Role of the hydrolytic-acidogenic phase on the removal of bisphenol A and sildenafil during anaerobic treatment.

This paper presents the main results of the removal of two pharmaceutical and personal care products (PPCPs), bisphenol A (BPA) and sildenafil (SDF), by applying anaerobic biological batch tests. The biomass used was previously acclimatized and the experiment lasted 28 days. The effect of factors such as compound (BPA and SDF), concentration and type of inoculum was assessed, considering the factorial experimental design. The results indicated that evaluated factors did not significantly affect the PPCPs elimination in the evaluated range with a confidence level of 95%. On the other hand, the removal percentages obtained with BPA were mainly related to mechanisms, such as sorption and abiotic reactions. Regarding SDF, biodegradation was the predominant mechanism of removal under the experimental conditions of this study; however, the degradation of SDF was partial, with percentages lower than 43% in the tests with hydrolytic/acidogenic inoculum (H/A) and lower than 41% in the tests with methanogenic inoculum (MET). Finally, these findings indicated that hydrolysis/acidogenesis phase is a main contributor to SDF biodegradation in anaerobic digestion. The study provides a starting point for future research that seeks to improve treatment systems to optimize the removal of pollutants from different water sources.

Expert Consensus on the Tapering of Oral Corticosteroids for the Treatment of Asthma. A Delphi Study.

Rationale: There is a need to minimize oral corticosteroid (OCS) use in patients with asthma to prevent their costly and burdensome adverse effects. Current guidelines do not provide recommendations for OCS tapering in patients with asthma.Objectives: To develop expert consensus on OCS tapering among international experts.Methods: A modified Delphi method was used to develop expert consensus statements relating to OCS use, tapering, adverse effects, adrenal insufficiency, and patient-physician shared decision-making. Initial statements proposed by experts were categorized, filtered for repetition, and presented back to experts over three ranking rounds to obtain consensus (≥70% agreement).Measurements and Main Results: One hundred thirty-one international experts participated in the study, and 296 statements were ranked. Numerous recommendations and guidance regarding appropriate OCS use were established. Experts agreed that OCS tapering should be attempted in all patients with asthma receiving maintenance OCS therapy, with personalization of tapering rhythm and speed. The importance of recognizing individual adverse effects was also established; however, a unified approach to the assessment of adrenal insufficiency was not reached. Shared decision-making was considered an important goal during the tapering process.Conclusions: In this Delphi study, expert consensus statements were generated on OCS use, tapering, adverse-effect screening, and shared decision-making, which may be used to inform clinical practice. Areas of nonconsensus were identified, highlighting uncertainty among the experts around some aspects of OCS use in asthma, such as adrenal insufficiency, which underscores the need for further research in these domains.

Efficacy of dietary inclusion of biologically treated pruning peach trees by-products on growth performance, blood biochemicals and economic efficiency of New Zealand White rabbits.

This work examined the influences of partial replacement of clover hay with 15 or 30% of untreated pruning peach trees by-products (UPPT) or those biologically treated (BTPPT) with effective microorganisms (EM1) on growing rabbit performance. Seventy-five NZW weaned rabbits (6-weeks-old; average body weight 657 g) were assigned randomly into five groups. Five pelleted diets were used, control and other four diets (15 or 30% UPPT or BTPPT were replaced of clover hay). The biological treatments improved the chemical composition of pruning peach trees by-product, in terms of increasing crude protein and decreasing crude fiber as compared to UPPT. Final body weight, body weight gain, feed conversion ratio and performance index values were enhanced when rabbits fed either 15 or 30% BTPPT. Digestibilities of crude protein, crude fiber, nitrogen free extract, total digestible nutrients and digestible energy were increased with rabbits fed diets containing BTPPT. Carcass traits studied, moisture, crude protein (CP), ash, ether extract (EE) of rabbits meat, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, total cholesterol, creatinine and urea were not different between the applied treatments. Net revenue and economic efficiency were increased with the biological treatment. Conclusively, BTPPT could be used up to 30% with positive effects on growth performance, physiological functions and economic efficiency in NZW growing rabbits.

