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Translational Psychiatry Jul 2023Obsessive-compulsive disorder (OCD) is a frequent and debilitating mental illness. Although efficacious treatment options are available, treatment resistance rates are...
Obsessive-compulsive disorder (OCD) is a frequent and debilitating mental illness. Although efficacious treatment options are available, treatment resistance rates are high. Emerging evidence suggests that biological components, especially autoimmune processes, may be associated with some cases of OCD and treatment resistance. Therefore, this systematic literature review summarizing all case reports/case series as well as uncontrolled and controlled cross-sectional studies investigating autoantibodies in patients with OCD and obsessive-compulsive symptoms (OCS) was performed. The following search strategy was used to search PubMed: "(OCD OR obsessive-compulsive OR obsessive OR compulsive) AND (antib* OR autoantib* OR auto-antib* OR immunoglob* OR IgG OR IgM OR IgA)". Nine case reports with autoantibody-associated OCD/OCS were identified: five patients with anti-neuronal autoantibodies (against N-methyl-D-aspartate-receptor [NMDA-R], collapsin response mediator protein [CV2], paraneoplastic antigen Ma2 [Ma2], voltage gated potassium channel complex [VGKC], and "anti-brain" structures) and four with autoantibodies associated with systemic autoimmune diseases (two with Sjögren syndrome, one with neuropsychiatric lupus, and one with anti-phospholipid autoantibodies). Six patients (67%) benefited from immunotherapy. In addition, eleven cross-sectional studies (six with healthy controls, three with neurological/psychiatric patient controls, and two uncontrolled) were identified with inconsistent results, but in six studies an association between autoantibodies and OCD was suggested. In summary, the available case reports suggest an association between OCD and autoantibodies in rare cases, which has been supported by initial cross-sectional studies. However, scientific data is still very limited. Thus, further studies on autoantibodies investigated in patients with OCD compared with healthy controls are needed.
Topics: Humans; Autoantibodies; Cross-Sectional Studies; Obsessive-Compulsive Disorder; Receptors, N-Methyl-D-Aspartate; Brain
PubMed: 37400462
DOI: 10.1038/s41398-023-02545-9 -
American Journal of Reproductive... Sep 2023The current standard prevention of obstetric complications in patients with antiphospholipid antibody syndrome (APS) is the use of combination low-dose aspirin and low... (Review)
Review
PROBLEM
The current standard prevention of obstetric complications in patients with antiphospholipid antibody syndrome (APS) is the use of combination low-dose aspirin and low molecular weight heparin. However, 20-30% of women still experience refractory obstetrical APS. Hydroxychloroquine (HCQ) is an immunomodulatory agent that has been shown in laboratory studies to decrease thrombosis risk, support placentation, and minimize the destructive effects of antiphospholipid antibodies. The objective of this study was to evaluate the risk of pregnancy loss upon treatment with HCQ among women with refractory obstetrical APS.
METHOD OF STUDY
A systematic review was conducted according to PRISMA guidelines. Studies that evaluated the use of HCQ during pregnancy in women with primary APS were included. The primary outcomes of interest were live birth and pregnancy losses after treatment with HCQ.
RESULTS
Twelve studies met inclusion criteria. Three retrospective cohort studies demonstrated improved live birth rate, and four studies demonstrated a reduction in pregnancy loss rate. Two case reports also demonstrated a benefit in the use of HCQ compared to previous obstetrical outcomes.
CONCLUSIONS
Our findings suggest a significant benefit of HCQ in addition to aspirin and heparin for patients with APS to mitigate the risk of antiphospholipid antibody mediated obstetrical complications. Randomized controlled trials with standardized patient selection criteria need to be conducted to corroborate these findings.
Topics: Pregnancy; Humans; Female; Antiphospholipid Syndrome; Birth Rate; Hydroxychloroquine; Retrospective Studies; Antibodies, Antiphospholipid; Abortion, Spontaneous; Aspirin
PubMed: 37641373
DOI: 10.1111/aji.13761 -
Lupus Jan 2024While the prevalence of antiphospholipid antibodies (aPL) in venous and arterial thrombotic events had already been estimated by previous studies, the prevalence of aPL...
