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OBJECTIVE: The novel description of antibodies to lipoprotein lipase (anti-LPL) associated with dyslipoproteinemia prompted us to analyze the association of anti-LPL with clinical and serologic features in patients with systemic lupus erythematosus (SLE) and its link to markers of inflammation that are known to be involved in atherogenesis. METHODS: Enzyme-linked immunosorbent assay was used to test for the presence of anti-LPL antibodies in 66 consecutive patients with SLE. Clinical and laboratory evaluation, including a fasting lipid profile, autoantibody screening, an assessment for markers of inflammation (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR]), and the SLE Disease Activity Index (SLEDAI) were performed at the time of inclusion in the study. Exclusion criteria were any conditions that affect the lipid profile. SLE patients were categorized into 2 groups according to detection of these anti-LPL antibodies, as follows: anti-LPL+ and anti-LPL-. RESULTS: Anti-LPL antibody IgG was detected in 25 SLE patients (37.8%). Triglyceride levels were significantly higher in the anti-LPL+ group (112.4 +/- 50.2 versus 89.9 +/- 54.5 mg/dl in the anti-LPL- group; P = 0.033), but no significant differences between the 2 groups were detected for total, high-density lipoprotein, and low-density lipoprotein cholesterol levels. A higher frequency of elevated CRP levels and ESRs was observed in the anti-LPL+ group compared with the anti-LPL- group (44% and 17.1%, respectively [P = 0.023] and 52% and 19.5%, respectively [P = 0.013]). Moreover, SLE patients with anti-LPL antibodies also had significantly higher levels of CRP (11.1 +/- 16.4 versus 2.4 +/- 2.6 mug/ml; P = 0.036) and higher ESRs (33.4 +/- 29.8 versus 16.5 +/- 11.8 mm/hour; P = 0.020). Anti-LPL titers had a significant positive correlation with the CRP level (r = 0.56, P < 0.001), the ESR (r = 0.55, P < 0.001), the SLEDAI score (r = 0.45, P < 0.001), anti-double-stranded DNA (anti-dsDNA; r = 0.52, P < 0.001), and anticardiolipin IgG antibodies (r = 0.25, P = 0.04), and a significant negative correlation was detected with total hemolytic complement activity (CH100) (r = -0.34, P = 0.005). Reinforcing these findings, multiple regression analysis also revealed a significant association of anti-LPL with the CRP level (P = 0.025) and anti-dsDNA (P < 0.001). Importantly, a comparison of positive and negative anti-dsDNA sera revealed similar mean CRP levels (P = 0.56) and ESRs (P = 0.102), contrasting with the SLEDAI score (P = 0.004) and CH100 (P = 0.008). CONCLUSION: These data support the link between inflammation, immune response, and dyslipoproteinemia in SLE, introducing anti-LPL as a possible new player that may ultimately help in understanding the complex events of atherogenesis in this disease. [ABSTRACT FROM AUTHOR]

Background: Hyaluronic acid (HA) has been largely used in clinical practice for rheumatic diseases. However, the effects of oral HA on these diseases are poorly understood., Aim: To review articles evaluating oral HA's effects on rheumatic patients., Methods: PubMed was searched for articles on oral HA and rheumatic diseases between 1966 and May 2024., Results: Eleven articles were found with 597 patients. The diseases investigated were OA (n=10) and low back pain (n=1). Age varied from 40 to 70 years old, and female gender ranged from 43% to 75%. Follow-up ranged from 4 weeks to 12 months. The oral HA dosage varied from 30 mg to 300 mg/day. Concerning outcome, 9/11 articles observed improvement in rheumatic diseases in the following parameters: VAS pain, WOMAC, joint function, SF-36, Lequesne index, and stiffness. Two studies evaluated cytokines and observed a reduction of them after oral HA therapy. Adverse effects were rare and mild., Conclusion: Oral HA seems to be a safe and effective therapy for OA and low back pain patients, although more studies should be done on the latter condition., Competing Interests: None., (© The Author(s).)

Competing Interests: No conflict of interest was declared by the author.

Competing Interests: There are no conflicts of interest.

Introduction: Patients with fibromyalgia (FM) have innumerable complaints due to the central amplification of somatic stimuli. The aim of this paper was to review the ear complaints in patients with FM., Methods: A review of articles published in PubMed/MEDLINE, Embase, Web of Science, and Scopus from 1966 to June 2023 was performed., Results: Seventeen papers were included in the review. They showed that patients with FM have a higher hearing loss rate, mostly at high frequencies, and hyperacusis. The prevalence of vestibular symptoms (tinnitus, dizziness) and hyperacusis was higher than in the general population, reaching 87.0% of the sample. Subjective findings did not always correspond to objective results. In some studies, the degree of FM severity was associated with ear symptoms; in others, it was not., Conclusions: Ear complaints in patients with FM are linked to subjacent disease and may be related to stimuli central amplification., (© 2024. The Author(s).)

High-dose cyclophosphamide without stem cell rescue is a radical therapy for refractory autoimmune diseases. The objective was to review the results of high-dose cyclophosphamide without stem cell rescue in autoimmune diseases. PubMed, Scielo, and Embase databases were systematically searched for articles on high-dose cyclophosphamide without stem cell rescue treating autoimmune diseases between 1966 and September 2022. Twenty-nine studies were identified, including a total of 404 patients. The diseases most studied were systemic lupus erythematosus (n=113), multiple sclerosis (n=99), aplastic anemia (n=86), and myasthenia gravis (n=33). Most authors used the posology of 50mg/kg/day over four days of cyclophosphamide associated with Mesna, prophylactic antibiotics, G-CSF (granulocyte colony-stimulating factor), and support of red blood cells, and platelet transfusion. The most common side effects were febrile neutropenia, alopecia, and gastrointestinal complaints. Regarding outcomes, most of the studies demonstrated improvement of the underlying autoimmune disease, some long-lived, but relapses and failures were also identified. In conclusion, high-dose cyclophosphamide without stem cell rescue is an effective option for treating severe autoimmune diseases. This procedure is relatively safe when the appropriate supportive care measures are taken.