Bioremediation of industrial effluents: A synergistic approach.

Industrial wastewater consists of inorganic and organic toxic pollutants that pose a threat to environmental sustainability. The organic pollutants are a menace to the environment and life forms than the inorganic substances and pose teratogenic, mutagenic, carcinogenic, and other serious detrimental effects on the living entities, moreover, they have a gene-altering effect on aquatic life forms and affect the soil fertility and quality. Removal of varying effluents having recalcitrant contaminants with conventional treatment technologies is strenuous. In contrast to physical and chemical methods, biological treatment methods are environmentally friendly, versatile, efficient, and technically feasible with low operational costs and energy footprints. Biological treatment is a secondary wastewater treatment system that utilizes the metabolic activities of microorganisms to oxidize or reduce inorganic and organic compounds and transform them into dense biomass, which later can be removed by the sedimentation process. Biological treatment in bioreactors is an ex situ method of bioremediation and provides the benefits of continuous monitoring under controlled parameters. This paper attempts to provide a review of bioremediation technologies discussing most concerning widespread bioreactors and advances used for different industrial effluents with their comparative merits and limitations.

Biological Treatments for Pediatric Psoriasis: State of the Art and Future Perspectives.

Psoriasis is a chronic systemic inflammatory disease that primarily affects the skin and is associated with multiple comorbidities with a considerable reduction in quality of life of affected patients. One-third of psoriasis cases begin in childhood and are associated with significant medical comorbidities such as obesity, metabolic syndrome, arthritis, and psychiatric disorders. In addition, because of its chronic nature and frequent relapses, psoriasis tends to require long-term treatment. Treatment of pediatric psoriasis usually involves the same methods used for adults. However, most treatments for pediatric psoriasis are used off-label, and research in this regard is still lacking. Targeted therapies involving the use of newly developed biologic drugs are also increasingly being applied to childhood psoriasis. This review summarizes the clinical features of pediatric psoriasis and focuses mainly on the updated concepts of pathogenesis and biological treatments of pediatric psoriasis.

Diagnosis and Management of Severe Asthma in Switzerland: Analysis of Survey Results Conducted with Specialists and General Practitioners.

BACKGROUND: Severe asthma commonly affects 5-10% of the asthmatic population and accounts for approximately 50% of the overall asthma costs. OBJECTIVE: This analysis investigated how severe asthma is diagnosed, treated, and managed by specialists and general practitioners (GPs) in Switzerland. METHODS: Two surveys, one each among specialists (N = 44) and GPs (N = 153), were conducted to understand their self-perception on diagnosis, treatment, and management of severe asthma. RESULTS: Fifty-five percent of the specialists felt very confident and 43% confident in recognizing the symptoms of severe asthma and diagnosing severe asthma. In contrast, 9% of the GPs were very confident and 59% confident in diagnosing severe asthma. More specific diagnostic tests for severe asthma, like total and specific immunoglobulin E levels and measurement of the fraction of exhaled nitric oxide, were run by specialists (χ2 = 171.4; df = 15, p < 0.001). GPs and specialists were using different measurements to assess severe asthma (χ2 = 385.2; df = 13, p < 0.001) and their prescribing patterns differed significantly (χ2 = 189.8; df = 10, p < 0.001). GPs referred patients with severe asthma if the diagnosis was unclear (24%), if treatment failure occurred (26%), and if the patients were at high risk (41%). CONCLUSIONS: Oral corticosteroids (OCSs) are considered as background therapy for severe asthma by GPs and specialists. In order to reduce the OCS burden, there is a need to improve the awareness for other add-on therapies. A joint collaboration between GPs and specialists is the key to leverage therapeutic strategies together.

Adsorptive batch and biological treatments of produced water: Recent progresses, challenges, and potentials.