BACKGROUND
While the prevalence of antiphospholipid antibodies (aPL) in venous and arterial thrombotic events had already been estimated by previous studies, the prevalence of aPL in subjects with Thrombotic Microangiopathy (TMA) is still not fully elucidated. Thus, we conducted a systematic review to estimate the frequency of aPL in subjects with biopsy-proven renal TMA.
METHODS
We conducted in the PubMed database a search for English-language studies investigating the presence of aPL in subjects with biopsy-proven renal TMA from January 1985 to December 2022. Keywords used in the search included: 'antiphospholipid syndrome', 'antiphospholipid antibodies' and 'thrombotic microangiopathy'. Cohorts of HUS patients were excluded due to the risk of over-estimating the prevalence of aPL in these populations. The median frequency for positive aPL including anticardiolipin antibodies (aCL), antibodies against β2-glycoprotein-I (anti-β2GPI) and lupus anticoagulant (LA) was then calculated.
RESULTS
522 articles were identified through the literature search. Six studies, assessing the prevalence of aPL in 211 subjects with renal TMA, were retrieved. The overall aPL prevalence was estimated as 24.4% (range 22-56). The estimated prevalence of aCL (IgG/IgM), anti-β2GPI, (IgG/IgM) and LA was 4.0% (range 3-27), 4.0% (range 3-16) and 18.9% (range 13-25), respectively. APS was diagnosed in 16.3% (range 11-29) of the patients. Of note, a high level of heterogeneity was observed when comparing the reported aPL profiles for each study.
CONCLUSIONS
This comprehensive systematic analysis of studies investigating the prevalence of aPL in renal TMA showed that, despite the high heterogeneity of the included studies, aPL are present in about one case out of four renal-TMA cases.
Topics: Humans; Antiphospholipid Syndrome; Antibodies, Antiphospholipid; Prevalence; Lupus Erythematosus, Systemic; Lupus Coagulation Inhibitor; Antibodies, Anticardiolipin; Thrombotic Microangiopathies; Immunoglobulin G; Immunoglobulin M
PubMed: 38116607
DOI: 10.1177/09612033231217351 -
Journal of Clinical Medicine Aug 2023Antiphospholipid antibody (aPL)-associated thrombophilia has been implicated in various adverse pregnancy outcomes, including preterm birth and impaired fetal... (Review)
Review
Antiphospholipid antibody (aPL)-associated thrombophilia has been implicated in various adverse pregnancy outcomes, including preterm birth and impaired fetal development. This systematic review aimed to elucidate the relationship between aPL-associated thrombophilia and these outcomes, as well as to identify potential modifiers of this relationship such as maternal age, coexisting maternal medical conditions, type of aPL antibodies involved, and the timing of thrombophilia diagnosis during gestation. We conducted a comprehensive literature search in PubMed, Web of Science, Cochrane, and Scopus in May 2023, covering literature published within the last 10 years. Eight articles, involving 2935 patients, were eligible for inclusion in the review. Single aCL was the most common type of aPL found in patients, with rates up to 61.0% in some studies, followed by single LA and single ab2GPI. Multiple aPL antibody positivity was found to be associated with a higher risk of preterm birth, with odds ratios ranging from 1.29 to 9.61. Patient characteristics and previous pregnancy history varied significantly across the studies. Risk factors such as diabetes mellitus, thrombosis, and systemic lupus erythematosus were also variable across the studies, but presence of these risk factors did not consistently affect the risk of preterm birth. Furthermore, although a triple positive aPL test was the most important risk factor for preterm birth, it was observed that thrombophilia treatment during pregnancy significantly reduced the risk by 2.44 times (95% CI = 1.18-6.20). This review supports the evidence for aPL-associated thrombophilia being a significant contributor to preterm birth and fetal developmental abnormalities. Further research is required to investigate the exact mechanisms and to determine the best clinical management for patients with aPL-associated thrombophilia during pregnancy.
PubMed: 37629357
DOI: 10.3390/jcm12165316 -
Annals of the Rheumatic Diseases May 2024To analyse the new evidence (2018-2022) for the management of systemic lupus erythematosus (SLE) to inform the 2023 update of the European League Against Rheumatism...
