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Background: The detection of antiphospholipid antibodies (aPL) is of interest because of their importance in the pathogenesis of arterial or venous thrombosis. They could be a "second hit" of an inflammatory event such as infection. The aim of our study was to assess the performance of antiphospholipid antibody biomarker to predict in-hospital mortality in intensive care unit (ICU) septic patients.Methods: We conducted a prospective single-center observational study including consecutive critically ill septic adults admitted to the intensive care unit. Clinical and laboratory data including enzyme-linked immunosorbent assay for antiphospholipid antibodies (anticardiolipin (aCL), antiphosphatidylserine (aPS)) were obtained. Blood samples were collected on days 1, 3, 5, 8, and 10 of hospitalization. The primary study endpoint was ICU mortality defined as death before ICU discharge. Secondary end points included correlation between SOFA score and biological parameters.Results: A total of 53 patients were enrolled. 18.8% of patients were aPL positive. In-hospital mortality rate was 60%. Multivariate analysis showed that age and aCL at days 3 and 5 along with SOFA at day 3 were independent outcome predictors. A significant positive correlation existed between SOFA at days 3, 5, and 8 and antiphospholipid antibody concentrations.Conclusions: Our data showed that antiphospholipid was useful biomarkers for the prediction of mortality in critically ill septic patients. We found a positive correlation between SOFA score and antiphospholipid antibodies. [ABSTRACT FROM AUTHOR]

Objective To compare the curative effect of intravitreal injection of triamcinolone acetonide and aflibercept on diabetic retinopathy (DR) cystoid macular edema. Methods A total of 102 patients with DR cystoid macular edema admitted to the hospital were enrolled between July 2018 and July 2021. According to random number table method, they were divided into the control group (intravitreal injection of triamcinolone acetonide) and the observation group (intravitreal injection of aflibercept), 51 cases in each group. All were followed up for half a year. The clinical curative effect, visual acuity, central subfield macular thickness (CSMT), macular volume, scores of quality of life, and levels of cytokines in aqueous humor (vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), human angiopoietin-like protein 4 (ANGPTL4)] at different time points (before and at 6 months after surgery) were compared between the two groups. The times of drugs injection and occurrence of adverse reactions in both groups were statistically analyzed. Results The total effective rate in observation group was higher than that in the control group (96.08% vs 82.35%) (P < 0.05). After 6 months of treatment, visual acuity was improved, and CSMT and macular volume were decreased in both groups. Also, the above changes were more significant in the observation group than those in the control group (P < 0.05). After 6 months of treatment, levels of cytokines in aqueous humor were decreased in both groups. The levels of VEGF, MCP-1, and ANGPTL4 in observation group were lower than those in the control group (P < 0.05). After 6 months of treatment, quality of life scores in observation group were higher than those in the control group (P < 0.05). In the follow-up period, average times of drugs injection in the observation group were more than those in the control group, and the incidence of adverse reactions was lower than that in control group (5.88% vs 21.57%) (P < 0.05). Conclusion The curative effect of intravitreal injection of both triamcinolone acetonide and aflibercept is good on DR cystoid macular edema. The curative effect of aflibercept is better, which can improve visual acuity and quality of life, and regulate cytokines in aqueous humor, with high safety. However, aflibercept has a high price, and further research is needed to determine whether its price can be matched with clinical benefits. In clinic, medication plan should be selected according to the actual situation. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis estimates the prevalence of common comorbid health disorders in adults with rheumatoid arthritis (RA). A multi-database search strategy was undertaken. Screening, data extraction and quality assessment were carried out by two independent reviewers. A meta-analysis and meta-regression were used to generate a pooled prevalence estimate and identify relevant moderators. After study selection, 33 studies (74633 participants) were included in the meta-analysis. Some 31 studies were judged to be of low risk of bias, and two studies were judged to be at moderate risk of bias. The three most common comorbidities in RA were anxiety disorders (62.1%, 95% Cl: 43.6%; 80.6%), hypertension (37.7%, 95% Cl: 29.2%; 46.2%) and depression (32.1%, 95% Cl: 21.6%; 42.7%). There was substantial statistically significant heterogeneity for all comorbidities (I2 ≥77%). Meta-regression identified that the covariate of mean age (unit increase) had a statistically significant effect on the prevalence of hypertension (+2.3%, 95% Cl: 0.4%; 4.2%), depression (−0.5%, 95% Cl: −0.6%; −0.4%) and cancer (0.5%, 95% Cl: 0.2%; 0.8%) in adults with RA. A country's income was identified to have a statistically significant effect on the prevalence of depression, with low-to moderate-income countries having 40% (95% Cl: 14.0%; 66.6%) higher prevalence than high-income countries. No studies consider health inequalities. It is concluded that comorbidities are prevalent among people with RA, particularly those associated with mental health and circulatory conditions. Provision of health services should reflect the importance of such multimorbidity and the consequences for quality and length of life. [ABSTRACT FROM AUTHOR]

Giant cell arteritis (GCA) is the most common vasculitis among elderly people. The clinical spectrum of the disease is heterogeneous, with a classic/cranial phenotype, and another extracranial or large vessel phenotype as the two more characteristic patterns. Permanent visual loss is the main short-term complication. Glucocorticoids (GC) remain the cornerstone of treatment. However, the percentage of relapses with GC alone is high, and the rate of adverse events affects more than 80% of patients, so it is necessary to have alternative therapeutic options, especially in patients with worse prognostic factors or high comorbidity. MTX is the only DMARD that has shown to reduce the cumulative dose of GC, while tocilizumab is the first biologic agent approved due to its ability to decrease the relapse rate and lower the cumulative GC doses. However, apart from the IL-6 pathway, there are other pro-inflammatory cytokines and growth factors involved in the typical intima hyperplasia and vascular remodeling of GCA. Among them, the more promising targets in GCA treatment are the IL12/IL23 axis antagonists, IL17 inhibitors, modulators of T lymphocytes, and inhibitors of either the JAK/STAT pathway, the granulocyte-macrophage colony-stimulating factor, or the endothelin, all of which are updated in this review. [ABSTRACT FROM AUTHOR]

