Redox Regulation by Priming Agents Toward a Sustainable Agriculture.

Plants are sessile organisms that are often subjected to a multitude of environmental stresses, with the occurrence of these events being further intensified by global climate change. Crop species therefore require specific adaptations to tolerate climatic variability for sustainable food production. Plant stress results in excess accumulation of reactive oxygen species leading to oxidative stress and loss of cellular redox balance in the plant cells. Moreover, enhancement of cellular oxidation as well as oxidative signals has been recently recognized as crucial players in plant growth regulation under stress conditions. Multiple roles of redox regulation in crop production have been well documented, and major emphasis has focused on key redox-regulated proteins and non-protein molecules, such as NAD(P)H, glutathione, peroxiredoxins, glutaredoxins, ascorbate, thioredoxins and reduced ferredoxin. These have been widely implicated in the regulation of (epi)genetic factors modulating growth and health of crop plants, with an agricultural context. In this regard, priming with the employment of chemical and biological agents has emerged as a fascinating approach to improve plant tolerance against various abiotic and biotic stressors. Priming in plants is a physiological process, where prior exposure to specific stressors induces a state of heightened alertness, enabling a more rapid and effective defense response upon subsequent encounters with similar challenges. Priming is reported to play a crucial role in the modulation of cellular redox homeostasis, maximizing crop productivity under stress conditions and thus achieving yield security. By taking this into consideration, the present review is an up-to-date critical evaluation of promising plant priming technologies and their role in the regulation of redox components toward enhanced plant adaptations to extreme unfavorable environmental conditions. The challenges and opportunities of plant priming are discussed, with an aim of encouraging future research in this field toward effective application of priming in stress management in crops including horticultural species.

NLRP3 (rs10754558) gene polymorphism and tumor necrosis factor alpha as predictors for disease activity and response to methotrexate and adalimumab in psoriasis.

BACKGROUND: Psoriasis has a global prevalence of 1-3%, with variations observed across different ethnic groups and geographical areas. Disease susceptibility and response to anti-tumor necrosis factor-α (TNFα) drugs suggest different genetic regulatory mechanisms which may include NLR family pyrin domain containing 3 (NLRP3) polymorphism. Evaluation of the NLRP3 gene polymorphism, the serum level of CRP and TNFα in psoriasis patients and assessment of the NLRP3 (rs10754558) gene polymorphism, CRP and TNFα with disease severity and their role as biomarkers for response to Methotrexate and Adalimumab in psoriasis. The study had a total of 75 patients diagnosed with psoriasis vulgaris, who were compared to a control group of 75 healthy individuals. RESULTS: There was a highly significant difference in NLRP3 genotypes and alleles distribution between psoriasis patients and controls (P = 0.002,0.004). The heterozygote genotype GC (OR = 3.67,95%CI:1.75-7.68, P = 0.0006), was linked with increased risk of psoriasis. Additionally, The GC genotype was significantly associated with nonresponse to psoriasis therapy (OR = 11.7,95%CI:3.24-42.28, P = 0.0002). Regarding serum CRP and TNFα levels, there was a highly statistically significant difference between psoriasis patients and controls (P < 0.0001), and there was also a highly statistically significant difference between responders and non-responders in psoriasis patients regarding PASI 50 (P < 0.0001). CONCLUSIONS: The NLRP3 (rs10754558) genotypes GC was associated with the severe form of psoriasis and with nonresponse to psoriasis medication. Therefore, NLRP3 (rs10754558) gene polymorphism is an important prognostic biomarker in psoriasis patients. The serum TNFα can be used as a predictor for response to therapy in psoriasis patients. More research for evaluation of role of the NLRP3 gene polymorphism in the genetic risks and treatment outcomes associated with psoriasis is still required.

Patient-reported outcome measures and health economics in regenerative periodontal therapy: A systematic review and meta-analysis.