Objective: Fibromyalgia (FM) subjects are treated with antidepressant agents; in most cases, these drugs lose efficacy or have adverse effects. Ketamine is an anesthetic drug used in FM in some studies. This article aims to systematically review the safety and efficacy of ketamine in fibromyalgia (FM) patients., Materials and Methods: We systematically searched articles on FM and ketamine published at Pubmed from 1966 to 2021. This study was registered at PROSPERO., Results: There were only 6 articles published in this field, with a total of 115 patients. The female sex was predominant (88 to 100%). The age varied from 23 to 53 years old. Disease duration ranged from 1 month to 28 years. The dosage of ketamine changed from 0.1 mg/kg-0.3-0.5 mg/kg in intravenous infusion (4/5) and subcutaneous application (1/5). Regarding outcomes, the Visual analog scale (VAS) before ketamine was from 59 to 100 mm and after treatment from 2 to 95 mm. Most short-term studies had a good response. Only the study with 8 weeks of follow-up did not observe a good response. Side effects were common; all appeared during the infusion and disappeared after a few minutes of the ketamine injection., Conclusions: The present study demonstrates the effectiveness and safety of ketamine in FM patients in the short term. Although, more studies, including long-term follow-up studies, are still needed., (© 2024. The Author(s).)

Cannabis has been used in rheumatic diseases as therapy for chronic pain or inflammatory conditions. Herein, the authors systematically review the rheumatological diseases in which cannabis has been studied: systemic sclerosis, fibromyalgia, osteoarthritis, rheumatoid arthritis, osteoporosis, polymyalgia rheumatica, gout, dermatomyositis, and psoriatic arthritis. We systematically searched PubMed for articles on cannabis and rheumatic diseases between 1966 and March 2023. Twenty-eight articles have been selected for review. Most of them (n=13) were on fibromyalgia and all of them but one showed important reduction in pain; sleep and mood also improved. On rheumatoid arthritis, two papers displayed decrease in pain and in one of them a reduction in inflammatory parameters was found. In scleroderma there was a case description with good results, one study on local use for digital ulcers also with good outcomes and a third one, that disclosed good results for skin fibrosis. In dermatomyositis a single study showed improvement of skin manifestations and in osteoarthritis (3 studies) this drug has demonstrated a good analgesic effect. Several surveys (n=5) on the general use of cannabis showed that rheumatological patients (mixed diseases) do use this drug even without medical supervision. The reported side effects were mild. In conclusion, cannabis treatment is an interesting option for the treatment of rheumatological diseases that should be further explored with more studies., Competing Interests: No conflict of interest was declared by the authors.

Objective: Psoriatic arthritis (PsA) is a chronic inflammatory disorder affecting the joints, skin and entheses. Despite the importance of the topic, few studies have investigated the association between PsA and sexual function. The purpose of this study was to assess sexuality and the prevalence of sexual dysfunction (SD) in patients with PsA., Methods: This was an observational, cross-sectional single-center study on 23 PsA patients (male=12; female=11) evaluated with 2 male questionnaires (MSQ= Male Sexual Quotient, and IIEF=International Index of Erectile Function) and 2 female questionnaires (FSQ= Female Sexual Quotient, and FSFI=Female Sexual Function Index) validated for Brazilian Portuguese, in order to determine changes in sexual function. Clinical parameters, musculoskeletal activity and skin activity were also analyzed to identify factors associated with SD., Results: The mean age was 52.1±9.7 years (males) and 49.1±9.6 years (females). Clinically, the patients had low skin and peripheral joint disease activity or were in remission. The mean time of PsA was 10±6.2 years, and 65.2% had a steady sexual partner. The mean MSQ score was 75.8±16.8. The prevalence of SD was 91.7% in men (IIEF), with a predominance of mild SD. The mean FSQ score was 64.9±24.1. The prevalence of SD was 72.7% in women (FSFI), with low domain scores. Also, a significant association was found between female age and total and domain-specific FSFI scores. PASI (Psoriasis Area and Severity Index) and the general satisfaction domain (IIEF) were significantly correlated., Conclusion: This study found a high prevalence of SD in PsA patients. Age had a negative impact on female sexual function. Physicians need to be more aware of SD in this population to provide early multidisciplinary treatment and minimize the impact of the disease on the quality of life of patients and their partners., Competing Interests: No conflict of interest was declared by the authors.

Competing Interests: The authors declare no conflict of interest.

Competing Interests: The authors have no conflicts of interest to declare.

Background: Dehydroepiandrosterone (DHEA) is an adrenal hormone used to treat rheumatic conditions such as systemic lupus erythematosus (SLE), Sjogren's syndrome (SS), rheumatoid arthritis (RA) with controversial results., Aim: To review the results of DHEA use in rheumatic diseases., Methods: PubMed, Scielo, Scopus, and Embase databases were systematically searched for articles on the treatment of rheumatic diseases with DHEA between 1966 and April 2023., Results: Twenty-one studies were identified: 13 in SLE, 5 in SS, 2 in RA, and 1 in fibromyalgia. DHEA use in SLE has shown a mild to moderate effect on disease activity, a positive effect on bone mineral density (BMD), and improved fatigue. The studies on SS showed a decrease in symptoms of dry mouth, but its performance did not differ from placebo in disease activity. In RA, a questionable effect on disease activity was noted. The only study on fibromyalgia failed to show any improvement. The drug was well tolerated; mild androgenic effects were the most common complaints., Conclusion: DHEA seems to have a place in SLE treatment, where it improves BMD and disease activity. The use in RA, SS, and FM is questionable., Competing Interests: The authors declare no conflict of interest., (© 2023 The Mediterranean Journal of Rheumatology (MJR).)

Competing Interests: No conflict of interest was declared by the authors.

