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Background: Severe atopic dermatitis (AD) is a complex disease requiring systemic treatment. This study aimed to assess the effectiveness of combined therapy consisting of dupilumab and sublingual dust mite allergen immunotherapy (SLIT-HDM) in patients with severe AD and HDM allergies. Methods: Patients diagnosed with severe AD were included in this randomised, placebo-controlled, double-blind 12-month trial; they received SLIT for HDMs and/or dupilumab for 12 months and were compared with patients on cyclosporine. The primary outcomes for the treatment arms were changes in the Eczema Area and Severity Index (EASI), body surface area (%BSA), and Investigator Global Assessment (IsGA) over 12 months. The secondary outcomes were the proportion of patients who achieved IsGA success and reduced medication scores. Results: Significant improvements were observed in all analysed groups after 12 months of therapy based on the EASI, %BSA, and IsGA. However, the most substantial changes were observed in the groups treated with dupilumab or a combination of SLIT-HDM and dupilumab. Additionally, the proportion of patients who achieved an IsGA reduction was significantly greater in the group receiving combination therapy than in the other groups (9/14 [64% of the group receiving SLIT-HDM] vs. 11/14 [73% of the group receiving dupilumab] vs. 15/17 [88% of the group receiving dupilumab and SLIT-HDM] vs. 7/13 [53% of the group receiving cyclosporine]) (p < 0.05). Conclusions: In patients with severe AD and HDM allergies, combination treatment with dupilumab and allergen immunotherapy for HDMs may increase the therapeutic benefit over treatment with these methods separately.

Determination of the hypericin–photodynamic (HY–PDT) effect on the secretion of cytokines secreted by the skin cells, may be the basis for using the immunomodulatory effect of photodynamic action in the treatment of inflammatory skin diseases. The study aimed to evaluate the cytotoxic and immunomodulatory effects of hypericin (HY) in photodynamic therapy (PDT) performed in vitro on cultures of selected skin cell lines. The study used two human cell lines, primary dermal fibroblast (HDFa) and primary epidermal keratinocytes (HEKa). The MTT test was used to define the metabolic activity of treated cells. Cell supernatants subjected to sublethal PDT were assessed to determine the interleukins: IL-2, IL-8, IL-10, IL-11, IL-19, IL-22, and metalloproteinase 1 (MMP-1). The results confirm the destructive effect of HY–PDT and the immunomodulatory effects of sublethal doses on the selected skin cells, depending on the concentration of HY and the light doses. No statistically significant differences were noted in IL-2 and IL-10 concentration after HY–PDT for HEKa and HDFa lines. After using HY–PDT, the concentration of IL-8, MMP-1, IL-22, and IL-11 significantly decreased in the HEKa line. Moreover, the concentration of IL-19 and MMP-1 significantly decreased in the HDFa line. The concentration of IL-11 in the HDFa line after using only the HY, without the light, increased but decreased after HY–PDT. Our experiment confirmed that HY–PDT has not only a cytotoxic effect but, used in sublethal doses, also presents immunomodulatory properties. These may be an advantage of HY–PDT when used in the treatment of persistent skin inflammation, connected with the release of pro-inflammatory cytokines resistant to conventional treatment methods.

Background: Allergen immunotherapy remains a widely recognized and widely used method for the treatment of selected allergic diseases. Currently, according to the European Academy Of Allergy and Clinical Immunology (EAACI) guidelines, venom immunotherapy (VIT) may be considered for patients over 60. Nevertheless, no separate studies have confirmed the efficacy and safety of this therapy. This study aimed to evaluate the short-term effectiveness of VIT against wasp allergens in an ultra-rush protocol for older patients compared to young patients. Methods: Among the 113 patients included in this study, 51 were older than 60 years (Group A), and 62 formed the control “young group” (age range: 18–35 years). All patients were desensitized to wasp venom using the ultra-rush protocol according to Muller and aqueous solutions of vaccines containing wasp venom. A basophil activation test (Basotest, Orpegen Pharma, Germany) and intracutaneous tests with dilutions of wasp allergen and specific IgE to extract wasp venom were performed at the start and after six months of VIT. The safety of VIT was assessed on the basis of the international Mueller scale. Results: One hundred and eleven patients with confirmed wasp allergies completed six months of VIT: 51 participants over 60 years of age (Group A) and 60 young people (Group B). No systemic adverse reactions were observed during the VIT induction phase. However, large local reactions were noted in 17% of older patients and 20% of young patients at a similar level (p > 0.05). During maintenance VIT, two mild grade I systemic reactions were confirmed in young patients. These symptoms resolved spontaneously. There were no such reactions in older patients. The effectiveness of VIT was tested using BAT. There was a statistically significant reduction in CD63 reactivity in 86% of patients in Group A, and a comparable and substantial decrease in 84% of young patients in Group B. According to the BAT test, the mean reductions in the area under the curve (AUC) after six months of VIT were significant (p < 0.05) and comparable between Groups A and B: −6.52 vs. 7.21. Conclusions: VIT against wasp venom is safe and effective in short-term observation, and is comparable to that used for young patients.

