Simultaneous Use Research Articles

‘Tracking Together’—Simultaneous Use of Human and Dog Activity Trackers: Results from a Factorial, Randomized Controlled Trial

‘Tracking Together’—Simultaneous Use of Human and Dog Activity Trackers: Results from a Factorial, Randomized Controlled Trial

A Novel, Rapid Response Renewable Biopolymer Neutron and Gamma Radiation Solid-State Detector for Dosimetry and Nuclear Reactor Flux-Power Mapping

A novel solid-state neutron and gamma radiation monitor-dosimeter based on biopolymer polylactic acid (PLA) is presented. The resulting detector (PLAD) technology takes advantage of property changes of the renewable PLA resin when subject to ionizing nuclear radiation. A simple yet rapid and accurate (±10%) low-cost (<$0.01/detector) mass loss upon dissolution (MLD) technique was successfully developed; MLD is based on a simple mass balance for discerning neutron and/or gamma doses using small (40 mg, ~4 mm diameter) ultra-low-cost (<$0.01) resin beads via dissolution in acetone. The GammaCellTM Co-60 irradiator, and the PUR-1 12 kW fission nuclear research reactor were utilized, respectively. Irradiation absorbed doses ranged from 1 to 100 kGy. Acetone bath temperature was varied from ~40 °C to ~54 °C. Results revealed a strong dependence of MLD on acetone bath temperature between neutron and gamma photon dose components; this allowed for the unique ability of PLAD to potentially perform as both a neutron-cum-gamma or as a gamma or neutron radiation dosimeter and intensity level detector. A linear trend is found for combined neutron and gamma radiation doses from 0 to 40 kGy when dissolution is conducted above 50 °C. The important potential ability to distinguish neutron from gamma radiation fields was scoped and found to be feasible by determining MLD at 45 °C. The potential was studied for simultaneous use as an in-core neutron and gamma monitor of an operating 3 GWt light-water reactor (LWR). Scoping tests were conducted with the pre-irradiated (@ 20 °C) PLAD resin beads followed by heating to in-core LWR coolant (300 °C) conditions for ~30 s corresponding to the time to reach ~40 kGy total doses in a typical 3 GWt LWR. MLD results were unaffected, indicating the exciting and unique potential for in situ (low-cost, accurate and rapid) simultaneous mapping of neutron and gamma radiation fluxes, related dosimetry, and fission power level monitoring.

Review of Predicting Synergistic Drug Combinations.

The prediction of drug combinations is of great clinical significance. In many diseases, such as high blood pressure, diabetes, and stomach ulcers, the simultaneous use of two or more drugs has shown clear efficacy. It has greatly reduced the progression of drug resistance. This review presents the latest applications of methods for predicting the effects of drug combinations and the bioactivity databases commonly used in drug combination prediction. These studies have played a significant role in developing precision therapy. We first describe the concept of synergy. we study various publicly available databases for drug combination prediction tasks. Next, we introduce five algorithms applied to drug combinatorial prediction, which include traditional machine learning methods, deep learning methods, mathematical methods, systems biology methods and search algorithms. In the end, we sum up the difficulties encountered in prediction models.

Oxidative Cross Dehydrogenative Coupling of N-Heterocycles with Aldehydes through C(sp3)-H Functionalization.

Existing methodologies for metal-catalyzed cross-couplings typically rely on preinstallation of reactive functional groups on both reaction partners. In contrast, C-H functionalization approaches offer promise in simplification of the requisite substrates; however, challenges from low reactivity and similar reactivity of various C-H bonds introduce considerable complexity. Herein, the oxidative cross dehydrogenative coupling of α-amino C(sp3)-H bonds and aldehydes to produce ketone derivatives is described using an unusual reaction medium that incorporates the simultaneous use of di-tert-butyl peroxide as an oxidant and zinc metal as a reductant. The method proceeds with a broad substrate scope, representing an attractive approach for accessing α-amino ketones through the formal acylation of C-H bonds α to nitrogen in N-heterocycles. A combination of experimental investigation and computational modeling provides evidence for a mechanistic pathway involving cross-selective nickel-mediated cross-coupling of α-amino radicals and acyl radicals.