Background: Glucocorticoids (GCs) are the cornerstone of polymyalgia rheumatica (PMR) therapy, but their long-term use (as is usually necessary in PMR patients) can induce many adverse events. Alternatives have long been sought. The primary aim of our narrative review is to provide an overview about the use of anti-tumor necrosis factor alpha (TNF-α) drugs in patients with PMR, and discuss advantages and disadvantages. Materials and methods: we performed a non-systematic literature search (PRISMA protocol not followed) on PubMed and Medline (OVID interface). Results and Conclusions: only two anti TNF-α drugs have been prescribed to PMR patients: infliximab in 62 patients and etanercept in 28 patients. These drugs were normally used in addition to GCs when significant comorbidities and/or relapsing PMR were present; less commonly, they were used as first-line therapy. In general, they have been scarcely successful in patients with PMR. Indeed, randomized controlled trials did not confirm the positive results reported in case reports and/or case series. However, an administration schedule and study design different from those proposed in the past could favour new scenarios in the interest of PMR patients. [ABSTRACT FROM AUTHOR]

Background: Little is known about the persistence and impact of non-rheumatic symptoms after acute chikungunya disease. We have studied the clinical presentation and long-term impact of rheumatic and non-rheumatic symptoms on health related quality of life (QoL) 2.5 years after disease onset. Additionally, the validity of the Curaçao Long-Term Chikungunya Sequelae (CLTCS) score in classifying disease severity over time was evaluated. Methodology/Principal findings: This prospective cohort study followed 248 chikungunya patients. Symptoms and SF-36 QoL were evaluated during baseline and follow-up at 2.5 years using questionnaires. Chikungunya disease status was classified using the CLTCS-score. At 2.5 years after disease onset patients were classified as being recovered (43%), mildly (35%) or highly (22%) affected. In comparison to mildly affected, highly affected patients reported the highest prevalence of ongoing rheumatic and non-rheumatic/psychological symptoms, with increased prevalence of arthralgia in the lower extremities (p =.01) and fatigue (p =.049) over time, and higher pain intensity (p <.001). Compared to mildly affected, being highly affected was associated with weakness in the lower extremities (OR: 1.90; CI: 1.29–2.80, p =.001) and worsened physical and mental QoL impairment. Conclusions: Patients are both physically and psychologically affected by rheumatic and non-rheumatic symptoms of long-term chikungunya disease. The CLTCS-score is an easy to use instrument for classifying long-term chikungunya disease severity and impact and can facilitate health care providers in identifying highly affected patients who are prone to develop severe QoL impairment. Highly affected patients are recommended to be treated in a multidisciplinary setting to improve physical and psychological functioning, and QoL. Author summary: Chikungunya disease manifestation is characterized by a sudden onset of non-rheumatic flu-like symptoms and debilitating rheumatic symptoms in the acute phase. Little is known about the persistence of non-rheumatic symptoms after acute disease. In this prospective cohort study we investigated the clinical manifestations and persistence of baseline rheumatic and non-rheumatic/psychological symptoms and their impact on health related quality of life (QoL) 2.5 years after disease onset. Moreover, we investigated the performance of the classification instrument the Curaçao Long-Term Chikungunya Sequelae (CLTCS) score in classifying chikungunya disease severity over time. We found that 57% of the patients were still affected 2.5 years after disease onset. An increase of mainly recurrent rheumatic and non-rheumatic/psychological symptoms including fatigue, insomnia, sombreness, and loss of vitality were reported, with a significantly higher symptom recurrence and pain intensity reported by highly affected patients. In addition, QoL assessment indicates that the disease burden impaired the physiological well-being of these patients. We also showed that the CLTCS-score can be used to easily identify highly affected patients. This study demonstrates that disease severity increases non-rheumatic symptoms and subsequent physiological impairments and suggests a multidisciplinary treatment approach to treat the psychological effects of long-term chikungunya disease. [ABSTRACT FROM AUTHOR]

T-helper 2 (Th2)-associated cytokines are involved in the pathogenesis of bullous pemphigoid (BP), an autoimmune skin disease. Increased expression of Th2 cytokines such as interleukin-4 (IL-4), IL-5, IL-6, IL-10, and IL-13 have been observed in serum, skin biopsies and/or blister fluid. This study aimed to uncover a possible association between Th2 cytokine genetic variations and susceptibility to BP. In a cohort study, blood samples of BP patients and controls were obtained and variations in IL-4 (rs2243250 and rs2070874), IL-4R (rs1805010), IL-5 (rs2069812), IL-6 (rs1800795), IL-10 (rs1800896, rs1800871, and rs1800872), and IL-13 (rs1800925 and rs20541) were genotyped by PCR-RFLP assays. Furthermore, quantitative expression levels of IL-13 gene were evaluated by real-time RT-PCR analysis. Among the studied variations, a significantly higher frequency of the C-allele was observed in IL-13 gene variation (rs1800925) in the healthy individuals than BP patients. This may indicate a protective effect of C-allele on predisposition to BP. Considering individuals carrying polymorphic genotypes compared to wild genotype, the minor G-allele of IL-4R rs1805010 and A-allele of IL-13 rs20541 had a promotive and protective effect, respectively, on predisposing to the development of BP. No significant difference in IL-13 mRNA expression was detected between BP patients and healthy individuals. Our results indicate that IL-13 rs1800925 variation may be a protective genetic marker for the development of BP. Given this preventive effect against BP, therapeutic strategies could potentially be developed interfering with the functions of IL-13 cytokine, which seems to be integral in the pathogenesis of eosinophilic inflammatory disorders, such as BP. [ABSTRACT FROM AUTHOR]

Spondyloarthritis (SpA) encompasses a group of inflammatory rheumatic diseases that share clinical and imaging characteristics as well as a common genetic basis. These diseases can affect 0.20-1.6% of the general population, limiting functioning and affecting the quality of life of patients. Considering the patient perspective in the management of the disease and ensuring patients are sufficiently prepared to participate in decision making is critical to treatment success, as well as for optimal health outcomes. The overall picture of impairments, limitations, and restrictions in activities or social participation for patients with SpA is not adequately assessed in SpA-specific instruments. Therefore, it is important to measure the broader range of impairments that can affect patients with SpA and integrate these into a single measure of overall functioning in daily life. The Assessment of SpondyloArthritis international Society Health Index (ASAS HI) is a recently introduced health instrument for evaluating SpA based on the International Classification of Functioning, Disability and Health (ICF) that could cover a good part of the health metric needs in SpA. This review addresses its origins, measurement properties, and use in routine clinical practice, as well as its prospects for future use. [ABSTRACT FROM AUTHOR]

