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Drug repurposing is a major field of value-added medicine. It involves investigating and evaluating existing drugs for new therapeutic purposes that address unmet healthcare needs. Several unmet needs in allergic rhinitis could be improved by drug repurposing. This could be game-changing for disease management. Current medications for allergic rhinitis are centered on continuous long-term treatment, and medication registration is based on randomized controlled trials carried out for a minimum of 14 days with adherence of 70% or greater. A new way of treating allergic rhinitis is to propose as-needed treatment depending on symptoms, rather than classical continuous treatment. This rostrum will discuss existing clinical trials on as-needed treatment for allergic rhinitis and real-world data obtained by the mobile health app MASK-air, which focuses on digitally-enabled, patient-centered care pathways.

Biomarkers for the diagnosis, treatment and follow-up of patients with rhinitis and/or asthma are urgently needed. Although some biologic biomarkers exist in specialist care for asthma, they cannot be largely used in primary care. There are no validated biomarkers in rhinitis or allergen immunotherapy (AIT) that can be used in clinical practice. The digital transformation of health and health care (including mHealth) places the patient at the center of the health system and is likely to optimize the practice of allergy. Allergic Rhinitis and its Impact on Asthma (ARIA) and EAACI (European Academy of Allergy and Clinical Immunology) developed a Task Force aimed at proposing patient-reported outcome measures (PROMs) as digital biomarkers that can be easily used for different purposes in rhinitis and asthma. It first defined control digital biomarkers that should make a bridge between clinical practice, randomized controlled trials, observational real-life studies and allergen challenges. Using the MASK-air app as a model, a daily electronic combined symptom-medication score for allergic diseases (CSMS) or for asthma (e-DASTHMA), combined with a monthly control questionnaire, was embedded in a strategy similar to the diabetes approach for disease control. To mimic real-life, it secondly proposed quality-of-life digital biomarkers including daily EQ-5D visual analogue scales and the bi-weekly RhinAsthma Patient Perspective (RAAP). The potential implications for the management of allergic respiratory diseases were proposed.

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The purpose of the study is to determine the expression of the core clock genes in buccal epithelial cells of healthy people with different chronotypes. Materials and methods. Fourteen healthy volunteers with a healthy periodontium and oral mucosa (7 women and 7 men) were selected for participation in the trial. The buccal epithelium sampling was performed at 07:00 am and 07:00 pm in one day by cytological brush. The surveyed patients were examined chronotypically using the Horn-Ostberg test. The determination of the mRNA expression of the Per1, Clock, Bmal1, Cry1 genes was performed by quantitative real-time PCR. Statistical analysis was performed using two-way analysis of variance followed by Bonferroni post hoc tests. Results. Per1 expression was higher in the morning, regardless of chronotype, age, and gender. The expression of the Clock demonstrated the prevalence of the evening in both chronotypes, in both men and women. Bmal1 was better expressed in the evening, regardless of age, gender, and chronotype. The expression of Cry1 did not show statistically significant differences between the indicators. Conclusions. The evening expression of Clock was higher in people with the evening chronotype than in people with the morning chronotype. The chronotype did not show any effect on the expression of Per1, Bmal1, and Cry1. Age and sex did not show any effect on the expression of the core clock genes.

In clinical and epidemiological studies, cut-offs of Patient-Reported Outcome Measures (PROMs) can be used to classify patients into groups of statistical and clinical relevance. However, visual analog scale (VAS) cut-offs in MASK-air® have not been tested.To calculate cut-offs for VAS global, nasal, ocular, and asthma symptoms.In a cross-sectional study design of all MASK-air® participants, we compared (i) approaches based on the percentiles (tertiles or quartiles) of VAS distributions, and (ii) data-driven approaches based on clusters of data from two comparators (VAS work and VAS sleep). We then performed sensitivity analyses for individual countries and for VAS levels corresponding to full allergy control. Finally, we tested the different approaches using MASK-air® real-world cross-sectional and longitudinal data to assess the most relevant cut-offs.We assessed 395,223 days from 23,201 MASK-air® users with self-reported allergic rhinitis. The percentile-oriented approach resulted in lower cut-off values than the data-driven approach. We obtained consistent results in the data-driven approach. Following the latter, the proposed cut-off differentiating "controlled" and "partly-controlled" patients was similar to the cut-off value which had been arbitrarily used (20/100). However, a lower cut-off was obtained to differentiate between "partly-controlled" and "uncontrolled" patients (35 versus the arbitrarily-used value of 50/100).Using a data-driven approach, we were able to define cut-off values for MASK-air® VASs on allergy and asthma symptoms. This may allow for a better classification of rhinitis and asthma patients according to different levels of control, supporting improved disease management.

The research aim is to identify the correlation between circadian rhythm in terms of changes in the chronotype of human working capacity and severity of psoriasis progression, obesity, and the disease impact on the quality of patients' life. Materials and Methods. The research focuses on the determination of the PASI, BMI, DIAG indexes and a patient's chronotype of working capacity. Results and Discussion. The results of the correlation analysis showed a very high negative correlation between chronotype of patients' working capacity and BMI. They also demonstrated a high negative correlation between PASI and DIAG indicators and chronotype of patients' working capacity. Conclusions. The circadian rhythm changes to the evening chronotype of human working capacity contribute to psoriasis worsening, weight gain, and negative impact of the disease on the quality of patients' life.

Psoriasis is one of the most common dermatoses, affecting from 2% to 4% of the world's population, according to the statistics from WHO. The recent increase in the incidence of comorbid psoriasis and obesity leads to severe, atypical, disabling, and treatment-resistant forms of dermatosis, which significantly impair the quality of life of patients, reduce the efficiency and social activity of patients, thus acquiring not only a medical but also a social significance. There is a theoretical justification for a possible role of circadian rhythm disorders, manifested by changes in eating behavior, reduced sleep duration, and individual chronotype of patients in the development of obesity, chronic low-intensity inflammation, and some chronic autoimmune diseases such as psoriasis. However, this issue remains understudied and insufficiently substantiated. Therefore, the aim of our research was to identify the correlation between the circadian rhythm in terms of changes in the chronotype of human working capacity and indicators of systemic inflammation in patients with extensive psoriasis and concomitant alimentary obesity. The results of correlation analysis showed a high negative correlation between the working capacity chronotype in patients and the level of IL-33, as well as a medium negative correlation between the working capacity chronotype in patients and the level of IL-6 and CRP. Therefore, changes in the circadian rhythm to the evening type of human working capacity chronotype may increase the level of systemic inflammation in patients with extensive vulgar psoriasis and concomitant alimentary obesity. Thus, further in-depth study of the relationship between systemic inflammation and circadian rhythm changes in patients with extensive vulgar psoriasis and concomitant alimentary obesity is promising and essential for the development of scientifically substantiated principles for early prevention and timely correction of these comorbidities.