Understanding patient responses to periodontal regeneration is crucial. This systematic review and meta-analysis addressed two key questions: (a) the impact of periodontal regeneration on patient-reported outcome measures (PROMs) for intrabony and furcation involvement and (b) the cost-effectiveness of periodontal regeneration for treating periodontal defects. Twenty-four studies were included, with 20 randomized clinical trials (RCTs) reporting patient-reported outcomes and five (three RCTs and two economic model-based studies) reporting cost-effectiveness outcomes. Results favored regeneration therapy over conventional flap surgery for intrabony defects, showing improvements in qualitative (i.e., amount of regenerated attachment apparatus) and quantitative parameters (i.e., probing and radiographic parameters). In terms of PROMs, regenerative treatments involving barrier membranes resulted in longer chair times and higher rates of complications (such as membrane exposure or edema) compared to flap with biologic agents or access flap alone. Despite this, oral health-related quality of life improved after both regenerative and extraction procedures. Economically, regeneration remained favorable compared to extraction and replacement or open flap debridement alone for periodontal defects. Single-flap variants in open flap debridement yielded similar outcomes to regenerative treatment, offering a potentially cost-effective option. Nevertheless, further discussion on the benefits of less-invasive flap designs is needed due to the lack of histological evaluation.

When should the use of biological agents be considered in persistent oligoarticular juvenile idiopathic arthritis patients?

The purpose of this study was to compare the demographic and clinical characteristics of the groups with and without bDMARDs added to the treatment of persistent oligoarticular juvenile idiopathic arthritis (JIA) patients on methotrexate (MTX) and also to determine the predictors of adding bDMARDs to treatment. This study included 86 oligoarticular JIA patients on MTX. Patients were divided into two groups receiving MTX (n = 69) and MTX plus bDMARD (n = 17). Predictors of adding bDMARDs were investigated by comparing demographic, clinical features and laboratory findings. Gender, age at diagnosis, time elapsed from the onset of symptoms to diagnosis, and disease duration, the number and distribution of affected joint at the time of diagnosis were similar in both groups. The mean JADAS10 at the time of diagnosis were 18.8 ± 4.2 and 19.5 ± 6.4 in the MTX and MTX plus bDMARDs groups, respectively (p = 0.68). JADAS10 at 3rd and 6th month were significantly higher in patients on MTX plus bDMARDs (p = 0.001, p = 0.004, respectively). In multivariate analysis, the risk of adding bDMARD was shown to increase 1.24-fold (p = 0.004, 95% CI: 1.07-1.43) for each point increase on the JADAS 10 at 3rd months. The number (p = 0.64) or type (p = 0.18) of joint involvement at disease onset were not predictors of adding a bDMARD. CONCLUSION: JADAS10 indicating ongoing severe disease activity at 3rd and 6th months rather than baseline JADAS10 is associated with the addition of bDMARDs. WHAT IS KNOWN: • Oligoarticular JIA patients have the best outcomes among JIA categories and respond favorably to first-line therapies such as non-steroidal anti-inflammatory drugs and intraarticular corticosteroid injections. • Clinically inactive disease rates have increased with the widespread use of biological agents in oligoarticular JIA patients who have not responded to initial therapies. WHAT IS NEW: • Approximately one-fifth of patients with persistent oligoarticular JIA on methotrexate may require the addition of a biological disease modifying anti-rheumatic drug during follow-up. • The JADAS10 calculated at 3 and 6 months is a valuable tool to identify patients who should be added biological disease modifying anti-rheumatic drugs in persistent oligoarticular JIA.

Efficacy of Biologics in Patients with Allergic Bronchopulmonary Aspergillosis: A Systematic Review and Meta-Analysis.