Background: This study aimed to demonstrate the gender and age-at-onset differences in rheumatoid arthritis (RA) in the western Algerian population and their impacts on patients' clinical features and medical management. Methods: A retrospective cross-sectional study was carried out at the Internal Medicine and Functional Rehabilitation Departments (University Hospital of Sidi-bel-Abbes region) based on medical records of over 306 RA patients diagnosed between 2016 and 2019 according to ACR 1987 criteria. Late-onset RA (LORA) was defined as disease onset at 51 years of age or older. All data were processed and analyzed via SPSS 22.0. Results:We enrolled 306 rheumatoid arthritis patients (85% women) with a mean age-at-onset of 52.47±12.14. Algerian RA women were more at risk of developing type 2 diabetes (P = 0.035), hypertension (P = 0.003), and thyroid disorders (P = 0.05). We did not find any significant relationship between clinical features, laboratory data, and gender. The LORA group comprised 60.5% of our study population with a higher number of comorbidities such as hypertension (P < 0.001), osteoporosis (P = 0.007), and scleroderma (P = 0.014). Nonetheless, we found evidence of an association between positive anti-CCP, RF rate, and age-at-onset (P = 0.001 and P < 0.001, respectively). Conclusions: Algerian RA women with LORA presented a higher prevalence of comorbidities, while Young-onset RA (YORA) was associated with a high rate of RF. [ABSTRACT FROM AUTHOR]

Behcet's syndrome (BS) is a chronic systemic inflammatory vasculitis with a wide range of clinical manifestations including recurrent oral and genital ulcers; cutaneous lesions; and ophthalmic, neurologic, and gastrointestinal involvement. BS has a global distribution but is particularly prevalent in so-called Silk Road populations. Disease onset is usually around the third or fourth decade of life, and the sex ratio is roughly 1:1. Both environmental and genetic factors contribute to the etiology of BS, although the detailed mechanisms remain unclear. At present, there is no laboratory examination with diagnostic value for BS; therefore, a diagnosis is made based on clinical manifestations. The International Study Group diagnostic criteria published in 1990 is the most widely used and recognized, but in order to improve sensitivity, the International Criteria for Behcet's Disease is developed in 2014. Evaluating disease activity in BS is an important basis for treatment selection and monitoring, the simplified Behcet's Disease Current Activity Form (2006 version) is a well-established scoring method. Given that multiple organs are affected in BS, it must be differentiated from other diseases with similar manifestations or that may be induced by drug treatment. The goal of BS treatment is to eradicate triggers and/or aggravating factors, alleviate and control clinical symptoms, prevent and treat any damage to organs, slow disease progression, and improve the patient's quality of life. The clinical management of BS depends on the affected organs and disease severity. In this review, we summarize the current state of knowledge of BS pathogenesis and therapeutic options. [ABSTRACT FROM AUTHOR]

Inflammation contributes centrally to cardiovascular diseases, and anti-inflammatory treatments can reduce cardiovascular events. The JAK–STAT pathway is an emerging target in inflammation, mainly in rheumatoid arthritis (RA) and chronic myeloproliferative neoplasms (MPNs), disorders that heighten cardiovascular risk. The aim of this study was to review the international literature on the relationship between dysregulation of the JAK–STAT pathway in RA/MPNs and cardiovascular risk and on the potential cardiovascular effects of JAK–STAT inhibitors. The JAK–STAT pathway sustains inflammatory and thrombotic events in autoimmune disorders such as RA and MPNs. Here, an imbalance exists between pro- and anti-inflammatory cytokines [increased levels of interleukin (IL)-6, IL-1-β, tumour necrosis factor-α, decreased levels of IL-10] and the over-expression of some prothrombotic proteins, such as protein kinase Cε, on the surface of activated platelets. This pathway also operates in atherosclerotic cardiovascular disease. JAK–STAT inhibitors may reduce cardiovascular events and related deaths in such conditions, but the potential of these agents requires more studies, especially with regard to cardiovascular safety, and particularly for potential prothrombotic effects. JAK–STAT inhibitors merit consideration to curb heightened cardiovascular risk in patients with RA and MPNs, with rigorous assessment of the potential benefits and risks. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis (PsA) is a highly heterogenous disease, with many different clinical manifestations inside or outside of the musculoskeletal system and the skin. It is often accompanied by comorbidities like cardiovascular diseases and mental health disorders. Acute phase reactants are not always elevated and specific markers for diagnosis and/or monitor the disease are lacking thus far. These characteristics possibly reflect the difficulty in agreement about a disease activity index for PsA. Many indices have been proposed over the last years, each of them considering different combinations of disease characteristics. We performed a literature search for relevant articles using PubMed and Embase. No data limits were applied. The keywords "Psoriatic arthritis" OR "PsA" AND "disease activity" AND "index" OR "indices" were used. Reference lists of relevant articles were also reviewed. Articles were also identified through searches of the authors' own files. In this review, we comparatively present the available indices (simple or composite) used for measuring activity in PsA, highlighting their weaknesses, strengths, and disparities. We comment also on the caveats and pitfalls that are encountered in assessment of disease activity, in relation to clinical practice and research. A widely accepted index for measuring disease activity in PsA is lacking. Other parameters, mostly related to patient-reported outcomes and to novel biomarkers might be included in the future, in such indices. Key points • Disease activity in PsA is multiparametric and its assessment is challenging due to many different phenotypes. • Many different indices are currently in use of PsA disease activity assessment. • Each PsA disease activity index has specific pros and cons. [ABSTRACT FROM AUTHOR]

Behçet's disease (BD) is a chronic, vasculitic disorder affecting all sizes of vessels. The disease rarely onsets at childhood and an early diagnosis is often challenging. Oral ulceration and fever of unknown cause are common initial manifestations that might confuse other inflammatory disorders. The clinical manifestation pattern in pediatric BD is heterogeneous and varies in different genders, ethnicities, and geographic regions. There are also some differences in clinical presentations and prognosis between pediatric and adult BD. The disease also affects children at an extremely young age with mostly benign outcomes compared with that in older children. A limited number of studies reported issues about pediatric BD, let alone studies of children's treatments. Currently, the recommendation of the treatment in pediatric BD is according to the guideline of adult BD. The heterogeneity of clinical features makes the treatment more complicated. The main goal of the treatment is to control the inflammatory process and prevent recurrences. We will discourse the definition, epidemiology, clinical features, diagnosis, and treatment of pediatric BD in this review. [ABSTRACT FROM AUTHOR]