Insect venom is one of the most common triggers of anaphylaxis in the elderly population. Venom immunotherapy (VIT) remains the only treatment for Hymenoptera venom allergy (HVA). However, little is known about the differences in indication for VIT in the group of patients aged 60 years and older. The objective of this study was to assess the clinical and diagnostic differences of HVA in elderly patients. The study compared data from patients aged ≥ 60 (N = 132) to data from patients aged from 11 to 60 years (N = 750) in terms of HVA severity, comorbidities, and immunological parameters, namely, intradermal testing (IDT), specific IgE (sIgE) levels against extracts and major allergenic molecules, and serum tryptase level (sBT). The severity of systemic HVA (I–IV Müller scale) did not differ between adults and seniors. However, the severity of cardiovascular reactions (IV) increased with age, while the frequency of respiratory reactions (III) decreased. No differences were found in the immunological parameters of sensitization IDT, venom-specific IgE concentrations, or sIgE against Api m 1, 2, 4, 5, and 10 between patients below and above 60 or 65 years of age. Differences were noted for sIgE against Ves v1 and Ves v5; they were higher and lower, respectively, in seniors. In the seniors group, sBT levels were higher. Elevated tryptase levels, along with the aging process, can represent a risk factor within this age category. Nevertheless, advanced age does not influence the immunological parameters of immediate HVA reactions, nor does it impact the diagnosis of HVA.

Atopic dermatitis (AD) is an abnormal inflammatory response in the skin to food, environmental IgE, or non-IgE allergens. This disease belongs to a group of inflammatory diseases that affect both children and adults. In highly developed countries, AD is diagnosed twice as often in children than in adults, which may possibly be connected to increased urbanization. The immune system’s pathomechanisms of AD involve humoral mechanisms with IgE, cellular T lymphocytes, dendritic cells occurring in the dermis, Langerhans cells occurring in the epidermis, and other cells infiltrating the site of inflammation (eosinophils, macrophages, mast cells, neutrophils, and basophils). Cytokines are small proteins that affect the interaction and communication between cells. This review characterizes cytokines and potential aspects of the treatment of atopic dermatitis, as well as new strategies that are currently being developed, including targeting cytokines and their receptors.

Research on the development of photodynamic therapy for the treatment of brain tumors has shown promise in the treatment of this highly aggressive form of brain cancer. Analysis of both in vivo studies and clinical studies shows that photodynamic therapy can provide significant benefits, such as an improved median rate of survival. The use of photodynamic therapy is characterized by relatively few side effects, which is a significant advantage compared to conventional treatment methods such as often-used brain tumor surgery, advanced radiotherapy, and classic chemotherapy. Continued research in this area could bring significant advances, influencing future standards of treatment for this difficult and deadly disease.