Background: Naltrexone has been approved for alcohol and opioid abuse by the FDA. At low-dose naltrexone (LDN) has been used in several diseases including chronic pain and autoimmune conditions, including rheumatic disorders., Aim: To review the use of LDN in rheumatic diseases: systemic sclerosis (SSc), dermatomyositis (DM), Sjögren's syndrome (SS), rheumatoid arthritis (RA), and fibromyalgia (FM)., Methods: PubMed and Embase databases were searched for articles on LDN and rheumatic diseases between 1966 and August 2022., Results: Seven studies in FM have been identified: in this disease LDN has showed beneficial effects on pain and well-being. In SS, two articles with 3 cases description showed that LDN may be of help in the pain treatment. LDN relieved pruritus in scleroderma (a case description with a series of 3 patients) and dermatomyositis (description of 3 patients in two articles). In RA a study using Norwegian Prescription Database showed that LDN was associated to reduction in the use of analgesic and DMARDs. No serious side effects were detected., Conclusion: This review shows that LDN is a promising and safe therapy to be used in some rheumatic disease. However, the data is limited and needs to be reproduced in larger studies., Competing Interests: The authors declare no conflict of interest., (© 2023 The Mediterranean Journal of Rheumatology (MJR).)

Competing Interests: No conflict of interest was declared by the author.

This study illustrates two patients who developed autoimmune/inflammatory syndrome induced by adjuvants (ASIA) with postural orthostatic tachycardia syndrome (POTS) after silicone breast implant (SBI) and improved after SBI extraction.

Competing Interests: The author declares no conflict of interest.

Background: Fibromyalgia (FM) patients are treated with antidepressants, and in most cases, these drugs lose efficacy or present side effects. Intravenous lidocaine (IL) is an anesthetic drug used in some FM trials., Aim: To systematically review the safety and efficacy of IL in FM patients., Methods: To systematically search PubMed for articles in English, Spanish, and Japanese with English Abstracts on FM and lidocaine between 1966 and February 2021. This study was registered at PROSPERO., Results: We found only ten articles published in this field, with a total of 461 patients. Females predominated varying from 95% to 100% in the studies. Age varied from 40.9 to 55 years old. Disease duration varied from 1 mo to 6.4 years. Lidocaine dose varied from 2 to 7.5 mg/kg via intravenous infusion. Follow-up period varied from 65.7 to 90 days. Regarding outcomes, most studies used the visual analogue scale (VAS) for pain; before short-term lidocaine administration, VAS was between 6.1 and 8.1 and after treatment was between 1.7 and 4.5 mm. Concerning long term lidocaine, VAS varied from 30% to 35.4% after lidocaine infusion. Side effects were observed in 0% to 39.6% of cases, they were usually mild or moderate., Conclusion: This study demonstrates the short-term effectiveness and safety of intravenous lidocaine in FM patients. However, more studies, including long-term follow-up, are still needed., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: Acute myocardial infarct/angina (AMI-A) is a possible complication in primary antiphospholipid syndrome (pAPS) patients. This study compares data obtained from pAPS patients with and without AMI-A., Methods: This cross-sectional study of 66 (85.2% female) pAPS patients (Sidney criteria). Demographics, clinical data, medication use, and antiphospholipid antibodies were evaluated. Patients were divided into two groups: pAPS with AMI-A and pAPS without AMI-A., Results: Sixty-six patients with primary APS (six with AMI-A and 60 without AMI-A) were selected. They were similar for demographics, disease duration, and anthropometrics (p > 0.05). Patients with AMI-A compared to those patients without AMI-A had more frequently dyslipidemia (66 vs. 28%, p = 0.05), systemic hypertension (83 vs. 37%, p = 0.02), and increased levels of lipoprotein (a) (116 ± 67 vs. 36 ± 35 mg/dl, p = 0.0002). Interesting, current physical activity (66.7 vs. 23%, p = 0.04) was more seen in the first group when compared to the second one. Patients with AMI-A used more statins (66 vs. 22%, p = 0.017) and acetylsalicylic (100 vs. 28%, p = 0.05). Higher median levels of IgM anticardiolipin antibodies [70 (0-120) vs. 9 (0-120), p = 0.03] were observed in the first group., Conclusions: pAPS patients and AMI-A have distinct clinical and laboratory spectra from those without AMI-A. It is characterized by dyslipidemia and hypertension, hyper lipoprotein(a), and a lower IgM anticardiolipin frequency., (© 2022. The Author(s).)

Obesity, diabetes, cardiovascular and respiratory diseases, cancer and smoking are risk factors for negative outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can quickly induce severe respiratory failure in 5% of cases. Coronavirus disease-associated liver injury may occur during progression of SARS-CoV-2 in patients with or without pre-existing liver disease, and damage to the liver parenchyma can be caused by infection of hepatocytes. Cirrhosis patients may be particularly vulnerable to SARS-CoV-2 if suffering with cirrhosis-associated immune dysfunction. Furthermore, pharmacotherapies including macrolide or quinolone antibiotics and steroids can also induce liver damage. In this review we addressed nutritional status and nutritional interventions in severe SARS-CoV-2 liver patients. As guidelines for SARS-CoV-2 in intensive care (IC) specifically are not yet available, strategies for management of sepsis and SARS are suggested in SARS-CoV-2. Early enteral nutrition (EN) should be started soon after IC admission, preferably employing iso-osmolar polymeric formula with initial protein content at 0.8 g/kg per day progressively increasing up to 1.3 g/kg per day and enriched with fish oil at 0.1 g/kg per day to 0.2 g/kg per day. Monitoring is necessary to identify signs of intolerance, hemodynamic instability and metabolic disorders, and transition to parenteral nutrition should not be delayed when energy and protein targets cannot be met via EN. Nutrients including vitamins A, C, D, E, B6, B12, folic acid, zinc, selenium and ω-3 fatty acids have in isolation or in combination shown beneficial effects upon immune function and inflammation modulation. Cautious and monitored supplementation up to upper limits may be beneficial in management strategies for SARS-CoV-2 liver patients., Competing Interests: Conflict-of-interest statement: The authors declare that this 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) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Sydenham's chorea is a cardinal manifestation of rheumatic fever, but it is more common in girls. We describe two boys who developed Sydenham's chorea and were successfully treated., Case 1: A 5-year-old boy started an involuntary movement of his hand, progressing to all the upper limbs, bilaterally. The family observed a deterioration in his handwriting skills. Heart auscultation did not reveal any murmur, and the oropharynx examination was normal. A brain magnetic resonance imaging, cerebrospinal fluid, and echocardiography were interpreted as normal. He was treated with valproate 2.5mL twice a day. Prophylaxis with benzathine penicillin was started using 600,000IU every 21 days. After four months, the patient was asymptomatic, and valproate was tapered off., Case 2: A 7-year-old boy with a long history of frequent otitis and pharyngitis started involuntary movements of his face and on his upper limbs, and also, his mother noted tics on his face. A brain magnetic resonance imaging and transthoracic echocardiography were normal. He was treated with haloperidol 10 drops (1mg) twice a day, and prophylaxis with benzathine penicillin was started using 600,000IU every 21 days. After three months, the patient was asymptomatic, all chorea manifestations resolved, haloperidol was then tapered off. In conclusion, this study illustrates two uncommon cases of boys who developed Sydenham's chorea and had a good outcome., (© 2021 The Mediterranean Journal of Rheumatology (MJR).)