Featured Application: The perception of the quality of life of the patient with diabetic foot depends on the physiological parameters present as well as on other factors such as gender. The co-existence of complications and diabetes mellitus is related to a worsening in quality of life compared to not presenting comorbidities. This study aimed to investigate whether there is a different impact on quality of life according to gender and to establish the physiological parameters that these patients have in relation to diabetes-related complications. The sampling was continuous non-probabilistic, involving legal age patients with diabetes mellitus. All of the participants were administered the generic SF-36 quality of life questionnaire. The presence of peripheral artery disease was considered from an ankle brachial index <0.9 and grade II to grade IV of the Leriche–Fontaine classification. Nerve dysfunction was detected from a neurotensiometer test, and the presence of diabetic foot was detected from a dermal examination and co-existence with arteriopathy and/or neuropathy. Men presented significantly better quality of life values on the mental health, emotional role and health transition scales. Despite this, in the presence of complications such as vasculopathy, neuropathy or diabetic foot, the perception of well-being changes, showing that men and women face the disease in different ways. Despite the fact that the physical parameters of diabetic patients are similar according to the complications that they present, the adult women in our environment have lower levels of quality of life than men in most cases. This may be related not only to pathophysiological differences but also to sociocultural factors. [ABSTRACT FROM AUTHOR]

An efficient and attractive Co/organophotoredox dual catalysis protocol has been developed allowing the stereoselective access to a wide variety of syn‐configured 1,3‐diols featuring quaternary carbon centers. The synthesis of the target molecules is achieved under ambient reaction conditions using modular and accessible reagents, substituted vinyl cyclic carbonates and aldehydes, and in short reaction times. Mechanistic control experiments suggest that the stereoselectivity can be rationalized via a preferred Zimmerman–Traxler transition state comprising a Co(allyl) species and an activated aldehyde. This newly developed process thus expands the use of base metal catalysis in the construction of challenging quaternary carbon stereocenters. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to evaluate dysfunctional high‐density lipoprotein cholesterol (HDL) by measuring myeloperoxidase (MPO)/paraoxonase 1 (PON1) ratio in patients with rheumatoid arthritis (RA) and to investigate the relationship between dysfunctional HDL and cardiovascular disease (CVD) in RA patients. Methods: Sixty‐seven healthy individuals and 130 RA patients were included in the study. Routine lipid panels (triglyceride (TG), low‐density lipoprotein cholesterol (LDL), HDL, total cholesterol (TC), PON1 and MPO levels were measured. Disease activity scores‐28 (DAS28) of RA patients were calculated. Cardiological examination records of the patients were assessed to detect patients who also have CVD. Results: There were no significant differences between RA and control groups in routine lipid profiles (P >.05 for all). MPO/PON1 ratios were significantly elevated in the RA group compared with the control group (P <.001). MPO/PON1 ratios were higher in RA patients with CVD history compared with those without CVD (P <.05). MPO/PON1 ratios were correlated with DAS28 scores (rho: 0.357, P <.001). Conclusion: HDL dysfunction determined by the MPO/PON1 ratio may be associated with the pathophysiology of increased CVD in RA. Thus, evaluating dysfunctional HDL levels by measuring the MPO/PON1 ratio in RA patients may allow more detailed patient follow‐up, as well as the reduction of CVD events in RA patients with therapeutic agents aiming to increase the functional properties of HDL by decreasing this ratio. [ABSTRACT FROM AUTHOR]

Objective: Patients with rheumatoid arthritis (RA) who also have diabetes mellitus (DM) might have worse clinical outcomes and adverse events compared to patients with RA who do not have DM. We evaluated the effects of DM on Health Assessment Questionnaire (HAQ) changes and outpatient infection rates in patients with RA.Methods: Using the American College of Rheumatology's Rheumatology Informatics System for Effectiveness (RISE) electronic health record-based registry, we identified patients with RA who had ≥ 1 rheumatologist visit with a HAQ measured in 2016 (index visit), ≥ 1 previous visit, and a subsequent outcome visit with the same HAQ measured at 12 months (± 3 months). We identified DM by diagnosis codes, medications, or laboratory values. Outpatient infection was defined by diagnosis codes or antiinfective medications. We calculated mean HAQ change and incidence rate (IR) of outpatient infections among patients with and without DM. Generalized linear models and Cox regression were used to calculate the adjusted mean HAQ change and HRs.Results: We identified 3853 RA patients with DM and 18,487 without DM. The mean HAQ change between index and outcome visit among patients with DM was 0.03 and without DM was 0.002 (P < 0.01). We identified 761 outpatient infections for patients with DM with an IR of 22.6 (95% CI 21.0-24.2) per 100 person-years and 3239 among patients without DM with an IR of 19.8 (95% CI 19.1-20.5). The adjusted HR of outpatient infections among patients with DM was 0.99 (95% CI 0.91-1.07), compared to patients without DM.Conclusion: Patients with RA with concomitant DM had greater worsening, or less improvement, in their functional status, suggesting additional interventions may be needed for RA patients with DM to optimize treatment and management of other comorbidities. [ABSTRACT FROM AUTHOR]

The author reflects on the added value of the Assessment of SpondyloArthritis International Society health index (ASAS HI) in the differentiation of the elements of the quality of life of patients with different spondyloarthritis (SpA) phenotypes. Also cited is the importance of ASAS HI in monitoring the health of SpA patients like emotional functions, sleep, pain, and mobility.

