risk AtheroEdge™ model (AtheroPoint™, CA, USA) that utilizes deep learning (DL) to accurately classify the risk of CVD/stroke in RA framework. The authors conducted a comprehensive search using the PRISMA technique, identifying 153 studies that assessed the features/biomarkers of RBBM and GBBM for CVD/Stroke. The study demonstrates how DL models can be integrated into the AtheroEdge™-aiP 3 framework to determine the risk of CVD/Stroke in RA patients. The findings of this review suggest that the combination of RBBM with GBBM introduces a new dimension to the assessment of CVD/Stroke risk in the RA framework. Synovial fluid levels that are higher than normal lead to an increase in the plaque burden. Additionally, the review provides recommendations for novel, unbiased, and pruned DL algorithms that can predict CVD/Stroke risk within a RA framework that is preventive, precise, and personalized., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: The present study validates the 2022 ACR/European Alliance of Associations for Rheumatology (EULAR) classification criteria for Takayasu's arteritis (TAK), compared with the 1990 ACR TAK classification criteria., Methods: The fulfilment of 2022 ACR/EULAR and 1990 ACR TAK criteria from four referral centres was assessed for TAK compared with extracranial giant cell arteritis (EC-GCA) and other controls. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio of a positive test (LR+) or negative test (LR-), and area under receiver operating characteristics curve (AUC) were calculated., Results: Among 504 patients with TAK (404 females) and 222 controls (151 females, 144 patients with EC-GCA), the 2022 ACR/EULAR criteria had better sensitivity (95.83% vs 82.94%) and NPV, but poorer specificity (63.51% vs 90.54%), PPV, LR+, LR- and AUC at the pre-determined cut-offs than the 1990 ACR criteria. The 2022 ACR/EULAR criteria had greater specificity (76.06% vs 57.62%) and AUC (0.845 vs 0.771), with similar sensitivity (93% vs 96.53%) in males as in females. The 2022 ACR/EULAR criteria performed similarly with only EC-GCA as controls (sensitivity 95.83%, specificity 60.42%, AUC 0.781). Sensitivity remained similar, whereas specificity was higher for 40-60 years vs <40 years. Cut-offs of ≥6 (sensitivity 91.87%, specificity 82.88%) and ≥7 (sensitivity 86.71%, specificity 86.49%), or removing the point for female sex (sensitivity 92.64%, specificity 81.08%) greatly improved the balance between sensitivity and specificity., Conclusion: The poor specificity of the 2022 ACR/EULAR TAK criteria in real-life settings was improved by increasing the cut-off to 6 or 7, or removing the point for female sex., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)