Background The application of allergen immunotherapy (AIT) in combination with biological agents has been found to increase both the safety and efficacy of the desensitisation procedure in patients with food and insect venom allergy. The aim of our study was to compare the effectiveness of AIT in patients with house dust mite (HDM)-driven asthma treated with and without omalizumab. Materials and methods The study was a placebo-controlled, three-armed, randomised, parallel-group, multicentre trial that included 52 patients with HDM-driven asthma. Only patients with monosensitisation to HDM were included. The study compared three patterns of therapy: omalizumab alone, HDM subcutaneous immunotherapy (SCIT-HDM)+ omalizumab, and SCIT alone. The main outcomes were evaluate the Asthma Control Questionnaire (ACQ) score, number of asthma exacerbations and reduction in the daily dose of inhaled steroids during 12 months of observation. Results All variants of therapy led to significantly improved ACQ scores and reduction of asthma exacerbations in all study groups after 12 months of treatment. A statistically significant reduction in the daily doses of inhaled corticosteroids in the group with omalizumab alone (650±150 µg versus 500±50 µg for p=0.003) or SCIT-HDM+omalizumab (550±250 µg versus 375±75 µg for p=0.001) was observed, favouring the latter group. Conclusion The efficacy of AIT for HDM-driven asthma is significantly increased by the combination of allergen vaccine with omalizumab.

Abstract Background Angioedema without urticaria (AWU) is a disease found in the elderly population but is still poorly studied. The aim of this study was to investigate potential factors, especially comorbidities, that may affect the induction of angioedema without urticaria in patients over 60 years of age. Methods This was an observational, retrospective study of 242 patients with a diagnosis of AWU and 263 controls. The inclusion criteria were as follows: at least one episode of confirmed AWU based on the ICD-10 code (T78.3) that required treatment in the last 15 years (2004–2019); age above 60 years; detailed medical history of comorbidities; and details regarding the use of drugs at that time. Serum functional and quantitative C1 inhibitor assays were performed, and serum C4 was measured. Comorbidities were grouped into the following panels: autoimmune, cancer, cardiac, metabolic, respiratory and allergic, liver failure and renal failure. Individual diseases were checked according to ICD code and treatment. Results In 1 (0.4%) patient, hereditary angioedema was confirmed. Decreased levels of C1INH were observed in 4 (1.65%) patients, dysfunction of C1INH was observed in 5 (1.76%) patients, and low levels of C4 were observed in 9 (3.71%) patients in the study group. The multiple logistic regression model revealed that patients with hyperuricemia or Hashimoto’s disease had a significantly higher chance of angioedema (OR = 3.21, 95% CI 2.92–3.66, p = 0.002; OR = 1.78 95% CI 1.37–2.21, p = 0.034, respectively). Conclusion The obtained results may indicate a significant influence of hyperuricemia or Hashimoto’s disease on angioedema manifestations.

Among the potential hazards of HDM immunotherapy (AIT) with HDM allergenic extracts is the possible initiation of de novosensitizations caused by a lack of complementarity between a given HDM vaccine’s content and a patient’s molecular sensitization profile. To investigate whether immunotherapy with HDM extracts affects changes in the profile of sensitizations to allergens contained in the extract and whether neosensitizations occur. Serum samples from patients with HDM allergies (N=63) who received 1 year of treatment with subcutaneous AIT were tested for allergen-specific IgE (sIgE) reactivity to 7 microarrayed HDM allergen molecules (Der p 1, 2,10,11,23; D far 1 and 2) with ImmunoCAP. The HDM non-AIT patients (N=22) who did not receive immunotherapy constituted the study’s control group. The obtained data were analysed at baseline and after 6 and 12 months. In the HDM-AIT group, no neosensitizations after 6 and 12 months of immunotherapy were reported. Conversely, in the HDM non-AIT group, only neosensitizations to Der p 10 were observed. In the study group, sIgE levels against the HDM extract of D. pteronyssinus, D. farinae, rDer p 1, rDer p 2 and Der f 2 decreased after 12 months of AIT (p< .05). SIgE levels against Der f 1, Der p 10, 11 and 23 remained unchanged in the course of 12 months of immunotherapy. In patients with allergic rhinitis with or without concomitant HDM-induced asthma treated with HDM AIT for 12 months, no neosensitizations related to the examined HDM molecules were observed.