Non-infectious uveitis (NIU) is a group of sight-threatening diseases that generates significant burden for the healthcare systems due to its adverse outcomes, irreversible structural complications in the eye with loss of visual function, limited clinical expertise and low-grade evidence for best practice. The usefulness of multidisciplinary care, specifically close collaboration between Rheumatologists and Ophthalmologists in NIU, has been emphasized in the literature. In this paper, the assessment tools and protocols used in our clinic are depicted and an overview of our activity with a brief description of the patients included in our registry, between 2018 and 2020 is provided. The cohort of 290 patients assessed in our NIU clinic, their demographics, sources of referral, details about immunosuppression treatment, and internal and external collaborations is described. This experience-based manuscript aims to describe the general functioning of our multidisciplinary NIU clinic, highlighting the benefits and drawbacks of multidisciplinary team management in patients with NIU, ultimately initiating a dialogue on what an NIU clinic should be and providing information for newly NIU clinics start-up. In conclusion, establishing a standardized and multidisciplinary clinic in NIU allows to systematically observe and follow-up this infrequent disease at a tertiary hospital level, thus improving quality of care delivery and research avenues. [ABSTRACT FROM AUTHOR]

The term ‘aortitis’ comprises a heterogeneous spectrum of diseases, with varied etiology and clinical presentations, whose common characteristic is the inflammation of the aortic wall. Since aortitis can mimic almost all common cardiovascular disorders, its clinical recognition remains a challenge. Some cases of aortitis remain undetected for a long time and may be diagnosed after severe life-threatening complications have already arisen. The diagnosis of aortitis is based on the presence of homogeneous circumferential thickening of the aortic wall detected on aortic imaging, or typical histological features in combination with clinical findings and laboratory parameters. Management of aortitis is usually conservative (immunosuppressive drugs in noninfectious aortitis; antimicrobial drugs in infectious). However, if vascular complications such as aortic aneurysm, rupture, or steno-occlusive events appear, aortic surgery or endovascular therapy may be required. This review article summarizes the current knowledge regarding the etiology, clinical presentation, diagnosis, and treatment of inflammatory diseases of the aorta to promote better clinical management of these entities. [ABSTRACT FROM AUTHOR]

Abnormal vasculature is a key feature of hereditary hemorrhagic telangiectasia (HHT) and can also present in the nail fold capillary beds. However, the exact prevalence and the clinical diagnostic value in HHT are still largely unknown. The nail fold can be easily and noninvasively inspected with a capillary microscope. We therefore retrospectively assessed the prevalence and diagnostic value of abnormal nail fold capillaries in all patients who were screened between January 2000 and July 2017 for the presence of HHT and underwent capillary microscopy in St Antonius Hospital, The Netherlands. Capillary microscopy results and clinical characteristics were extracted from medical files and the prevalence of abnormal nail fold capillaries was calculated and the diagnostic value of the Curaçao criteria with and without capillary microscopy results was assessed. Of the 1761 individuals screened, 923 (52%) were diagnosed with a clinical and/or genetic HHT diagnosis. In these patients, capillary microscopy was normal in 23% (n = 218), enlarged loops were seen in 11% (n = 99), and giant loops in 66% (n = 606). The sensitivity and specificity of the Curaçao criteria for the diagnosis of HHT without capillary microscopy results were 96% and 90%, respectively. The addition of the presence of giant loops to the Curaçao criteria led to a small increase in sensitivity to 97% without affecting the specificity. In conclusion, the prevalence of nail fold abnormalities in patients with HHT is high. Capillary microscopy can be a useful, easy, and noninvasive diagnostic tool in HHT. [ABSTRACT FROM AUTHOR]

Behçet's disease is a chronic, multisystem inflammatory disorder characterized by relapsing inflammation. Although its etiopathogenesis has not yet been clarified, both the adaptive and innate immune systems, genetic predisposition, and environmental factors have all been implicated. It is more frequent and more severe in males in the third and fourth decades of life. The eye is the most frequently involved organ in the course of the disease. Ocular involvement (Behçet's uveitis) is characterized by bilateral recurrent non-granulomatous panuveitis and occlusive retinal vasculitis. Recurrent inflammatory episodes in the posterior segment may lead to permanent vision loss due to irreversible retinal damage and complications such as macular scarring, macular atrophy, and optic atrophy. Early and aggressive immunomodulatory treatment and the use of biologic agents when needed are crucial for preventing recurrences and improving visual prognosis. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis is a highly prevalent disease identified by Dual Energy X-ray Absorptiometry (DEXA) that can be performed in an ambulatory (out-patient) or hospitalized population. We evaluated the use of baseline in-hospital DEXA screening to identify osteoporosis in ambulatory care and hospitalized patients; we also assessed specific risk factors for osteoporosis among these populations.Methods: We included a baseline initial DEXA from 6406 consecutive patients at our tertiary referral University Hospital.Results: Osteoporosis was diagnosed in 22.3% of the study population. In univariate analysis, osteoporosis risk factors were age, fracture history and low BMI (for all 3 sites), but also corticotherapy (lumbar spine and femoral neck) and male (lumbar spine). In multivariate analysis, age, fracture history, low BMI, and male increased osteoporosis risk. In-hospital screening yielded a higher percentage of osteoporosis positive scans than ambulatory care screening (31.8% vs 18.5%, p < 0.001). In-hospital screening targeted an older and more predominantly male population with a higher fracture history. Z-scores revealed that this difference was not only due to an older age of the population and mainly concerned cortical bone.Conclusions: In-hospital osteoporosis screening revealed more osteoporosis than screening in ambulatory practice and could be an additional tool to improve the identification and management of osteoporosis. In addition to typical risk factors, we identified male gender as associated with osteoporosis detection in our cohort. [ABSTRACT FROM AUTHOR]

Rheumatoid Arthritis (RA) is a chronic inflammatory disabling disease with significant impact on the Quality of Life (QOL) of patients. Information on the effects of RA on Health-related Quality of Life (HRQoL) is lacking in the Lebanese population. The objective of this study was to evaluate QOL of RA patients compared with non-RA subjects and to suggest possible predictors of their QOL in Lebanon. We conducted a case–control observational study among individuals visiting the external clinics at three hospitals and different private clinics; the QOL was measured using the SF-36 questionnaire administered face to face to the study population, applied to RA (N = 90) and non-RA (N = 180) groups. RA presented lower Physical Component Scores (PCS) and Mental Component Scores (MCS) as well as overall QOL scores. Among RA patients, MCS and QOL were significantly decreased with morning stiffness duration (β = −9.211, p = 0.013 and β = −9.190, p = 0.009, respectively). The frequency of practicing sport per week increases PCS and QOL (β = 6.692, p = 0.002 and β = 6.148, p = 0.003, respectively). Workability has a positive effect on PCS (β = 5.546, p = 0.022) and time between blood transfusion and the onset of the disease has a positive impact on MCS (β = 8.415, p = 0.007). To improve QOL of patients with RA, health professionals have to take these results into consideration while treating their patients. [ABSTRACT FROM AUTHOR]