Effect of ventilation patterns on indoor thermal comfort and air-conditioning cooling and heating load using simulation

Over the past three years, regulations have been implemented to combine natural ventilation (NV) and air conditioning to mitigate the risk of disease transmission, particularly in response to the COVID-19 outbreak. As we know, simultaneous use of NV and air conditioning can make it challenging to achieve indoor thermal comfort. This paper aims to analyze the effect of NV on the air conditioning`s cooling and heating load in a classroom through simulation. A simulation model was developed using EnergyPlus software with an OpenStudio interface software. Simulation results demonstrate that continuous use of NV alongside an air conditioner increases the cooling load from 1.06 to 1.75 times during summer and a 1.54 to 9.49 times heating load increase during winter. On the other hand, intermittent NV every hour results in a cooling load increase from 1.05 to 1.46 times in summer and a heating load increase from 1.13 to 4.63 times in winter. Moreover, employing NV based on the outside air temperature can reduce the cooling load at the air conditioner with set-point 26℃—28℃ from 0.94 to 0.88 times. The outcomes of this study are expected to serve as a reference for determining strategies that effectively combine NV and air conditioning to meet various needs without causing a significant increase in energy consumption. Additionally, the results are expected to be useful for reducing AC energy consumption in extremely hot and cold weather with some strategies of NV application.

Changes in markers of collagen metabolism in the blood serum of white rats during the filling of femur defects with implants based on polylactide and tricalcium phosphate with allogeneous mesenchymal stem cells

The use of synthetic materials in combination with osteogenesis stimulators is one of the advanced directions of the development of traumatology. The purpose of the study: based on the analysis of biochemical markers of collagen metabolism in the blood serum of laboratory rats with a femur defect, to evaluate the course of bone remodeling after filling the defect with implants based on polylactide and tricalcium phosphate with simultaneous and delayed administration of allogeneic mesenchymal stem cells (MSCs). On the model of a defect in the metaphysis of the femur in white rats, the indicators of collagen exchange in blood serum were studied: the content of protein-bound, free fractions, the amount of hydroxyproline (HOP), the ratio of the content of protein-bound HOP to free PB/F was calculated. Comparison of the results of different groups was performed using the Student-Fisher method. The difference was considered statistically significant if p<0.05. Filling the defect with implants led to a decrease in the content of protein-bound HOP by 16.69 % and 14.34 % on the 15th and 90th days (p<0.05), an increase in the content of free HOP by 74.96 %; 67.31 % and 56.74 % (p<0.001), the content of the amount of HOP by 25.37 %; 23.66 % and 18.28 % (p<0.05), and reduction of PB/F by 52.20 %; 49.90 % and 45.30 % (p<0.001) relative to intact on the 15th; 30th and 90th days. Addition of MSCs to the implants at the same time as the installation caused a decrease in the content of free HOP by 63.90 %; 54.63 % and 42.76 % on the 15th; on the 30th and 90th days (p<0.001), the total metabolite by 21.87 % and 18.58 % on the 15th and 30th days (p<0.05) and a decrease in PB/F by 47, 50 %; 43.20 %; 37.60 % on the 15th; on the 30th and 90th days (p<0.001) relative to the intact. Postponing the introduction of MSCs increased the content of free HOP by 40.48 % (p<0.001); 20.49 % and 16.58 % (p<0.05) with a lower PB/F by 38.20 %; 25.80 % and 23.40 % (p<0.05) on the 15th; 30th and 90th days relatively intact. When the defect was filled with implants without MSCs, a moderate inhibition of anabolism and rapid activation of collagen destruction was observed. With the simultaneous use of implants and MSCs, the rate of formation and intense destruction of collagen was observed. When the introduction of MSCs was delayed, a moderate rate of destruction was recorded, which most contributed to collagen metabolism.