Background and Objectives. Acquired angioedema is a relatively common revelation accompanying some diseases such as autoimmune or cancer. The study aimed to assess the incidence of one subtype of angioedema—C1-INH-AAE (acquired angioedema with C1 inhibitor deficiency). Material and methods. The study was retrospective and based on 1 312 patients with a final diagnosis of breast cancer, colorectal cancer, or lung cancer: 723 women and 589 men with a mean age of 58.2 ± 13.5 years. The cancer diagnosis according to the ICD (International Classification of Diseases)-10 code, medical history including TNM (Tumour, Node, Metastasis) staging, histopathology, and assessment of the occurrence of C1-INH-AAE angioedema were analysed. Results. C1-INH-AAE occurred more often in patients with cancer than in the control group, as follows: 327 (29%) vs. 53 (6%) for p < 0.05. C1-INH-AAEs were observed most often in the group of patients diagnosed with breast cancer compared to colorectal and lung groups: 197 (37%) vs. 108 (26%) vs. 22 (16%) (p < 0.05). A higher incidence of C1-INH-AAE was observed in the early stages of breast cancer. However, there was no relationship between the occurrence of C1-INH-AAE and the BRCA1 (Breast Cancer gene 1)/BRCA2 (Breast Cancer gene 2) mutation or histopathological types of breast cancer. Conclusion. Angioedema type C1-INH-AAE occurs more often in patients with selected neoplastic diseases, especially in the early stages of breast cancer.

Background and objectives: In psoriatic patients, stress is the most common aggravating factor. Despite the use of quality-of-life assessment questionnaires, diagnosing stress in psoriatic patients is not a flawless procedure. This study aimed to assess the usefulness of potential stress biomarkers in saliva for monitoring the treatment of psoriasis. Materials and methods: A total of 104 adult patients with severe psoriasis were included and randomly treated via biological treatment or symptomatic therapy: 84 received biological treatment, with 20 formed a control group receiving symptomatic therapy. The administered biological treatment was adalimumab, whilst in controls calcipotriol/betamethasone dipropionate topical gel and emollients were used. Patients were monitored monthly with a dermatological examination and the dispensing of a biological drug. During each of the four visits, the severity of the disease was assessed (PASI, BSA, and DLQI), and a sample of the patient’s saliva was taken. In all the participants, the saliva concentrations of immunoglobulin A (sIgA), α-amylase (sAA), and chromogranin A (CgA) were measured. Results: The majority of patients in both the study and control groups achieved clinical improvement, though favoring the group receiving biological treatment. The concentration of sIgA in the saliva was constantly increasing in the study group during subsequent visits (Fr = 27.26; p < 0.001). Meanwhile, there were no statistically significant changes in the control group during the same follow-up period (Fr = 6.66; p = 0.084). Levels of sAA underwent statistically significant changes in both groups (Fr = 58.02; p < 0.001—study group and Fr = 13.74; p = 0.003—control group). In the study group, a steady, statistically significant increase in sAA was observed from the first to the third visit. In the study group, a downward trend in CgA concentration was observed. In the control group, no significant differences in the level of CgA were obtained. Conclusions: sIgA, sAA, and CgA are potential markers of the severity of psoriasis and the associated stress reaction. Based on the presented observations, only sIgA and CgA seem to be valuable biomarkers for monitoring the effectiveness of the systemic treatment of psoriasis.

Tuning rules for PID and PI-PI servo controllers are developed using a pole placement approach with a multiple pole, i.e. a triple one in the case of PID and a quadruple for PI-PI. The controllers involve complex roots in the numerators of the transfer functions. This is not possible in the classical P-PI structure which admits real roots only. The settling time of the servos determined by the multiple time constant is the only design parameter. Nomograms to read out discrete controller settings in terms of the time constant and control cycle are given. As compared to the classical structures, the upper limit on the control cycle is now twice longer in the case of PID, and four times in the case of PI-PI. This implies that the settling times can be shortened by the same ratios. Responses of a PLC-controlled servo confirm the validity of the design.

