Safety of Transcranial Direct Current Electrical Stimulation in Dermatomyositis: A Case Report

Transcranial direct current stimulation (tDCS) has emerged as a nonpharmacological tool in physical rehabilitation. There have currently no studies that evaluated the safety and efficacy of tDCS in patients with dermatomyositis. Case-report: Three adult women with dermatomyositis were allocated randomly to intervention (i-tDCS, one patient) or not (sham-tDCS, two patients) of three consecutive days of tDCS and evaluated in four periods: before-tDCS (PRE), 15 minutes after-tDCS (0th POST), 15 days after-tDCS (15th POST), and 30 days after-tDCS (30th POST). The tDCS was safe throughout the protocol, without disease relapsing or adverse effects related to tDCS. Furthermore, the tDCS increased the muscle torque and total work of dominant and non-dominant elbow flexors in the patient with i-tDCS, when compared to two patients with sham-tDCS. Conclusions: The tDCS was safe and appeared to influence long-term strength in the limb of the patient with stable dermatomyo-sitis.

Tofacitinib as a Treatment for Refractory Dermatomyositis: A Case Report

In very scarce case reports and case series, tofacitinib has been a therapeutic alternative for dermatomyositis. To corroborate the literature, we described a refractory dermatomyositis that had a good outcome with tofacitinib. Case Report: An adult female patient presented with definite dermatomyositis and with refractoriness to high doses of intravenous and oral glucocorticoids, intravenous human immunoglobulin, several immunosuppressive drugs (methotrexate, azathioprine, and leflunomide) and two previous immunobiological drugs (rituximab and abatacept). However, the patient had a good outcome with tofacitinib. Conclusions: Tofacitinib appears to be a promising alternative therapy for refractory dermatomyositis.

Pain and Fatigue Perceptions of Patients with Systemic Autoimmune Myopathies before and during the COVID-19 Pandemic Period

Objective: To assess general pain and fatigue and their association with the disease status of patients with systemic autoimmune myopathies (SAMs), in terms of the impact of the COVID-19 pandemic on these parameters. Methods: This is a cross-sectional and prospective cohort study that included 72 patients with SAMs who were matched by age and gender with 67 healthy individuals. The patients engaged in an interview via a validity survey to measure disease status, and assess a visual analog scale (VAS) for pain and fatigue in two periods: before (phase I) and during (phase II) of the Brazilian COVID-19 pandemic. For cross-sectional analysis, patients’ data from phase I were compared to healthy individuals’ information, whereas for prospective analysis, data of the patients who were assessed in phase II were compared to the same patients’ data from phase I. Results: The patients had significantly more pain perception, comparable fatigue perception and fatigue severity, when compared to the healthy individuals. During the COVID-19 pandemic period, the disease activity, pain and fatigue perceptions, and fatigue severity remained unchanged. Despite this, the pain and fatigue perceptions correlated significantly with patients’ VAS, the patient health outcome, and fatigue severity. In addition, the pain perception correlated to creatine phosphokinase, whereas fatigue perceptions correlated to physicians' VAS. Conclusions: The study showed that patients with SAMs have significantly increased pain perceptions compared to healthy individuals. During the COVID-19 pandemic period, the pain and fatigue perceptions remained unchanged in patients with SAMs but they correlated to several disease status parameters.

Functional and Structural Arterial Vessel Features of Female Patients with Stable Dermatomyositis and Antisynthetase Syndrome