Overweight and obesity lead to the formation of a pro-inflammatory phenotype of the adipose tissue macrophages, but it is not known how exactly the balance of STAT1 and STAT6 transcription factors is implemented in the peripheral blood monocytes and how this affects the further polarization process in overweight. The article examines the level and ratio of expression of the STAT1 and STAT6 transcription factors in the polarization of the peripheral blood monocytes depending on the body weight. The study enrolled 20 women and men aged from 18 to 25 years. In terms of BMI, the subjects were divided into the following groups: individuals with normal body weight (BMI 18.50-24.99 kg/m2), represented by 5 women and 5 men; overweight individuals (BMI 25.00-29.99 kg/m2), including 5 men and 5 women. Using standard methods peripheral blood monocytes stimulated by LPS and γIFN, IL-4 was isolated and incubated for 3 and 7 days. PCR method was used to determine the expression level of the stat1 and stat6 genes in incubated cells. The concentration of IL-6 and TGFβ1 was measured in the supernatant on the 7th day of incubation, and TGFβ1 and hs-CRP in the serum of the subjects. The obtained results revealed a significant increase in the level of IL-6 in the supernatant of macrophages stimulated by LPS and γIFN in overweight individuals. The level of hs-CRP in the serum was also significantly higher in overweight individuals. It has been shown that under the conditions of overweight development, there is a significant increase in the level of expression of stat1 and stat6 genes in cells stimulated by IL-4. The obtained data indicate the presence of a preconditioning state of the peripheral blood monocytes with activation of signaling networks mainly in macrophages stimulated by the M2 phenotype under conditions of increased nutrients intake.

An indisputable link between psoriasis and obesity has recently been proven. Alimentary obesity exacerbates systemic inflammation in patients with psoriasis, complicating the course of dermatosis, causing deterioration of the dermatological index of quality of life of patients and frequent exacerbation of psoriasis, which leads to ineffectiveness of standard treatments. PPAR-activated receptors are the link between lipids and inflammation because lipids stimulate the chronic form of systemic inflammation and are ligands that activate PPAR. Thus, PPAR can be used as the main target when choosing a treatment for this comorbidity. To date, the literature has accumulated a large number of prospective observations indicating a positive effect of pioglitazone (PG) on systemic inflammation. The mechanism of action of this drug is aimed at suppressing chronic systemic delayed inflammation of low intensity. The anti-inflammatory effect of PG is associated with its activating effect on nuclear transcription factors of PPAR. Objective — to determine the effectiveness of the inclusion of different doses of pioglitazone in the complex treatment of patients with advanced psoriasis vulgar with concomitant alimentary obesity of I—II degree. Materials and methods. Clinical and immunological study of systemic inflammation. Results and discussion. The results of the study showed the effectiveness of this method of treatment, which depended on the dose of PG and the duration of treatment. The use of PG in the complex treatment of patients with vulgar psoriasis of moderate severity with concomitant alimentary obesity of I—II degree for 26 weeks led to a decrease in inflammation both locally, according to the Psoriatic Area and Severity Index, and at the systemic level due to reduction in the level of systemic inflammation, namely the level of interleukin-33, interleukin-6 and highly sensitive C-reactive protein in the blood serum.Conclusions. Long-term use of PG can be recommended for the personalized and comprehensive treatment of patients with comorbidity of psoriasis and alimentary obesity of I—II degree.

Objective The aim: To assess the CSF - 1 level in peritoneal fluid and menstrual blood of women with endometrioid disease and to investigate its diagnostic and prognostic specificity. Patients and methods Materials and methods: The study included 80 women of child-bearing age (mean age 30.95 ± 6.49 years) with benign gynaecological pathology of the ovaries and / or fallopian tubes. The women included in the study were divided into two groups: study group (n = 50, mean age 31.04 ± 6.3 years), consisting of patients with confirmed endometrioid disease, and control group (n = 30, mean age 30.8 ± 6.8 years), involving individuals without signs of endometriosis (p> 0.05). Results Results: We have found significantly higher level of CSF-1 content in the peritoneal fluid in the subjects of the study group (2027.05 ± 732.64 pg / ml) compared with those in the control group (1725.62 ± 466.06 pg / ml) (p = 0.029). There is a tendency towards an increase in CSF-1 level in women with endometriosis in its more severe stages and more severe and extended adhesions. The investigation of CSF-1 content in menstrual blood has demonstrated significant increase in its values in the women of the study group (9431.6 ± 2866.22 pg / ml) compared with the values in the control group (6637.12 ± 954.05 pg / ml), (p = 0.00004). Thus, there is a tendency towards the growth in CSF-1 level in peritoneal fluid and menstrual blood in women with endometriosis and concurrent increase in severity of the disease. Conclusion Conclusions: There has been found significant increase in CSF-1 content in women with endometrioid disease in both peritoneal fluid and menstrual blood (1.2 and 1.4 times, respectively). Thus, macrophage growth factor (CSF-1) can be used as a diagnostic and prognostic criterion in evaluating the progression of endomertioid disease.

У статті представлено літературний огляд проблеми використання інноваційних інструментів веб-спостереження, зокрема Google Trends (GT), з метою визначення точного початку сезону спор цвілі. Алергія на цвіль є значним пусковим механізмом розвитку поширених респіраторних розладів – алергічного риніту та астми, хронічного обструктивного захворювання легень тощо. Метою дослідження було вивчення сезонності запитів GT в Україні з кількістю спор Alternaria. Спори роду Alternaria – найпоширеніша складова повітря у всіх регіонах світу, що утворюють інфекційний посівний матеріал численних видів рослин, а також спричиняють важку інгаляційну алергію. Точне визначення настання сезону спор цвілі є вирішальним для підтвердження діагнозу алергії на цвіль та розробки персоналізованого лікування для пацієнтів з алергічним ринітом та астмою. Найбільш комплексним підходом є розвиток загальноєвропейської мережі моніторингу, яка поєднує всі ці стратегії. GT може бути корисним інструментом для диференціації сезонів спор Alternaria, особливо коли вони співпадають з сезоном цвітіння амброзії. Чотири терміни "нежить", "сльози", "задишка" та "кашель" (кирилицею) слід використовувати в Україні для пояснення впливу спор Alternaria. Поєднання запитів GT з кількістю спор може бути використано в масштабних епідеміологічних дослідженнях. Розвиток загальноєвропейської сигнальної мережі моніторингу алергічних захворювань зумовлює проблему перекладу пошукових термінів різними європейськими мовами. Отримані результати можна використовувати як ефективний інструмент запобігання або мінімізації впливу алергену на пацієнтів під час сезону Alternaria.