Produced water is responsible for the largest contribution in terms of waste stream volume associated with the production of oil and gas. Characterization of produced water is very crucial for the determination of its main components and constituents for optimal selection of the treatment method. This review aims to review and critically discuss various treatment options that can be considered cost-efficient and environmentally friendly for the removal of different pollutants from produced water. Great efforts and progresses were made in various treatment options, including batch adsorption processes, membrane filtration, advanced oxidation, biological systems, adsorption, coagulation, and combined processes. Chemical precipitation, membrane filtration, and adsorption have high removal efficiencies that can reach more than 90% for different produced water components. The most effective method among these methods is adsorption using different adsorbents media. In this review, date-pits activated carbons, microemulsions-modified date pits, and cellulose nanocrystals as low-cost adsorbents were thoroughly reviewed and discussed. Moreover, the potential of using biological treatments in the removal of various pollutants from produced water such as conventional activated sludge, sequential batch reactor, and fixed-film biological aerated filter reactors were systematically discussed. Generally, produced water can be utilized in various fields including habitat and wildlife, agricultural and irrigation sector, energy sector, fire control, industrial use also power regeneration. The degree of treatment will depend on the application that produced water is being reused in. For instance, to use produced water in oil and gas industries, water will require minimal treatment while for agricultural and drinking purposes high treatment level will be required. It can also be concluded that one specific technique cannot be recommended that will meet all requirements including environmental, reuse, and recycling for sustainable energy. This is because of various dominant factors including the type of field, platform type, chemical composition, geological location, and chemical composition of the production chemicals.

Economic Evaluation of Sequences of Biological Treatments for Patients With Moderate-to-Severe Rheumatoid Arthritis and Inadequate Response or Intolerance to Methotrexate in France.

OBJECTIVES: Biologic disease-modifying antirheumatic drugs (bDMARDs) are prescribed sequentially in the treatment of rheumatoid arthritis (RA). Healthcare decision makers continue to debate their use, mainly because of their high costs. Our aim was to perform an economic evaluation for France of bDMARD sequences for treatment of moderate-to-severe RA after inadequate response or intolerance to conventional DMARDs (eg, methotrexate). METHODS: A discretely integrated condition event simulation was developed to track the course of patients from first bDMARD through switches to further lines in a sequence. The model included 11 events, 91 conditions, and 21 controlling equations. Inputs were obtained from a meta-analysis of clinical trials, a French registry, national drug lists, and databases. Survival, time with minimal activity, quality-adjusted life-years (QALYs), and total costs were output. Structural and probabilistic sensitivity analyses were conducted. RESULTS: Sequences starting with etanercept biosimilars (ETB) cost less, with ETB-abatacept-infliximab the least expensive: the mean lifetime discounted total cost was €116 912 per patient, with a mean of 11.166 QALYs. Most other strategies were dominated or led to small QALY gains (0.0008-0.0329). Only ETB-tocilizumab-abatacept made it onto the efficiency frontier, but at €955 778 per QALY gained. These results were confirmed in several scenarios and uncertainty analyses. CONCLUSION: Given minor differences in QALYs gained between bDMARD sequences with large cost differences, starting with biosimilars was more efficient than starting with branded products. Our model and findings should provide French and other decision makers with useful tools to address the challenges of comparing sequences of treatments for RA.

Perylene pigment wastewater treatment by fenton-enhanced biological process.

Polycyclic aromatic hydrocarbons (PAHs) are regarded as priority pollutants owing to their toxic, mutagenic and carcinogenic characteristics. Perylene is a kind of 5-ring PAH with biological toxicity, and classified as a class III carcinogen by the World Health Organization (WHO). Nowadays, some of its derivatives are often used as industrial pigments. Hence, urgent attention is highly needed to develop new and improved techniques for PAHs and their derivatives removal from the environment. In this study, Fenton oxidation process was hybridized with the biological (anaerobic and aerobic) treatments for the removal of perylene pigment from wastewater. The experiments were carried out by setting Fenton treatment system before and between the biological treatments. The biological results showed that COD removal efficiency reached 60% during 24 h HRT with an effluent COD concentration of 1567.78 mg/L. After the HRT increased to 48 h, the COD removal efficiency was slightly increased (67.9%). However, after combining Fenton treatment with biological treatment (Anaerobic-Fenton-Aerobic), the results revealed over 85% COD removal efficiency and the effluent concentration less than 600 mg/L which was selected as the better treatment configuration for the biological and chemical combined system. The microbial community analysis of activated sludge was carried out with high-throughput Illumina sequencing platform and results showed that Pseudomonas, Citrobacter and Methylocapsa were found to be the dominant genera detected in aerobic and anaerobic reactors. These dominant bacteria depicted that the community composition of the reactors for treating perylene pigments wastewater were similar to that of the soil contaminated by PAHs and the activated sludge from treating PAHs wastewater. Economic analysis results revealed that the reagent cost was relatively cheap, amounting to 10.64 yuan per kilogram COD. This study vividly demonstrated that combining Fenton treatment with biological treatment was efficient and cost-effective.