BACKGROUND: Treatment of allergic bronchopulmonary aspergillosis (ABPA) is challenging. Biological therapies have been reported as adjunctive treatments for ABPA, primarily in case series or case reports. This study aimed to analyze the efficacy of biologics for managing ABPA both qualitatively and quantitatively. METHODS: All articles on APBA published in October 2023 were searched in PubMed, Web of Science, ClinicalTrials.gov, and Embase databases. The effects of interest were the mean changes from baseline for outcomes, including exacerbation rates, oral corticosteroids usage (OCS), and total immunoglobulin E (IgE) levels. Reported outcomes were quantitatively synthesized by usual or individual patient data (IPD) meta-analyses. PROSPERO registration number: CRD42022373396. RESULTS: A total of 86 studies were included in the systematic review including 346 patients. Sixteen studies on omalizumab were pooled for the usual meta-analysis. Omalizumab therapy significantly reduced exacerbation rates (- 2.29 [95%CI - 3.32, - 1.26]), OCS dosage (- 10.91 mg [95%CI - 18.98, - 2.85]), and total IgE levels (- 273.07 IU/mL [95%CI - 379.30, - 166.84]), meanwhile improving FEV1% predicted (10.09% [95%CI 6.62, 13.55]). Thirty-one studies on dupilumab, mepolizumab, or benralizumab were pooled to perform an IPD meta-analysis, retrospectively. Both dupilumab and mepolizumab significantly reduced exacerbation rates, OCS, and total IgE levels. Benralizumab showed a similar trend, but it was not statistically significant. Tezepelumab showed weak evidence of its effects on ABPA. All five biologics led to milder clinical symptoms (e.g., cough, wheezing) with serious adverse effects that happened once in omalizumab treatment. CONCLUSION: These results indicate the clinical benefit of omalizumab, dupilumab, and mepolizumab in patients with ABPA. Further randomized, controlled studies with a larger sample size and longer follow-up are needed to confirm these findings.

No clear influence of treatment escalation on flare prevention in serologically active clinically quiescent patients with systemic lupus erythematosus: a retrospective cohort study.

This study aimed to clarify the efficacy and safety of treatment escalation by initiating therapeutic agents in serologically active clinically quiescent (SACQ) patients with systemic lupus erythematosus (SLE). We retrospectively evaluated SACQ patients with SLE for ≥ 180 days, with the introduction of a therapeutic agent for SLE defined as exposure. The efficacy endpoints included the time to flare and time to remission, whereas the safety endpoint was the incidence of adverse events. The efficacy endpoints were assessed via Cox proportional hazards model with time-dependent covariates, which included exposure, serological activity, and prednisolone dose. Among 109 SACQ patients, 24 were initiated on the following therapeutic agents for SLE: hydroxychloroquine (10 patients), belimumab (6 patients), and immunosuppressive agents (8 patients). A total of 37 patients experienced a flare (8 and 29 patients during exposure and nonexposure periods, respectively). The time to flare was comparable between the exposure and control groups. Among 68 patients who were not in remission at the start of observation, 27 patients achieved remission (5 and 22 patients during exposure and nonexposure periods, respectively). Although both groups had a similar time to remission, the exposure group treated with belimumab had a significantly higher rate of remission than the control group. The adverse events were more frequent during the exposure period than during the nonexposure period. Thus, this study did not reveal a clear influence of treatment escalation on flare prevention and remission achievement.

Effects of biological agents on glycogen metabolism in psoriasis patients: A systematic review and meta-analysis.

The effectiveness and safety of biological agents for treating psoriasis have been confirmed; however, their effects on glucose metabolism biomarkers in psoriasis patients remain unclear. A systematic review and meta-analysis were performed according to PRISMA guidelines. The final analysis enrolled 12 studies, including eight randomized controlled trial (RCT) (n = 5628 patients) and four observational cohort studies (OBSs) (n = 393 patients). The meta-analysis comprising nine studies (six RCTs and three OBSs) revealed a slight reduction in the levels of HOMA-IR associated with the use of biological therapies in OBS (biological therapies vs. traditional therapies: WMD = -0.2, CI = -0.10 to 0.50, p = 0.02). Although a considerable number of studies were analysed, our review did not show a significant alteration in HOMA-IR levels among patients treated with biological therapies such as IL-17 inhibitors and IL-12/23 inhibitors at weeks 12-16 in RCTs. We also did not observe remarkable alterations in the fasting plasma glucose levels of patients in both OBS and RCT. Additional RCT on a larger scale and duration is required to provide more conclusive evidence regarding the effect of biological agents on glycogen metabolism in psoriasis.