Psoriasis is one of the most common chronic recurrent systemic autoimmune multifactorial diseases, affected the skin, joints, internal organs and systems of the body. Despite the significant prevalence of psoriasis and a large number of studies devoted this problem there is still no single view on the pathogenesis of this dermatosis. To clear up the pathogenesis of psoriasis, it seems to be reasonable to focus on the common comorbidities or multimorbidities, which may occur in the course of psoriasis, as this issue is still insufficiently studied. Recent reports have proven the evidences of indisputable link between psoriasis and obesity. The scientific literature extensively covers the issues of identical pathogenetic mechanisms of inflammatory processes in psoriasis and obesity. Given the current data on the role of systemic inflammation underlying the development of both psoriasis and obesity, the study of molecular mechanisms of its development and in particularly the role of proinflammatory nuclear transcription factors, thiazolidinediones have been found out as pathogenetically justified medicine of choice for the therapy of these diseases. In this study, we determined the effectiveness of using 30 mg of pioglitazone daily for 6 months in the course of treatment for patients with extensive psoriasis vulgaris of moderate severity, who were also diagnosed as having concomitant grade І-ІІ alimentary obesity that was supported by clinical and immunological findings evidenced of systemic inflammation. Analyzing the results obtained, we have found out the prolonged therapy with pioglitazone leads to a decrease in systemic inflammation and contributes to a milder recurrent course of psoriasis.

Psoriasis is one of the most common chronic recurrent systemic autoimmune multifactorial diseases, in which the skin, joints, internal organs and systems of the body are involved in the pathological process. Despite the significant prevalence of psoriasis and a large number of studies on this problem, there is still no single view on the pathogenesis of this dermatosis. To objectively understand the pathogenesis of psoriasis, it is necessary to take into account the insufficiently studied comorbidity of this pathology. Recently, an indisputable link between psoriasis and obesity has been proven. The scientific literature widely covers the issue of identical pathogenetic mechanisms of inflammatory processes in psoriasis and obesity. Given the current data on the role of systemic inflammation underlying the development of both psoriasis and obesity, the study of molecular mechanisms of its development and taking into account the role of proinflammatory nuclear transcription factors, thiazolidinediones are the pathogenetically justified drugs of choice for treatment of these diseases. In this study, we determined the effectiveness of using 15 mg of pioglitazone once a day for 6 months in the treatment of patients with extensive psoriasis vulgaris of moderate severity and concomitant grade І-ІІ alimentary obesity by clinical and immunological examination of systemic inflammation. Analyzing the results of the study, it was found that long-term use of pioglitazone, even in small doses, led to a decrease in systemic inflammation and contributed to a milder course of psoriasis in recurrence of the disease.

