IgE blockade with omalizumab reduces pruritus related to immune checkpoint inhibitors and anti-HER2 therapies.

BACKGROUND: Immunoglobulin E (IgE) blockade with omalizumab has demonstrated clinical benefit in pruritus-associated dermatoses (e.g. atopic dermatitis, bullous pemphigoid, urticaria). In oncology, pruritus-associated cutaneous adverse events (paCAEs) are frequent with immune checkpoint inhibitors (CPIs) and targeted anti-human epidermal growth factor receptor 2 (HER2) therapies. Thus, we sought to evaluate the efficacy and safety of IgE blockade with omalizumab in cancer patients with refractory paCAEs related to CPIs and anti-HER2 agents. PATIENTS AND METHODS: Patients included in this multicenter retrospective analysis received monthly subcutaneous injections of omalizumab for CPI or anti-HER2 therapy-related grade 2/3 pruritus that was refractory to topical corticosteroids plus at least one additional systemic intervention. To assess clinical response to omalizumab, we used the Common Terminology Criteria for Adverse Events version 5.0. The primary endpoint was defined as reduction in the severity of paCAEs to grade 1/0. RESULTS: A total of 34 patients (50% female, median age 67.5 years) received omalizumab for cancer therapy-related paCAEs (71% CPIs; 29% anti-HER2). All had solid tumors (29% breast, 29% genitourinary, 15% lung, 26% other), and most (n = 18, 64%) presented with an urticarial phenotype. In total 28 of 34 (82%) patients responded to omalizumab. The proportion of patients receiving oral corticosteroids as supportive treatment for management of paCAEs decreased with IgE blockade, from 50% to 9% (P < 0.001). Ten of 32 (31%) patients had interruption of oncologic therapy due to skin toxicity; four of six (67%) were successfully rechallenged following omalizumab. There were no reports of anaphylaxis or hypersensitivity reactions related to omalizumab. CONCLUSIONS: IgE blockade with omalizumab demonstrated clinical efficacy and was well tolerated in cancer patients with pruritus related to CPIs and anti-HER2 therapies.

Non-covalent anion structures in dissociative electron attachment to some brominated biphenyls.

The present work combines experiment and theory to reveal the behavior of bromo-substituted-biphenyls after an electron attachment. We experimentally determine anion lifetimes using an electron attachment-magnetic sector mass spectrometer instrument. Branching ratios of dissociative electron attachment fragments on longer timescales are determined using the electron attachment-quadrupole mass spectrometer instrument. In all cases, fragmentation is low: Only the Br- and [M-Br]- ions are detected, and [M-H]- is observed only in the case of 4-Br-biphenyl and parent anion lifetimes as long as 165 µs are observed. Such lifetimes are contradictory to the dissociation rates of 2- and 4-bromobiphenyl, as measured by the pulse radiolysis method to be 3.2 × 1010 and >5 × 1010 s-1, respectively. The discrepancy is plausibly explained by our calculation of the potential energy surface of the dissociating anion. Isolated in vacuum, the bromide anion can orbit the polarized aromatic radical at a long distance. A series of local minima on the potential energy surface allows for a roaming mechanism prolonging the detection time of such weakly bound complex anions. The present results illuminate the behavior recently observed in a series of bromo-substituted compounds of biological as well as technological relevance.

Outpatient dermatology consultations for oncology patients with acute dermatologic adverse events impact anticancer therapy interruption: a retrospective study.