Eosinophils: Old Players in a New Game.

Eosinophils are terminal polymorphonuclear cells with a high number of cytoplasmic granules that originate in bone marrow. Some are exosomes, which contain multiple molecules, such as specific eosinophilic proteins, cytokines, chemokines, enzymes, and lipid mediators that contribute to the effector role of these cells. Moreover, exosomes present a large number of receptors that allow them to interact with multiple cell types. Eosinophils play an important role in defense against infestations and are a key element in asthma and allergic diseases. Eosinophils are recruited to the inflamed area in response to stimuli, modulating the immune response through the release to the extracellular medium of their granule-derived content. Various mechanisms of degranulation have been identified. Polymorphonuclear leukocytes contain multivesicular bodies that generate exosomes that are secreted into the extracellular environment. Eosinophilic exosomes participate in multiple processes and mechanisms. Eosinophils participate actively in asthma and are hallmarks of the disease. The cells migrate to the inflammatory focus and contribute to epithelial damage and airway remodeling. Given their relevance in this pathology, new therapeutic tools have been developed that target mainly eosinophils and their receptors. In this manuscript, we provide a global, updated vision of the biology of eosinophils and the role of eosinophils in respiratory diseases, particularly asthma. We also summarize asthma treatments linked to eosinophils and new therapeutic strategies based on biological products in which eosinophils and their receptors are the main targets.

Biologics in juvenile idiopathic arthritis: a narrative review.

In the past years, pediatric rheumatology has seen a revolution in the treatments for rheumatic diseases, particularly juvenile idiopathic arthritis. Even if nonsteroidal anti-inflammatory drugs (NSAID), intra-articular corticosteroids (IAC) injections, and methotrexate remain the mainstay of the treatment for JIA patients, in aggressive disease, these treatments may be not sufficient to reach disease remission and to prevent long-term disability. Comprehension of immunological mechanisms involved in the pathogenesis of the diseases allowed to conceive new drugs targeting specific steps of the immune response. Several cytokines, like TNF alpha and IL-1, represent a very interesting target for biologic therapies. Due to the efficacy of these therapies, nowadays, "disease remission" in pediatric rheumatology is more and more frequent, especially in juvenile idiopathic arthritis patients, and the long-term outcomes have been significantly improved. Crucial to these advancements have been multicenter controlled clinical trials and long-term safety monitoring. CONCLUSIONS: Research in pediatric rheumatology has resulted in dramatic advances in diseases management. Biologic treatments have improved physical and functional outcomes and quality of life of patients with rheumatic disease. What is Known: • NSAID, intra-articular injection of corticoids, and methotrexate are the mainstay in treatment of JIA. • In aggressive JIA, these treatments may be not sufficient to reach disease remission and to prevent long term disability. What is New: • In recent years, management of JIA has significantly improved with the development of biologic therapies that allowed children with arthritis to reach a normal growth and to achieve a good long-term functional outcome.

[Ketamine administration in case of severe, therapy resistant depressed patient, case report]. / Ketamin alkalmazása súlyos, terápiarezisztens depressziós beteg esetében.