Chronic rhinosinusitis with nasal polyposis and biological agents: the ARIA-ITALY Survey.

Summary: Background. Chronic rhinosinusitis (CRS) is an inflammatory disease that affects the nasal mucosa and the paranasal sinuses. CRS can be associated by nasal polyposis (CRSwNP phenotype) in up to 30% of patients and it is frequently associated with bronchial asthma. CRSwNP shows predominantly an underlying activation of type 2 inflammatory pathways with the involvement of eosinophils, IgE, interleukin (IL)-4, IL-5 and IL-13. Biological drugs that target these inflammatory cytokines are currently a therapeutic option recognized by guidelines for the treatment of uncontrolled form of the disease. Methods. As part of the activity of the "ARIA-Italy" working group, a panel of 255 Italian Ear, Nose and Throat (ENT) specialists, pneumologists and immuno-allergologists actively participated in this national survey and answered a series of questions geared toward understanding the main criteria for patient characterization and therapeutic decision, highlighting multidisciplinarity, and the implementation of the management of CRSwNP patients, as a part of the precision medicine concept and the appropriate use of the biologicals. Results. Two hundred and fifty-five experts and specialists participated in the survey. Conclusions. The results of this survey obtained from an extensive number of active specialists throughout Italy allow some important concluding remarks to be drawn. The main points of agreement were that multidisciplinary care teams provide many benefits but that, once the team is established, meetings and communication between members must be coordinated. Finally, the dissemination of national disease registries and the continuous updating of guidelines and position papers related to CRSwNP and comorbidities should be encouraged.

The relationship between TNF-α, IL-1, IL-12, IL-17, IL-23, IL-36 expression and treatment response in psoriasis histopathologically and immunohistochemically.

AIM: There is no marker that can predict whether there is resistance to treatment in patients with psoriasis. In this study, we investigated the relationship between the staining rates of TNF-α, IL-1, IL-12, IL-17, IL-23, and IL-36 markers immunohistochemically from cutaneous biopsy and the treatment success. METHODS: The patients who were followed up in the dermatology clinic with the diagnosis of plaque-type psoriasis vulgaris and received biological treatment and previously had cutaneous biopsy were included in the study. The cutaneous biopsies of the cases that met the conditions were re-sectioned and subjected to immunohistochemical examination for TNF-α, IL-1, IL-12, IL-17, IL-23, and IL-36. RESULTS: Comparing the staining scores with psoriasis area severity index (PASI); A statistically significant positive correlation was found between PASI and TNF-α staining score (p = 0.034). A statistically significant positive correlation was found between PASI and IL-17 staining score (p = 0.004). When the staining scores and PASI response rates of psoriasis treatment were evaluated in terms of correlation; there was a positive correlation between TNF-α, IL-17, and IL-23 immunohistochemical staining rates and PASI response rates. CONCLUSIONS: In line with the data obtained from our study, we think that making immunohistochemical scoring before the biological treatment decision in psoriasis patients will be beneficial in treatment selection. In this respect, our study may open a new era in the selection of biological treatments for psoriasis.

Real-life management of psoriasis with biological agents during pregnancy.

BACKGROUND: French guidelines recommend stopping biologic treatment of psoriasis between 3 and 24 weeks before conception in accordance with the relevant Summary of Product Characteristics (SmPC). The aim of this study was to evaluate the real-life practice of dermatologists in the management of pregnant women with psoriasis previously treated with biologic agents. We wished to assess the level of practitioner adherence to the relevant SmPCs. MATERIAL AND METHODS: We conducted a study in collaboration with GRPso and Resopso. A computerized questionnaire was completed by the practitioners. We performed descriptive statistics and studied the profile of the practitioners, their level of confidence with continuation of biological agents during pregnancy, and their reported practices on the use of biological agents in pregnancy. Statistical analyses were performed using XLSTAT. A p-value of less than 0.05 was considered significant. RESULTS: A total of 63 dermatologists (women: 71%; mean age 43.8 years) participated in this study, the majority of whom were hospital-based (87%). Recommendations were followed by 36.5% of practitioners, while 44% reported discontinuing biologic agents on diagnosis of pregnancy, and 20.5% reported using these agents during pregnancy. Among dermatologists with more than ten years of experience, 19% reported following the SmPC. Among dermatologists with a patient base >200 (patients treated with biologic agents for psoriasis), 19% reported following the SmPC compared to 54% of practitioners with less than 50 patients. The mean age of dermatologists following the SmPC was 41 years vs. 47 years for those not following the SmPC. DISCUSSION: The majority of practitioners do not follow recommendations on discontinuation of biologic agents before the planning of pregnancy by patients.

