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Background: Pulmonary involvement in systemic juvenile idiopathic arthritis (SJIA) is a rare but dangerous complication. The main risk factors are already known, such as macrophage activation syndrome, a refractory course of systemic juvenile arthritis, infusion reaction to interleukin 1 and/or interleukin 6 blockers, trisomy 21, and eosinophilia. However, information about respiratory system involvement (RSI) at the onset of SJIA is scarce. Our study aimed to evaluate the specific features of children with SJIA with RSI and their outcomes. Methods: In a single-center retrospective cohort study, we compared the information from the medical records of 200 children with SJIA according to ILAR criteria or SJIA-like disease (probable/possible SJIA) with and without signs of RSI (dyspnea, shortness of breath, pleurisy, acute respiratory distress syndrome, and interstitial lung disease (ILD)) at the disease onset and evaluated their outcomes (remission, development of chronic ILD, clubbing, and pulmonary arterial hypertension). Results: A quarter (25%) of the SJIA patients had signs of the RSI at onset and they more often had rash; hepato- and splenomegaly; heart (pericarditis, myocarditis), central nervous system, and kidney involvement; hemorrhagic syndrome; macrophage activation syndrome (MAS, 44.4% vs. 9.0%, p = 0.0000001); and, rarely, arthritis with fewer active joints, compared to patients without RSI. Five patients (10% from the group having RSI at the onset of SJIA and 2.5% from the whole SJIA cohort) developed fibrosing ILD. All of them had a severe relapsed/chronic course of MAS; 80% of them had a tocilizumab infusion reaction and further switched to canakinumab. Unfortunately, one patient with Down's syndrome had gone. Conclusion: Patients with any signs of RSI at the onset of the SJIA are required to be closely monitored due to the high risk of the following fibrosing ILD development. They required prompt control of MAS, monitoring eosinophilia, and routine checks of night oxygen saturation for the prevention/early detection of chronic ILD.

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This work helps address recent calls for systematic water quality assessment in Central Asia and considers how nutrient and salinity sources, and transport, affect water quality along the continuum from the cryosphere to the lowland plains. Spatial and, for the first time, temporal variations in stream water pH, temperature, electrical conductivity, and nitrate and phosphate concentrations are presented for four catchments (485-13,500 km2), all with glaciers and major urban areas. The catchments studied were: Kaskelen (Kazakhstan), Ala-Archa (Kyrgyzstan), Chirchik (Uzbekistan) and the Kofarnihon (Tajikistan). Measurements were made in cryosphere, stream water, groundwater, reservoir and lake samples over a 22-month period at fortnightly intervals from 35 sites. The results highlight that glacier, permafrost and rock glacier outflows were primary and secondary nitrate sources (>1 mg N L-1) to the headwaters, and there were major increases in salinity and nitrate concentrations where rivers receive inputs from agriculture and settlements. Overall, the water quality complied with national and World Health Organization standards, however there were pollution hot-spots with shallow urban groundwaters contaminated with nitrate (>11 mg N L-1) and stream electrical conductivity above 800 µS cm-1 in some agricultural areas indicative of high salinity. Phosphate concentrations were generally low (<0.06 mg P L-1) throughout the catchments, though elevated (>0.2 mg P L-1) in urban areas due to effluent contamination. A melt water dilution effect along the main river channels was discernible, in the electrical conductivity and nitrate concentration seasonal dynamics, 100 s of km from the headwaters. Thus, the input of relatively clean water from the cryosphere is an important regulator of main channel water quality in the urban and farmed lowland plains adjacent to the Tien Shan and Pamir. Improved sewage treatment is needed in urban areas.