Background and objectives: Allergen immunotherapy (AIT) is not a first-line therapy in atopic dermatitis (AD) and its effectiveness has been criticised. Objectives: The efficacy and safety of AIT in adult patients with AD and monosensitisation to house dust mites (HDMs) were investigated. Materials and Methods: A total of 37 patients were included in this double-blind, placebo-controlled study. Patients were eligible if they were diagnosed with AD; had moderate-to-severe AD according to the Eczema Area and Severity Index (EASI) with at least 7.1 points, the % BSA (body surface area) scale with at least 16 points, and the IsGA (investigator global assessment) scale with 3 points; had positive skin prick tests (SPTs); and were positive for the specific immunoglobulin E (sIgE) response to D. pteronyssinus and D. farinae extracts, as well as Der p 1 and Der f1. The patients received Purethal mites (20,000 AUeq/mL, HAL Allergy, Leiden, The Netherlands) with the extract allergens D. pteronyssinus and D. farinae (50/50%) or a placebo for 12 months. The primary outcomes included changes in EASI, % BSA, and IsGA due to SCIT between the start and after 12 months of therapy. Results: In the study group, significant improvement was observed in terms of the EASI score from 43 ± 8.2 to 21 ± 5.9 points, % BSA from 72 ± 18 to 28 ± 11 points, and IsGA from 4.5 ± 0.5 to 1.5 ± 0.5 points in comparison with the placebo after 1 year of AIT. Additionally, the proportion of patients who achieved success in the IsGA (IsGA < 2) was significantly better in comparison to the placebo with 13/20 (65%) vs. 4/14 (29%), respectively (p < 0.05). Conclusions: HDM-AIT effectively improved atopic dermatitis in patients that strictly qualified for desensitisation with a confirmed monovalent mite allergy.

Simulation is a powerful process for perfectly planning and dimensioning web systems. However, a successful analysis using a simulation model usually requires variable load intensities. Furthermore, as the client’s behavior is subject to frequent changes in modern web systems, such models need to be adapted as well. Based on web systems observation, we come across the need for tools that allow flexible definitions of web systems load profiles. We propose Timed Colored Petri Nets (TCPN) event generators for web environments that could be used to drive simulations for performance evaluation. The article proposes the systematization of the generators for future development. The theoretical part focuses on a classification with a division into deterministic/stochastic and untimed/timed generators. Next, in this study, we investigate representative models of generators from different classes based on the formalism of TCPN. We perform model design and simulation processes using CPN Tools software. Finally, we present a case study involving workload analysis of a web system that processes requests from the designed generator.

Background and objectives: Atopic dermatitis (AD) and psoriasis (PS) are systemic inflammatory diseases with complex and distinct immune mechanisms. That the same factors may aggravate both diseases cannot be ruled out. The aim of this study was to assess the potential differences between a sensitization to inhaled allergens and the immunological profiles of patients diagnosed with AD and PS in comparison with healthy controls. Materials and methods: A total of 139 patients with AD, 115 with PS, and 142 controls were included in the prospective study. Patients were eligible if they were diagnosed with mild to severe AD or PS and between 18 and 65 years of age. In all the participants, the serum concentrations of specific IgE (sIgE) for common inhaled allergens were measured. In all the subjects, the cytokine serum blood profiles for TNF-α, IFN-γ, Il-2, Il-4, Il-5, Il-6, Il-8, Il-12, Il-17, Il-18, Il-22, and Il-24 were measured via an ELISA. Results: The patients with AD had positive sIgE results more frequently than the patients with PS and the controls (113 vs. 36 vs. 21, respectively). A sensitization to mites was dominant in the patients with AD (p < 0.05), and a sensitization to Aspergillus was dominant in the patients with PS (p < 0.05). The patients with multiple allergies to inhaled allergens had a lower risk of developing PS (OR = 0.65; 95% CI: 0.43–0.86) but a greater risk of severe AD (OR = 3.77; 95% CI: 3.25–3.96). The mean concentrations of the most tested cytokines were comparable in the patients with AD and PS. However, high serum concentrations of Il-4, Il-5, and Il-6 were only dominant in the AD group. There were no relationships between the increased serum concentrations of individual cytokines and allergies to the individually examined allergens. Conclusion: Inhalation-dependent IgE sensitizations were prevalent in the AD patients but were also possible in the PS patients; they were often without clinical manifestations in the latter group. The investigated cytokine profiles indicated their high convergence in the studied patients and confirmed the active inflammatory nature of AD and PS.