Treatment selection in the clinical practice of systemic lupus erythematosus: results from the Kyushu Collagen Disease Network for Systemic Lupus Erythematosus (KCDN-SLE) registry.

OBJECTIVES: This study aimed to describe the treatment selection for systemic lupus erythematosus (SLE) using data from the Kyushu Collagen Disease Network for SLE (KCDN-SLE) registry, a multicenter prospective registry in Japan. METHODS: This study used data from patients registered between August 2022 and November 2023. Clinical characteristics, purpose of agent initiation, other candidate agents, and short-term efficacy and safety were evaluated. RESULTS: We analyzed 69 previously treated patients with SLE (mean age 43.7 years; 62 females, 7 males). Hydroxychloroquine, biological agents, and immunosuppressive agents were initiated during the maintenance phase in 12, 41, and 16 patients, respectively. In patients with active organ involvement, hydroxychloroquine and biological agents were widely used for initiation. In those who already achieved treatment goals, biological agents alone were predominantly selected. The SLE Disease Activity Index 2000 score and prednisolone dose declined significantly over a 6-month follow-up period. Among 48 patients with active disease, 22 achieved a lupus low disease activity state, but this had no evident association with the initiation of a biological agent. In total, 14 adverse events, predominantly infections, were observed. CONCLUSIONS: Biological agents were used preferentially, and the therapeutic agents were appropriately effective and mostly achieved the purpose of agent initiation.

The Effectiveness of Biological Agents on Chronic Rhinosinusitis with Nasal Polyposis in Patients with Comorbid Asthma: A Multicenter Real-Life Study from Türkiye.

Background and Objectives: Real-life data on the efficacy of biologic agents (BAs) on asthma-comorbid CRSwNP are needed. Our primary goal is to investigate the effects of BAs on CRSwNP symptoms, as well as endoscopic and tomography scores. Our secondary goal is to show a reduction in the frequency of acute sinusitis exacerbations and the need for surgery. Materials and Methods: We conducted a multicenter, retrospective, real-life study. We screened the patients with asthma-comorbid CRSwNP treated with omalizumab or mepolizumab. A total of 69 patients (40 F/29 M; omalizumab n = 55, mepolizumab n = 14) were enrolled. We compared the visual analog scale (VAS), sinonasal outcome test-22 (SNOT-22), nasal congestion score (NCS), Lund-Mackay computed tomography score (LMS), and total endoscopic polyp scores (TPS) before and after BAs. We evaluated the endoscopic sinus surgery (ESS) and acute exacerbations of chronic rhinosinusitis (AECRS) frequencies separately, according to the BAs. Results: The overall median (min-max) age was 43 (21-69) years. The median (min-max) of biologic therapy duration was 35 (4-113) months for omalizumab and 13.5 (6-32) for mepolizumab. Significant improvements were seen in VAS, SNOT-22, and NCS with omalizumab and mepolizumab. A significant decrease was observed in TPS with omalizumab [95% CI: 0-4] (p < 0.001), but not with mepolizumab [95% CI: -0.5-2] (p = 0.335). The frequency of ESS and AECRS were significantly reduced with omalizumab [95% CI: 2-3] (p < 0.001) and [95% CI: 2-5] (p < 0.001); and mepolizumab [95% CI: 0-2] (p = 0.002) and [95% CI: 2-8.5] (p < 0.001), respectively. There was no significant difference in LMS with either of the BAs. Conclusions: Omalizumab and mepolizumab can provide a significant improvement in the sinonasal symptom scores. BAs are promising agents for CRSwNP patients with frequent exacerbations and multiple surgeries.