Funding Information: IA reports personal fees from Roxall, Menarini, UCB, Faes Farma, Sanofi, Bial, Amgen, Abbott, Bayer, Organon. SBA reports grants from TEVA, personal fees from TEVA, AstraZeneca, Boehringer Ingelheim, GSK, Sanofi, Mylan. JB reports personal fees from Chiesi, Cipla, Hikma, Menarini, Mundipharma, Mylan, Novartis, Sanofi‐Aventis, Takeda, Teva, Uriach, other from KYomed‐Innov, personal fees from Purina, other from MASK‐air. VC reports personal fees from Thermofisher. PCM reports personal fees from Abbvie, AZ, Bial, GSK, Mylan, Medinfar, Novartis, Sanofi. LC reports personal fees from Malesci, Menarini, Astra Zeneca, Novartis. AC reports grants and personal fees from Astrazeneca, GSK, Sanofi, personal fees from Boehringer‐Ingelheim, Chiesi, Glenmark, Novartis, personal fees from Mylan, Abdi‐Ibrahim. PD reports personal fees and non‐financial support from Stallergenes Greer, ALK‐Abello, Astra Zeneca, CHIESI, MYLAN/Meda Pharma, Novartis, GlaxoSmithKline, Sanofi, IQVIA personal fees from MENARINI. JAFonseca reports participation in SME that has mHealth technologies for patients with asthma. JCI reports personal fees from Abbott Ecuador, Bago Bolivia, Faes Farma, Laboratorios Casasco, Sanofi. LK reports grants and personal fees from Allergopharma, LETI Pharma,MEDA/Mylan, Sanofi, personal fees from HAL Allergie, Allergy Therapeut., Cassella med, grants from ALK Abelló, Stallergenes, Quintiles, ASIT biotech, Lofarma, AstraZeneca, GSK, Inmunotk, and Membership: AeDA, DGHNO, Deutsche Akademie für Allergologie und klinische Immunologie, HNO‐BV, GPA, EAACI. VK reports other from Norameda, BerlinCHemie Menarini. PK reports personal fees from Adamed, AstraZeneca, Berlin Chemie Menarini, Boehringer Ingelheim, Chiesi, GSK, Novartis, Polpharma. DLL reports personal fees from Allakos, Amstrong, Astrazeneca, Chiesi, DBV Technologies, Grunenthal, GSK, Mylan/Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, Alakos, Gossamer, Carnot, grants from Sanofi, Astrazeneca, Novartis, Circassia, UCB, GSK, Purina institute, Abvvie, Lilly, Pfizer. BL reports grants and personal fees from Meda, personal fees from Glenamrk. RL reports grants and personal fees from GSK, AZ, Chiesi, personal fees from Novartis, Sanofi. MM reports personal fees from Novartis, Gsk, Menarini, Az, Chiesi, Sanofi, Pfizer. RM reports personal fees from Angelini Pharma ALK, Allergopharma, Allergy Therapeutics, Friulchem, Hexal, Servier, Klosterfrau, Bayer, FAES, GSK, MSD, Johnson&Johnson, Meda, Stada, UCB, Nuvo, Menarini, Mundipharma, Pohl‐Boskamp, Laboratoire de la Mer, Sidroga, Lek, PRO‐AdWise, grants and personal fees from Bencard, Stallergenes, Ursapharm, HAL BV, grants from Leti, Optima, BitopAG, Hulka, Inmunotek, Cassella‐med GmbH & Co. KG, ASIT biotech, grants, personal fees and non‐financial support from Lofarma, non‐financial support from Roxall, Atmos, Bionorica, Otonomy, Ferrero, personal fees and non‐financial support from Novartis. OP reports grants and personal fees from ALK‐Abelló, Allergopharma, Stallergenes Greer HAL Allergy Holding B.V./HAL Allergie GmbH, Bencard Allergie GmbH/Allergy Therapeutics, Lofarma, ASIT Biotech Tools S.A., Laboratorios LETI/LETI Pharma, Anergis S.A., GlaxoSmithKline, personal fees from MEDA Pharma/MYLAN, Mobile Chamber Experts (a GA2LEN Partner), Indoor Biotechnologies, Astellas Pharma Global, EUFOREA, ROXALL Medizin, Novartis, Sanofi‐Aventis and Sanofi‐Genzyme, Med Update Europe GmbH, streamedup! GmbH, John Wiley and Sons, AS, Paul‐Martini‐Stiftung (PMS), Regeneron Pharmaceuticals Inc., RG Aerztefortbildung, Institut für Disease Management, Springer GmbH, AstraZeneca, IQVIA Commercial, Ingress Health, grants from Pohl‐Boskamp, Inmunotek S.L., Biomay, Circassia. NGPapadopoulos reports personal fees from Novartis, Nutricia, HAL, MENARINI/FAES FARMA, SANOFI, MYLAN/MEDA, BIOMAY, AstraZeneca, GSK, MSD, ASIT BIOTECH, Boehringer Ingelheim, grants from Gerolymatos International SA, Capricare. ATB reports personal fees from AstraZeneca, GSK, Novartis, IQVIA/Abbvie, Mylan, Bial, Leti, grants and personal fees from Teva. STS reports personal fees from ERT, Roche products, Novartis, Sanofi Pharma, AstraZeneca, ALK‐ Abelló grants from Glaxo Smith Kline. IT reports grants from GSK, Boehringer Ingelheim, AZ, personal fees from Novartis, Astra Zeneca, Chiesi, TZ reports Organizational affiliations: Committee member: WHO‐Initiative “Allergic Rhinitis and Its Impact on Asthma” (ARIA); Member of the Board: German Society for Allergy and Clinical Immunology (DGAKI); Head: European Centre for Allergy Research Foundation (ECARF). President: Global Allergy and Asthma European Network (GA2LEN); Member: Committee on Allergy Diagnosis and Molecular Allergology, World Allergy Organization (WAO). Funding Information: MASK‐air® has been supported by EU grants (POLLAR, EIT Health; Structural and Development Funds, Twinning, EIP on AHA and H2020) and educational grants from Mylan‐Viatris, ALK, GSK, Novartis and Uriach 1 1 Publisher Copyright: © 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd. Background: Different treatments exist for allergic rhinitis (AR), including pharmacotherapy and allergen immunotherapy (AIT), but they have not been compared using direct patient data (i.e., “real-world data”). We aimed to compare AR pharmacological treatments on (i) daily symptoms, (ii) frequency of use in co-medication, (iii) visual analogue scales (VASs) on allergy symptom control considering the minimal important difference (MID) and (iv) the effect of AIT. Methods: We assessed the MASK-air® app data (May 2015–December 2020) by users self-reporting AR (16–90 years). We compared eight AR medication schemes on reported VAS of allergy symptoms, clustering data by the patient and controlling for confounding factors. We compared (i) allergy symptoms between patients with and without AIT and (ii) different drug classes used in co-medication. Results: We analysed 269,837 days from 10,860 users. Most days (52.7%) involved medication use. Median VAS levels were significantly higher in co-medication than in monotherapy (including the fixed combination azelastine-fluticasone) schemes. In adjusted models, azelastine-fluticasone was associated with lower average VAS global allergy symptoms than all other medication schemes, while the contrary was observed for oral corticosteroids. AIT was associated with a decrease in allergy symptoms in some medication schemes. A difference larger than the MID compared to no treatment was observed for oral steroids. Azelastine-fluticasone was the drug class with the lowest chance of being used in co-medication (adjusted OR = 0.75; 95% CI = 0.71–0.80). Conclusion: Median VAS levels were higher in co-medication than in monotherapy. Patients with more severe symptoms report a higher treatment, which is currently not reflected in guidelines. publishersversion published

Aim. Breast cancer (BC) is a heterogeneous disease which develops under the selective “pressure” of the tumor microenvironment. Therefore, it is promising and important to study tumor-associated macrophages as the innate immunity cells. The innate immunity system supposedly is able to regulate tumor immune surveillance and does not necessarily require the innate link. Object and methods. Materials of the study were intraoperative tissue of tumors and ipsilateral lymph nodes in radical mastectomy. Immunohistochemical characteristics of removed tumors (ER, PR, HER2, Ki67) were used for organizing two balanced groups of patients with primary BC. In the first group, there were no metastases into the regional lymph nodes, N0, whereas in the second one there was primary metastatic BC, N1. The groups included three patients with non-luminal HER2+, luminal A, luminal HER2-negative, luminal HER2+, and triple-negative BC, with 15 patients in each group, with a total of 30 patients. Results. The main idea of the work was to find the differences between the quantities of CD68+ and CD163+ macrophages, localized in tumor biopsy samples between the groups of patients with non-metastatic BC (N0) and with metastases (N1), balanced by the clinical values of ER, PR, HER2 (non-luminal HER2+, luminal A, luminal B HER2+, luminal B HER2-, and triple-negative BC). The results of statistical processing of average quantitative indicators of CD68+TAM, CD163+M2-like macrophages and CD68/CD163 (macrophage index M1) between groups N0 and N1 did not reveal a significant difference. However, when comparing the calculated immune-positive macrophages from all fields of view (40×lens), which were 5-17 for each specimen, a significant increase in CD68+TAM in the metastasis group was established. Comparison of average quantitative indicators of CD68+, CD163+ and CD68/CD163 between groups BC N0 and N1 showed no significant differences (the Mann-Whitney test). We determined the IHC characteristics of BC for each biopsy sample, including Ki67 and G-grade. Therefore, a statistical check of their correlation relationships with average quantitative indicators of CD68+, CD163+ and CD68/CD163 macrophages was conducted, which revealed a reliable relationship between CD68+ and Ki67, expressed as a percentage, and between ER/PR (in the clinical interpretation: +/-) and CD68+, CD163+, but not CD68/CD163.Conclusions. 1. The number of CD68+TAM was significantly higher in the focus of the primary BC of patients with metastases in the regional lymph nodes. 2. We detected a reverse correlation between CD68+TAM, CD163+M2-like macrophages and the clinical value of ER/PR. Consequently, an increase in the number of TAMs (in particular, M2) in the primary ER+/ PR+BC with metastases may not have a predictive value for metastasis, or ER+/PR+ BC possibly metastasizes without a significant increase in TAM. 3. The revealed differences are confirmed by reliable statistical calculations and relate to the effect of an exceptionally pathological process, since patients did not receive treatment before radical mastectomy. 4. Interpretation of personal data on the number of CD68+TAM and CD163+M2- like macrophages still needs to be developed.