Introduction: Dermatomyositis (DM) and antisynthetase syndrome (ASS) show a high frequency of metabolic syndrome, which can be preceded by endothelial dysfunction and arterial stiffness. To date, only one study has evaluated these vessel parameters in DM, and no study of ASS exists. Therefore, the aim of the study was to assess the structural and functional arterial of arterial vessels in DM and ASS. Methods: This cross-sectional study enrolled 21 adult female patients (14 DM and 7 ASS) who were age-, gender- and ethnicity-matched to 12 healthy individuals. Patients using lipid lowering agents or prednisone at doses ≥ 0.25 mg/kg/day, and patients with uncontrolled systemic arterial hypertension, diabetes mellitus, cardiac insufficiency, and disease activity were excluded. Arterial stiffness was evaluated using carotid-femoral pulse wave velocity (PWV), and endothelial function was evaluated using dependent flow-mediated dilatation (FMD) of the brachial artery. Results: The mean age of patients with DM or ASS were 45.4 ± 8.6 and 44.0 ± 6.1 years, respectively (P = 1.000), and patients were predominantly of white ethnicity. Six DM patients and three ASS patients had systemic arterial hypertension, whereas 9 DM patients and six ASS patients had dyslipidemia. Endothelial baseline diameter, hyperemia diameter and FMD values were similar among the three groups (P > 0.05). Moreover, the median FMD values were also similar between the patients with DM and patients with ASS [8.3% (4.5% - 10.9%) vs. 6.0% (−1.8% - 8.2%);P = 0.585]. The PWV values were comparable among the three groups (P = 0.253). In addition, no difference was observed between patients with DM and patients with ASS (7.4 ± 0.8 m/s vs. 7.4 ± 0.9 m/s;P = 1.000). Conclusions: Despite the high prevalence of dyslipidemia and systemic arterial hypertension, our female patients with stable DM and ASS had FMD and PWV values comparable to those of the control group.

Transcranial Direct Current Stimulation Is Safe and Relieves Post-Herpetic Neuralgia in Patient with Dermatomyositis: A Case Report

To the best of our knowledge, this is the first report in the literature showing the efficacy of transcranial direct current stimulation (tDCS) in treating refractory post-herpetic neuralgia in a patient with dermatomyositis. In addition, our results showed that tDCS sessions are safe and do not lead to disease relapse. Therefore, despite the limitations of being a case report, this study provides encouraging results that need to be widely explored in studies with a representative number of patients and with an appropriate design for patients with this systemic rheumatic autoimmune disease.

Role of vitamin D deficiency and comorbidities in COVID-19

Recent manuscripts described the incidence of vitamin D hypovitaminosis in coronavirus disease 2019(COVID-19)patients.Vitamin D deficiency is also common in patients with comorbidities that are associated with a poor COVID-19 prognosis.In this letter,we review the literature regarding the association of comorbidities,vitamin D deficiency,and COVID-19.

Transcranial Direct Current Stimulation Combined with Peripheral Neuromuscular Stimulation Improves Quality of Life, Fatigue, and Pain in a Patient with Rheumatoid Arthritis and Refractory Radicular Pain Related to Spinal Stenosis

Background: Transcranial direct current stimulation (tDCS) has emerged as an adjuvant noninvasive neuromodulation tool to control fatigue and pain. To date, no studies have assessed the safety and efficiency of tDCS in patients with rheumatoid arthritis and with fatigue, poor quality of life, and refractory radicular pain associated with spinal stenosis. Case Presentation: An 85-year-old woman patient presented with rheumatoid arthritis in remission, refractory radicular pain-associated spinal stenosis, fatigue, and impaired quality of life. The patient underwent 16 daily sessions of tDCS intervention (2 mA, 20 min, positively and negatively charged electrodes were positioned at C1 and Fp2, respectively), in addition to simultaneous peripheral neuromuscular electrical stimulation (frequency of 100 Hz and amplitude of 500 μs). After the intervention, neither disease relapse nor clinical intercurrence occurred. Moreover, there was a significant and sustained improvement in her health-related quality of life, with a reduction in the level of pain and chronic fatigue. Conclusion: The present case report shows that tDCS is safe and may be an adjuvant tool for the treatment of pain and fatigue in patients with systemic autoimmune disease, as well as for improving quality of life. Further studies are required to corroborate this case report.

^(11)C-PK11195 plasma metabolization has the same rate in multiple sclerosis patients and healthy controls:a cross-sectional study