Biological and chemical contamination of illegal, uncontrolled refuse storage areas in Poland.

This study focused on assessing the microbiological and chemical contamination of air, soil and leachate in uncontrolled refuse storage areas in central Poland. The research included an analysis of the number of microorganisms (culture method), endotoxin concentration (gas chromatography-mass spectrometry), heavy metals level (atomic absorption spectrometry), elemental characteristics (elemental analyser), cytotoxicity assessment against A-549 (human lung) and Caco-2 (human colon adenocarcinoma) cell lines (PrestoBlue™ test) and toxic compound identification (ultra-high-performance liquid chromatography-quadrupole time-of-flight ultrahigh-resolution mass spectrometry). Microbial contamination differed depending on the dump and the group of tested microorganisms. The number of bacteria was: 4.3 × 102 - 1.8 × 103 CFU m-3 (air); 1.1 × 103 - 1.2 × 106 CFU mL-1 (leachate); 1.0 × 106 - 3.9 × 106 CFU g-1 (soil). Respectively, for air and soil the number of fungi was: 2.2 × 102 - 4.6 × 102 CFU m-3; 1.8 × 102 - 3.9 × 103 CFU g-1. Metal levels (Fe, Mn, Pb, Zn, Al, Hg, Cd, Cu, Cr) were higher than in the control sample; however, the average concentrations did not exceed the permissible standards. The cytotoxicity of soil and leachate samples depended on the dump, sample and cell line tested. The leachates were more cytotoxic than soil extracts. Compounds belonging to pesticides, surfactants and biocides, chemicals and/or polymer degradation products, medicinal drugs and insect repellents were found. The detection of potential pathogens in the air, soil and leachate, the presence of toxic compounds and the confirmation of the cytotoxic effect of leachate and soil on human cell lines justify the need for further research on the risks posed by illegal dumps. These studies should aim at developing a unified assessment method and a method to minimise the risk of contaminants spreading in the environment, including harmful biological agents.

Cogan's syndrome is more than just keratitis: a case-based literature review.

BACKGROUND: Cogan's syndrome (CS) is a rare autoimmune disorder characterized by non-syphilitic interstitial keratitis (IK) and Menière-like cochlear vestibular symptoms, which may also have systemic effects. Corticosteroids are first-line treatment. DMARDs and biologics have been used to treat ocular and systemic symptoms of CS. CASE PRESENTATION: This is a case of a 35-year-old female who reported hearing loss, eye redness and photophobia. Her condition progressed to a sudden sensorineural hearing loss, tinnitus, and constant vertigo accompanied by cephalea. CS was diagnosed after excluding other diseases. The patient still developed bilateral sensorineural hearing loss after receiving hormone, methotrexate, cyclophosphamide, and a variety of biological agents. Joint symptoms were relieved after treatment with a JAK inhibitor (tofacitinib), and hearing did not deteriorate further. CONCLUSIONS: CS should be involved in the differential diagnosis of keratitis. Early identification and intervention of this autoimmune disease can minimize disability and irreversible damage.

Effects of sulfasalazine in axial spondyloarthritis on COVID-19 outcomes: real-life data from a single center.