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BACKGROUND: Systemic lupus erythematosus (SLE) is the most frequent and serious systemic connective tissue disease. Nowadays there is no clear guidance on its treatment in childhood. There are a lot of negative effects of standard-of-care treatment (SOCT), including steroid toxicity. Rituximab (RTX) is the biological B-lymphocyte-depleting agent suggested as a basic therapy in pediatric SLE. AIM: To compare the benefits of RTX above SOCT. METHODS: The data from case histories of 79 children from the Saint-Petersburg State Pediatric Medical University from 2012 to 2022 years, were analyzed. The diagnosis of SLE was established with SLICC criteria. We compared the outcomes of treatment of SLE in children treated with and without RTX. Laboratory data, doses of glucocorticosteroids, disease activity measured with SELENA-SLEDAI, and organ damage were assessed at the time of initiation of therapy and one year later. RESULTS: Patients, treated with RTX initially had a higher degree of disease activity with prevalence of central nervous system and kidney involvement, compared to patients with SOCT. One year later the disease characteristics became similar between groups with a more marked reduction of disease activity (SELENA-SLEDAI activity index) in the children who received RTX [-19 points (17; 23) since baseline] compared to children with SOCT [-10 (5; 15.5) points since baseline, P = 0.001], the number of patients with active lupus nephritis, and daily proteinuria. During RTX therapy, infectious diseases had three patients; one patient developed a bi-cytopenia. CONCLUSION: RTX can be considered as the option in the treatment of severe forms of SLE, due to its ability to arrest disease activity compared to SOCT.

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Hemophagocytic syndrome is a key point in the pathogenesis of severe forms of multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C). The factors associated with hemophagocytosis in patients with MIS-C were assessed in the present study of 94 boys and 64 girls ranging in age from 4 months to 17 years, each of whose HScore was calculated. In accordance with a previous analysis, patients with HScore ≤ 91 (n = 79) and HScore > 91 (n = 79) were compared. Patients with HScore > 91 had a higher frequency of symptoms such as cervical lymphadenopathy, dry cracked lips, bright mucous, erythema/swelling of hands and feet, peeling of fingers, edematous syndrome, hepatomegaly, splenomegaly, and hypotension/shock. They also had a higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and D-dimer levels, and a tendency to anemia, thrombocytopenia, and hypofibrinogenemia. They more often needed acetylsalicylic acid and biological treatment and were admitted to ICU in 70.9% of cases. Conclusion: The following signs of severe MIS-C were associated with HScore > 91: myocardial involvement, pericarditis, hypotension/shock, and ICU admission.

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Multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C) is a life-threatening condition that often requires intensive care unit (ICU) admission. The aim of this study was to determine risk factors for severe/life-threatening course of MIS-C. The study included 166 patients (99 boys, 67 girls) aged 4 months-17 years (median 8.2 years). The criterion of severity was the fact of ICU admission. To conduct a comparative analysis, MIS-C patients were divided into two groups: patients hospitalized in the ICU (n = 84, 50.6%) and those who did not need ICU admission (n = 82, 49.4%). Patients with a more severe course of MIS-C were significantly older. They had a higher frequency of signs such as rash, swelling, hepatomegaly, splenomegaly, and neurological and respiratory symptoms. Hypotension/shock and myocardial involvement were much more common in patients with severe MIS-C. These patients had a more significant increase in CRP, creatinine, troponin, and D-dimer levels. Additionally, the presence of macrophage activation syndrome was higher in patients admitted to the ICU. Conclusion: Nineteen predictors of severe course of MIS-C were found, out of which hepatomegaly, splenomegaly, D-dimer > 2568 ng/mL, troponin > 10 pg/mL were mainly associated with the probability of being classified as early predictors of severe MIS-C requiring ICU admission.