BACKGROUND:An increased prevalence of allergies and an increased incidence of breast cancer have been observed. The hypothesis that atopy may have a protective effect against the risk of different types of breast cancer was evaluated. METHODS:In this study, 11,101 patients (11,101 women with a mean age of 55.2±14.7 years) with different types of breast cancer were tested for allergies. Allergies were confirmed based on the retrospective analysis of allergy diagnostic procedures in patients who had been previously diagnosed with breast cancer. The retrospective prevalence rates of active allergic diseases, including allergic rhinitis, bronchial asthma and atopic dermatitis, were assessed. All patients were also analyzed for bronchial asthma and allergic rhinitis according to the relevant guidelines. A group of healthy control patients was used for the comparisons. RESULTS:The women with breast cancer had a significantly lower incidence of IgE-mediated allergic diseases than the controls. The odds ratios (ORs) for allergic rhinitis, atopic dermatitis, and bronchial asthma were 0.61 (95% CI: 0.57-0.73), 0.17 (95% CI: 0.11-0.44), and 0.73 (95% CI: 0.65-0.83), respectively. The mean serum concentrations of total IgE were significantly lower in the study population of women with breast cancer than in the patients of the control group (39.2 ± 26.2 kU/L vs. 108.5 ± 38.5 kU/L; p = 0.002). CONCLUSION:Our results suggest that the overall incidence of allergies, especially allergic rhinitis, is lower in patients with certain types of cancer than in individuals who did not have cancer. Further studies are needed to confirm our findings.

The stick-slip is one of negative phenomena caused by friction in servo systems. It is a consequence of complicated nonlinear friction characteristics, especially the so-called Stribeck effect. Much research has been done on control algorithms suppressing the stick-slip, but no simple solution has been found. In this work, a new approach is proposed based on genetic programming. The genetic programming is a machine learning technique constructing symbolic representation of programs or expressions by evolutionary process. In this way, the servo control algorithm optimally suppressing the stick-slip is discovered. The GP training is conducted on a simulated servo system, as the experiments would last too long in real-time. The feedback for the control algorithm is based on the sensors of position, velocity and acceleration. Variants with full and reduced sensor sets are considered. Ideal and quantized position measurements are also analyzed. The results reveal that the genetic programming can successfully discover a control algorithm effectively suppressing the stick-slip. However, it is not an easy task and relatively large size of population and a big number of generations are required. Real measurement results in worse control quality. Acceleration feedback has no apparent impact on the algorithms performance, while velocity feedback is important.

Introduction and objective The aim of the study was to evaluate the differences between asthma and COPD on the basis of the prevalence and profile of IgE-dependent sensitization to inhaled allergens, and the blood serum levels of select Th1/Th2 cytokines. Material and methods 103 patients with COPD (114 patients with asthma and 121 controls) were included in the study. A skin prick test with common inhaled allergens was performed, and serum levels of IgE were measured in all subjects. Lymphocyte profiles were measured via the whole-blood method using fresh 10-ml blood samples treated with EDTA. The following surface antigens were measured: CD3, CD29, CD16, CD56, CD4, CD8, and HLA-DR. The Th1/Th2 profile in blood serum was determined using Th1/Th2 cytokine kits. Results IgE-dependent sensitization to environmental allergens was found in 34 (33.3%) patients with COPD, 46 (40%) patients with asthma and in 14 (11.5%) volunteers. The odds ratio of sensitization in patients with COPD reached 0.89 (95% CI: 0.57–1.08) and it was more frequent than in the control population with an odds ratio of 0.71 (95% CI: 0.64–0.88). The serum concentration of IL-2 was significantly higher in patients with COPD and asthma than in controls. In the subgroup of patients with non-allergic asthma, similar serum concentrations were observed for all analyzed cytokines, except for IFN-gamma, which was lower in patients with COPD. Conclusions Both the prevalence and profile of IgE-dependent sensitization to inhaled allergens did not differ between asthma and COPD. Both Th2 and Th1 played a role in the immunopathology of asthma and COPD. Abbreviations COPD – Chronic Obstructive Pulmonary Disease; FEV1 – forced expiratory volume in one second; FVC – forced expiratory volume; GINA – Global Initiative for Asthma; GOLD – Global Initiative for Chronic Obstructive Lung Disease; MMRC – Modified Medical Research Council; Th1 – lymphocyte helper 1; Th2 – lymphocyte helper 2