OBJECTIVES
To analyse the new evidence (2018-2022) for the management of systemic lupus erythematosus (SLE) to inform the 2023 update of the European League Against Rheumatism (EULAR) recommendations.
METHODS
Systematic literature reviews were performed in the Medline and the Cochrane Library databases capturing publications from 1 January 2018 through 31 December 2022, according to the EULAR standardised operating procedures. The research questions focused on five different domains, namely the benefit/harm of SLE treatments, the benefits from the attainment of remission/low disease activity, the risk/benefit from treatment tapering/withdrawal, the management of SLE with antiphospholipid syndrome and the safety of immunisations against varicella zoster virus and SARS-CoV2 infection. A Population, Intervention, Comparison and Outcome framework was used to develop search strings for each research topic.
RESULTS
We identified 439 relevant articles, the majority being observational studies of low or moderate quality. High-quality randomised controlled trials (RCTs) documented the efficacy of the type 1 interferon receptor inhibitor, anifrolumab, in non-renal SLE, and belimumab and voclosporin, a novel calcineurin inhibitor, in lupus nephritis (LN), when compared with standard of care. For the treatment of specific organ manifestations outside LN, a lack of high-quality data was documented. Multiple observational studies confirmed the beneficial effects of attaining clinical remission or low disease activity, reducing the risk for multiple adverse outcomes. Two randomised trials with some concerns regarding risk of bias found higher rates of relapse in patients who discontinued glucocorticoids (GC) or immunosuppressants in SLE and LN, respectively, yet observational cohort studies suggest that treatment withdrawal might be feasible in a subset of patients.
CONCLUSION
Anifrolumab and belimumab achieve better disease control than standard of care in extrarenal SLE, while combination therapies with belimumab and voclosporin attained higher response rates in high-quality RCTs in LN. Remission and low disease activity are associated with favourable long-term outcomes. In patients achieving these targets, GC and immunosuppressive therapy may gradually be tapered. Cite Now.
PubMed: 38777375
DOI: 10.1136/ard-2023-225319 -
Lupus Sep 2023Children with lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) are characterized by prolonged activated partial thromboplastin time (APTT) and prothrombin time...
OBJECTIVE
Children with lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) are characterized by prolonged activated partial thromboplastin time (APTT) and prothrombin time (PT), lupus anticoagulant positivity and low prothrombin (factor II, FII) levels. Bleeding or thrombosis tendencies related to LAHPS in children can occur due to the development of anti-prothrombin antibodies that are usually linked to autoimmune or infectious diseases.
METHODS
We report three pediatric cases of LAHPS and describe details on their clinical symptoms, laboratory characteristics, treatment. PubMed, Medline, and Web of Science searches were conducted on LAHPS in children between 1960 and 2023; articles in English were included.
RESULTS
The coagulation profile revealed prolonged PT and APTT, with low prothrombin levels (19.4%, 21.0% and 12.9%, respectively) and positive lupus anticoagulant in 3 pediatric cases. Fifty-nine relevant articles reported 93 pediatric LAHPS cases (mean age: 9 years (0.8-17 years)); 63 females and 30 males, 87 patients presented with minor to severe bleeding diathesis, and 3 patients presented with thrombosis events. Among 48 patients ≥9 years old, 36 had SLE; among 45 patients <9 years, 29 had viral infection. When all patients were divided into two groups based on age, associated disease, and factor II level, Pearson's χ2 tests were performed, =.00, and there was clinical significance between autoimmune and infectious disease in patients ≥9 years old and <9 years old, and in patients FII level ≤10% and >10%. LAHPS patients with autoimmune disease had a protracted course and needed prolonged treatment with immune-modulating therapy, while those patients with infectious disease resolved spontaneously or needed short-term immune-modulating therapy.
CONCLUSION
LAHPS caused by autoimmune disease are common in patients ≥9 years old, especially SLE, and FII level ≤10% is often reported in patients caused by autoimmune disease, suggesting that children ≥9 years old diagnosed with LAHPS-related autoimmune disease should pay special attention to the FII level. While LAHPS caused by infectious disease is more frequently observed in patients <9 years, especially viral infection. Early diagnostic investigations are critical to differentiating LAHPS caused by autoimmune or infectious disease, as the prognosis, treatment and outcome are distinct.
