BackgroundThe availability of methotrexate and the introduction of multiple biological agents have revolutionized the treatment of juvenile idiopathic arthritis (JIA). Several international and national drug registries have been implemented to accurately monitor the long-term safety/efficacy of these agents. This report aims to present the combined data coming from Pharmachild/PRINTO registry and the national registries from Germany (BiKeR) and Sweden.MethodsDescriptive statistics was used for demographic, clinical data, drug exposure, adverse events (AEs) and events of special interest (ESIs). For the Swedish register, AE data were not available.ResultsData from a total of 15,284 patients were reported: 8274 (54%) from the Pharmachild registry and 3990 (26%) and 3020 (20%) from the German and the Swedish registries, respectively. Pharmachild children showed a younger age (median of 5.4 versus 7.6 years) at JIA onset and shorter disease duration at last available visit (5.3 versus 6.1–6.8) when compared with the other registries. The most frequent JIA category was the rheumatoid factor–negative polyarthritis (range of 24.6–29.9%). Methotrexate (61–84%) and etanercept (24%–61.8%) were the most frequently used synthetic and biologic disease-modifying anti-rheumatic drugs (DMARDs), respectively. There was a wide variability in glucocorticoid use (16.7–42.1%). Serious AEs were present in 572 (6.9%) patients in Pharmachild versus 297 (7.4%) in BiKeR. Infection and infestations were the most frequent AEs (29.4–30.1%) followed by gastrointestinal disorders (11.5–19.6%). The most frequent ESIs were infections (75.3–89%).ConclusionsThis article is the first attempt to present a very large sample of data on JIA patients from different national and international registries and represents the first proposal for data merging as the most powerful tool for future analysis of safety and effectiveness of immunosuppressive therapies in JIA.Registry registrationThe Pharmachild registry is registered at ClinicalTrials.gov (NCT01399281) and at the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) (http://www.encepp.eu/encepp/viewResource.htm?id=19362). The BiKeR registry is registered at ENCePP (http://www.encepp.eu/encepp/viewResource.htm?id=20591).Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1780-z) contains supplementary material, which is available to authorized users.

Immune modulation is a very modern medical field for targeting viral infections. In the race to develop the best immune modulator against viruses, curcumin, as a natural product, is inexpensive, without side effects, and can stimulate very well certain areas of the human immune system. As a bright yellow component of turmeric spice, curcumin has been the subject of thousands of scientific and clinical studies in recent decades to prove its powerful antioxidant properties and anticancer effects. Curcumin has been shown to influence inter- and intracellular signaling pathways, with direct effects on gene expression of the antioxidant proteins and those that regulate the immunity. Experimental studies have shown that curcumin modulates several enzyme systems, reduces nitrosative stress, increases the antioxidant capacity, and decreases the lipid peroxidation, protecting against fatty liver pathogenesis and fibrotic changes. Hepatitis B virus (HBV) affects millions of people worldwide, having sometimes a dramatic evolution to chronic aggressive infection, cirrhosis, and hepatocellular carcinoma. All up-to-date treatments are limited, there is still a gap in the scientific knowledge, and a sterilization cure may not yet be possible with the removal of both covalently closed circular DNA (cccDNA) and the embedded HBV DNA. With a maximum light absorption at 420 nm, the cytotoxicity of curcumin as photosensitizer could be expanded by the intravenous blue laser blood irradiation (IVBLBI) or photobiomodulation in patients with chronic hepatitis B infection, Hepatitis B e-antigen (HBeAg)-positive, noncirrhotic, but nonresponsive to classical therapy. Photobiomodulation increases DNA repair by the biosynthesis of complex molecules with antioxidant properties, the outset of repairing enzyme systems and new phospholipids for regenerating the cell membranes. UltraBioavailable Curcumin and blue laser photobiomodulation could suppress the virus and control better the disease by reducing inflammation/fibrosis and stopping the progression of chronic hepatitis, reversing fibrosis, and diminishing the progression of cirrhosis, and decreasing the incidence of hepatocellular carcinoma. Photodynamic therapy with blue light and curcumin opens new avenues for the effective prevention and cure of chronic liver infections and hepatocellular carcinoma. Blue laser light and UltraBioavailable Curcumin could be a new valuable alternative for medical applications in chronic B viral hepatitis and hepatocarcinoma, saving millions of lives.