Herein, we describe a patient with antiphospholipid syndrome (APS) associated with nonradiographic axial spondyloarthritis (NRAS). A 31-year-old woman with a past medical history of uveitis experienced a pulmonary thromboembolism in March 2014 and was treated with rivaroxaban (20 mg/day). Five months later, she started complaining of low back pain. The results on contrast-enhanced sacroiliac magnetic resonance imaging were normal. Laboratory tests revealed positive HLA-B27 and the presence of lupus anticoagulant and IgM anticardiolipin. The diagnoses of APS and NRAS were made. The patient was treated with rivaroxaban for APS and sulfasalazine (2 g/day), respectively. As she showed the presence of lupus anticoagulant antibodies in blood, she did not receive nonsteroidal anti-inflammatory drugs. After 6 months, the patient was asymptomatic, without lumbar pain; she also showed normalization of the erythrocyte sedimentation rate and the C-reactive protein and vitamin D levels, good control of lumbar pain, and no new uveitis episodes. The APS was also stable. To the best of our knowledge, this is the first reported case of NRAS associated with APS., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Jozélio Freire De Carvalho and Antoniella Fernanda Mendanha Sousa.)

Background: Obstetric haemorrhage continues to be a leading cause of maternal mortality, contributing to more than a quarter of the 2,443,000 maternal deaths reported between 2003 and 2009. During this period, about 70% of the haemorrhagic deaths occurred postpartum. In addition to other identifiable risk factors for greater postpartum blood loss, the duration of the third stage of labour (TSL) seems to be important, as literature shows that a longer TSL can be associated with more blood loss. To better describe the association between the duration of TSL and postpartum blood loss in women receiving active management of third stage of labour (AMTSL), this secondary analysis of the WHO CHAMPION trial data has been conducted., Methods: This was a secondary analysis of the WHO CHAMPION trial conducted in twenty-three sites in ten countries. We studied the association between the TSL duration and blood loss in the sub cohort of women from the CHAMPION trial (all of whom received AMTSL), with TSL upto 60 min and no interventions for postpartum haemorrhage. We used a general linear model to fit blood loss as a function of TSL duration on the log scale, arm and center, using a normal distribution and the log link function. We showed this association separately for oxytocin and for Heat stable (HS) carbetocin., Results: For the 10,040 women analysed, blood loss rose steeply with third stage duration in the first 10 min, but more slowly after 10 min. This trend was observed for both Oxytocin and HS carbetocin and the difference in the trends for both drugs was not statistically significant (p-value = 0.2070)., Conclusions: There was a positive association between postpartum blood loss and TSL duration with either uterotonic. Blood loss rose steeply with TSL duration until 10 min, and more slowly after 10 min. Study registration The main trial was registered with Australian New Zealand Clinical Trials Registry ACTRN12614000870651 and Clinical Trial Registry of India CTRI/2016/05/006969., (© 2021. The Author(s).)

Background: The Coronavirus 2019 (COVID-19) pandemic has had a negative impact on the population's behavior. In this context, the effect of the COVID-19 pandemic on drug treatment of patients with peripheral arterial disease (PAD) and intermittent claudication (IC) remains unclear., Objectives: To analyze the impact of the COVID-19 pandemic on drug treatment of patients with PAD and IC., Methods: In this cross-sectional, observational study, 136 patients with PAD and IC were recruited from our database and answered a questionnaire by telephone involving the following questions: a) precautions related to COVID-19; b) general health status; and c) treatment of diseases. Subsequently, patients were divided into two groups according to difficulty in obtaining their drugs (DOD: difficulty obtaining drugs, or NDOD: no difficulty obtaining drugs) and overall health was compared between groups., Results: Seventeen percent of patients reported difficulties with obtaining drugs during the pandemic. A higher proportion of these patients reported being sadder (56.5% vs. 24.8%, P < 0.01) and having more difficulty sleeping (56.5% vs. 24.8%, P < 0.01) than of the patients in the NDOD group (P <0.01). The groups did not differ in terms of impairment of walking capability, anxiety, stress, or depression (P> 0.05)., Conclusions: A higher proportion of patients in the DOD group reported being sadder and having greater difficulty sleeping compared to the NDOD group during the COVID-19 pandemic., Competing Interests: Conflicts of interest: No conflicts of interest declared concerning the publication of this article., (Copyright© 2021 The authors.)