Objective - In our case report we present the treatment of a female patient suffering from therapy resistant depression. This procedure is not in practice in Hungary at present, the aim of our work to reproduce the findigs of international studies in domestic circumstances. Matter - Major depression is a common, chronic and severe mental disorder, with 16.2% lifetime prevalence. Many international randomized, placebo controlled trials found administration of ketamine infusion effective in depressed patients. Methods - Since ketamine is an anesthetic agent, its administration was performed in the post-operative monitoring room of our hospital operating-room, supervised by an anesthesiologist. According to formerly published data, a dose of 0.5 mg/kg of body weight was administered intravenously in 40 minutes by perfusor. The drug was administered in a same manner fifteen days later. Subject - The patient was admitted to our inpatient ward with severe depression. During two months of combined antidepressant therapy her condition has not improved significantly. Approval for off label drug indication was granted with urgency by the National Institute of Quality and Organizational Development in Healthcare and Medicines. Results - During the two treatments the Hamilton Depression Rating Scale 21 items rating scale score was reduced to 8 from the baseline 28, the Hamilton Anxiety Rating Scale score was reduced to 6 from 25, Beck Depression Inventory was reduced to 9 from 20. Upon administration of the drug no severe adverse event was detected, the mild dissociative state related to ketamine was ceased in a short period of time. Discussion - With administration of 0.5 mg/kg ketamine the authors managed to achieve rapid improvement in a therapy resistant depressed patient, without permanent side effects. Our future plan is to repeat the use of the drug within a double-blind, placebo controlled trial in order to prove its efficacy in hospital settings.

Why use a thermophilic aerobic membrane reactor for the treatment of industrial wastewater/liquid waste?

This paper describes the advantages of thermophilic aerobic membrane reactor (TAMR) for the treatment of high strength wastewaters. The results were obtained from the monitoring of an industrial and a pilot scale plant. The average chemical oxygen demand (COD) removal yield was equal to 78% with an organic loading rate (OLR) up to 8-10 kgCOD m(-3) d(-1) despite significant scattering of the influent wastewater composition. Total phosphorus (TP) was removed with a rate of 90%, the most important removal mechanism being chemical precipitation (as hydroxyapatite, especially), which is improved by the continuous aeration that promotes phosphorus crystallization. Moreover, surfactants were removed with efficiency between 93% and 97%. Finally, the experimental work showed that thermophilic processes (TPPs) are complementary with respect to mesophilic treatments.

Autoimmunity and Cancer: Two Stations on the Same Continuum.

INTRODUCTION: Autoimmunity has been associated with different types of cancer, including hematological malignancies like lymphomas, and solid tumors. Additionally, the potential role of medication-induced immunosuppression should be considered. AIM: Our study aimed to investigate the relationship between autoimmunity and the development of cancer, as well as the impact of immunosuppressive drugs on increasing cancer risk. METHODS: The study sample was composed of patients who developed cancer after the administration of biological agents for the treatment of autoimmune disorders. Selected patients were treated in our hospital between 1st January 2011 and 31st December 2021 and followed up in internal medicine, gastroenterology, or dermatology consult. From 434 patients with autoimmune diseases using biological agents, only 20 developed cancer, which was our final study sample. The data analysis was performed using the IQVIR package version 2.0.2 (IQVIA, Durham, NC). A p-value of <0.05 was considered statistically significant. RESULTS: We found a significant correlation between long-term corticosteroid therapy and an increased risk of cancer. However, the effect of biological therapies on cancer risk was not statistically significant. It's worth noting that our sample size was small, so we cannot extrapolate these findings. CONCLUSIONS: Physicians need to be aware that treating autoimmune diseases with immunosuppressive therapies may contribute to the development of cancer. Further research is needed to determine the impact of such treatments on cancer prognosis.

Management of methyl mercaptan contained in waste gases - an overview.

Methyl mercaptan is a typical volatile organosulfur pollutant contained in many gases emitted by urban waste treatment, various industries, natural gas handling, refining processes, and energy production. This work is a comprehensive overview of the scientific and practical aspects related to the management of methyl mercaptan pollution. The main techniques, including absorption, adsorption, oxidation, and biological treatments, are examined in detail. For each method, its capability as well as the technical advantages and drawbacks have been highlighted. The emerging methods developed for the removal of methyl mercaptan from natural gas are also reviewed. These methods are based on the catalytic conversion of CH3SH to hydrocarbons and H2S.