Changes in the Gut Microbiota Composition during Implantation of Composite Scaffolds Based on Poly(3-hydroxybutyrate) and Alginate on the Large-Intestine Wall.

The development of biopolymer scaffolds for intestine regeneration is one of the most actively developing areas in tissue engineering. However, intestinal regenerative processes after scaffold implantation depend on the activity of the intestinal microbial community that is in close symbiosis with intestinal epithelial cells. In this work, we study the impact of different scaffolds based on biocompatible poly(3-hydroxybutyrate) (PHB) and alginate (ALG) as well as PHB/ALG scaffolds seeded with probiotic bacteria on the composition of gut microbiota of Wistar rats. Implantation of PHB/ALG scaffolds on the large-intestine wall to close its injury showed that alpha diversity of the gut microbiota was not reduced in rats implanted with different PHB/ALG scaffolds except for the PHB/ALG scaffolds with the inclusion of Lactobacillus spheres (PHB/ALG-L). The composition of the gut microbiota of rats implanted with PHB/ALG scaffolds with probiotic bacteria or in simultaneous use of an antimicrobial agent (PHB/ALG-AB) differed significantly from other experimental groups. All rats with implanted scaffolds demonstrated shifts in the composition of the gut microbiota by individual operational taxonomic units. The PHB/ALG-AB construct led to increased abundance of butyrate-producing bacteria: Ileibacterium sp. dominated in rats with implanted PHB/ALG-L and Lactobacillus sp. and Bifidobacterium sp. dominated in the control group. In addition, the PHB/ALG scaffolds had a favourable effect on the growth of commensal bacteria. Thus, the effect of implantation of the PHB/ALG scaffold compared to other scaffolds on the composition of the gut microbiota was closest to the control variant, which may demonstrate the biocompatibility of this device with the microbiota.

From a mutation to a drug

Malignant melanoma is a dangerous skin cancer, accounting for the majority of skin cancer-related deaths. Many patients with this cancer have the V600E mutation in the BRAF gene. This mutation causes constitutive activation of the MAPK/ERK signaling pathway, significantly contributing to the process of carcinogenesis. We discuss the drug design process on the example of a specific BRAF V600E inhibitor, vemurafenib. We begin with the most commonly used drug design methods. The second part of the article focuses on vemurafenib. We analyze the invention of this BRAF V600E inhibitor and its analogue as well as the course of three stages of clinical trials. Then we provide information about other popular drugs for malignant melanoma, i.e. dacarbazine, ipilimumab and dabrafenib, and about the advantages of therapy with the simultaneous use of two inhibitors. Finally, we briefly discuss the role of artificial intelligence in the future of drug design.

One-stage cartilage repair using the autologous matrix-induced chondrogenesis combined with simultaneous use of autologous adipose tissue graft and adipose tissue mesenchymal cells technique: clinical results and magnetic resonance imaging evaluation at five-year follow-up

PurposeTo evaluate medium-term outcomes of knee cartilage defects repair by autologous matrix-induced chondrogenesis combined with simultaneous use of autologous adipose tissue graft and adipose tissue mesenchymal cells, defined as LIPO-AMIC technique.MethodsThe LIPO-AMIC technique has been used in ICRS degree III–IV knee defects. Eighteen patients have been prospectively evaluated during two and five years both clinically and by MRI.ResultsPatients showed progressive significant improvement of all scores starting early at six months, and further increased values were noted till the last follow-up at 60 months. Mean subjective pre-operative IKDC score of 36.1 significantly increased to 86.4 at 24 months and to 87.2 at 60 months. Mean pre-operative Lysholm score of 44.4 reached 93.5 at two years and 93.5 at five years. MRI examination showed early subchondral lamina regrowth and progressive maturation of repair tissue and filling of defects. The mean total MOCART score showed that a significative improvement from two year follow-up (69.1 points) to last follow-up was 81.9 points (range, 30–100 points, SD 24). Complete filling of the defect at the level of the surrounding cartilage was found in 77.8%.ConclusionsAdipose tissue can represent ideal source of MSCs since easiness of withdrawal and definite chondrogenic capacity. This study clearly demonstrated the LIPO-AMIC technique to be feasible for treatment of knee cartilage defects and to result in statistically significant progressive clinical, functional and pain improvement in all treated patients better than what reported for the AMIC standard technique, starting very early from the 6-month follow-up and maintaining the good clinical results more durably with stable results at mid-term follow-up.