Aims: Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) has various mechanisms and represents different clinical syndromes from anaphylaxis to severe bronchospasm. The prevalence of aspirin hypersensitivity among patients with asthma and nasal polyps reaches 25.6%. Respiratory reactions associated with aspirin or other NSAIDs are not immunological. The basis of these reactions is non-allergic hypersensitivity of the cross-reactive type. Desensitization followed by long-term aspirin therapy is an effective method of treating hypersensitivity to aspirin or other NSAIDs. Using aspirin 600-1200 mg/day can significantly alleviate the symptoms of asthma, allergic rhinitis. Methods: We successfully applied aspirin desensitization for method of patients with hypersensitivity to NSAIDs. According to the method, an hour before the desensitization, daily montelukast 10 mg was taken orally, then aspirin every 3 hours. Results: Three patients underwent desensitization of aspirin. The dose was selected individualy depending on the clinical manifestations of drug-induced adverse reactions (AR). ARs during desensitization were treated by iv dexamethasone administration. Subsequent doses did not cause AR. Doses of aspirin were increased to a maximum of 1250 mg daily, and were continued for the long-term use. Conclusion: It is possible to conclude that the initial dose of aspirin should be 16-40mg; it is possible to increase the dose if the initial dosage is well tolerated; symptoms of moderate intolerance are treated by 4-8 mg iv dexamethasone; prior to desensitization, we recommended to use montelukast 10 mg, it is safe to practice desensitization of aspirin according to a personalized technique by a specialist in an intensive care unit.

Today, there have been numerous studies that show the emergence and development of various pathologies accompanied by the activation of free radical reactions. It should be noted that the current clinical experience and results of experimental studies indicate the important role of oxidative stress in the formation and progression of cardiovascular pathology, and a series of reports are devoted to the study and comparison of the distinctive features of free radical lipid oxidation and proteins in patients with endothelial dysfunction and various functional classes of angina. Despite the considerable period that has elapsed since the Chernobyl disaster, the medical and biological problems of long-term effects of ionizing radiation are remaining relevant. However, it should be noted that according to some authors, the ideas of lipid peroxidation, mainly based on in vitro studies, do not meet the requirements for recognizing the existence of a metabolic process or metabolic pathway. In recent years, the Department of Internal Medicine # 3 with Phthisiology has conducted the number of multidirectional studies focused on various aspects of free radical pathology in experimental and clinical medicine on cardiology, nephrology, immunology, haematology, pulmonology, and gastroenterology. According to the results of the literature review and comprehensive analysis of the conducted research, we can point out that the study of the role of free radical processes in experimental and clinical medicine is still remaining quite relevant. The scientific search and practical value of these studies can lead to new insight in the context of an overall deterioration of the environment and exposure to negative environmental factors.

Bordetella avium pneumonia immunocompromised the patient with subsequent complication by a rare opportunistic Raoultella planticola infection, which became a nosocomial pathogen in the healthcare setting.

Co-medication is common among patients with allergic rhinitis (AR), but its dimension and patterns are unknown. This is particularly relevant since AR is understood differently across European countries, as reflected by rhinitis-related search patterns in Google Trends. This study aims to assess AR co-medication and its regional patterns in Europe, using real-world data.We analysed 2015-2020 MASK-airWe analysed 222,024 days (13,122 users), including 63,887 days (28.8%) under monotherapy and 38,315 (17.3%) under co-medication. The median 'VAS Global Symptoms' was 7 for no medication days, 14 for monotherapy and 21 for co-medication (p .001). Medication use peaked during the spring, with similar patterns across different European regions (defined geographically or by Google Trends). Oral HAllergic rhinitis medication patterns are similar across European regions. One third of treatment days involved co-medication. These findings suggest that patients treat themselves according to their symptoms (irrespective of how they understand AR) and that co-medication use is driven by symptom severity.

Introduction: Obese asthma is a complex syndrome, which includes different phenotypes of disease. At present, these phenotypes only have started to acquire a sufficient understanding. It was suggested that IL-26 is a potential biomarker of disease severity in asthma without signs of Th2-mediated inflammation. In this study, we investigated the serum and exhaled levels of IL-26 and its associations with the level of systemic inflammation, lung functions, and body weight in obese and non-obese moderate-to-severe asthmatic patients. Material and Methods: The study included 10 healthy subjects, 10 obese subjects without lung pathologies, 10 non-obese asthmatics (NOA) (BMI 18.5–24.9 kg/m²), and 40 obese asthmatics (OA) (BMI 25.0–49.9 kg/m²). During the visit, patients' examination and spirometry with the bronchodilator reversibility test were conducted, the exhaled breath condensate (EBC) was obtained, and the blood samples were collected. The level of IL-26, interleukin-1β (IL-1β), interleukin-4 (IL-4), interleukin-6 (IL-6), TNF-α, interleukin-10 (IL-10), total and specific immunoglobulin E (IgE), and high sensitive C reactive protein (hs-CRP) were measured using the ELISA kits. Statistical comparison between 2 groups was analyzed using the Mann–Whitney rank-sum test. Chi-square with Yates' correction was used to compare frequencies. Spearman's rank test was used for correlating nonparametric variables. The Receiver Operating Characteristic (ROC) curve and the area under ROC curve (AUC) were used for evaluating the diagnostic power of IL-26 as a possible biomarker. Results: NOA had a reversible airway obstruction with reduced FEV1, FEV1/FVC, FVC 25/75, and positive post-bronchodilator test (PBT), significantly increased serum levels of IL-10, IL-4, and slightly increased IL-26. NOA had significantly increased exhaled IL-26 in comparison with healthy subjects. The obese subjects had a normal ventilatory pattern without airway obstruction, and differences in serum IL-26, IL-10, and IL-4 concentrations in comparison with healthy subjects. Obese subjects had a significant escalation of hs-CRP and no differences in the levels of exhaled IL-26, IL-10, and hs-CRP as compared with healthy subjects. OA had reduced FEV1, FEV1/FVC, and FEV25–75 in comparison with non-obese asthmatics. OA had elevated IL-26, IL-10, IL-4, and hs-CRP concentrations as compared with healthy subjects. These patients had a partial similarity with both non-obese asthmatics (elevated IL-26, IL-10, and IL-4) and obese subjects (elevated, IL-1β, IL-6, TNF-α, hs-CRP). OA had a reduced concentration of exhaled IL-26 in comparison with NOA and elevated exhaled IL-10 in comparison with obese subjects. Furthermore, OA had an increased concentration of IL-1β and TNF-α in comparison with healthy individuals and NOA. Exhaled IL-26 concentration distinguished non-obese asthmatics from healthy subjects, asthmatic patients from non-asthmatics (healthy and obese subjects), all asthmatic patients from non-asthmatics (healthy and obese subjects). Conclusions: Exhaled IL-26 elevated in obese and non-obese moderate-to-severe asthmatic patients. Exhaled IL-26 might be a perspective biomarker in non-obese and obese asthmatics. The obese asthmatic phenotype comprised the combined systemic and local airway inflammation.