Background: Specific allergen immunotherapy to Hymenoptera venom (VIT) is a basic treatment for patients allergic to Hymenoptera venom. The aim of the study was to evaluate the safety of an ultra-rush regimen compared with the rush and conventional protocols. Materials and methods: In 31 patients with an allergy to bee venom and 82 with an allergy to wasp venom, the allergic adverse reactions during VIT were monitored. Patients were selected based on the criteria established by EAACI (European Academy of Allergy and Clinical Immunology) recommendations. Adverse reactions during the ultra-rush immunotherapy were measured, documented and classified according to the criteria of Mueller. Ultra-rush, rush or conventional protocols of the initial phase VIT using the Venomenhal vaccine (Hal Allergy, Leiden, Netherlands) were conducted. Results: Six (13.7%) patients on the ultra-rush regimen, 5 (14.3%) patients on the rush regimen and 9 (26.5%) on conventional VIT experienced an allergic reaction. There were no associations between the adverse allergic reactions and the following factors: gender, total IgE and allergen-specific IgE to wasp or bee venom before the VIT and cardiological drugs that were used. Conclusion: We found that the ultra-rush protocol (similar to the rush protocol) using the Venomenhal vaccine is safer than the conventional protocol.

Abstract Background Allergen specific immunotherapy (AIT) in elderly patients is controversial, and there is still little evidence supporting the safety and efficacy of this treatment in this population. The study objective was to evaluate the safety and efficacy of AIT for house dust mite allergens in patients over 65 years of age with allergic rhinitis (AR) and a documented allergy to house dust mites. The primary endpoint was the change from baseline in the mean average adjusted symptom score (AAdSS) and the total combined rhinitis score (TCRS) difference in the least square means for the label compared to placebo. Methods Fifty-eight AR elderly patients who were monosensitized to house dust mites were individually randomized in comparable numbers to one of two parallel groups with the following interventions: 2 years of perennial AIT using PURETHAL Mites or placebo. The symptoms and medication scores were presented as the AAdSS and TCRS. Quality of life, based on the rhinoconjunctivitis quality of life questionnaire (RQLQ), nasal allergen provocation responsiveness, serum allergen-specific IgG4 to D. pteronyssinus and D. farinae and Der p1 and Der p2 were monitored. The intent-to-treat population was analysed. Results After 24 months of AIT, AAdSS significantly decreased from 4.27 ± 1.58 to 1.82 ± 0.71 (p

Background and objectives: Biological treatment is an important and effective therapy for psoriasis. During the COVID-19 pandemic, it remains unclear whether this type of therapy affects the course of SARS-CoV-2 infection. The aim of the study was to observe patients with psoriasis undergoing biological or other systemic treatment in relation to the impact of SARS-CoV-2 infection on the course of psoriasis and the COVID-19 disease itself. Materials and methods: A one-year observational study included 57 patients with diagnosed psoriasis who qualified for biological treatment and a group of 68 similar patients who were administered a different systemic treatment. Patients were analyzed monthly for psoriasis (including Psoriasis Area Severity Index (PASI) assessment) and constantly for SARS-CoV-2 infection (telephone contact). Cases of COVID-19 were confirmed by Polymerase Chain Reaction (PCR) at the study center. Results: SARS-CoV-2 infection was confirmed by a positive Real Time Polymerase Chain Reaction (RT-PCR) test in eight patients (14.0%) with psoriasis on biological therapy. None of the cases in this group required hospitalization for COVID-19. Similar data were obtained in the control group. Specifically, 11 (16%) patients were confirmed to be infected with SARS-CoV-2. These results were statistically comparable (p > 0.05). In the group of patients undergoing biological treatment, six (75%) of eight patients developed an exacerbation of psoriasis during SARS-CoV-2 infection, and similar results were noted in the control group, with eight (72%) patients experiencing an exacerbation of psoriasis. Conclusions: Patients with psoriasis who were administered biological treatment or other systemic therapy may experience a mild course of SARS-CoV-2 infection but might also experience a temporary exacerbation of skin lesions.