Electronic digital devices and a risk of functional disorders of the visual analyzer in students of different age

The aim of our study was to perform hygienic assessment of use of electronic digital devices and its relationship with likely disorders of the visual analyzer in students of different age. Our research object is represented by students of different age (5th grade (n = 55), 11th grade (n = 67) and the 6th year of HEI (n = 102)). This study focused on examining a relationship between disorders of the visual analyzer and use of electronic digital devices (EDDs) by students of different ages (5th and 1th grades in school, 6th year in HEI). We conducted social research by using a group indirect survey that relied on a specifically designed questionnaire consisting of 13 questions. Answers were collected by using Google Forms online platform. Students were established to use a smartphone (99.6 % of the respondents) and / or laptop (83 %) in their everyday activities. We analyzed duration of an activity involving use of various devices and established that 95 % of the respondents did not adhere to the existing hygienic standards when using EDDs and spent more than 4 hours a day on using them. The regression analysis revealed an association between myopia development and simultaneous use of various EDDs (R2 = 0.68; р < 0.0001). A contribution made to developing eyesight disorders by working with a laptop equaled 62 % whereas contributions made by watching TV and use of smart-watch equaled 19 % and 10 % respectively. Our assessment of a relative risk established that use of a laptop (PC) for more than 4 hours a day increased likelihood of myopia by 8.6 times (RR = 8.6; 95 % CI = 1.4–54.9, р < 0.05). Development of other functional disorders in school students was primarily associated with watching TV (85–89 %). Therefore, our study findings provide more precise data on the established relationship between improper EDDs use and disorders of the visual analyzer in students of different age. They provide solid grounds for implementation of relevant prevention activities.

Laboratory investigation of hydraulic jump in divergent-convergent conversions

Hydraulic jump is used as a significant energy-dissipater downstream of hydraulic structures, spillways, gates, and chutes. The novelty of this study is the simultaneous use of divergent-convergent basins to investigate the hydraulic jump characteristics. All experiments were conducted in a channel with a length of 11 m, a depth of 0.7 m and a width of 0.48 m. The results obtained from the divergent-convergent basin models have been compared with those of the sudden divergent basin, gradual divergent basin, classical basin and also with previous research. The results indicate that the ratios of depth (y2/y1) and jump length (Lj/y1) in the divergent-convergent basin have decreased by 48.6% and 122.9%, respectively, compared to the classic basin. These values are equal to 33.8% and 46.2% for the sudden divergent basin, respectively, and 31.7% and 69.9%, respectively, for the gradual divergent basin. In comparison with the classical basins, the energy dissipation in the divergent-convergent basin has increased by 26.8%. Finally, by using dimensional analysis and regression method, several equations were developed to predict the ratio of conjugate depths, length and energy dissipation for the divergent-convergent basins. According to this research, it can be concluded that the divergent-convergent basins with smaller dimensions and more energy dissipation have a much better performance than the standard ones.