Introduction. The master clock, which is located in the suprachiasmatic nucleus (SCN), harmonizes clock genes present in the liver to synchronize life rhythms and bioactivity with the surrounding environment. The reversed feeding disrupts the expression of clock genes in the liver. Recently, a novel role of PPAR-γ as a regulator in correlating circadian rhythm and metabolism was demonstrated. This study examined the influence of PPAR-γ agonist pioglitazone (PG) on the mRNA expression profile of principle clock genes and inflammation-related genes in the mouse liver disrupted by reverse feeding. Methods. Mice were randomly assigned to daytime-feeding and nighttime-feeding groups. Mice in daytime-feeding groups received food from 7 AM to 7 PM, and mice in nighttime-feeding groups received food from 7 PM to 7 AM. PG was administered in the dose of 20 mg/kg per os as aqueous suspension 40 μl at 7 AM or 7 PM. Each group consisted of 12 animals. On day 8 of the feeding intervention, mice were sacrificed by cervical dislocation at noon (05 hours after light onset (HALO)) and midnight (HALO 17). Liver expressions of Bmal1, Clock, Rev-erb alpha, Cry1, Cry2, Per1, Per2, Cxcl5, Nrf2, and Ppar-γ were determined by quantitative reverse transcription PCR. Liver expression of PPAR-γ, pNF-κB, and IL-6 was determined by Western blotting. Glucose, ceruloplasmin, total cholesterol, triglyceride concentrations, and ALT and AST activities were measured in sera by photometric methods. The null hypothesis tested was that PG and the time of its administration have no influence on the clock gene expression impaired by reverse feeding. Results. Administration of PG at 7 AM to nighttime-feeding mice did not reveal any influence on the expression of the clock or inflammation-related genes either at midnight or at noon. In the daytime-feeding group, PG intake at 7 PM led to an increase in Per2 and Rev-erb alpha mRNA at noon, an increase in Ppar-γ mRNA at midnight, and a decrease in Nfκb (p65) mRNA at noon. In general, PG administration at 7 PM slightly normalized the impaired expression of clock genes and increased anti-inflammatory potency impaired by reversed feeding. This pattern was supported by biochemical substrate levels—glucose, total cholesterol, ALT, and AST activities. The decrease in NF-κB led to the inhibition of serum ceruloplasmin levels as well as IL-6 in liver tissue. According to our data, PG intake at 7 PM exerts strong normalization of clock gene expression with a further increase in Nrf2 and, especially, Ppar-γ and PPAR-γ expression with inhibition of Nfκb and pNF-κB expression in daytime-feeding mice. These expression changes resulted in decreased hyperglycemia, hypercholesterolemia, ALT, and AST activities. Thus, PG had a potent chronopharmacological effect when administered at 7 PM to daytime-feeding mice. Conclusions. Our study indicates that reversed feeding induced the disruption of mouse liver circadian expression pattern of clock genes accompanied by increasing Nfκb and pNF-κB and IL-6 expression and decreasing Nrf2 and PPAR-γ. Administration of PG restored the clock gene expression profile and decreased Nfκb, pNF-κB, and IL-6, as well as increased Nrf2, Ppar-γ, and PPAR-γ expression. PG intake at 7 PM was more effective than at 7 AM in reversed feeding mice.

Allergen immunotherapy (AIT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many guidelines or national practice guidelines have been produced but the evidence- based method varies, many are complex and none propose care pathways. This paper reviews care pathways for AIT using strict criteria and provides simple recommendations that can be used by all stakeholders including health professionals. The decision to prescribe AIT for the patient should be individualized and based on the relevance of the allergens, the persistence of symptoms despite appropriate medications according to guidelines as well as on the availability of good-quality and efficacious extracts. Allergen extracts cannot be regarded as generics. Immunotherapy is selected by specialists for stratified patients. There are no currently available validated biomarkers that can predict AIT success. In adolescents and adults, AIT should be reserved for patients with moderate/severe rhinitis or for those with moderate asthma who, despite appropriate pharmacotherapy and adherence, continue to exhibit exacerbations that appear to be related to allergen exposure, except in some specific cases. Immunotherapy may be even more advantageous in patients with multimorbidity. In children, AIT may prevent asthma onset in patients with rhinitis. mHealth tools are promising for the stratification and follow up of patients.

Tumor-associated macrophages (TAM) of the M2-type dominate in tumors and produce molecules, favorable for their growth, stimulating tumor growth. However, changing the M2-type for M1 can slow down or arrest this growth. For realization of the M1 / M2 modulation direction in the treatment of carcinoma / breast cancer (BC), a substantiated diagnosis and confirmation of the TAM negative prognosis is necessary. Therefore, the aim of the study was to evaluate the relation of tumor associated macrophages to the postoperative prognosis / survival of patients with 5 molecular-biological types of breast carcinoma. Materials of the study were intraoperative tissues of tumors and ipsilateral lymph nodes in radically removed mammary glands. Pathomorphological study of lymph nodes was conducted to clarify the diagnosis in relation to N0/1. The density of TAM infiltration was determined by immunohistochemical staining of CD68 and CD163 in 30 samples of five molecular biological types of breast cancer (three clinical cases of each type). Immunohistochemical (IHC) studies for the determination of TAM and M2-like macrophages were conducted using streptavidin-peroxidase method. The quantitative representation of CD68 + and CD163 + Mph is very different from patient to patient and also within one sample, which depends, in particular, on the morphological characteristics of breast cancer, studied by the biopsy. The density of infiltration by CD163 + macrophages of the BC focus negatively correlated with postoperative survival, which did not reach statistical significance, but is included in the general concept of a negative prognosis of infiltration by M2-like macrophages. Further research is needed to confirm the negative significance of the ТАМ infiltration density in the BC primary focus for postoperative prognosis. Promising is the development of differential diagnosis and approach to the treatment of breast cancer, taking into account the levels of its infiltration by subpopulations of TAM.