Seed bio-priming with beneficial Trichoderma harzianum alleviates cold stress in maize.

Maize is one of the major crops in the world and the most productive member of the Gramineae family. Since cold stress affects the germination, growth, and productivity of corn seeds, the present study aimed to investigate the effect of seed biopriming with Trichoderma harzianum on the tolerance of two genotypes of maize seedlings to cold stress. This study was conducted in triplicates in factorial experiment with a complete randomized block design (CRBD). The study was conducted in the greenhouse and laboratory of the University of Mohaghegh Ardabili, Ardabil, Iran. Experimental factors include two cultivars (AR68 cold-resistant and KSC703 cold-sensitive maize cultivars), four pretreatment levels (control, biopriming with T. harzianum, exogenous T. harzianum, and hydropriming), and two levels of cold stress (control and cold at 5 °C) in a hydroponic culture medium. The present study showed that maize leaves' establishment rate and maximum fluorescence (Fm) are affected by triple effects (C*, P*, S). The highest establishment (99.66%) and Fm (994 units) rates were observed in the KP3 control treatment. Moreover, among the pretreatments, the highest (0.476 days) and the lowest (0.182 days) establishment rates were related to P0 and P3 treatments, respectively. Cultivar A showed higher chlorophyll a and b, carotenoid content, and establishment rate compared to cultivar K in both optimal and cold conditions. The highest root dry weight (11.84 units) was obtained in cultivar A with P3 pretreatment. The pretreatments with T. harzianum increased physiological parameters and seedling emergence of maize under cold and optimal stress conditions. Pretreatment and cultivar improved catalase activity in roots and leaves. Higher leaf and root catalase activity was observed in the roots and leaves of cultivar K compared to cultivar A. The cold treatment significantly differed in peroxidase activity from the control treatment. Cultivar K showed higher catalase activity than cultivar A. The main effects of pretreatment and cold on polyphenol oxidase activity and proline content showed the highest polyphenol oxidase activity and proline content in hydropriming (H) treatment. Cold treatment also showed higher polyphenol oxidase activity and proline content than cold-free conditions.

The economic burden and quality of life of patients with psoriasis treated with biologics in China.

BACKGROUND: Although biologics improve the quality of life of psoriasis patients, they also impose a substantial economic burden. There is a lack of research addressing the economic and humanistic impact of biologics in China. OBJECTIVE: This cross-sectional investigation aims to assess the economic cost, quality of life, and patient satisfaction among individuals with psoriasis treated with biologics and non-biologics. METHODS: From July 2021 to December 2022, eligible patients with psoriasis were recruited through both on-site and online questionnaire completion. The questionnaires collected sociodemographic data, clinical characteristics of psoriasis, economic costs associated with treatment, and the Dermatological Life Quality Index (DLQI). RESULTS: 481 patients with a mean age of 40.8 ± 13.4 years old were included and classified into a non-biologic (n = 195) and biologic (n = 286) treatment group. The direct medical cost for non-biologics patients was 7,249 CNY, accounting for 70.0% of the total cost, while biologics patients incurred 15,176 CNY, making up 94.3% of the total cost. The non-biologic group had higher costs related to hospitalization, self-purchase of drugs, and indirect costs than the biologic treatment group. Additionally, DLQI scores were higher in the non-biologic group. CONCLUSION: Patients in the biologic group experienced a higher economic burden and better quality of life than those in the non-biologic group.

Sequential application of activated sludge and phytoremediation with aquatic macrophytes on tannery effluents: in search of a complete treatment.