BACKGROUND: Dermatologic adverse events (dAEs) of anticancer therapies may negatively impact dosing and quality of life. While therapy interruption patterns due to dAEs have been studied in hospitalized cancer patients, similar outcomes in outpatient oncodermatology are lacking. OBJECTIVES: To analyse the therapy interruption patterns, clinico-histopathologic characteristics and management outcomes of outpatient dermatology consultations for acute dAEs attributed to the most frequently interrupted class of oncologic agents. METHODS: We performed a retrospective cohort study of all cancer patients who received a same-day outpatient dermatology consultation for acute dAEs at our institution from 1 January to 30 June 2015. Relevant data were abstracted from electronic medical records, including demographics, oncologic history and explicit recommendations by both the referring clinician and consulting dermatologist on anticancer therapy interruption. Consultations with the most frequently interrupted class of oncologic treatment were characterized according to clinico-histopathologic features, dermatologic management and clinical outcomes. RESULTS: There were 426 same-day outpatient dermatology consultations (median age 59, 60% female, 30% breast cancer), of which 295 (69%) had systemic anticancer therapy administered within 30 days prior. There was weak inter-rater agreement between referring clinicians and consulting dermatologists on interruption of anticancer treatment (n = 150, κ = 0.096; 95% CI -0.02 to 0.21). Seventy-three (25%) consultations involved interruption by the referring clinician, most commonly targeted therapy (24, 33%). Maculopapular rash was commonly observed in 23 consultations with 25 dAEs attributed to targeted agents (48%), and topical corticosteroids were most frequently utilized for management (22, 38%). The majority (83%) of consultations with targeted therapy-induced dAEs responded to dermatologic treatment and 84% resumed oncologic therapy, although three (19%) at a reduced dose. Rash recurred only in two instances (13%). CONCLUSIONS: A high frequency of positive outcomes in the management of targeted therapy-induced dAEs by outpatient consulting dermatologists and low recurrence of skin toxicity suggests impactful reductions in interruption of anticancer therapy.

[The attitude to health in modern family].

The purpose of survey is to identify behavioral characteristics in family life-style and intra-family educational practices in dynamics of observation as health indicator. The life-style is analyzed according the results of questionnaire survey of 297 respondents, fostering school age children. The comparative analysis of behavior of adults and children is carried out based on the results of questionnaire surveys in 2007 and 2013. The verbal affirmations concerning importance of health and observance of healthy life-style in family have no concordance with actual behavior. The deterioration of of family function in healthy generation fostering is established. About 36,7% of parents pay no attention to their children. The passivity concerning organization of comfortable domestic conditions and inadequate medical activity in children health support are manifested by parents. The responsibility of parents for health of their children decreases too. The changing of priorities in hierarchy of life values occurs. The health loses its primary value. The decreasing of health in adults and children is logical due to effect relationship between life-style and health.

Role of epigenetic deregulation in hematogenous dissemination of malignant uveal melanoma.

It has become increasingly clear that epigenetic deregulation plays a fundamental role in cancer. Although the understanding of molecular, genetic and transcriptional alterations involved in the initiation and progression of uveal melanoma (UM) has grown significantly in recent years, little attention has been paid to the role of epigenetic changes. In cancer, epithelial-to-mesenchymal transition (EMT) enables trans-differentiation of epithelial tumor cells, endowing them with migratory and invasive properties. EMT-inducing transcription factors have been shown to interact with multiple epigenetic modifiers, thus reflecting the reversible nature of EMT. Therefore, the epigenetic therapy targeting these interactions may provide a promising therapeutic option, especially since no improvement in survival of patients with metastatic UM has been achieved using traditional approaches. This review summarizes current knowledge of epigenetic regulation of EMT in UM and emphasizes the need for deeper understanding of these highly dynamic and reversible processes. The potential for targeting individual members of the epigenetic machinery is also addressed.

Association of Target Therapy Gene Expression with Metastasizing of Clear-Cell Renal Cell Carcinoma.

We analyzed association of the levels of VEGFA, RAF1, and mTOR gene expression in the tissue of clear-cell renal cell carcinoma (ccRCC) with tumor metastasizing. Significant association with metastases was found only for VEGFA gene: OR=6.641, 95%CI=2.111-20.696. The risk of metastasis associated with reduced expression of VEGFA gene - 2.467, 95%CI=1.238-4.915. An association of VEGFA gene expression with the time to the metastasis appearance was revealed (p=0.0005). Reduced expression of the VEGFA gene is associated with reduction of the time to metastasis appearance; the median of this time is shifted from 46 to 2 months. Analysis of tumor samples with reduced expression of the VEGFA gene revealed association of increased expression of RAF1 (p=0.003) and mTOR genes (p=0.038) with metastasis.