Reported COVID-19 deaths in Germany are relatively low as compared to many European countries. Among the several explanations proposed, an early and large testing of the population was put forward. Most current debates on COVID-19 focus on the differences among countries, but little attention has been given to regional differences and diet. The low-death rate European countries (e.g. Austria, Baltic States, Czech Republic, Finland, Norway, Poland, Slovakia) have used different quarantine and/or confinement times and methods and none have performed as many early tests as Germany. Among other factors that may be significant are the dietary habits. It seems that some foods largely used in these countries may reduce angiotensin-converting enzyme activity or are anti-oxidants. Among the many possible areas of research, it might be important to understand diet and angiotensin-converting enzyme-2 (ACE2) levels in populations with different COVID-19 death rates since dietary interventions may be of great benefit.

Background: Google Trends (GT) searches trends of specific queries in Google, which potentially reflect the real-life epidemiology of allergic rhinitis. We compared GT terms related to ragweed pollen allergy in American and European Union countries with a known ragweed pollen season. Our aim was to assess seasonality and the terms needed to perform the GT searches and to compare these during the spring and summer pollen seasons. Methods: We examined GT queries from January 1, 2011, to January 4, 2017. We included 15 countries with a known ragweed pollen season and used the standard 5-year GT graphs. We used the GT translation for all countries and the untranslated native terms for each country. Results: The results of “pollen,” “ragweed,” and “allergy” searches differed between countries, but “ragweed” was clearly identified in 12 of the 15 countries. There was considerable heterogeneity of findings when the GT translation was used. For Croatia, Hungary, Romania, Serbia, and Slovenia, the GT translation was inappropriate. The country patterns of “pollen,” “hay fever,” and “allergy” differed in 8 of the 11 countries with identified “ragweed” queries during the spring and the summer, indicating that the perception of tree and grass pollen allergy differs from that of ragweed pollen. Conclusions: To investigate ragweed pollen allergy using GT, the term “ragweed” as a plant is required and the translation of “ragweed” in the native language needed.

Background Grass pollen allergy is an important trigger for the development of respiratory disorders. Defining the grass pollen season onset is critical for correct allergy diagnosis and personalized therapy. The development of a pan-European sentinel network for allergic diseases has raised the problem of translating the Google search terms into different European languages as well as defining specific pollen season characteristics in different regions. Grass pollen allergy was investigated due to high allergenicity and wide expansion of grass pollen in Europe. Objectives The aim of this study was to examine which translations of “hay fever”, “grass”, and “rhinitis” could be used in the native Cyrillic languages, especially in Ukrainian and Russian, and to compare the seasonality of allergic respiratory queries in Ukraine with the grass pollen counts. Methods Google Trends (GT) was used to search Google queries concerning grass pollen allergy: “allergy”, “hay fever”, “runny nose”, “grass”, “asthma”, and “pollen”. The Cyrillic terms in Ukrainian and Russian were used. The search was done for the period from 2013 to 2017. Pollen collection from 2013 to 2016 was conducted using volumetric methods. Average daily temperatures were obtained from http://gismeteo.ua . Correlations were assessed by Spearman (R) test. Results The Ukrainian Google users searched the Cyrillic equivalents for “runny nose”, “grass”, and “asthma”. Due to the GT queries profile, Ukraine had a “D” pattern according to the classification, developed by Bousquet J et al (2017). In Ukraine, the Poaceae pollen season generally occurred between the second ten-day period of May and the last ten-day period of July. The Poaceae pollen season started with a concentration of pollen grains of 8.0 m−3. This concentration provoked the growth of GT “grass”, “allergy”, “hay fever”, and “asthma” queries. Conclusions The terms “grass”, “allergy”, “hay fever”, and “asthma” (in their Cyrillic equivalents) are required in Ukraine to account for the grass pollen exposure by GT. The study of GT may be a useful tool to make an assessment of the grass pollen season for the prevention and minimization of exposure to significant grass pollen concentrations.

Background: Severe asthma is a serious condition with a significant burden on patients' morbidity, mortality, and quality of life. Some biological therapies targeting the IgE and interleukin-5 (IL5) mediated pathways are now available. Due to the lack of direct comparison studies, the choice of which medication to use varies. We aimed to explore the beliefs and practices in the use of biological therapies in severe asthma, hypothesizing that differences will occur depending on the prescribers’ specialty and experience. Methods: We conducted an online survey composed of 35 questions in English. The survey was circulated via the INterasma Scientific Network (INESNET) platform as well as through social media. Responses from allergists and pulmonologists, both those with experience of prescribing omalizumab with (OMA/IL5) and without (OMA) experience with anti-IL5 drugs, were compared. Results: Two hundred eighty-five (285) valid questionnaires from 37 countries were analyzed. Seventy-on percent (71%) of respondents prescribed biologics instead of oral glucocorticoids and believed that their side effects are inferior to those of Prednisone 5 mg daily. Agreement with ATS/ERS guidelines for identifying severe asthma patients was less than 50%. Specifically, significant differences were found comparing responses between allergists and pulmonologists (Chi-square test, p < 0.05) and between OMA/IL5 and OMA groups (p < 0.05). Conclusions: Uncertainties and inconsistencies regarding the use of biological medications have been shown. The accuracy of prescribers to correctly identify asthma severity, according to guidelines criteria, is quite poor. Although a substantial majority of prescribers believe that biological drugs are safer than low dose long-term treatment with oral steroids, and that they must be used instead of oral steroids, every effort should be made to further increase awareness. Efficacy as disease modifiers, biomarkers for selecting responsive patients, timing for outcomes evaluation, and checks need to be addressed by further research. Practices and beliefs regarding the use of asthma biologics differ between the prescriber's specialty and experience; however, the latter seems more significant in determining beliefs and behavior. Tailored educational measures are needed to ensure research results are better integrated in daily practice.