Influence of nanoparticle size on the mechanical and tribological characteristics of TiO2 reinforced epoxy composites

Photosensitive resins (PSR) were exposed to challenging operational conditions in different technological domains. It is desirable to enhance the mechanical durability of PSR for its usage in real-world applications. We use TiO2 to improve the mechanical strength and durability of PSR and comprehend nanoparticles' impact on PSR's durability. Herein, we compare the mechanical properties of photosensitive resins (PSR) and TiO2-based polymer nanocomposites (T@PNCs) with varying nanoparticle sizes [1 μm and 20 nm]. Firstly, the ultrasonic dual mixing (UDM) technique is employed, which involves the simultaneous use of ultrasonic mixing and stirring to produce nanocomposites of T@PNCs slurry. Before printing, the initial designs were created using solidworks software, and 3D-Printing was performed using a 3D Moon Ray Printer. Rod and flat specimens were printed, and their structural and mechanical strength were analyzed. The experimental results suggest that larger nanoparticles, measuring 1 μm, decrease the mechanical durability of T@PNCs. However, reducing the size of nanoparticles in polymer nanocomposites (PNCs) to 20 nm increases mechanical resilience, leading to improved flexural and tensile strength. Our experimental results demonstrate that the nanoparticles' size strongly influences PSR's mechanical properties.

Efficacy of TTFields in high-grade gliomas: a protocol for systematic review and meta-analysis

IntroductionDespite their recent FDA(Food and Drug Administration) approval, tumour treatment fields (TTFields) have not seen acceptance as part of standard of care (SOC) for the treatment of high-grade gliomas (HGGs)....

Determinants of Simultaneous Use of Soil Fertility Information Sources among Smallholder Farmers in the Central Highlands of Kenya

Soil fertility decline is a significant drawback to food and nutritional security in sub-Saharan Africa. However, information and knowledge barriers seriously impede the adoption, effective use, and scaling up of soil fertility management innovations, especially by smallholder farmers who produce the bulk of the region’s food needs. Apart from the knowledge that smallholder farmers seek soil fertility information from diverse sources, which they apply simultaneously, there is limited knowledge of farmers’ information-seeking behaviour regarding which sources are used simultaneously and the factors influencing these choices. We employed a cross-sectional survey study design to determine the simultaneous use of soil fertility information sources of 400 smallholder farming households in the Central Highlands of Kenya. We analysed the data using descriptive statistics, principal component analysis (PCA), and a multivariate probit model. The PCA distinguished seven categories of information sources farmers use: local interpersonal, cosmopolite interpersonal, aggregative, print/demonstration, broadcast media, community-based, and progressive learning sources. The intensity of use revealed that most of the smallholders used soil fertility information sources simultaneously and primarily as complements. The determinants of simultaneous use of soil fertility information sources were farmer location, marital status, main occupation, age, farming experience, exposure to agricultural training, group membership, arable land and livestock units owned, soil fertility status, soil fertility change, and soil testing. This study’s findings have implications for information dissemination strategies involving using multiple complementary sources of knowledge for improved soil health and productivity.

Effectiveness of hemocoagulase, tranexamic acid, and their combination for reducing blood loss in bimaxillary orthognathic surgery: a retrospective study.

Orthognathic surgery is a corrective intervention for maxillofacial deformities. Bleeding is a major concern for oral and maxillofacial surgeons. Various agents, such as hemocoagulase, tranexamic acid, and aprotinin have been developed to reduce intraoperative bleeding and transfusion requirements. Therefore, in this study we aimed to investigate the effects of hemocoagulase and tranexamic acid, as well as their simultaneous use, to reduce bleeding during orthognathic surgery. Patients and. This retrospective study included patients who had undergone simultaneous orthognathic surgery of the maxilla and mandible between January 2013 and September 2022 and were classified into three groups based on drugs administered: hemocoagulase (Botropase), tranexamic acid, and a combination of both drugs. We recorded patient age, sex, weight, blood loss, and duration of surgery. Red blood cell (RBC), hemoglobin, hematocrit, and platelet levels were measured before, immediately after, and one day after surgery. No statistically significant differences were found in blood loss, RBC, hemoglobin, hematocrit, or platelet levels between any of the groups. There were no differences in the drug effects between Le Fort I and bilateral mandibular sagittal split osteotomies, with or without double genioplasty. However, there were significant reductions in RBC, hemoglobin, hematocrit, and platelet levels during genioplasty. Tranexamic acid, hemocoagulase, and their combination had similar efficacy in patients who underwent Le Fort Ⅰ and bilateral mandibular sagittal split osteotomies with and without genioplasty.