INTRODUCTION: Compared to biological agents, little is known about the impact of sulfasalazine therapy on COVID-19 outcomes in patients with Axial Spondyloarthritis (AxSpA). Therefore, we aimed to evaluate the COVID-19 severity in AxSpAs receiving sulfasalazine and biologic-agent. MATERIALS AND METHODS: A total of 219 SARS-CoV-2 positive AxSpA patients were retrospectively analyzed. COVID-19 pneumonia, hospitalization rate, and length of stay were used to determine COVID-19 severity. AxSpA patients were mainly grouped and compared as sulfasalazine and non-sulfasalazine. Afterward, we excluded no-treatment patients to reveal the drug's effects more clearly and regrouped AxSpA patients as sulfasalazine-monotherapy (34.3%), biologic-monotherapy (33.7%), and sulfasalazine + biologic (7.3%). RESULTS: Fifty-nine percent of the patients were male and the mean age was 45.0 years. Peripheral arthritis was 35% and uveitis 15%. In total, 41.5% of them have received sulfasalazine and 41.0% biologic agents, and the remaining patients with no AxSpA-specific treatment. In the first comparison, the sulfasalazine group had a higher age, more frequent COVID-19 pneumonia, hospitalization, and longer hospitalization than a non-sulfasalazine group. In the pairwise comparison of 3 treatment groups, the demographic and clinical features, the hospitalization rate and the length of hospital stay were similar but the sulfasalazine-monotherapy group had a higher frequency of COVID-19 pneumonia than the biologic-monotherapy group (23% vs. 7%, p = 0.008). CONCLUSION: Our results imply sulfasalazine may be related to more severe COVID-19 in AxSpA patients. These patients should be followed more carefully in the presence of COVID-19, regardless of reasons such as age, comorbidity, and extra-axial disease, and consideration of discontinuing sulfasalazine maybe even thought.

Immune Reactions in Major Types of Oncological Treatment.

In recent years, there has been a noticeable development in oncological treatment, including chemotherapy and biological treatment. Despite their significant effectiveness, they are not free from side effects, such as allergic and dermatological reactions. These reactions can vary in severity and outcome, including potential death. Examples, among others, are type I-IV hypersensitivity reactions of various origins and skin reactions including rashes, itching and redness, but also severe cutaneous syndromes. Due to the therapy used, these may include Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms, drug-induced hypersensitivity syndrome and acute generalized exanthematous pustulosis. In some cases, it is necessary to interrupt therapy, which may result in a poorer outcome and shorten the patient's survival. This paper reviews various types of research documents published since 2016. It aims to systematize the latest knowledge and highlight the need for further research into ways to avoid adverse reactions.

Immunogenicity and Safety of Adjuvanted Recombinant Zoster Vaccine in Rheumatoid Arthritis Patients on Anti-Cellular Biologic Agents or JAK Inhibitors: A Prospective Observational Study.

Rheumatoid arthritis (RA) patients on JAK inhibitors (JAKi) have an increased HZ risk compared to those on biologic DMARDs (bDMARDs). Recently, the Adjuvanted Recombinant Zoster Vaccine (RZV) became available worldwide, showing good effectiveness in patients with inflammatory arthritis. Nevertheless, direct evidence of the immunogenicity of such a vaccine in those on JAKi or anti-cellular bDMARDs is still lacking. This prospective study aimed to assess RZV immunogenicity and safety in RA patients receiving JAKi or anti-cellular bDMARDs that are known to lead to impaired immune response. Patients with classified RA according to ACR/EULAR 2010 criteria on different JAKi or anti-cellular biologics (namely, abatacept and rituximab) followed at the RA clinic of our tertiary center were prospectively observed. Patients received two shots of the RZV. Treatments were not discontinued. At the first and second shots, and one month after the second shot, from all patients with RA, a sample was collected and RZV immunogenicity was assessed and compared between the treatment groups and healthy controls (HCs) receiving RZV for routine vaccination. We also kept track of disease activity at different follow-up times. Fifty-two consecutive RA patients, 44 females (84.61%), with an average age (±SD) of 57.46 ± 11.64 years and mean disease duration of 80.80 ± 73.06 months, underwent complete RZV vaccination between February and June 2022 at our center. At the time of the second shot (1-month follow-up from baseline), anti-VZV IgG titer increased significantly in both groups with similar magnitude (bDMARDs: 2258.76 ± 897.07 mIU/mL; JAKi: 2059.19 ± 876.62 mIU/mL, p < 0.001 for both from baseline). At one-month follow-up from the second shot, anti-VZV IgG titers remained stable in the bDMARDs group (2347.46 ± 975.47) and increased significantly in the JAKi group (2582.65 ± 821.59 mIU/mL, p = 0.03); still, no difference was observed between groups comparing IgG levels at this follow-up time. No RA flare was recorded. No significant difference was shown among treatment groups and HCs. RZV immunogenicity is not impaired in RA patients on JAKi or anti-cellular bDMARDs. A single shot of RZV can lead to an anti-VZV immune response similar to HCs without discontinuing DMARDs.