A 23-year-old woman was diagnosed with Graves' disease 5 months ago with decompensated thyroid function, for which she is taking thiamazole and propranolol. She developed progressive respiratory dyspnoea [New York Heart Association (NYHA) class III] and frequent palpitations. On emergency admission, the patient was tachypnoeic, hypotensive (77/54 mm Hg) and tachycardic (120 beats per minute), with an oxygen saturation of 94%. She also presented with cold, swollen and shaky extremities, with extended capillary filling time, and a significant reduction in heart sounds. Echocardiogram showed massive pericardial effusion compatible with cardiac tamponade. Pericardiocentesis was performed, with a drainage of 1420 mL serosanguinolent fluid, with prompt haemodynamic recovery. Analysis of the pericardial fluid showed exudates. A diagnosis of pericardial effusion secondary to Graves' disease was determined and corticotherapy, lithium carbonate, cholestyramine and phenobarbital were prescribed. An oral iodine-131 was performed and the patient showed reasonable control of the clinical manifestations of hyperthyroidism. After 3 months, the patient showed no symptoms of hyperthyroidism and a new echocardiogram revealed a significant reduction in pericardial effusion., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Chikungunya virus (CHIKV) infection is caused by an arbovirus prevalent in various parts of the world. The virus can induce autoantibodies and rheumatic diseases, such as rheumatoid arthritis and spondylarthritis. However, until now, no case of Sjögren syndrome (SS) was described associated with CHIKV. In this article, we describe a 49-year-old female with polyarthralgia and a temporary rash on her trunk and arms. Her physical examination showed polyarthritis of her ankles and wrists. Serologies for CHIKV were interpreted as positive with IgM 6.5 (normal range < 0.8) and negative for IgG. Antinuclear antibodies were positive at a titer of 1:640 as well as anti-Ro/SS-A. The diagnosis of subacute CHIKV infection was determined. The Schirmer test, Rose Bengal, and salivary scintigraphy were positive and the diagnosis of SS was confirmed. She was treated with hydroxychloroquine, methotrexate, and a single dose of betamethasone depot. This is the first report on CHIKV associated with SS. Sequence analysis of the CHIKV proteome versus SS autoantigens showed an extensive peptide sharing between the virus and numerous SS autoantigens, thus supporting the hypothesis that autoimmune cross-reactivity might causally link CHIKV to SS.

Background: The combination of long reads and long-range information to produce genome assemblies is now accepted as a common standard. This strategy not only allows access to the gene catalogue of a given species but also reveals the architecture and organization of chromosomes, including complex regions such as telomeres and centromeres. The Brassica genus is not exempt, and many assemblies based on long reads are now available. The reference genome for Brassica napus, Darmor-bzh, which was published in 2014, was produced using short reads and its contiguity was extremely low compared with current assemblies of the Brassica genus., Findings: Herein, we report the new long-read assembly of Darmor-bzh genome (Brassica napus) generated by combining long-read sequencing data and optical and genetic maps. Using the PromethION device and 6 flowcells, we generated ∼16 million long reads representing 93× coverage and, more importantly, 6× with reads longer than 100 kb. This ultralong-read dataset allows us to generate one of the most contiguous and complete assemblies of a Brassica genome to date (contig N50 > 10 Mb). In addition, we exploited all the advantages of the nanopore technology to detect modified bases and sequence transcriptomic data using direct RNA to annotate the genome and focus on resistance genes., Conclusion: Using these cutting-edge technologies, and in particular by relying on all the advantages of the nanopore technology, we provide the most contiguous Brassica napus assembly, a resource that will be valuable to the Brassica community for crop improvement and will facilitate the rapid selection of agronomically important traits., (© The Author(s) 2020. Published by Oxford University Press GigaScience.)

The objectives of this study were to determine the main variables which act in the adaptive profile and the dynamic of the thermoregulatory responses of Sindi and Girolando dairy cows in tropical conditions using multivariate analyses as the auxiliary method. Thirty dairy cows were evaluated, in which the data were collected monthly during 12 months. Rectal temperature (R T ) and respiratory rate (R R ) were measured twice a day (morning and afternoon), along with meteorological variables (air temperature, relative humidity, and wind speed), and later the Black Globe and Humidity Index and Radiant Heat Load were calculated. Blood samples were collected for estimating the levels of triiodothyronine (T 3 ), thyroxine (T 4 ), hemoglobin concentration (HC), red blood cells (RBC), packet cell volume (PCV), mean corpuscular volume (MCV), white blood cells (WBC), glucose (GLU), cholesterol (CHO), triglycerides (TRI), creatinine (CRE), total protein (TP), urea (URE), albumin (ALB), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). The more active variables in the adaptive profile for Sindi cows were T 4 , PCV, RBC, WBC, TRI, CRE, HC, T 3 , and URE, while PCV, RBC, ALB, TP, R T , R R , URE, ALT, and AST variables were more active for Girolando cows. All animals were classified according to their corresponding group when considering all variables under study. The classification error percentage was > 40% in the Sindi cows when the physiological responses were considered, whereas an 80% success rate was observed in Girolando cows in the winter and summer seasons. The physiological responses of the dairy cows are similar in winter and distinct in summer in tropical conditions.

The panniculitides remain as one of the most challenging areas for clinicians, as they comprise a heterogeneous group of inflammatory diseases involving the subcutaneous fat with potentially-shared clinical and histopathological features. Clinically, most panniculitides present as red edematous nodules or plaques. Therefore, in addition to a detailed clinical history, a large scalpel biopsy of a recent-stage lesion with adequate representation of the subcutaneous tissue is essential to specific diagnosis and appropriate clinical management. Herein we review the panniculitides of particular interest to the rheumatologist.