Topics: Female; Male; Humans; Child; Child, Preschool; Hypoprothrombinemias; Lupus Coagulation Inhibitor; Prothrombin; Lupus Erythematosus, Systemic; Antiphospholipid Syndrome; Autoimmune Diseases
PubMed: 37480550
DOI: 10.1177/09612033231191153 -
Annals of Medicine and Surgery (2012) May 2024The optimal treatment regimen for patients with Hughes syndrome remains unclear. Therefore, the authors sought to compare the outcomes of warfarin vs. factor Xa... (Review)
Review
BACKGROUND
The optimal treatment regimen for patients with Hughes syndrome remains unclear. Therefore, the authors sought to compare the outcomes of warfarin vs. factor Xa inhibitors in patients with Hughes syndrome.
METHODS
MEDLINE, Embase, and Cochrane Central databases were searched for randomized controlled trials (RCTs) comparing 8 efficacy and safety of warfarin and factor Xa inhibitors in patients with Hughes syndrome. Recurrent thrombosis, all-cause mortality, stroke, adverse reactions, and bleeding were among 10 outcomes of interest. Mantel-Haenszel weighted random-effects model was used to calculate 11 relative risks (RRs) with 95% CIs.
RESULTS
The analysis included 625 patients from four RCTs and one post-hoc analysis. Meta-analysis showed a statistically non-significant difference between factor Xa inhibitors and warfarin in the recurrent thrombosis risk (arterial or venous) [RR 2.77 (95%, CI 0.79, 9.65); =0.11, I=50%]. Consistent results were revealed among patients with a previous history of arterial thrombosis [RR 2.76 (95% CI 0.93, 8.16); =0.75, I=0%], venous thrombosis [RR 1.71 (95% CI 0.60, 4.84); =0.31, I=15%] and patients who were triple antiphospholipid antibodies (aPL) positive [RR 4.12 (95% CI 0.46, 37.10); 21 =0.21, I=58%]. Factor Xa inhibitors were significantly associated with an increased risk of stroke [RR 8.51 (95% CI 2.35, 13.82); =0.47, I=0%].
CONCLUSION
Factor Xa inhibitors exhibited an increased risk of stroke among patients with Hughes syndrome. In addition, although not significant, the higher RRs among patients on factor Xa inhibitors may indicate a higher risk of thrombotic events associated with factor Xa inhibitors.
PubMed: 38694373
DOI: 10.1097/MS9.0000000000001999 -
Rheumatology International Nov 2023To optimize patient prognosis, patient needs, including unmet needs, should be adequately assessed. However, such needs are more challenging to report and, consequently,...
To optimize patient prognosis, patient needs, including unmet needs, should be adequately assessed. However, such needs are more challenging to report and, consequently, more likely to go unmet compared with the needs reported by physicians. We aimed to determine the appropriate direction of future research on unmet medical needs in rheumatic diseases in Japan by conducting a literature review. We searched PubMed and Web of Science using 23 terms linked to unmet medical needs for major rheumatic diseases in Japan. Further, we collected articles on health-related quality of life and investigated the scales used for assessment, as well as whether the terms "unmet needs" or "unmet medical needs" were used. We identified 949 papers on 10 diseases, including systemic lupus erythematosus, systemic sclerosis, dermatomyositis, juvenile idiopathic arthritis, adult-onset Still's disease, antiphospholipid syndrome, mixed connective tissue disease, Takayasu arteritis, Sjögren's syndrome, and Behçet's disease; 25 of the 949 papers were selected for full-text review. Fifteen articles on five diseases were related to health-related quality of life. The term "unmet needs" was used in only one article. Six out of 15 studies used the 36-item short form survey, whereas the scales used in other studies differed. The optimal treatment plan determined by a physician may not necessarily align with the best interests of the patient. In clinical research, cross sectional and standardized indicators of health-related quality of life should be employed along with highly discretionary questionnaires to assess and optimize resource allocation in healthcare and simultaneously achieve patient-desired outcomes.
Topics: Adult; Humans; Japan; Cross-Sectional Studies; Quality of Life; Rheumatic Diseases; Arthritis, Juvenile
PubMed: 37597057
DOI: 10.1007/s00296-023-05425-z