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BACKGROUND: Pediatric lupus nephritis (LN) is one of the most serious manifestations of systemic lupus erythematosus (SLE) in children, determining the outcomes of the disease. There are no standardized treatment protocols for pediatric LN, and the role of biologics has not yet been conclusively defined. OBJECTIVES: analyze the safety and efficacy of rituximab biosimilar BCD020 in pediatric patients with lupus nephritis. METHODS: in a retrospective cohort study, the data from the case histories of 25 patients with LN (10 boys and 15 girls) with an onset age of 13 (9-16) years, who failed conventional non-biologic treatment or developed corticosteroid dependence/toxicity, were included. The diagnosis was made using Systemic Lupus International Collaborating Clinics (SLICC) classification criteria. Rituximab biosimilar BCD020 was prescribed in a dosage of 375 mg/m2 every week (2-4 infusions) with repeated courses every 6-12 months (2-4 infusions) according to disease activity, B-cell depletion, and IgG levels. The dynamics of clinical and laboratory data, the activity of the disease by SLEDAI, and corticosteroid doses were assessed at the onset and during the rituximab trial. RESULTS: The main patient's characteristics were: Pre-rituximab non-biologic conventional treatment included: cyclophosphamide 15 (60%), MMF 8 (32%), azathioprine 3 (12%), hydroxychloroquine 12 (48%), and pulse therapy of methylprednisolone followed by oral methylprednisolone 25 (100%). The time before rituximab was 7.0 (3.0-24.0) months, and the whole observation period was 7.0 (0; 24) months. The initial pre-rituximab treatment slightly reduced SLEDAI levels and the proportion of patients with LN. A significant reduction of SLEDAI, the anti-dsDNA level, proteinuria, hematuria, C4 complement, ESR, and the median corticosteroid dose by 80% from the initial value, as well as the proportion of patients without corticosteroids, was observed after rituximab administration. Two deaths were observed due to catastrophic SLE with macrophage activation syndrome, accompanied by a severe infection (invasive aspergillosis, n = 2). Three patients developed serious adverse events: pneumonia (n = 2), transient agranulocytosis (n = 1) after the third rituximab infusion, and meningitis, caused by Listeria monocytosis, after the first rituximab infusion. Eight patients received antibacterial treatment for different respiratory infections without hospital admissions. CONCLUSIONS: Rituximab biosimilar BCD020 showed effectiveness in LN, whereas previous non-biologic treatment was insufficiently effective. Randomized controlled trials are required to evaluate the efficacy and safety of rituximab and evaluate the benefits when compared with conventional SLE treatment.

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The prevalence of diabetes mellitus is one of the major medical problems that the modern world is currently facing. Type 1 and Type 2 diabetes mellitus both result in early disability and death, as well as serious social and financial problems. In some cases, synthetic drugs can be quite effective in the treatment of diabetes, though they have side effects. Plant-derived pharmacological substances are of particular interest. This review aims to study the antidiabetic properties of secondary plant metabolites. Existing review and research articles on the investigation of the antidiabetic properties of secondary plant metabolites, the methods of their isolation, and their use in diabetes mellitus, as well as separate articles that confirm the relevance of the topic and expand the understanding of the properties and mechanisms of action of plant metabolites, were analyzed for this review. The structure and properties of plants used for the treatment of diabetes mellitus, including plant antioxidants, polysaccharides, alkaloids, and insulin-like plant substances, as well as their antidiabetic properties and mechanisms for lowering blood sugar, are presented. The main advantages and disadvantages of using phytocomponents to treat diabetes are outlined. The types of complications of diabetes mellitus and the effects of medicinal plants and their phytocomponents on them are described. The effects of phytopreparations used to treat diabetes mellitus on the human gut microbiota are discussed. Plants with a general tonic effect, plants containing insulin-like substances, plants-purifiers, and plants rich in vitamins, organic acids, etc. have been shown to play an important role in the treatment of type 2 diabetes mellitus and the prevention of its complications.

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BACKGROUND: Several cases of skin and central nervous system vasculopathy associated with COVID-19 in children have been published, but the information is rather limited. Our study aimed to describe these cases of vasculitis associated with COVID-19 in children. METHODS: In the retrospective-prospective case series study we included information regarding four children with COVID-19-associated vasculitis. In every case, we had a morphological description and the etiology was confirmed via real-time polymerase chain reaction during a tissue biopsy. RESULTS: The most involved systems were skin (4/4), respiratory (3/4), cardiovascular (2/4), nervous (1/4), eye (1/4), kidney (1/4), and inner year (1/4). All patients had increased inflammatory markers and thrombotic parameters (D-dimer). No patient met the criteria for multisystem inflammatory syndrome in children. Two patients met polyarteritis nodosa criteria, one met Henoch-Schonlein purpura criteria, and one met unclassified vasculitis criteria. All patients were treated with systemic glucocorticosteroids (two-pulse therapy). Non-biologic DMARDs were prescribed in all cases; 1/4 patients (25%) was treated with intravenous immunoglobuline, and 3/4 (75%) were treated with biologics (etanercept, tocilizumab, and adalimumab). CONCLUSIONS: Vasculitis associated with COVID-19 could be a life-threatening condition; SARS-CoV-2 might be a new trigger or etiological agent for vasculitis and other immune-mediated diseases. Further research and collection of similar cases are required.