Emerging Plasmodium vivax resistance to chloroquine (CQ) may undermine malaria elimination efforts in South America. CQ-resistant P. vivax has been found in the major port city of Manaus but not in the main malaria hot spots across the Amazon Basin of Brazil, where CQ is routinely coadministered with primaquine (PQ) for radical cure of vivax malaria. Here we randomly assigned 204 uncomplicated vivax malaria patients from Juruá Valley, northwestern Brazil, to receive either sequential (arm 1) or concomitant (arm 2) CQ-PQ treatment. Because PQ may synergize the blood schizontocidal effect of CQ and mask low-level CQ resistance, we monitored CQ-only efficacy in arm 1 subjects, who had PQ administered only at the end of the 28-day follow-up. We found adequate clinical and parasitological responses in all subjects assigned to arm 2. However, 2.2% of arm 1 patients had microscopy-detected parasite recrudescences at day 28. When PCR-detected parasitemias at day 28 were considered, response rates decreased to 92.1% and 98.8% in arms 1 and 2, respectively. Therapeutic CQ levels were documented in 6 of 8 recurrences, consistent with true CQ resistance in vivo In contrast, ex vivo assays provided no evidence of CQ resistance in 49 local P. vivax isolates analyzed. CQ-PQ coadministration was not found to potentiate the antirelapse efficacy of PQ over 180 days of surveillance; however, we suggest that larger studies are needed to examine whether and how CQ-PQ interactions, e.g., CQ-mediated inhibition of PQ metabolism, modulate radical cure efficacy in different P. vivax -infected populations. (This study has been registered at ClinicalTrials.gov under identifier NCT02691910.)., (Copyright © 2019 American Society for Microbiology.)

Introduction: Infliximab infusion generally occurs in 2-4 h. Recent studies have suggested the possibility of accelerated infusion (1 h) of this drug., Objective: To evaluate the safety of accelerated infliximab infusion in patients with rheumatic diseases. In addition, patient satisfaction was also assessed., Methods: A prospective, single-center, non-randomized study with 34 patients with rheumatic diseases was conducted from July to November 2016. Patients with the following were excluded: history of allergic reaction to biologics, asthma or severe atopy. All patients previously received a 2- to 3-h infliximab infusion. The infusion rate was accelerated to 1 h, and premedication was excluded. The infusion was monitored in all patients., Results: A total of 34 patients were included in the study [rheumatoid arthritis (n = 16), ankylosing spondylitis (n = 15), psoriatic arthritis (n = 2) and enteropathic arthropathy (n = 1)], with an average age of 48.7 ± 18.6 years; 55.5% of the patients were female, and 29.4% were white. The duration of disease was 9.5 ± 9.2 years, and the duration of infliximab use was 38.9 ± 27.6 months, with a mean dose per infusion of 414.2 ± 158.1 (range, 200-800) mg. The mean infliximab infusion time prior to the study was 2.2 ± 0.4 h. A total of 6 (17.6%) patients received premedication. The premedication was suspended. There were no adverse effects during or after infusion. Ninety-seven percent of the patients and 100% of the health workers were satisfied with the accelerated infusion., Conclusion: Our data support the safe use of accelerated infliximab infusion in rheumatic patients, with high satisfaction among patients and health workers.

Background: Little has been published about the epidemiology of Granulomatosis with polyangiitis (GPA) in South America, especially in the intertropical zone, and no epidemiological data from Brazil are available. The purpose of the present study was to draw a clinical and demographic profile of GPA patients living in Northeastern Brazil based on laboratory, histological and imaging findings, and evaluate the frequency of organic involvement., Methods: Clinical, epidemiological and treatment data of GPA patients were collected retrospectively and compared with the literature., Results: The cohort included 25 GPA patients (84% female) aged 45.8 ± 16.1 years. Renal and ear-nose-throat (ENT) manifestations were the most common (both 64%). One third (32%) of the patients had 24-h proteinuria > 1 g, 50% had creatinine clearance < 50 mL/min at the time of diagnosis, and 33% had recurrent kidney damage during disease progress. The affected organs included lungs (60%), joints (44%), skin (32%), peripheral nervous system (28%), eyes (28%) and heart (16%). ENT involvement (n = 16/64%) was less frequent in our region than in São Paulo (n = 115/85.8%). Renal (n = 16/64%) and pulmonary (n = 15/60%) involvement was less frequent in our region than in the U.K. (renal n = 30/90%; pulmonary n = 28/84.8%)., Conclusion: Most of our patients were female, presented the generalized form and were diagnosed late. The frequency of the main clinical manifestations (ENT, renal and pulmonary) was lower than that observed at higher latitudes, suggesting the existence of a Northeast Brazilian clinical and epidemiological profile and adding to our knowledge of this rare condition.

Background: Vitamin D deficiency and insufficiency have been reported in fibromyalgia. However, to the best of our knowledge, only one study has evaluated the role of 25-hydroxyvitamin D [25(OH)D] supplementation on fibromyalgia symptoms., Objectives: To analyze the effects of 3 months of 25(OH)D supplementation on symptoms of fibromyalgia., Methods: This study included 11 female patient. Demographic and clinical data, tender points, visual analog scale results, and pre- and post-serum levels of 25(OH)D supplementation were analyzed. The levels of 25(OH)D were measured by a radioimmunologic test., Results: Patients with fibromyalgia diagnosis and 25(OH)D values ≤ 30 ng/ml were recruited to receive 50,000 IU of oral vitamin D once every week for 3 months. The disease was diagnosed based on the American College of Rheumatology criteria. The median age of all patients was 48.5 (28-67) years and 63.4% were Caucasian. Disease duration varied from 1-10 years. The 25(OH)D levels increased significantly after 3 months, 18.4 (15.5-25.8) ng/ml vs. 33.8 (28-58) ng/ml, P = 0.01. Interestingly, an improvement of visual analog scale scores was observed at 3 months, 90 (0-100) vs. 30 (0-80), P = 0.002. Eight patients (72.2%) responded that they experienced a very significant improvement in symptoms. In addition, a trend for reduction of the number of tender points was observed after 3 months, 17 (11-18) vs. 10 (0-18), P = 0.07., Conclusions: The 25(OH)D levels and disease symptoms in patients with fibromyalgia and vitamin D deficiency/insufficiency seem to improve with vitamin D supplementation.