^(11)C-PK11195 is a positron emitter tracer used for Positron Emission Tomography(PET)imaging of innate immune cell activation in studies of neuroinflammatory diseases.For the image quantitative analysis,it is necessary to quantify the intact fraction of this tracer in the arterial plasma during imaging acquisition(plasma intact fraction).Due to the complexity and costs involved in this analysis it is important to evaluate the real necessity of individual analysis in each 11C-PK11195 PET imaging acquisition.The purpose of this study is to compare 11CPK11195 plasma metabolization rate between healthy controls and multiple sclerosis(MS)patients and evaluate the interference of sex,age,treatment,and disease phenotype in the tracer intact fraction measured in arterial plasma samples.11C-PK11195 metabolization rate in arterial plasma was quantified by high performance liquid chromatography in samples from MS patients(n=50)and healthy controls(n=23)at 20,45,and 60 minutes after 11C-PK11195 injection.Analyses were also stratified by sex,age,treatment type,and MS phenotype.The results showed no significant differences in the metabolization rate of healthy controls and MS patients,or in the stratified samples.In conclusion,11C-PK11195 metabolization has the same rate in patients with MS and healthy controls,which is not affected by sex,age,treatment,and disease phenotype.Thus,these findings could contribute to exempting the necessity for tracer metabolization determination in all 11C-PK11195 PET imaging acquisition,by using a population metabolization rate average.The study procedures were approved by the Ethics Committee for Research Projects Analysis of the Hospital das Clinicas of the University of Sao Paulo Medical School(approval No.624.065)on April 23,2014.

Association between the CYBA and NOX4 genes of NADPH oxidase and its relationship with metabolic syndrome in non-alcoholic fatty liver disease in Brazilian population

Background: Oxidative stress has been implicated in the progression of severe forms of non-alcoholic fatty liver disease(NAFLD). NADPH oxidase produces reactive oxygen species. In the present study, we investigated for the first time two single nucleotide polymorphisms(SNPs) in the regulatory region of genes encoding NADPH oxidase 4(NOX4) and p22 phox(CYBA) in NAFLD.Methods: A total of 207 biopsy-proven NAFLD patients [simple steatosis(n = 27); nonalcoholic steatohepatitis(NASH)(n = 180)] were evaluated. Genomic DNA was extracted from peripheral blood cells, and polymorphisms in CYBA(unregistered) and NOX4(rs3017887) were determined by direct sequencing of PCR.Results: Associations of CYBA-675 T/A with high-density lipoprotein(HDL)(TT vs TA vs AA; P < 0.01) and triglycerides(TGL)(TT vs XA; P < 0.01) were observed only in NASH patients. For polymorphisms in the NOX4 gene, NOX4(rs3017887) CA + AA genotypes was significant associated with alanine aminotransferase(ALT)(CA + AA vs CC; P = 0.02). However, there was no association of SNPs in the CYBA and NOX4 genes encoding the NADPH oxidase system proteins and the presence of NASH. Regarding the clinical results, it was observed that the most advanced degrees of fibrosis occurred in patients diagnosed with type 2 diabetes mellitus(66.9% vs 37.5%, P < 0.01) and those who were more obese(32.2 vs 29.0 kg/m2,P < 0.01). In addition, serum glucose and insulin levels increased significantly in the presence of NASH.Conclusions: There were associations between the presence of the allele A in the NOX4 SNP and a higher concentration of ALT in the NAFLD population; between the presence of the AA genotype in the polymorphism of the CYBA-675 T/A CYBA gene and a higher level of TGL and lower HDL in NASH patients. The presence of metabolic syndrome was associated with advanced degrees of fibrosis in NAFLD patients.

Intestinal inflammation and the microbiota:Beyond diversity

The recent manuscript entitled“Relationship between clinical features and intestinal microbiota in Chinese patients with ulcerative colitis”reported a difference in the intestinal microbiota of patients with ulcerative colitis according to the severity of the colitis.The influence of the intestinal microbiota on the development and progress of gastrointestinal disorders is well established.Besides the diversity in the microbiome,the presence of virulence factors and toxins by commensal bacteria may affect an extensive variety of cellular processes,contributing to the induction of a proinflammatory environment.

SARS-CoV-2 infection in liver transplant recipients:A complex relationship

The recent manuscript reviewed investigations involving liver damage in coronavirus disease 2019(COVID-19)patients,and COVID-19 in patients with previous chronic hepatological diseases,such as patients with liver graft.The literature presents several conflicting results concerning the anti-SARS-CoV-2 response in patients with solid organ transplants,in liver transplant recipients.Therefore,we would like to humbly state a few points for consideration involving liver transplant recipients and COVID-19,such as the time since transplantation,comorbidities,and immunosuppressive regimens.