Combination of selected biochemical markers and cervical length in the prediction of impending preterm delivery in symptomatic patients.

The pathophysiology of preterm delivery (PTD) is complex and multifactorial.It occurs in 8-12% of all deliveries, and the rate of PTD has increased during the past years in spite of intensive efforts towards early detection and prompt treatment. Fifty-eight pregnant women were eligible to join the study if they attended the University Clinic for Gynecology and Obstetrics, Skopje and were admitted to Department of High Risk pregnancy Unit with symptoms of preterm labor (PTL) (symptoms of uterine activity judged by the assessing physician to be indicative of PTL) at 24.0 to 36.6 weeks gestation.Test specimens for fetal fibronectin (fFN), phosphorylated insulin like growth factor binding protein 1 (phIGFBP-1), IL-6, and IL-2R and measuring the cervical length via transvaginal ultrasound were performed for each patient. The best statistical model for predicting PTL in the present study was to use a combination of the phIGFBP-1 test, a positive fFN test, cervical length less than 21.5 mm, levels of IL-6 higher than 1,305 pg/ml in the cervico-vaginal fluid (CVF), and serum levels of C-reactive protein (CRP) higher than 6.1 mg/L which was excellent at identifying the patients that were to deliver within 14 days of admittance.

[New opportunities in the diagnosis of ulcerative colitis].

PURPOSE OF THE STUDY: to analyze the expression of markers of apoptosis and proliferation in patients with ulcerative colitis. MATERIALS AND METHODS: in 80 patients with ulcerative colitis the analysis of expression of apoptosis marker BAX and proliferation marker Ki-67, as well as the cell cycle regulator p53 in biopsy materials of the mucous membrane of the colon was carried out. THE RESULTS: decreased cell proliferative activity and increase of the apoptosis rate depending on the severity, the localization of the inflammatory process and its endoscopic activity were registered.

[Health promoting schools and health of schoolchildren (analytical review)].

The determinants of the decrease in health of the school age children, connected with their studies are discussed. The educational institutions are considered as the subjects of healthy way of life formation and strengthening of health of schoolchildren. There is a number of"health schools", using in their activity various approaches and health promoting methods for preservation and strengthening of health of schoolchildren. The results of activity of these schools are shown.

[Parental life style as a determinant of children's health].

The paper considers a family in the context of an attitude towards health. The focus of attention in children is their parental lifestyle they imitate in their behavioral model. A sociological survey of parents (n = 328) and adolescent schoolchildren (n = 344) has established that by the time of leaving school, the children form behavioral norms accepted in their families. There is devaluation of family values and lesser parenteral responsibility for children's health. The pedagogical unsoundness of the parents to cultivate healthy lifestyle (HLS) habits in children is due to their personal example, inadequate HLS motivation, and the spread of bad habits.

[Schoolchildren's attitude towards health in the aspect of tobacco smoking: a sociohygienic study].

The paper presents the results of a sociological survey of 1093 Moscow 6th-11th form schoolchildren. Their awareness and real behavior are analyzed in the context of smoking and health. The adolescents have been found to have superficial knowledge of the negative effect of smoking on health. Among the schoolchildren, the prevalence of varying intensity smoking is 45.6%. Susceptibility to smoking increases by 3 and 5 times in the middle and senior classes, respectively. The number of smoking adolescents peaks (41.1%) in the 10th-11th classes. This group of adolescents shows no gender differences: the smoking boys and girls are 42.1 and 40.0%, respectively. Despite the fact that the adolescents have a firm grasp of health protection, the reality shows a substantial difference between the acceptable values and real behavior.

Resistance of oat breeding lines to grain contamination with Fusarium langsethiae and T-2/HT-2 toxins.