The objective is to compare the time to fulfillment of 1987 and 2010 ACR/EULAR classification criteria between female and male patients with rheumatoid arthritis (RA) and to assess the potential impact of gender on the time to DMARD therapy. Time from first provider-documented joint swelling to fulfillment of 1987 and 2010 ACR/EULAR criteria was measured in a population-based cohort of adults with incident RA, who were stratified by male or female gender. Disease characteristics, time to start of DMARD therapy, and choice of initial DMARD were compared between groups. The study included 214 patients with RA (148 females and 66 males). Median times from first joint swelling to fulfillment of 1987 (6.5 vs 2.5 days, p = 0.48) and 2010 (1 vs 0 days, p = 0.34) classification criteria were not different between female and male patients overall. There was no difference in time to first DMARD therapy in female vs male patients (15.5 vs 16 days, p = 0.90), and methotrexate was used most frequently as first DMARD in both genders (61% female vs 64% male, p = 0.76). Among the 49 female and 20 male RF/ACPA-negative patients, females experienced a higher median time from first joint swelling to fulfillment of the 1987 (65 vs 11 days, p = 0.063) and 2010 (65 vs 0 days, p = 0.035) classification criteria. Overall, there was no significant delay in meeting 1987 and 2010 ACR/EULAR classification criteria between female and male RA patients, though time to meeting both 1987 and 2010 criteria was slightly longer in males compared with females. Among seronegative patients, females experienced a significant delay to meeting 2010 criteria from first clinically detected synovitis. [ABSTRACT FROM AUTHOR]

For a searchable version of these abstracts, please visit www.acrabstracts.org. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate quality of life in patients with established rheumatoid arthritis (RA) and identify the factors that negatively affect it. Methods: This was a cross-sectional study with patients with established RA from a rheumatology center in Ecuador. The RA Quality of Life (RAQoL) questionnaire was used to assess QoL and the Health Assessment Questionnaire — disability index (HAQ-DI) questionnaire for functional capacity. In addition, demographics, clinical characteristics, and markers of disease activity were included. Data were analyzed using SPSS 22. Results: Of 186 patients, 89.8% were women, with a mean age of 51 years, 86.6% had symmetrical polyarticular involvement, 40.3% erosions, 46.8% morning stiffness, 46.8% xerophthalmia, and 39.2% fatigue. Depression was the most frequent comorbidity — 42.5%. The mean HAQ-DI score was 0.8, and 26.9% had functional disability. The mean RAQoL score was 7.2. Xerophthalmia, xerostomia, fatigue, morning stiffness, and depression were related to higher scores in the RAQoL (p<0.05). The mean RAQoL was higher in patients with more disease activity and comorbidities (p<0.05). Likewise, patients with functional disability had a mean RAQoL score of 15.6 versus 4.1 in patients without disability (p<0.05). There were positive correlations between RAQoL and ESR, CRP, painful-joint count, swollen-joint count, VAS of pain, and physician assessment (p<0.05). Conclusion: QoL is severely affected in patients with RA. Depression, fatigue, morning stiffness, pain, high disease activity, and disability have a negative effect on QoL in RA. Likewise, patients with more comorbidities and extraarticular manifestations show worse QoL. [ABSTRACT FROM AUTHOR]

Behçet's syndrome (BS) is a complex disease that shows important heterogeneity in clinical findings and physiopathology. Its treatment can be problematic as BS manifestations in different organs may respond differently to the same drug. The cornerstone of therapy for inducing remission is corticosteroids whereas immunomodulatory and immunosuppressive agents such as colchicine, azathioprine, cyclosporine-A, interferon-alpha, and cyclophosphamide are used as steroid-sparing agents and to prevent further relapses. However, a considerable number of patients continue to have mucocutaneous lesions despite therapy, and some patients require more aggressive treatment for refractory major organ involvement. Tumor necrosis factor alpha inhibitors, especially infliximab and adalimumab, are increasingly used for various refractory BS manifestations despite the lack of controlled studies. In this review, we aim to focus on both the traditional and new treatment modalities for BS, with more emphasis on recent data on newer agents. [ABSTRACT FROM AUTHOR]

Low-grade inflammation is recognized as an important factor in the development and progression of a multitude of diseases including type 2 diabetes mellitus and cardiovascular disease. The potential of using antibody-based therapies that neutralize key players of low-grade inflammation has gained scientific momentum as a novel therapeutic strategy in metabolic diseases. As interleukin-6 (IL-6) is traditionally considered a key pro-inflammatory factor, the potential of expanding the use of anti-IL-6 therapies to metabolic diseases is intriguing. However, IL-6 is a molecule of a very pleiotropic nature that regulates many aspects of not only inflammation but also metabolism. In this review, we give a brief overview of the pro- and anti-inflammatory aspects of IL-6 and provide an update on its role in metabolic regulation, with a specific focus on glucose homeostasis and adipose tissue metabolism. Finally, we shall discuss the metabolic implications and clinical potential of blocking IL-6 signaling, focusing on glucose homeostasis and lipid metabolism. [ABSTRACT FROM AUTHOR]

Inflammatory rheumatic diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) show a striking female predominance ranging from 3:1 in RA up to 9:1 in SLE. The background for those gender bias is not fully understood yet, but seems to be the result of a complex interaction between sex hormones, (epi-)genetics, and possibly even the composition of gut microbiota. Moreover, time of disease onset, the clinical phenotype including co-morbidities as well as the course of the diseases during life differ between genders. The patient's sex therefore plays an emerging role for individual therapy decisions and co-morbidity screening in rheumatologic care. Male lupus patients, for example, tend to show more severe features such as renal involvement, pleurisy, and serositis, when being compared to female patients. Among RA patients, women are more likely to acquire conditions like thyroid dysfunctions, fibromyalgia, and depression than their male counterparts. These examples emphasize the importance of the patient's gender for the clinical routine and the resulting implications for prevention and therapy. The present article is going to review potential causes for the female predominance of rheumatic diseases and will examine the gender's impact on the disease phenotype, symptom severity, co-morbidities, and quality of life. For reasons of scope, the focus will be on RA and SLE as two of the most important rheumatic diseases with a large socioeconomic impact on society due to their incidence as well as mortality. [ABSTRACT FROM AUTHOR]

The authors discuss a post hoc comparative analysis of two studies that verified the construct validity properties of Assessment of SpondyloArthritis International Society-Health Index in patients with axSPA and psoriatic arthritis (PsA). Topics mentioned include the declaration of Helsinki, the Disease Activity index for PsA, and disease features of both study populations.