Large primary hepatic gastrinoma in young patient treated with trisegmentectomy: A case report and review of the literature

Primary hepatic gastrinoma is a rare disease, with fewer than 40 cases reported in the medical literature. Because it is located in an organ in which metastases are common, its diagnosis is difficult. We report a case of a 19 years old male patient with a history of gastric ulcers since the age of nine. Following gastric surgery, an antrectomy and a vagotomy, there was some alleviation of symptoms. Subsequently, the patient reported various intermittent episodes of diarrhea, diffuse abdominal pain, and vomiting. The patient underwent tomography, which revealed the presence of a hepatic mass measuring 19.5 cm × 12.5 cm × 17 cm. Primary hepatic gastrinoma was diagnosed based on laboratory examinations that indicated hypergastrinemia and a positron emission tomography/magnetic resonance study with somatostatin analogue that confirmed the liver as the primary site. After hepatic trisegmentectomy(Ⅱ, Ⅲ, Ⅳ, Ⅴ, Ⅷ), the patient's symptoms improved. The case is notable for the presence of a rare tumor with uncommon dimensions.

Traditional and Non-Traditional Risk Factors Involved with Endothelial Dysfunction and Arterial Stiffness in Autoimmune Rheumatic Diseases

Autoimmune rheumatic diseases (ARDs) have been closely associated with accelerated plaque progression and the development of atherosclerosis, which lead to high morbidity and mortality rates for cardiovascular diseases. Endothelial dysfunction and arterial stiffness are greatly evidenced in several studies in the early phase of atherosclerosis. In ARDs, endothelial dysfunction and arterial stiffness are related to traditional and non-traditional risk factors. To date, no studies have clearly analyzed the main parameter involved in endothelial dysfunction and arterial stiffness. In this context, the present narrative review’s purpose was to describe the main factor in endothelial dysfunction and arterial stiffness in different ARDs. Endothelial dysfunction and arterial stiffness are related to traditional risk factors (i.e., hypertension, diabetes, dyslipidemia, metabolic syndrome, sedentary behavior) and non-traditional risk factors (linked to the immune mechanisms involved in these diseases). Moreover, in the present study, these associations were systemically analyzed in ankylosing spondylitis, antiphospholipid syndrome, rheumatoid arthritis, psoriatic arthritis, systemic autoimmune myopathies, systemic lupus erythematosus and systemic sclerosis. The present review shows that the relationship of traditional risk factors and non-traditional risk factors related to ARDs works in the worsening of function and structural properties of arterial vessels, leading to high cardiovascular morbidity and mortality.

Effects of Exercise Training on Endothelial Function,Arterial Structure,and Physical Conditioning in Patients with Systemic Autoimmune Myopathies:A Case Series Study

Introduction. Exercise training has been effective in improving endothelial function and decreasing arterial stiffness in several systemic autoimmune diseases. However, to date, no studies have assessed patients with systemic autoimmune myopathies (SAM). Methods. Five female patients with definite SAM (3 dermatomyositis and 2 polymyositis) who underwent a 12-week, twice-a-week, exercise training program were assessed prospectively. The following parameters were assessed: endothelial function measured by flow-mediated dilatation (FMD), carotid femoral by pulse wave velocity (PWV), disease status by International Myositis Assessment & Clinical Studies Group (IMACS) set score, the ventilatory anaerobic threefold (VAT), respiratory compensation point (RCP), maximum effort (ME), maximal oxygen uptake (VO2max) measured by ergospyrometer, and strength and muscle function. Results. Mean age of the patients and duration of disease were 43.9 and 10.5 years, respectively. The median FMD and PWV were 10.2% and 7.1 m/s. After exercise training, important FMD reduction was observed in 4 out of 5 patients, whereas the PWV parameters decreased in only 2 out of 5 patients. The exercise training was safe, without clinical intercurrences or disease relapses. Moreover, an increase in strength and functionality was observed. Concerning aerobic capacity, there was a decrease in the VAT and an increase in ME, without al-terations in the maximum oxygen consumption. Conclusions. In general, exercise training does not alter endothelial function and PWV values, but improves muscle strength and function and also, does not lead to disease reactivation (Clinical Trials (NCT03092167)).

The aryl hydrocarbon receptor and the gut–brain axis

The aryl hydrocarbon receptor(AHR)is a ligand-activated transcription factor initially identified as the receptor for dioxin.Almost half a century after its discovery,AHR is now recognized as a receptor for multiple physiological ligands,with important roles in health and disease.In this review,we discuss the role of AHR in the gut–brain axis and its potential value as a therapeutic target for immune-mediated diseases.