Fusarium disease of oats reduces yield quality due to decreasing germination that is caused by the contamination of grain with mycotoxins produced by Fusarium fungi. The aim of this study was to characterize the resistance of naked breeding lines of oats to fungal grain infection and to contamination with T-2 and HT-2 toxins. Thirteen naked oat breeding lines and two naked varieties, Nemchinovsky 61 and Vyatskiy, as well as a husked variety Yakov, were grown under natural conditions in the Nemchinovka Federal Research Center in 2019-2020. The contamination of grain with fungi was determined by the mycological method and real-time PCR. The analysis of mycotoxins was carried out by ELISA. In oats, Alternaria (the grain infection was 15-90 %), Cochliobolus (1-33 %), Cladosporium (1-19 %), Epicoccum (0-11 %), and Fusarium (3-17 %) fungi prevailed in the grain mycobiota. The predominant Fusarium species were F. poae (its proportion among Fusarium fungi was 49-68 %) and F. langsethiae (29-28 %). The highest amounts of F. langsethiae DNA ((27.9-71.9) × 10-4 pg/ng) and T-2/HT-2 toxins (790-1230 µg/kg) were found in the grain of husked oat Yakov. Among the analysed naked oat lines, the amount of F. langsethiae DNA varied in the range of (1.2-42.7) × 10-4 pg/ng,and the content of T-2/HT-2 toxins was in the range of 5-229 µg/kg. Two oat breeding lines, 54h2476 and 66h2618, as well as a new variety, Azil (57h2396), can be characterized as highly resistant to infection with Fusarium fungi and contamination with mycotoxins compared to the control variety Vyatskiy.

[New alkyl cationic glycerolipids with heterocyclic polar domain are responsible for disorders in the leukemia cells cycle and cells apoptosis].

A series of new modifications of alkyl cationic glycerolipids with hetero polar domain has been synthesized. The most active compound rac-N-(4-[(2-ethoxy-3-octadecyloxy)prop-1-yloxycarbonyl]butyl)-N'-etylimidazoliyiodid in micromolar concentrations causes a delay of cell cycle in phase G1, DNA fragmentation and apoptosis of cell line leukemia.

[Comorbidity in chronic obstructive pulmonary disease].

AIM: To investigate comorbidity in chronic obstructive pulmonary disease (COPD) and its contribution to lethality of patients with pulmonary disease. MATERIAL AND METHODS: Case histories of 125 COPD and 54 osteoarthritis (OA) patients matched by sex and age have been analysed retrospectively. Mean comorbidity index (CI) in COPD patients was two times higher than in OA patients (p < 0.001). RESULTS: The CI rose with growing severity of a COPD course (p < 0.01). Follow-up of 77 COPD patients for 3-5 years distinguished a group of patients with unfavorable outcomes. In lethal outcomes CI-3 points occurred significantly more frequently (p < 0.001). A significant correlation exists between CI and time from the moment of CI estimation to the patient's death (r = -0.54; p < 0.05). Thus, CI can be used in clinical practice as a simple method of risk of death for COPD patients. A rise of CI over 3 scores indicates a high risk of a COPD patient's death which should be considered in management of COPD patients.

The treatment results in patients with lmphoma disease in the orbit.