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Introduction: Meaning is an important psychological resource both in situations of accomplishment and in situations of ongoing adversity and psychological crisis. Meaning in life underlies the reasons for staying alive both in everyday and in critical circumstances, fulfilling a buffering function with respect to life adversities. Aim: The aim of the present study was to reveal the role of both meaningfulness, including specific sources of meaning and reasons for living, and meaninglessness (alienation) in patients suffering from profound crisis situations with or without suicidal intentions and behavior. Methods: The sample included 148 patients (all Caucasian) who were referred to a crisis center in Moscow, Russia. Seventy-seven patients (54 females, mean age 32.00 ± 11.98 years) reported a current crisis situation in their life but denied suicidal thoughts or behavior. Twenty-nine patients (21 females, mean age 31.55 ± 13.76 years) reported suicidal ideations but denied suicidal attempts or self-harming behavior. Forty-two patients (31 females, mean age 30.64 ± 11.38 years) had episodes of suicidal attempts or self-harming behavior accompanied by suicidal intentions. There were no significant gender or age differences between groups.Participants completed a number of measures of different aspects of meaning and meaninglessness, well-being, ill-being and psychological resources. For some patients (N = 74), a clinical checklist was completed by their doctors assessing 28 various characteristics associated with the patient's clinical status. Results and discussion: Meaningfulness and reasons for living were more helpful in distinguishing between reactions to profound crisis situations (suicidal intentions versus non-suicidal behavior) than were measures of well-being, ill-being, meaning crisis or personality resources. In both suicidal and non-suicidal crisis patients meaningfulness predicted more positive reasons for living. The relationship between meaningfulness and most reasons for living remained significant after controlling for clinically appraised suicidal "readiness," acute stress and lack of social support. Self-transcendence was the major specific source of meaning predicting higher reasons for living after adjusting for general meaningfulness. Conclusion: The data cast some light on the psychological meaning of suicide. It follows that prevention efforts are to be focused not on eliminating the factors "pushing" one to suicidal behavior, but rather on supporting inner strengths conducive of a positive decision, to be, through enhancing meaningfulness and reasons for living.

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BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. METHODS: This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. RESULTS: A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR = 1.022, 95%CI 1.007‒1.038 and OR = 1.025, 95%CI 1.001‒1.051, respectively), while thromboprophylaxis use was protective (OR = 0.199, 95%CI 0.061‒0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR = 1.062, 95%CI 1.017-1.109 and OR = 2.438, 95%CI 1.023-5.813, respectively). CONCLUSIONS: Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration.

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Objective: Macrophage activation syndrome (MAS) is a life-threatening, potentially fatal condition associated with systemic juvenile idiopathic arthritis (sJIA). Interleukin-1 (IL-1) is a key cytokine in the pathogenesis of sJIA MAS. Many cases of MAS are medically refractory to traditional doses of biologic cytokine inhibitors and may require increased dosing. When MAS occurs in the setting of sJIA treated with the IL-1 receptor antagonist (IL-1Ra), anakinra, increased anakinra dosing may be beneficial. Increased dosing of another IL-1 inhibitor, canakinumab, a monoclonal antibody to IL-1ß, has not been reported to treat refractory MAS in the setting of sJIA. Methods: Retrospective data collection extracted from the electronic medical record focused on canakinumab usage and dosing in 8 children with sJIA who developed MAS at a single academic center from 2011 to 2020. Results: Eight sJIA children (five girls) with median age 8.5 years (range, 0.9-14.2 years) were included in the present study. Five children developed MAS at disease onset and three during ongoing canakinumab therapy. MAS resolved in all eight children with canakinumab treatment. When the canakinumab dosing was insufficient or MAS developed during canakinumab therapy, the dosing was temporally up-titrated (four patients, maximum 300 mg per dose) without observed side effects. Conclusion: This report provides evidence for the efficacy and safety of short-term increased doses (2-3-times normal) of canakinumab in treating sJIA associated MAS. Further study of the efficacy and safety of increased doses of canakinumab for treatment of MAS in children with sJIA is warranted.