Prerequisites and objective: Abdominal obesity is a common metabolic disease characterized by excessive accumulation of white adipose tissue, with excessive production of inflammatory mediators that activate transcriptional nuclear factors, in particular the nuclear factor kB. Hepcidin is the main hormone in the systemic regulation of iron. Its expression increases with elevated level of pro-inflammatory cytokines, as a result of which the concentration of iron in the blood plasma decreases, which reliably results in the activation of NF-kB. Therefore, the aim of the research was to determine the level of expression of ІКβα in subcutaneous adipose tissue in iron deficiency anemia concurrent with obesity. Methods: The study included 40 female women. Hemogram parameters, parameters of iron metabolism (serum iron, ferritin, hepcidin, total iron binding ability of serum, saturation of transferrin by iron) in serum and level of expression of the IkBα gene in subcutaneous adipose tissue were evaluated. Research results. The examined women had an average age of 40.3 ± 7.59 years. In the distribution of patients due to the cause and degree of severity of IDA, there was no reliable difference between the groups. The control group consisted of 10 obese women without IDA. Expression of IkBα by subcutaneous adipose tissue in female patients with IDA with and without obesity compared with the control group did not display a significant difference between the groups (p

Objective: The aim of this study was to determine the effect of quercetin on the indicators of chronic systemic inflammation (CSI) in stable coronary artery disease (CAD). Methods: This study included 85 patients with CAD, stable angina pectoris, functional class (FC) II, and heart failure (НF) 0-І. Each patient was prescribed beta-blockers, statins, and aspirin. In addition, a total of 30 patients, forming the study group received quercetin at a daily dose of 120 mg for two months, while the remaining 55 patients made up the control group. The levels of cytokines, such as tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and interleukin-10 (IL-10) in serum and the expression of the inhibitor of kappa B α (IkBα) gene in blood mononuclear cells, were determined. Results: The increased levels of IL-1β and TNF-α, as well as a moderate increase in IL-10 levels, were detected in the serum of patients with CAD. The expression of the IkBα gene (2–δСt) did not differ significantly between the groups. Under the influence of quercetin, levels of IL-1β and TNF-α were reduced and IL-10 levels tended to decrease. In contrast, the serum levels of these cytokines did not change significantly in the control group. The administration of quercetin decreased the expression of the IkBα gene (0.0092 ± 0.0033 against 0.0261 ± 0.0166, р = 0.003; 2–δδСt, 2.82 ± 1.39 times) in contrast to the control group. Conclusion: Quercetin showed anti-inflammatory properties in patients with CAD, indicating a decrease in transcriptional activity of the nuclear factor of transcription kappa B (NF-kB). Keywords: Coronary artery disease, Quercetin, Chronic systemic inflammation, Cytokines, Nuclear factor of transcription kappa B

Today, the issue of timely diagnosis and treatment of polytrauma remains highly relevant. Polytrauma is a severe pathological process that involves simultaneous onset and development of several pathological conditions and is characterized by underlying disorders of all types of metabolism, changes on the part of central nervous system, cardiovascular and respiratory tract. The given clinical case proves us expediency of developing the personified approach to management of patients with polytrauma, using the individual algorithms.

INHIBITION OF MARKERS OF THE IMMUNE INFLAMMATION IN BRONCHIAL ASTHMA INFLUENCED BY FULLERENE C60 NANOPMATERIALS

SARS-CoV-2 is a global threat that influenced healthcare systems around the world. This virus caused an infection in humans with different clinical signs and syndromes, severity, and mortality. The key components of the COVID-19 molecular pathogenesis are coronavirus entry and replication, antigen presentation, humoral and cellular immunity, cytokine storm, coronavirus immune evasion. The analysis of recent literature displayed possible molecular targets in the key components of the COVID-19 pathogenesis. Some of these targets might have gene polymorphisms that influenced the COVID-19 course. Unfortunately, several findings are still putative or extrapolated from SARS and MERS experimental investigations or clinical trials. We systematised original data about gene polymorphisms of possible molecular targets and associations with the COVID-19 course. Most data were obtained for angiotensin-converting enzymes 1 and 2, TMPRSS2 gene polymorphisms. Only a few results were found for gene polymorphisms of adhesion molecules, interferon system components, cytokines, and transcriptional factors, oxidative stress and metabolic molecules, as well as haemocoagulation. Understanding the host gene variability and its associations with COVID-19 can provide insights into the disease pathogenesis, individual susceptibility to SARS-CoV-2 infection, severity, complications, and mortality prognosis for the disease. Besides, these data might help in the identification of appropriate targets for intervention., Gene, Polymorphism, Infection, SARS-CoV-2, COVID-19, Pathogenesis

Introduction Introduction: Tumor-associated macrophages are an important prognostic factor and have been shown to be associated with invasion and migration of various types of cancer. Unlike M1-macrophages, which have pro-inflammatory and anti-cancer activity, M2-macrophages are immunosuppressive, promoting the restoration of the intracellular matrix, and therefore they contribute to the tumor growth. The aim: To study the quantitative characteristic and localization of CD68+ and CD163+ M2-like TAM that infiltrate non-luminal HER2-enriched carcinomas of BC in the primary focus without metastases and in paired specimens with metastases in the lymph nodes, as well as the pathomorphological characteristics of this type of BC. Material and methods The material of the study were intraoperative tissues of tumors and ipsilateral lymph nodes at radical removal of mammary glands. Immunohistochemical characteristics of the removed tumors (ER, PR, HER2, Ki67) were used to organize two groups of patients with primary BC according to the N1 / 0 status. Results The statistical processing of the entire set of digital data confirmed a significant increase in CD68+TAM, but not CD163+M2 under metastatic conditions (p

Pharmacists are trusted health care professionals. Many patients use over-the-counter (OTC) medications and are seen by pharmacists who are the initial point of contact for allergic rhinitis management in most countries. The role of pharmacists in integrated care pathways (ICPs) for allergic diseases is important. This paper builds on existing studies and provides tools intended to help pharmacists provide optimal advice/interventions/strategies to patients with rhinitis. The Allergic Rhinitis and its Impact on Asthma (ARIA)-pharmacy ICP includes a diagnostic questionnaire specifically focusing attention on key symptoms and markers of the disease, a systematic Diagnosis Guide (including differential diagnoses), and a simple flowchart with proposed treatment for rhinitis and asthma multimorbidity. Key prompts for referral within the ICP are included. The use of technology is critical to enhance the management of allergic rhinitis. However, the ARIA-pharmacy ICP should be adapted to local healthcare environments/situations as regional (national) differences exist in pharmacy care. ispartof: ALLERGY vol:74 issue:7 pages:1219-1236 ispartof: location:Denmark status: published