Background and Objectives: Atopic dermatitis (AD) is a disease with a complex pathophysiology involving immune-mediated reactions that lead to skin lesions that are typically localized and recurrent. Following the outbreak of the COVID-19 (coronavirus disease 2019) pandemic, attempting to assess the impact of SARS-CoV-2 infection on diseases caused by complex immune mechanisms has become important. The aim of this study was to assess the impact of SARS-CoV-2 infection on the course of AD, including immunosuppressive therapy, in patients with a severe form of the disease. Materials and Methods: A retrospective analysis of 21 adults aged 18 to 52 years with AD diagnosed with COVID-19, including patients requiring hospitalization, was performed. Results: During SARS-CoV-2 infection, temporary exacerbation of skin lesions and/or skin pruritus was observed in nine (43%) patients but without the need for systemic treatment intervention. Patients with severe AD who received immunosuppressive therapy most often manifested mild exacerbation of skin symptoms. The skin condition improved in three patients. There was no significant effect of disease severity on the risk of severe COVID-19 (HR = 0.45; 95% CI: 0.32–0.65). Conclusions: The course of atopic dermatitis during SARS-CoV-2 infection may be different from the severity of its symptoms due to the lack of a significant influence. The immunosuppressive treatment used in patients with severe AD did not significantly affect the course of SARS-CoV-2 infection.

Chronic and infected leg ulcers (LUs) are painful, debilitating, resistant to antibiotics, and immensely reduce a patient’s quality of life. The purpose of our study was to demonstrate the efficacy of photodynamic therapy (PDT) for the treatment of infected chronic LUs. Patients were randomized into two experimental groups: the first group received 5-aminolevulinic acid photodynamic therapy (ALA-PDT) (10 patients), and the second group of 10 patients received local octenidine dihydrochloride (Octenilin gel) exposed to a placebo light source with an inserted filter that mimiced red light. In the PDT group, we used 20% ALA topically applied for 4 hrs and irradiation from a Diomed laser source with a wavelength of 630 nm at a fluency of 80 J/cm2. ALA-PDT was performed 10 times during a 14-day hospitalization in 10 patients of both sexes aged 40–85 years with chronic leg ulcers. Treatments were carried out at 3-week intervals for 3–5 cycles. At 8-month follow-up with the PDT group, complete remission (CR) was obtained in four patients (40%), partial response (>50% reduction in ulcer diameter) in four patients (40%), and no response in two patients (20%) who additionally developed deterioration of the local condition with swelling, erythema, and inflammation. To assess the degree of pain during the trials, we used a numeric rating scale (NRS). From the preliminary results obtained, we concluded that PDT can be used to treat leg ulcers as a minimally invasive and effective method with no serious side effects, although further studies on a larger group of patients with LUs are warranted.

A problem to determine a production schedule which minimises the cost of energy used for manufacturing is studied. The scenario assumes that each production task has assigned constant power consumption, price of power from conventional electrical grid system is defined by time-of-use tariffs, and a component of free of charge renewable energy is available for the manufacturing system. The objective is to find the most cost-efficient production plan, subject to constraints involving predefined precedence relationships between the tasks and a bounded makespan. Two independent optimisation approaches have been developed, based on significantly different paradigms, namely mixed-integer linear programming and tabu search metaheuristic. Both of them have been verified and compared in extensive computational experiments. The tabu search-based approach has turned out to be generally more efficient in the sense of the obtained objective function values, but advantages of the use of linear programming have also been identified. The results confirm that it is possible to develop efficient computational methods to optimise energy cost under circumstances typical of manufacturing companies. The set of numerous benchmark instances and their solutions have been archived and it can be reused in further research.

Background Allergen immunotherapy (AIT) is effective in patient with local allergic rhinitis (LAR). However, AIT may not always achieve the optimal treatment effect. Objective To present short study with clinical cases of LAR combined therapy with sublingual immunotherapy (SLIT) and omalizumab in patients with house dust mite (HDM) allergy and compared it to therapy with omalizumab alone. Methods Patients with severe LAR and hypersensitivity to HDMs were included. SLIT for HDMs was launched in a perennial protocol using SQ-HDM SLIT tablets with omalizumab. The total rhinitis symptom score (TRSS), total medication score (TMS) and combined total score (CTS) were assessed after one year. Results After 12 months, significant improvements in all analyzed parameters in the patients on SLIT+ omalizumab therapy were observed: a reduction in the TRSS from 1.21 ± 0.33 to 0.6 ± 0.28 (p