Polymyalgia rheumatica (PMR) is a chronic inflammatory disease which affects the connective vascular tissue, characterized by pain accompanied by morning stiffness, predominantly of the neck muscles, hip and shoulder girdle. Usually, patients with this disease are >50 years of age and biological inflammatory syndrome is present with an increase in both the erythrocyte sedimentation rate and C-reactive protein levels, aspects similar to giant cell arteritis. The aim of the present review was to depict the current pathogenic hypothesis, diagnostic and treatment approach for patients with PMR, and novelties since the development of the currently used 2012 European League Against Rheumatism and American College of Rheumatology provisional classification criteria. PMR is a prevalent disease that can occasionally prove difficult to diagnose and treat. Possibly, the most abundant type of evidence and data revealed over the past decade have been acquired through musculoskeletal imaging, with implications in diagnosis, disease monitoring and relapse, prognosis and changes with treatment. Further research on pathophysiology is required to gain a deeper understanding of the underlying processes, which will serve as the foundation for future personalized treatments. In addition, there is an increasing demand for improved diagnostic techniques, which should include a further development of various imaging modalities, in order to provide accurate diagnosis and appropriate therapy. [ABSTRACT FROM AUTHOR]

Purpose: Uveitis accounts for 10-15% of all cases of blindness in the developed world. Uveitic macular edema (UME) is a primary cause of permanent visual impairment in patients with uveitis. Because proinflammatory mediators elicit inflammation and lead to UME, we determined the profiles of proinflammatory mediators associated with complications, such as ME, in the vitreous humor of patients with panuveitis related to Behçet's disease (BD) and sarcoidosis., Methods: In this retrospective study, we enrolled 21 patients with uveitis, including 6 with BD and 15 with sarcoidosis, and 15 patients with idiopathic epiretinal membrane (iERM) at the Department of Ophthalmology, Kyushu University Hospital, between January 2008 and April 2016. Vitreous concentrations of 32 proinflammatory mediators, including cytokines and soluble receptors of tumor necrosis factor (TNF) and interleukin (IL)-6 families, were assessed using a bead-based multiplex assay and their association with clinical data was examined., Results: The levels of proinflammatory mediators, including a proliferation-inducing ligand (APRIL), B cell activating factor belonging to the TNF family (BAFF), soluble cluster of differentiation 30 (sCD30), soluble TNF receptor-1 (sTNFR1), sTNFR2, TNF-α, IL-6, and soluble IL-6 receptor-α (sIL-6Rα), were significantly higher in patients with uveitis. With regard to clinical parameters in patients with uveitis, vitreous levels of BAFF and sIL-6Rα were prominently elevated in patients with UME compared to in those without UME (P < 0.01, respectively)., Conclusions: Our results suggest that elevated vitreous levels of BAFF and sIL-6Rα are associated with the pathogenesis of UME in patients with panuveitis related to BD and sarcoidosis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The primary aim of the study was to evaluate the efficacy of tumor necrosis factor (TNF)-α blockers adalimumab (ADA) and infliximab (IFX) in refractory sight-threatening retinal vasculitis (RV) during a 12-month follow-up period. Secondary aims were to evaluate (i) any impact of concomitant conventional disease-modifying anti-rheumatic drugs (cDMARDs) and different lines of biologic therapy; (ii) any difference in terms of efficacy between ADA and IFX; (iii) consequences of biotherapies on the best-corrected visual acuity (BCVA); (iv) corticosteroid-sparing effect; and (vi) ocular complications during anti-TNF-α treatment. Demographic, clinical, and therapeutic data were retrospectively collected from the medical records and statistically analyzed. Forty-eight patients (82 eyes) were recruited, 22 (45.8%) of which received IFX and 26 (54.2%) ADA. The percentages of patients achieving RV remission within 3 and 12 months were 54 and 86%, respectively. A significant decrease in RV detection was identified from baseline to 3-month (p < 0.0001) and 12-month (p < 0.0001) assessments and between 3-month and 12-month visits (p = 0.004). No differences were identified in terms of RV resolution between (i) patients undergoing monotherapy and those co-administered with cDMARDs at 3-month (p = 0.560) and 12-month (p = 0.611) follow-up; (ii) biologic-naïve patients and those already exposed to other biologics at 3-month (p = 0.497) and 12-month (p > 0.99) visits; and (iii) patients treated with ADA and those treated with IFX (p = 0.357). During the study period, a statistically significant corticosteroid-sparing effect was observed (p = 0.0002), while BCVA values did not significantly change (p = 0.950). Anti-TNF-α monoclonal antibodies have proved excellent results in patients with recalcitrant sight-threatening RV. [ABSTRACT FROM AUTHOR]

For a searchable version of these abstracts, please visit www.acrabstracts.org. [ABSTRACT FROM AUTHOR]

Ocular involvement is a common manifestation of inflammatory rheumatic diseases, often requiring a multidisciplinary collaboration between rheumatologists and ophthalmologists. The aim of this study was to standardize “red flags” for referral for rheumatologists and ophthalmologists using a Delphi consensus for the management of rheumatic diseases with ocular involvement. The scientific board comprised 11 Italian hospital-based rheumatologists (N = 6) and ophthalmologists (N = 5). A systematic review identified potential red flags for referral. The panel developed 19 statements consisting of (a) referral from ophthalmologist to rheumatologist (b) referral from rheumatologist to ophthalmologist and (c) overarching principles relating to multidisciplinary roles/goals and management. Voting was performed anonymously using an online Delphi method. Each participant expressed a level of agreement on each statement using a 5-point scale (1=“strongly disagree”; 5=“strongly agree”). Total cumulative agreement was defined as the sum of the percentage of response to items 4 (“agree”) and 5 (“absolutely agree”), consensus defined as ≥ 80% cumulative agreement for each statement. Positive consensus among 11 participants was reached for 15/19 (78.9%) statements. Statements not reaching consensus were discussed in a face-to-face meeting prior to the second vote (10 participants). Positive consensus was reached for all 19 statements, with final total cumulative agreement of 90-100%. This is the first Delphi consensus undertaken to standardize red flags for referral to rheumatologists and ophthalmologists for patients with rheumatic diseases and ocular involvement. [ABSTRACT FROM AUTHOR]