Uncovering the Underworld of Axial Spondyloarthritis.

Axial spondyloarthritis (axial-SpA) is a multifactorial disease characterized by inflammation in sacroiliac joints and spine, bone reabsorption, and aberrant bone deposition, which may lead to ankylosis. Disease pathogenesis depends on genetic, immunological, mechanical, and bioenvironmental factors. HLA-B27 represents the most important genetic factor, although the disease may also develop in its absence. This MHC class I molecule has been deeply studied from a molecular point of view. Different theories, including the arthritogenic peptide, the unfolded protein response, and HLA-B27 homodimers formation, have been proposed to explain its role. From an immunological point of view, a complex interplay between the innate and adaptive immune system is involved in disease onset. Unlike other systemic autoimmune diseases, the innate immune system in axial-SpA has a crucial role marked by abnormal activity of innate immune cells, including γδ T cells, type 3 innate lymphoid cells, neutrophils, and mucosal-associated invariant T cells, at tissue-specific sites prone to the disease. On the other hand, a T cell adaptive response would seem involved in axial-SpA pathogenesis as emphasized by several studies focusing on TCR low clonal heterogeneity and clonal expansions as well as an interindividual sharing of CD4/8 T cell receptors. As a result of this immune dysregulation, several proinflammatory molecules are produced following the activation of tangled intracellular pathways involved in pathomechanisms of axial-SpA. This review aims to expand the current understanding of axial-SpA pathogenesis, pointing out novel molecular mechanisms leading to disease development and to further investigate potential therapeutic targets.

Intestinal Behcet's Disease: A Review of the Immune Mechanism and Present and Potential Biological Agents.

Behcet's disease (BD) is a chronic and recurrent systemic vasculitis involving almost all organs and tissues. Intestinal BD is defined as BD with predominant gastrointestinal involvement, presenting severe complications such as massive gastrointestinal hemorrhage, perforation, and obstruction in some cases. To some extent, intestinal BD is classified as a member of inflammatory bowel disease (IBD), as it has a lot in common with classical IBD including Crohn's disease (CD) and ulcerative colitis (UC). Certainly, the underlying pathogenesis is not the same and dysregulation of immune function is believed to be one of the main pathogeneses in intestinal BD, although the etiology has not been clear up to now. Biological agents are an emerging category of pharmaceuticals for various diseases, including inflammatory diseases and cancers, in recent decades. Based on the deep understanding of the immune mechanism of intestinal BD, biological agents targeting potential pathogenic cells, cytokines and pathways are optimized options. Recently, the adoption of biological agents such as anti-tumor necrosis factor agents has allowed for the effective treatment of patients with refractory intestinal BD who show poor response to conventional medications and are faced with the risk of surgical treatment. In this review, we have tried to summarize the immune mechanism and present potential biological agents of intestinal BD.

Gain of Function and Loss of Control: Genetic Modification of Microbial Agents - Viruses "On Steroids".

Gain of Function refers to genetic modification to enhance certain properties of a biological agent. "Dual use research" refers to experiments which have a primary goal of benefitting humanity, but which could produce harm if misapplied. So, for example, a virus which was being genetically modified (GM) for altruistic reasons might become more transmissible or resistant to vaccines or antimicrobial medications. Such a GM virus has bioterrorism potential. The UN Biological Weapons Convention has not been universally approved and 10 States are not signatories to the Convention. The control of such experiments is variously controlled in certain jurisdictions but in Australia these experiments are well regulated through the Gene Technology Act 2000 (Cth), the National Health Security Act 2007 (Cth) and the Crimes (Biological Weapons) Act 1976 (Cth). The controls on such experiments in Europe and the United States are less precise. There are examples in the United States and Europe where the security provisions to contain microorganisms undergoing research including genetic modification have been breached. This threatens the health and safety of laboratory workers and the wider community.