Objectives To describe risk factors for inflammatory bowel disease (IBD) development in a cohort of children with juvenile idiopathic arthritis (JIA). Methods JIA patients who developed IBD were identified from the international Pharmachild register. Characteristics were compared between IBD and non-IBD patients and predictors of IBD were determined using multivariable logistic regression analysis. Incidence rates of IBD events on different disease-modifying anti-rheumatic drugs (DMARDs) were calculated, differences between therapies were expressed as relative risks (RR). Results Out of 8,942 patients, 48 (0.05%) developed IBD. These were more often male (47.9% vs 32.0%) and HLA-B27 positive (38.2% vs 21.0%) and older at JIA onset (median 8.94 vs 5.33 years) than patients without IBD development. They also had more often a family history of autoimmune disease (42.6% vs 24.4%) and enthesitis-related arthritis (ERA) (39.6% vs 10.8%). The strongest predictors of IBD on multivariable analysis were ERA (OR: 3.68, 95% CI: 1.41–9.40) and a family history of autoimmune disease (OR: 2.27, 95% CI: 1.12–4.54). Compared with methotrexate monotherapy, the incidence of IBD on etanercept monotherapy (RR: 7.69, 95% CI: 1.99–29.74), etanercept with methotrexate (RR: 5.70, 95% CI: 1.42–22.77) and infliximab (RR: 7.61, 95% CI: 1.27–45.57) therapy was significantly higher. Incidence on adalimumab was not significantly different (RR: 1.45, 95% CI: 0.15–13.89). Conclusion IBD in JIA was associated with ERA and a family history of autoimmune disease. An increased IBD incidence was observed for etanercept therapy regardless of concomitant methotrexate use.

In recent decades, researchers around the world have been studying intensively how micro-organisms that are present inside living organisms could affect the main processes of life, namely health and pathological conditions of mind or body. They discovered a relationship between the whole microbial colonization and the initiation and development of different medical disorders. Besides already known probiotics, novel products such as postbiotics and paraprobiotics have been developed in recent years to create new non-viable micro-organisms or bacterial-free extracts, which can provide benefits to the host with additional bioactivity to probiotics, but without the risk of side effects. The best alternatives in the use of probiotics and postbiotics to maintain the health of the intestinal microbiota and to prevent the attachment of pathogens to children and adults are highlighted and discussed as controversies and challenges. Updated knowledge of the molecular and cellular mechanisms involved in the balance between microbiota and immune system for the introspection on the gut–lung–brain axis could reveal the latest benefits and perspectives of applied photobiomics for health. Multiple interconditioning between photobiomodulation (PBM), probiotics, and the human microbiota, their effects on the human body, and their implications for the management of viral infectious diseases is essential. Coupled complex PBM and probiotic interventions can control the microbiome, improve the activity of the immune system, and save the lives of people with immune imbalances. There is an urgent need to seek and develop innovative treatments to successfully interact with the microbiota and the human immune system in the coronavirus crisis. In the near future, photobiomics and metabolomics should be applied innovatively in the SARS-CoV-2 crisis (to study and design new therapies for COVID-19 immediately), to discover how bacteria can help us through adequate energy biostimulation to combat this pandemic, so that we can find the key to the hidden code of communication between RNA viruses, bacteria, and our body.

This single-blind, placebo-controlled study assesses the efficacy of synergic administration of intravenous laser blood irradiation (ILBI) and etanercept in selected subtypes of juvenile idiopathic arthritis (JIA). Etanercept is a tumor necrosis factor alpha blocking agent with recognized importance in JIA. Laser radiation has immunomodulatory effects in animal and human studies. Fourteen patients (Group I) received ILBI and 9 patients (Group II) received placebo laser. ILBI was performed in addition to ongoing JIA medication, including etanercept. ILBI was administrated in 3 sets of 5 consecutive daily sessions, with a 7-week interval between every set of sessions. Evaluation was performed using ACR (American College of Rheumatology) Pediatric Criteria (ACR Pedi) at study enrollment and at 10 and 20 weeks, respectively. After 10 weeks, 85.7% of the patients in Group I fulfilled Pedi 30 criteria, compared to only 55.6% of the patients in Group II. After 20 weeks, all patients in both groups had a Pedi 30 response. In Group I, 92.8% of the subjects met the Pedi 50 response, compared to only 55.6% in the placebo group. One patient in Group I responded best, fulfilling Pedi 70 criteria. If applied synergistically, ILBI and etanercept would have an increased efficacy in promoting JIA remission.