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This review is a collection of general information about chromium, aluminum, nickel and iron. We tried to include not only the data about absorption, metabolism, interactions with other elements and the importance of those microelements in the human body but also their toxic and mutagenic effects. Moreover, we examined their effect on human fibroblast and stem cell cultures which may be important due to abuse of supplementation in the population nowadays.

In this review the authors discuss that COVID-19 has already had a direct impact on the physical health of many people and that it appears to have put at risk the mental health of large populations. In this review, we also discuss the relationship between mental disorders and the SARS-CoV-2 infection. We convey the disorders’ risk factors and the more serious mental disorder consequences of COVID-19. People with mental health disorders could be more susceptible to the emotional responses brought on by the COVID-19 epidemic. The COVID-19 pandemic may adversely influence the mental health of patients with already diagnosed mental disorders. For the aim of dealing better with the psychological problems of people afflicted by the COVID-19 pandemic, new psychological procedures are required.

Mastocytosis is a hematopoietic neoplasm characterized by expansion of KIT D816V-mutated clonal mast cells in various organs and severe or even life-threatening anaphylactic reactions. Recently, hereditary α-tryptasemia (HαT) has been described as a common genetic trait with increased copy numbers of the α-tryptase encoding gene, TPSAB1, and associated with an increased basal serum tryptase level and a risk of mast cell activation. The purpose of our study was to elucidate the clinical relevance of HαT in patients with mastocytosis. TPSAB1 germline copy number variants were assessed by digital polymerase chain reaction in 180 mastocytosis patients, 180 sex-matched control subjects, 720 patients with other myeloid neoplasms, and 61 additional mastocytosis patients of an independent validation cohort. α-Tryptase encoding TPSAB1 copy number gains, compatible with HαT, were identified in 17.2% of mastocytosis patients and 4.4% of the control population (P < .001). Patients with HαT exhibited higher tryptase levels than patients without HαT (median tryptase in HαT+ cases: 49.6 ng/mL vs HαT− cases: 34.5 ng/mL, P = .004) independent of the mast cell burden. Hymenoptera venom hypersensitivity reactions and severe cardiovascular mediator-related symptoms/anaphylaxis were by far more frequently observed in mastocytosis patients with HαT than in those without HαT. Results were confirmed in an independent validation cohort. The high prevalence of HαT in mastocytosis hints at a potential pathogenic role of germline α-tryptase encoding TPSAB1 copy number gains in disease evolution. Together, our data suggest that HαT is a novel emerging robust biomarker in mastocytosis that is useful for determining the individual patient´s risk of developing severe anaphylaxis.

In the current classification of the World Health Organization (WHO), bone marrow mastocytosis (BMM) is a provisional variant of indolent systemic mastocytosis (ISM) defined by bone marrow involvement and absence of skin lesions. However, no additional diagnostic criteria for BMM have been proposed. Within the registry dataset of the European Competence Network on Mastocytosis, we compared characteristics and outcomes of 390 patients with BMM and 1175 patients with typical ISM. BMM patients were significantly older, predominantly male, had lower tryptase and lower burden of neoplastic mast cells, and displayed a higher frequency of allergic reactions, mainly triggered by Hymenoptera, than patients with typical ISM. The estimated 10-year progression-free survival of BMM and typical ISM was 95.9% and 92.6%, respectively. In BMM patients defined by WHO-based criteria, the presence of one B-Finding and tryptase level ≥125 ng/mL were identified as risk factors for progression in multivariate analyses. BMM patients without any of these risk factors were found to have better progression-free survival (p < 0.05) and better overall survival (p < 0.05) than other ISM patients. These data support the proposal to define BMM as a separate SM variant characterized by SM criteria, absence of skin lesions, absence of B-Findings, and tryptase levels

Recently, interest in glucagon-like peptide-1 (GLP-1) and other peptides derived from preproglucagon has increased significantly. GLP-1 is a 30-amino acid peptide hormone produced in L-type enteroendocrine cells as a response to food intake. GLP-1 is rapidly metabolized and inactivated by the dipeptidyl peptidase IV enzyme before the hormone leaves the intestine, which increases the likelihood that GLP-1 action is transmitted through sensory neurons in the intestine and liver through the GLP-1 receptor. The main actions of GLP-1 are to stimulate insulin secretion (i.e. act as incretin hormone) and inhibit glucagon secretion, thus contributing to the reduction of postprandial glucose spikes. GLP-1 also inhibits motility and gastrointestinal secretion, and therefore acts as part of the „small bowel brake” mechanism. GLP-1 also appears to be a physiological regulator of appetite and food intake. Because of these effects, GLP-1 or GLP-1 receptor agonists are now increasingly used to treat type 2 diabetes. Reduced GLP-1 secretion may contribute to the development of obesity, and excessive secretion may be responsible for postprandial reactive hypoglycemia. The use of GLP-1 agonists opens up new possibilities for the treatment of type 2 diabetes and other metabolic diseases. In the last two decades, many interesting studies covering both the physiological and pathophysiological role of GLP-1 have been published, and our understanding of GLP-1 has broadened significantly. In this review article, we have tried to describe our current understanding of how GLP-1 works as both a peripheral hormone and as a central neurotransmitter in health and disease. We focused on its biological effects on the body and the potential clinical application in relation to current research.