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Objectives: Uveitis is the most frequent extra-articular manifestation of juvenile idiopathic arthritis (JIA). Our study is aimed to evaluate the possible difference in arthritis course depending on uveitis presence in patients with JIA, treated with biologics. Methods: From our database of patients with JIA treated with biologics, we extracted patients to whom the first agent was administrated with or without MTX. The exclusion criteria included treatment with current systemic corticosteroids, infliximab, rituximab, observation period <3 years, and no missing data. After selection, 175 patients were eligible for analysis. We evaluated clinically significant flare with joint involvement (which required change of biologic or non-biologic DMARD) and time to flare. We compared two groups: (i) patients with uveitis (n = 32) and (ii) patients without uveitis (n = 143). For statistical analysis, we used Cox's regression models, the log-Rank test, x 2 test, and the Mann-Whitney test. Results: There was no difference in gender distribution and achievement of arthritis remission between groups. Patients in the non-uveitis group predominantly received etanercept (64.3%). In the uveitis group, the most prescribed biologic agent was adalimumab (71.9%). The presence of uveitis increased the risk of JIA flare, OR = 3.8 (95% CI: 1.7; 8.7), and the cumulative probability of joint flare, RR = 4.5 (95% CI: 1.7; 12.1), p =.003, after adjustment on methotrexate, RR = 3.1 (1.6; 6.), p =.0008. In the subgroup of patients treated with adalimumab, the absence of methotrexate increased the cumulative probability of flare [RR = 6.5 (95% CI: 1.4; 31.1), p = 0.02]. Conclusion: The presence of uveitis proved to be a risk factor in JIA flare. Methotrexate can decrease the cumulative flare probability. Further trials are required.

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We introduce and evaluate an approach for the simultaneous retrieval of aerosol and surface properties from Airborne Visible/Infrared Imaging Spectrometer Classic (AVIRIS-C) data collected during wildfires. The joint National Aeronautics and Space Administration (NASA) National Oceanic and Atmospheric Administration Fire Influence on Regional to Global Environments and Air Quality field campaign took place in August 2019, and involved two aircraft and coordinated ground-based observations. The AVIRIS-C instrument acquired data from onboard NASA's high altitude ER-2 research aircraft, coincident in space and time with aerosol observations obtained from the Aerosol Robotic Network (AERONET) DRAGON mobile platform in the smoke plume downwind of the Williams Flats Fire in northern Washington in August 2019. Observations in this smoke plume were used to assess the capacity of optimal-estimation based retrievals to simultaneously estimate aerosol optical depth (AOD) and surface reflectance from Visible Shortwave Infrared (VSWIR) imaging spectroscopy. Radiative transfer modeling of the sensitivities in spectral information collected over smoke reveal the potential capacity of high spectral resolution retrievals to distinguish between sulfate and smoke aerosol models, as well as sensitivity to the aerosol size distribution. Comparison with ground-based AERONET observations demonstrates that AVIRIS-C retrievals of AOD compare favorably with direct sun AOD measurements. Our analyses suggest that spectral information collected from the full VSWIR spectral interval, not just the shortest wavelengths, enables accurate retrievals. We use this approach to continuously map both aerosols and surface reflectance at high spatial resolution across heterogeneous terrain, even under relatively high AOD conditions associated with wildfire smoke.