Background: Malaria burden in Brazil has reached its lowest levels in 35 years and Plasmodium vivax now accounts for 84% of cases countrywide. Targeting residual malaria transmission entrenched in the Amazon is the next major challenge for ongoing elimination efforts. Better strategies are urgently needed to address the vast reservoir of asymptomatic P. vivax carriers in this and other areas approaching malaria elimination., Methods: We evaluated a reactive case detection (RCD) strategy tailored for P. vivax transmission in farming settlements in the Amazon Basin of Brazil. Over six months, 41 cases detected by passive surveillance triggered four rounds of RCD (0, 30, 60, and 180 days after index case enrollment), using microscopy- and quantitative real-time polymerase chain reaction (qPCR)-based diagnosis, comprising subjects sharing the household (HH) with the index case (n = 163), those living in the 5 nearest HHs within 3 km (n = 878), and individuals from 5 randomly chosen control HHs located > 5 km away from index cases (n = 841). Correlates of infection were identified with mixed-effects logistic regression models. Molecular genotyping was used to infer local parasite transmission networks., Principal Findings/conclusions: Subjects in index and neighbor HHs were significantly more likely to be parasitemic than control HH members, after adjusting for potential confounders, and together harbored > 90% of the P. vivax biomass in study subjects. Clustering patterns were temporally stable. Four rounds of microscopy-based RCD would identify only 49.5% of the infections diagnosed by qPCR, but 76.8% of the total parasite biomass circulating in the proximity of index HHs. However, control HHs accounted for 27.6% of qPCR-positive samples, 92.6% of them from asymptomatic carriers beyond the reach of RCD. Molecular genotyping revealed high P. vivax diversity, consistent with complex transmission networks and multiple sources of infection within clusters, potentially complicating malaria elimination efforts., Competing Interests: The authors have declared that no competing interests exist.

In 2014, tofacitinib, a target-specific, synthetic disease modifying anti rheumatic drug (DMARD) and a selective inhibitor of Janus kinase (JAK) was approved for use in Brazil. This position paper aims to update the recommendations of the Brazilian Society of Rheumatology (SBR) on the treatment of rheumatoid arthritis (RA) in Brazil, specifically regarding the use of target-specific synthetic DMARDs. The method of this recommendation consisted of a literature review of scientific papers held on the Medline database. After this review, a text was produced, answering questions in Pico structure, considering efficacy and safety issues of tofacitinib use for RA treatment in different scenarios (such as first-line treatment after failure with methotrexate [MTX] or other conventional synthetic DMARDs after failure with biological therapy). Based on existing evidence, and considering the available data on efficacy, safety and cost of medications available to treat the disease in Brazil, the RA Commission of SBR, after a process of discussion and voting on proposals, established the following position on the use of tofacitinib for treatment of RA in Brazil: "Tofacitinib, alone or in combination with MTX, is an alternative for RA patients with moderate or high activity after failure of at least two different synthetic DMARDs and one biological DMARD." The level of agreement with this recommendation was 7.5. This position may be reviewed in the coming years, in the face of a greater experience with the use of this medication., (Copyright © 2015 Elsevier Editora Ltda. All rights reserved.)

Smoking is a risk factor for thromboangiitis obliterans (TAO, Buerger's disease) and arteriosclerosis, but there are few cases of coronary heart disease (CAD)-associated Buerger's disease. A literature search for articles in English, Spanish and French published between 1966 and 2012 on patients with coronary involvement and TAO revealed 12 patients. We describe an additional case with involvement of the central nervous system, myocardium and large-diameter proximal arteries. The main clinical manifestations in these 13 cases were lower limb claudication and acute thoracic pain. The histologic findings showed thrombosis with unbroken internal elastic lamina and intimal clusters of granulocytes; coronary angiography revealed predominant involvement of the left anterior descending and right coronary artery. Treatment included coronary bypass procedures, coronary angiopiasty, smoking cessation, and anticoagulant therapy. A complete therapeutic response was observed in half the patients. This review of all published cases of TAO patients with coronary symptoms, together with our patient, demonstrates the rarity of this clinical association. Patients under age 40 with CAD but no prominent cardiovascular risk factors besides smoking should be evaluated for the presence of Buerger's disease.

Background and Aims: To date chloroplast genomes are available only for members of the non-protein amino acid-accumulating clade (NPAAA) Papilionoid lineages in the legume family (i.e. Millettioids, Robinoids and the 'inverted repeat-lacking clade', IRLC). It is thus very important to sequence plastomes from other lineages in order to better understand the unusual evolution observed in this model flowering plant family. To this end, the plastome of a lupine species, Lupinus luteus, was sequenced to represent the Genistoid lineage, a noteworthy but poorly studied legume group., Methods: The plastome of L. luteus was reconstructed using Roche-454 and Illumina next-generation sequencing. Its structure, repetitive sequences, gene content and sequence divergence were compared with those of other Fabaceae plastomes. PCR screening and sequencing were performed in other allied legumes in order to determine the origin of a large inversion identified in L. luteus., Key Results: The first sequenced Genistoid plastome (L. luteus: 155 894 bp) resulted in the discovery of a 36-kb inversion, embedded within the already known 50-kb inversion in the large single-copy (LSC) region of the Papilionoideae. This inversion occurs at the base or soon after the Genistoid emergence, and most probably resulted from a flip-flop recombination between identical 29-bp inverted repeats within two trnS genes. Comparative analyses of the chloroplast gene content of L. luteus vs. Fabaceae and extra-Fabales plastomes revealed the loss of the plastid rpl22 gene, and its functional relocation to the nucleus was verified using lupine transcriptomic data. An investigation into the evolutionary rate of coding and non-coding sequences among legume plastomes resulted in the identification of remarkably variable regions., Conclusions: This study resulted in the discovery of a novel, major 36-kb inversion, specific to the Genistoids. Chloroplast mutational hotspots were also identified, which contain novel and potentially informative regions for molecular evolutionary studies at various taxonomic levels in the legumes. Taken together, the results provide new insights into the evolutionary landscape of the legume plastome., (© The Author 2014. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The management and surgical interventions of problems directly or indirectly arising from rheumatoid arthritis vary drastically. Anesthesiologists and rheumatologists should be aware of the peculiarities of the anesthetic preoperative assessment of these patients, including the assessment of possible disorders of the airways, in addition to the intra-operative management and analysis of relevant pharmacological parameters. It is critical that the anesthetist is familiar with the peculiarities of the disease and the specific characteristics of drugs used in its treatment: thus, he/she will be able to plan the best possible anesthetic technique for the surgery in question, offering safety and comfort to his/her patient. It is up to the rheumatologist to know the procedure to which the patient will be submitted to and be aware of the most appropriate anesthetic technique in each case. This will allow a better interaction between the rheumatologist and the anesthesiologist in the pre-anesthetic evaluation, through the sharing of relevant information on the articular and systemic involvement by the disease that might interfere with preoperative and intraoperative management. Furthermore, the information on the pre-anesthetic assessment and the choice of anesthetic technique will enable the rheumatologist to clarify any doubts that his/her patient and family may have, as well as to guide them as to whether or not the medications in use should be maintained, and eventually about the need for a supplemental dose of corticosteroid. The objective of this review is to acquaint the rheumatologist with key concepts related to the anesthetic preoperative assessment of patients diagnosed with RA, mainly including general notions that dictate the choice of the anesthetic technique.