Enhancement of copper metal dissolution in sulfuric acid solution with oxygen and ultrasound

A new method for copper metal dissolution by simultaneous use of oxygen and ultrasound was proposed to enhance the copper dissolution rate in sulfuric acid (H2SO4). The influence factors such as ultrasonic power, oxygen flow rate, reaction temperature, initial copper ion (Cu2+) and H2SO4 concentration was studied to study the dissolution behaviour of copper metal. The dissolution rate of Cu could reach 7.52 g h−1 L−1 after the ultrasonic strengthening, which is 1.83 times higher than that without ultrasonic irradiation (4.109 g h−1 L−1). The study of leaching kinetics found that the Cu leaching process with and without ultrasound were both controlled by surface chemical reaction. The ultrasound could significantly reduce the apparent activation energy of the leaching reaction from 43.52 kJ mol−1 to 28.40 kJ mol−1. Characteristics revealed that the cavitation effect of ultrasound could increase the specific surface area of copper metal and oxygen bubble, and enhance the oxidizing capability of this leaching system, which is beneficial for the dissolution of Cu. Therefore, ultrasonic-assisted technology has provided novel insights for the hydrometallurgical recovery of copper.

Performance assessment of wheat genotypes based on the superiority index using additive main and multiplicative interaction effects and BLUP analysis

The simultaneous use of additive main and multiplicative interaction effects (AMMI) and best linear unbiased predictors (BLUP) has been reflected in the multi-location evaluation of trials for number of crops. The additional advantages of both these approaches would be combined in superiority index (SI) to have an edge over the commonly used approaches. The promising wheat genotypes had been considered under multi location trails in Peninsular zone of India during the cropping seasons of 2018-2019 and 2019-2020. The highly significant environmental effects contributed 44.1% & 35.3% of total sum of squares in the AMMI analysis, 20.6% & 26.2% were augmented by G × E interaction, while 10.8% & 7.5% were contributed by the genotypes.Wheat genotypes of UAS3001, MACS6222, GW322, and DDW48 expressed their superiority in BLUP values. Superiority indexes and adaptability measures had identified WHD964 and DDW48 genotypes for the second year of study. More than 75% variations among the considered measures were due to the first two interaction principal components (IPCA’s) under Biplot analysis. Number of superiority index measures were clustered with adaptability measures in the same quadrant. Superiority index, the weighted measure of yield and consistent performance of genotypes would be more appropriate for stability and adaptabilities studies.

Ceramic membrane reactor integrated with UV/O3/Catalyst Beads for treating real textile wastewater: Enhanced effluent quality, fouling control and molecular transformations of DOM

A ceramic membrane reactor (CMR) was employed to treat real textile wastewater with the simultaneous use of UV, O3, and photocatalytic beads for dissolved organic matter (DOM) transformation and membrane fouling control. The O3 treatment exhibited high performance in color removal. Simultaneous use of UV and ozonation (UV/O3) resulted in 91% and 64% color and chemical oxygen demand (COD) removal, respectively, and delayed (3-fold) fouling time compared to UV alone. A combination of TiO2-loaded polymeric beads with UV/O3 (UV/O3/Beads) further enhanced the color (96%) and COD (86%) removal as well as improved fouling control by 9-folds compared to the control (Air alone) experiment. Three-dimensional excitation-emission matrix (3-D EEM) fluorescence spectra revealed minimum DOM and synergistic effects of UV, O3, and photocatalytic beads (UV/O3/Beads) in the degradation of fluorescent DOM. The •OH radicals were leading in degrading organic pollutants during the treatment. Transformations of heteroatomic DOMs were confirmed by the Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). S-containing compounds in the treated samples appeared in a reduced state (lower H/C and O/C ratios), indicating the transformation of R–SO3 to R–S–R. Whereas N-containing DOM was mostly oxidized. UV/O3 rapidly transformed dye molecules to colorless, creating suitable conditions for photocatalytic beads for accelerated degradation of pollutants. Also, the PTR-TOF-MS analysis revealed the successful removal of toxic VOCs (Methanethiol, Allylamine, Cyclohexenes, Butanes, Propanes, and Hydrazines) from wastewater by the UV/O3/Beads treatment. Based on these findings, DOM transformations could be better understood, and the simultaneous application of heterogeneous photocatalysis and UV/O3 could be safely recommended as a promising technology for treating industrial wastewater.