INTRODUCTION: Lymphoma is a malignant disease that can affect several structures of the orbit and eye adnexa. In the area of orbit the non-Hodgkins lymphoma (NHL) is typical, which may be indolent or aggressive. Indolent subtypes include MALT (mucosa-associated lymphoid tissue), follicular lymphoma (FL), lymphoplasmocytic lymphoma (LPL). Conversely, subtypes such as diffuse large cell lymphoma (DLBCL), mantle cell lymphoma (MCL) and Burkitt lymphoma (BL) are aggressive. The disease can be presented as primary or secondary malignancy of the orbit. MATERIAL AND METHODS: A group of 35 patients from the Department of Ophthalmology, Faculty of Medicine, Comenius University in Bratislava in the period from January 1 2009 to December 31 2016 with diagnosed non-Hodgkins lymphoma located in the area of the orbit. For all patients, the generally valid diagnostic criteria for the NHL in the eye area were met. We processed the first signs of disease, the proportion of women and men with NHL, the percentage of NHL types in the orbit area. Statistically, we evaluated the age at which NHL occurred in patients and evaluated the incidence of the disease over the reference period. We have statistically processed the forms of the applied therapy, their adverse effects, the recurrence of the disease, the presence of other malignancies in the lymphoma patient. RESULTS: Of the total number of NHL patients in orbit region 13 (37%) were male and 22 (63%) female. The overall mean age at which lymphoma was diagnosed was 60 years. Median for the total age of patients was 61. In women, a slightly higher average age and median was found. On the other hand, lower values of both parameters were present in men. The modus of both sexes was the same, 70 years. We have seen various first symptoms in our group. We found that the most common symptom is red eye, and the rarest is the deterioration of the central visual acuity. The longest lasting symptom was swelling of eyelids (on average, up to 10 years) and the shortest described eye itching. Overall, the average duration of symptoms was 28 months, with a median of 13 months. In our group of patients were 3 % of LPL, 6 % of Burkitts lymphoma, 6 % of FL, 8 % of MCL, 17 % of DLBCL, and 60 % of malignant lymphoma. MALT lymphoma occurred in 62 % in orbital and 38 % in conjunctival localization. In 2 patients with MALT lymphoma of the conjunctiva to start with systemic therapy wasn't neccessary. In 21 patients with MALT lymphoma excisional biopsy or orbitotomy was the first step to diagnose lymphoma disease in 3 cases; in 18 patients the infiltration of the orbit or conjunctiva occured 1 to 3 years after primary diagnose of systemic lymphoma disease. In general, NHL localization was 29 % in conjunctiva and 71 % in the orbital area. In 9 % of the orbital lymphoma, we observed lymphoma ingrowth to the conjunctiva. Systemic therapy was initiated in patients in II. stage and higher stage of the disease according to the Ann Arbor system. Totally 63 % of the group were treated by systemic therapy. Recurrence occurred in 5 patients, representing 14 % of the observed, but only in one patient with MALT lymphoma. Preoperative and postoperative (excisional biopsy, orbitotomy) central visual acuity (CVA) stayed unchanged, postoperative swelling did not affect CVA, and CVA didn't change even during long-term follow-up. CONCLUSION: Careful differential diagnosis determines the therapy of the disease, since the primary symptoms are usually nonspecific for ocular lymphoma. Significant factors for therapy include tumor grading and clinical staging by AJCC 2009 (American Joint Committee on Cancer, Chicago, Illinois). Correct evaluation of the symptoms is an important step to indicate excisional biopsy or orbitotomy: After histopathological results we can start adequate therapy in the cooperation with oncohematologist. Key words: conjunctival tumors, orbit, lymfoma, orbitotomy.

[Dynamics of thyroxine and triiodothyronine concentration in the rat blood at early times after subtotal removal of the thyroid gland or under effects of different I-131 action]. / Dinamika kontsentratsii tiroksina i triiodtironina v krovi krys v rannie sroki posle subtotal'nogo udaleniia shchitovidnoi zhelezy ili vozdeistviia razlichnykh aktivnostei 131I.

The alterations of amount of thyroid hormones have the characteristic dynamics that manifest itself by initial reduction with following partial or complete restoration of T3 and T4 concentration in rat blood after surgical or radioactive injuries of thyroid gland. Through presence of threshold of several dozens Gy for early dose-dependent hypothyroidism, the thyroid gland seems to be relatively radioresistant organ. Thyroid hormones concentration in blood has restored to normal level after experimental injuries which shows high restoration potential of thyroid gland function.

[Biological properties and serological types and groups of pneumococci isolated from suppurative meningitis patients]. / Biologicheskie svoistva i serologicheskie tipy i gruppy pnevmokokkov, vydelennykh ot bol'nykh gnoinymi meningitami.

The results of the study of the biological and serological properties of pneumococci isolated from the cerebrospinal fluid and the blood of patients with purulent meningitides are presented. Serological types were determined in 64 pneumococcal strains. They were found to belong to 16 known serological types and groups; of these, 10 had been included into the existing 14-component polysaccharide capsular pneumococcal vaccine. Serotypes 1, 19, 6, 12 and 20 were most frequently isolated from patients irrespective of their age; from children meningococci of serotype 12 were most frequently isolated. In lethal cases types 1, 19 and 2 were isolated from adults and type 12, from children. At the moment of isolation pneumococci possessed biological characteristics typical of this species.