A major cause of morbidity and mortality in the context of the antiphospholipid syndrome (APS) is the occurrence of thrombotic events. Besides the pathogenic roles of antiphospholipid antibodies (aPL), other risk factors and medical conditions, which are conditions for traditional risk of an individual without the APS, can coexist in this patient, raising their risk of developing thrombosis. Therefore, the clinical and laboratory investigation of comorbidities known to increase cardiovascular risk in patients with antiphospholipid antibody syndrome is crucial for the adoption of a more complete and effective treatment. Experimental models and clinical studies show evidence of association between APS and premature formation of atherosclerotic plaques. Atherosclerosis has major traditional risk factors: hypertension, diabetes mellitus, obesity, dyslipidemia, smoking, and sedentary lifestyle that may be implicated in vascular involvement in patients with APS. The influence of nontraditional risk factors as hyperhomocysteinemia, increased lipoprotein a, and anti-oxLDL in the development of thromboembolic events in APS patients has been studied in scientific literature. Metabolic syndrome with all its components also has been recently studied in antiphospholipid syndrome and is associated with arterial events.

Objectives: A review of the literature reports neonatal thrombosis and antiphospholipid antibodies cases through a retrospective study that focuses on the pathogenesis and main clinical and laboratory manifestations of this disease., Methods: The case reports were selected from PubMed. The keywords used to search were neonatal, antiphospholipid syndrome, thrombosis, and antiphospholipid antibodies. References that were published from 1987 to 2013 were reviewed., Results: Twenty-one cases of neonatal thrombosis and antiphospholipid antibodies were identified. Ten children were born preterm (before 37 weeks). Arterial involvement (17/21) was predominant, of which stroke (12/17) was the most prevalent clinical manifestation. Anti-cardiolipin antibodies were predominant (13/21) in the antiphospholipid antibody profiles. Treatments were based on the use of symptomatics such as antiepileptics (8/21), and 6/21 patients received heparin. There were 4 deaths (4/21); otherwise, the children recovered well, especially the neonates who suffered from strokes (9/12)., Conclusion: Neonatal thrombosis and antiphospholipid antibodies are rare. The development of thrombotic manifestations in neonates seems not to be associated exclusively with the aPL, but their etiology may be linked to pre- and perinatal events. We noted good therapeutic responses, especially in stroke patients, who presented with favorable outcomes in 82% of the cases.

Yellow fever is an infectious disease, endemic in South America and Africa. This is a potentially serious illness, with lethality between 5 and 40% of cases. The most effective preventive vaccine is constituted by the attenuated virus strain 17D, developed in 1937. It is considered safe and effective, conferring protection in more than 90% in 10 years. Adverse effects are known as mild reactions (allergies, transaminases transient elevation, fever, headache) and severe (visceral and neurotropic disease related to vaccine). However, little is known about its potential to induce autoimmune responses. This systematic review aims to identify the occurrence of autoinflammatory diseases related to 17D vaccine administration. Six studies were identified describing 13 possible cases. The diseases were Guillain-Barré syndrome, multiple sclerosis, multiple points evanescent syndrome, acute disseminated encephalomyelitis, autoimmune hepatitis, and Kawasaki disease. The data suggest that 17D vaccination may play a role in the mechanism of loss of self-tolerance.

Background: The purpose of the present study was to compare dynamic muscle strength, functional performance, fatigue, and quality of life in premenopausal systemic lupus erythematosus (SLE) patients with low disease activity versus matched-healthy controls and to determine the association of dynamic muscle strength with fatigue, functional performance, and quality of life in SLE patients., Methods: We evaluated premenopausal (18-45 years) SLE patients with low disease activity (Systemic lupus erythematosus disease activity index [SLEDAI]: mean 1.5 ± 1.2). The control (n = 25) and patient (n = 25) groups were matched by age, physical characteristics, and the level of physical activities in daily life (International Physical Activity Questionnaire IPAQ). Both groups had not participated in regular exercise programs for at least six months prior to the study. Dynamic muscle strength was assessed by one-repetition maximum (1-RM) tests. Functional performance was assessed by the Timed Up and Go (TUG), in 30-s test a chair stand and arm curl using a 2-kg dumbbell and balance test, handgrip strength and a sit-and-reach flexibility test. Quality of life (SF-36) and fatigue were also measured., Results: The SLE patients showed significantly lower dynamic muscle strength in all exercises (leg press 25.63%, leg extension 11.19%, leg curl 15.71%, chest press 18.33%, lat pulldown 13.56%, 1-RM total load 18.12%, P < 0.001-0.02) compared to the controls. The SLE patients also had lower functional performance, greater fatigue and poorer quality of life. In addition, fatigue, SF-36 and functional performance accounted for 52% of the variance in dynamic muscle strength in the SLE patients., Conclusions: Premenopausal SLE patients with low disease activity showed lower dynamic muscle strength, along with increased fatigue, reduced functional performance, and poorer quality of life when compared to matched controls.