Два алфавита для одного миноритарного языка как угроза его существованию (на примере лезгинского языка)

The paper deals with the failed attempt of the Republic of Azerbaijan to introduce an additional Latin-based alphabet for the Lezgian language, which has been using the Cyrillic script since the late 30s of the 20th century to the present day. It provides a brief history of Lezgian script from ancient times to the present day, analyzes the current state and condition of Lezgian being spoken on the territory corresponding to its historical base – the Republic of Dagestan (Russia) and the Republic of Azerbaijan – and establishes its status as a minority and vulnerable language. With reference to the Latin-based alphabet of Lezgian which was in use from 1928 to 1938 and apparently has been offered as such in the Republic of Azerbaijan, linguistic disadvantages of the possible transition of Lezgian alphabet to the Latin script are revealed. The example of Lezgian suggests that an attempt by the state to provide a language which is recognized as a minority and, to some extent, even minorized language in it with an extra alphabet, as well as the lack of it at all, can be regarded as a real threat to the very existence of the language. The author concludes that despite the fact that there are a few other examples of biscriptalism represented by majority and official languages, to the development and existence of which the simultaneous use of another script in another country poses no threat, in case of Lezgian the biscriptalism could have a destructive impact on its development and cause social risks such as the loss of ethnic and cultural identity of Lezgian speakers, the division of the Lezgi people into two separate groups totally devoid of ethnic consciousness and their subsequent irreversible assimilation.

Outcomes of MIS-C patients treated with anakinra: a retrospective multicenter national study.

The treatment of multisystem inflammatory syndrome in children unresponsive to first-line therapies (IVIG and/or steroids) is challenging. The effectiveness of IL-1 receptor antagonist, anakinra, is debated. We conducted an anonymous retrospective multicenter study on MIS-C patients treated with anakinra in Italy from January 2020 to February 2021. Our study outcomes included the percentage of patients who required further therapeutic step-up, the percentage of patients who experienced fever resolution within 24 h and a reduction of CRP by half within 48 h, and the percentage of patients who developed Coronary Artery Anomalies (CAA) during follow-up. 35 cases of MIS-C were treated in 10 hospitals. Of these, 13 patients started anakinra while in the ICU, and 22 patients started anakinra in other wards. 25 patients (71.4%) were treated with corticosteroids at a starting dose 2-30 mg/Kg/day plus IVIG (2 g/Kg), 10 patients (28.6%) received only corticosteroids without IVIG. Anakinra was administered intravenously to all patients in Group A (mean dose 8 mg/Kg/day), and subcutaneously in Group B (mean dose 4 mg/Kg/day). Only two patients required further treatment step-up and no patients developed CAA after receiving anakinra. The most commonly observed side effect was an increase in ALT, occurring in 17.1% of patients. In this retrospective cohort of severe MIS-C patients treated with anakinra we report favorable clinical outcomes with a low incidence of side effects. The simultaneous use of steroids ± IVIG in these patients hinders definitive conclusions regarding the need of IL-1 inhibition in MIS-C treatment.