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Objectives: Heart involvement in multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C) is a new challenging problem, requiring fast and reliable diagnostics and appropriate treatment. The aim of this study is to describe heart involvement in patients with MIS-C. Study Design: In this retrospective, multicenter cohort study, data of 122 patients were included. All patients met WHO and CDC criteria of MIS-C. Results: Various types of heart involvement in MIS-C patients were observed. Patients with solely coronary artery lesions (CAL, n = 10, 8.2%) had typical features of Kawasaki disease: younger age, thrombocytosis and normal ferritin level, without giant CA aneurysms, thrombosis, myocardial infarction, shock, and ICU admission. Patients with solely myocardial involvement (MI, n = 30, 24.6%) had an older onset age, elevated ferritin, LDH, the highest D-dimer, H score, and thrombocytopenia level. The following clinical signs were associated with MI: gastrointestinal and central nervous system disorder, sore throat, swelling face, splenomegaly, shock, and treatment in the intensive care unit required. Patients with a combination of CAL and MI (n = 10, 8.2%) had symptoms similar to patients with solely MI, except for impressive thrombocytopenia. Shock and ICU admission were found in 34.7% of patients without heart involvement (n = 72, 59%). One major criterion [troponin > 32 pg/ml (52 points)] or at least two minor criteria [face swelling (32 points) and D-Dimer > 1,300 ng/ml (29 points)] were associated with MI (>32 points) with a sensitivity of 67.5% and a specificity of 88.9%. Conclusion: The above-suggested criteria can be added to routine diagnostic procedures to confirm MI in MIS-C patients.

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The beneficial properties of algae make them perfect functional ingredients for food products. Algae have a high energy value and are a source of biologically active substances, proteins, fats, carbohydrates, vitamins, and macro- and microelements. They are also rich in polyunsaturated fatty acids, proteins, mycosporine-like amino acids, polysaccharides, polyphenols, carotenoids, sterols, steroids, lectins, halogenated compounds, polyketides, alkaloids, and carrageenans. Different extraction parameters are used depending on the purpose and the substances to be isolated. In this study, the following parameters were used: hydromodule 1:10 and an extraction duration of 1-2 h at the extraction temperature of 25-40 °C. A 30-50% solution of ethanol in water was used as an extractant. Algae extracts can be considered as potential natural sources of biologically active compounds with antimicrobial activity and antiviral properties. The content of crude protein, crude fat, and carbohydrates in U. Prolifera, C. racemosa var. peltata (Chlorophyta), S. oligocystum and S. fusiforme (SF-1) was studied. It was found that C. muelleri (Bacillariophyta), I. galbana (Haptophyta), and T. weissflogii (Bacillariophyta) contain about 1.9 times more omega-3 than omega-6 fatty acids. N. gaditana (Ochrophyta), D. salina (Chlorophyta), P. tricornutum (Bacillaryophyta) and I. galbana (Haptophyta) extracts showed inhibitory activity of varying intensities against E. coli or P. aeruginosa. In addition, algae and algae-derived compounds have been proposed to offer attractive possibilities in the food industry, especially in the meat sector, to evolve functional foods with myriad functionalities. Algae can increase the biological activity of food products, while the further study of the structure of compounds found in algae can broaden their future application possibilities.

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JAK-inhibitors are small molecules blocking the JAK-STAT pathway that have proven effective in the treatment of different immune-mediated diseases in adults and juvenile idiopathic arthritis (JIA). AIM OF STUDY: To evaluate the safety and efficacy of tofacitinib in children with different rheumatic diseases. MATERIAL AND METHODS: We extracted information from 24 children with the following diagnosis: JIA (n = 15), undifferentiated systemic autoinflammatory diseases (SAIDs) (n = 7), and juvenile dermatomyositis (JDM) (n = 2) who have been treated with tofacitinib for a period of longer than 6 months. The treatment outcomes were classified according to the opinion of the attending physicians as having a complete response (CR), i.e., the absence of disease activity, or a partial response (PR)-a significant improvement of symptoms and disease activity, or no response (NR)-no changes in disease activity. RESULTS: CR was achieved in 10/24 patients; 7/15 among JIA patients, 1/2 among JDM patients, 4/7 among SAID patients, and PR in 5/15 of JIA, 1/2 of JDM, and 3/7 of SAID patients. Three non-responders with JIA discontinued tofacitinib. Corticosteroids were successfully tapered off in 11/14 patients and discontinued in 2/14 patients. Four patients had side effects not requiring treatment discontinuation: liver enzyme elevation (n = 2), hypercholesterolemia (n = 1), lymphadenitis (n = 1). CONCLUSION: JAK-inhibitors are effective new therapies for the treatment of multiple immune-mediated diseases. Our experience has shown the best results in patients with JIA and JIA-associated alopecia, and type I interferonopathies. More data from randomized controlled clinical trials are needed to use JAK-inhibitors safely in pediatric rheumatic diseases.