Takayasu arteritis (TAK) is a challenging chronic, granulomatous, large-vessel systemic vasculitis, mostly due to difficulties in early diagnosis and assessing actual disease activity. Since there are no specific diagnostic laboratory tests, biomarkers, or autoantibodies, many patients experience considerable delay in diagnosis. Remembering the possibility of TAK together with the use of acute phase responses and appropriate imaging studies may be helpful for early diagnosis. Since there may be discrepancies between systemic and vascular wall inflammation, using only acute phase responses is not reliable in assessing current disease activity. Therefore, physical examination and new imaging findings should also be used to assess current disease activity. Despite its limitations, the Indian Takayasu Clinical Activity Score (ITAS2010) may also be helpful for this purpose. The rationale of medical treatment is to suppress both vascular and systemic inflammation with appropriate systemic immunosuppression, including corticosteroids and conventional immunosuppressive agents. In cases of refractory disease activity, leflunomide and biologic agents such as TNF inhibitors and tocilizumab may be tried. In selected cases with persistent lesions that cannot be reversed with medical treatment, endovascular interventions including balloon angioplasty, stent and stent graft replacement, or surgery may be tried. However, such procedures should be performed after suppression of inflammation, i.e. during inactive disease. Prognosis of TAK is probably getting better with lower mortality rates reported in recent years, probably due to the use of more effective medical treatments as well as the use of endovascular interventions when necessary and available. [ABSTRACT FROM AUTHOR]

To describe disease activity and disability during the first year of follow-up, from rheumatoid arthritis (RA) patients who discontinue tofacitinib after they end participation in a clinical trial. From 2008 to 2016, 36 patients were enrolled in the “Long term follow-up study with tofacitinib (and methotrexate) for RA treatment”. At the end of the study, tofacitinib was discontinued and patients were proposed to enter an observational study; 35 agree and had scheduled evaluations at baseline, at 15 and 30 days of follow-up, at month 2 and 3, and thereafter every 3 months. Disease activity was evaluated as per DAS28-ESR and disability as per HAQ. During follow-up, treatment was treat-to-target oriented, only conventional DMARDs were indicated. Descriptive statistics and nonparametric test were used. The study was approved by IRB. Patients were primarily females (N = 34), had median (Q25-75) age of 52 years (45-58), and had received tofacitinib for a median of 7.9 years (6.3-8.3). The proportion of patients with remission and low disease activity decreased from day 30 of follow-up and recovered after 270 days, meanwhile patients with high disease activity increased from 0% at baseline to 6.3% at 1 year. At study entry, 20 patients had remission/low disease activity; during follow-up, 85% deteriorated after (median) 30 days; among them, 23.5% recovered their baseline status after a median of 172.5 days. The HAQ showed a similar behavior, but 66.7% recovered. A substantial proportion of RA patients deteriorated outcomes early after tofacitinib cessation; some patients recovered baseline status with traditional DMARDS. [ABSTRACT FROM AUTHOR]

A new titanium(III)-catalyzed reductive annulation constructed a series of diversely functionalized 1,5-diols in good to excellent yields with respect to a wide scope of vinyl epoxide-aldehyde substrates. Taken together with a Diels-Alder reaction and a substrate-controlled diastereoselective cyclopropanation as additional key steps, the synthetic utility of this novel method has been preliminarily explored by the first and concise total synthesis of the Euphorbia diterpenoid (±)-pepluanol A. [ABSTRACT FROM AUTHOR]

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Retroperitoneal fibrosis (RPF) is a rare disease characterised by fibrous tissue proliferation in the retroperitoneum, with encasement of the ureters and large vessels of the abdomen as the most destructive of potentially severe complications. It can either be idiopathic, or secondary to infections, malignancies, or the use of certain drugs. The idiopathic form accounts for approximately 75% of the cases, and is usually responsive to immunosuppressive therapy. In recent years, the emergence of a new clinical entity, IgG4-related disease (IgG4-RD), shed light on many fibro-inflammatory disorders once thought to be separate clinical entities, although frequently associated in the so-called multifocal fibrosclerosis. Among these, together with sclerosing pancreatitis and cholangitis, pseudotumour of the orbit, idiopathic mediastinal fibrosis and other conditions, is idiopathic retroperitoneal fibrosis (IRF). Both IRF and IgG4-RD can be associated with a wide variety of disorders, usually governed by immune-mediated (and particularly auto-immune) mechanisms. In our review, we discuss the clinical and therapeutic challenges IRF presents to the internist, as well as the meaning of its recent inclusion in the IgG4-RD spectrum from a clinical practice standpoint. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor-α (TNF-α) blockers are a popular therapeutic choice in a number of inflammatory diseases. Thus far, five TNF- α blockers have been approved for clinical use (etanercept, infliximab, adalimumab, golimumab. and certolizumab). Despite being considered relatively safe, serious side effects associated with immune suppression have been reported, including central and peripheral nervous system (CNS) demyelinating disorders. It is still elusive whether these events are mere coincidence or a side effect of anti-TNF-α use. In this paper, we review the published case reports of CNS demyelination associated with anti-TNF-α therapy and present the follow-up of our 4 previously reported patients who developed neurologic symptoms suggestive of CNS demyelination after having received anti-TNF-α treatment. We also discuss the possible role of TNF-α blockers in demyelination. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is characterized by a wide variety of manifestations and a difficult disease control in some patients. We present the case of a 51-year-old woman who presented with a flare of SLE including arthritis and pleuropericarditis that responded to neither leflunomide, methotrexate, nor high doses of prednisone. After initiating treatment with belimumab, the patient experienced a quick and notorious improvement. She remains stable to this day while continuing belimumab therapy. [ABSTRACT FROM AUTHOR]