Tannery effluents with a high organic matter load (indicated by their COD level) have to be treated before they are discharged, so as to minimize their negative impact on the environment. Using field mesocosm systems, this study evaluated the feasibility of treating such effluents through bioaugmentation with activated sludge, followed by phytoremediation with aquatic macrophytes (Lemnoideae subfamily). Regardless of its quality, the activated sludge was able to remove approximately 77% of the COD from effluents with a low initial organic load (up to 1500 mg/L). The macrophytes then enhanced removal (up to 86%), so the final COD values were permissible under the current legislation for effluent discharge. When the initial organic load in the undiluted effluents was higher (around 3000 mg/L), the COD values obtained after consecutive bioaugmentation and phytoremediation were close to the legally allowed limits (583 mg/L), which highlights the potential of phytoremediation as a tertiary treatment. This treatment also brought total coliform counts down to legally acceptable values, without plant biomass decreasing over time. Moreover, the plant biomass remained viable and capable of high COD removal efficiency (around 75%) throughout two additional reuse cycles. These findings indicate that the efficiency of the biological treatments assayed here depends largely on the initial organic load in the tannery effluents. In any case, the sequential application of activated sludge and aquatic macrophytes proved to be a successful alternative for remediation.

Cost of Illness, Quality of Life, and Work Productivity in Axial Spondyloarthritis Patients Receiving Biological Treatments in Greece.

Objectives: To estimate the cost of illness, quality of life and work productivity in patients with Axial Spondyloarthritis (Axial SpA) under biological treatment in Greece. Methods: We conducted a prospective study of 12-month duration, of patients with Axial SpA from a tertiary hospital in Greece. Adult patients fulfilling the Assessment of SpondyloArthritis international Society (ASAS) criteria were enrolled at the beginning of biological treatment due to active disease [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) >4] and failure of first line treatment. All participants completed questionnaires about quality of life, financial costs and work productivity at the same time with the disease activity assessment. Results: 74 patients of whom 57 (77%) with a paid job, were included in the study. The total annual cost for Axial SpA patients is € 9,012.40 while the average cost of acquisition and administration of the drugs is € 8,364. The mean BASDAI in the 52 weeks of follow-up, was decreased from 5.74 to 3.2 and the mean Health Assessment Questionnaire (HAQ) also from 1.13 to 0.75. Work productivity of these patients as measured with the Work Productivity and Activity Impairment Questionnaire (WPAI), was significantly impaired at the baseline and improved after the initiation of biological treatment. Conclusions: The cost of illness in patients receiving biological treatments in Greece is high. However, these treatments except from the well-established positive effect on disease activity, can improve remarkably the work productivity and quality of life of Axial SpA patients.

Biological treatments for pediatric Netherton syndrome.

Netherton syndrome (NS) is a rare and potentially life-threatening genetic skin disease responsible for skin inflammation and scaling, hair abnormalities and severe allergic manifestations. NS is caused by loss-of-function variants in Serine Peptidase Inhibitor Kazal-Type 5 (SPINK5), encoding the serine protease inhibitor LEKTI. NS patients have a profound skin barrier defect caused by unopposed kallikrein-related proteases activity (KLKs). They develop severe skin inflammation with eczematous-like lesions and high serum IgE levels. Multiomics studies have revealed that the IL-17/IL-36 pathway is the most predominant upregulated pathway in NS. It is associated with a Th2 signature with complement activation in the ichthyosis linearis circumflexa subtype, and with interferon and Th9 activation in the scaly erythrodermic form. Several case reports proved the efficacy of different biotherapies targeting IL-17A, IL-12/IL-23, IL-4R and IL-13R, TNF-a and IL-1ß in pediatric NS patients. Intravenous immunoglobulins (IVIG) have also shown efficacy. These studies showed no severe side effects. At present, IL-17 blockade seems to be the most efficient treatment, but case reports remain limited with small numbers of patients and no placebo-control. Additional pathways must also be explored, and more efficient strategies could be used to block IL-17 and IL-23 pathways. In the future, the combination of specific strategies aiming at repairing the initial skin barrier defect could potentiate the efficacy of biologics. The current reports suggest that biological therapy is safe and often effective at pediatric age. However, controlled clinical trials that include a larger number of patients need to be conducted to reach more reliable conclusions.