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Objectives: Diagnostic between multisystem inflammatory syndrome associated with COVID-19 in children (MIS-C) and Kawasaki disease (KD) can make difficulties due to many similarities. Our study aimed to create a Kawasaki/MIS-C differentiation score (KMDscore) allowing discrimination of MIS-C and KD. Study design: The retrospective multicenter cohort study included clinical, laboratory, and instrumental information about MIS-C (n = 72) and KD (n = 147). The variables allowed to discriminate both conditions used to construct and validate the diagnostic score called the KMDscore. Results: Patients with MIS-C were older, had earlier admission to the hospital, had a shorter time before fever resolution, two times frequently had signs of GI and CNS involvement observed, and had more impressive thrombocytopenia, higher level of CRP, ferritin, ALT, AST, LDH, creatinine, triglycerides, troponin, and D-dimer compared to KD patients. Respiratory signs in MIS-C were presented with pleuritis, acute respiratory distress syndrome, oxygen dependency, lung infiltration, and ground-glass opacities in CT. The heart involvement with fast progression of myocarditis provided the severity of MIS-C and ICU admission due to 12 times higher arterial hypotension or shock and required cardiotonic. No differences in the frequency of CA lesions were seen in the majority of cases. Five criteria, CRP >11 mg/dl (18 points), D-dimer >607 ng/ml (27 points), age >5 years (30 points), thrombocytopenia (25 points), and GI involvement (28 points), were included in the KMDscore. The summa >55 points allowed to discriminate MIS-C from KD with a sensitivity of 87.5% and specificity of 89.1%. Conclusion: The KMDscore can be used to differentiate the diagnostic of MIS-C from KD.

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Annual global satellite-based estimates of fine particulate matter (PM2.5) are widely relied upon for air-quality assessment. Here, we develop and apply a methodology for monthly estimates and uncertainties during the period 1998-2019, which combines satellite retrievals of aerosol optical depth, chemical transport modeling, and ground-based measurements to allow for the characterization of seasonal and episodic exposure, as well as aid air-quality management. Many densely populated regions have their highest PM2.5 concentrations in winter, exceeding summertime concentrations by factors of 1.5-3.0 over Eastern Europe, Western Europe, South Asia, and East Asia. In South Asia, in January, regional population-weighted monthly mean PM2.5 concentrations exceed 90 µg/m3, with local concentrations of approximately 200 µg/m3 for parts of the Indo-Gangetic Plain. In East Asia, monthly mean PM2.5 concentrations have decreased over the period 2010-2019 by 1.6-2.6 µg/m3/year, with decreases beginning 2-3 years earlier in summer than in winter. We find evidence that global-monitored locations tend to be in cleaner regions than global mean PM2.5 exposure, with large measurement gaps in the Global South. Uncertainty estimates exhibit regional consistency with observed differences between ground-based and satellite-derived PM2.5. The evaluation of uncertainty for agglomerated values indicates that hybrid PM2.5 estimates provide precise regional-scale representation, with residual uncertainty inversely proportional to the sample size.

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Lockdowns during the COVID-19 pandemic provide an unprecedented opportunity to examine the effects of human activity on air quality. The effects on fine particulate matter (PM2.5) are of particular interest, as PM2.5 is the leading environmental risk factor for mortality globally. We map global PM2.5 concentrations for January to April 2020 with a focus on China, Europe, and North America using a combination of satellite data, simulation, and ground-based observations. We examine PM2.5 concentrations during lockdown periods in 2020 compared to the same periods in 2018 to 2019. We find changes in population-weighted mean PM2.5 concentrations during the lockdowns of -11 to -15 µg/m3 across China, +1 to -2 µg/m3 across Europe, and 0 to -2 µg/m3 across North America. We explain these changes through a combination of meteorology and emission reductions, mostly due to transportation. This work demonstrates regional differences in the sensitivity of PM2.5 to emission sources.