Background Mastocytosis is a clinically heterogeneous, usually acquired disease of the mast cells with a survival time that depends on the onset of the disease and ranges from skin-limited to systemic disease, including indolent and more aggressive variants. The crucial element in pathogenesis is the presence of oncogenic KIT somatic mutation D816V. Further epigenetic alterations are responsible for regulating the expression of genes. It is essential to identify indicators of disease progression, and the specific clinical picture to establish an appropriate therapeutic strategy. Objective The aim of this study was to analyze the relation of mastocytosis symptoms and epigenetic changes, and to identify epigenetic predictors of the disease. Methods Global DNA methylation profile analysis was performed in peripheral blood collected from 73 patients with indolent systemic mastocytosis (ISM) and 43 healthy adult volunteers. Levels of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) were determined using an ELISA-based method, while the methylation of the Alu and LINE-1 repeats were assayed with the quantitative methylation-specific PCR technique. A questionnaire interview was conducted among the study participants to collect data on possible epigenetic modifiers. Additionally, the methylation profile was compared between three human mast cell lines: ROSA KIT D816V, ROSA KIT WT, and HMC-1.1 KIT V560G, in order to assess the association between KIT mutations and methylation profile. Results A significantly lower level of DNA hydroxymethylation (5-hmC) in the blood was found in patients with ISM as compared to the controls (0.022% vs. 0.042%, p = 0.0001). Differences in the markers of global DNA methylation (5-mC, Alu, LINE-1) were not statistically significant, although they did indicate generally higher DNA methylation in patients with mastocytosis. The 5-hmC level was significantly associated with allergy (p = 0.011) in patients with ISM, showing a higher level of 5-hmC in patients with allergy as compared to patients without allergy. The in vitro study revealed significant differences between the studied cell lines at the level of 5-mC, Alu, and LINE-1. Conclusions This study confirms that epigenetic changes are involved in mastocytosis, and suggests that allergy may be an important epigenetic modifier of the disease. A possible association between KIT mutations and methylation status observed in human mast cell lines requires further investigation in human studies. Clinical implications Epigenetic alterations are involved in mastocytosis pathology. The possible role of allergy as an important epigenetic modifier suggests the more impaired function of mast cells in ISM patients without allergy. Capsule summary Decreased DNA demethylation in the blood DNA of patients with ISM confirms that epigenetic alterations are involved in mastocytosis pathology. We observed a possible role of allergy as an important epigenetic modifier. There is a possible association between KIT mutations and the methylation status observed in human mast cell lines.

Summary Introduction: Plants are a rich source of healing substances. Cancer is a leading cause of death worldwide while breast cancer is the most common cancer among women. Circulating tumour cells (CTCs) are potential founder cells for metastasis. Therefore, their assessment may be used for monitoring of treatment as well as detecting cancer metastatis. Hence, it is suggested that the number of CTCs may be a valuable tumour biomarker during therapy. Objective: The purpose of this study was to detect CTCs in breast cancer and to validate the method of assessment of CTC count using CytoTrack CT11 technology. Methods: MCF-7 cells were sorted by a FACSARIA flow cytometer from blood samples derived from patients who have not been diagnosed with cancer. Identification and quantitative assessment of MCF-7 cells in blood samples were determined by flow sorting. Then, blood samples containing MCF-7 cells or without MCF-7 were scanned with the use of an automated fluorescence scanning microscope. Results: In in vitro model analysing the glass CytoDisc™ with stained MCF-7 cells, we noted the correlation between the amount of observed tumour cells and expected number of tumour cells. Moreover, coefficient of variation in case of the recovery rate of the assumed number of MCF-7 cells was 30%, 17%, 18% and 15%, respectively. Conclusion: Our study suggest that CTCs could be predictive factor in patients with metastatic cancer especially in breast cancer.

Summary Introduction: Osteoporosis is a chronic metabolic disease with multifactorial etiology. One of possible osteoporosis causes may be impairment of osteoclasts function which leads to increased bone resorption. This may be a result of many metabolic changes. It is believed that changes of folate-methionine metabolism in osteoporosis play an essential role in the etiology of this disease. Objective: The aim of this study was to examine how polymorphisms of SLC19A1 and FOLR3 genes may play the key role in folate-methionine pathway and influence on the etiology of osteoporosis. Results: The statistically overrepresentation of mutated GG genotype of FOLR3 (rs11235449) was observed in the control group compared to the osteopenia (34.9% in osteopenia vs. 37.8% in controls, p=0.025, OR=0.61). As to the SLC19A1 (rs3788200) polymorphism we have noted the statistically significant over-representation of wild-type GG genotype (35.8% vs. 26.2%, p=0.046, OR=1.57) and overrepresentation of wild-type G allele (56.9% vs. 50.2%, p=0.061, OR=1.31) in osteopenia group if compared to the controls. Conclusions: In our study we shown the protective role of mutated GG genotype of FOLR3 (rs11235449) polymorphism to osteopenia progress and possible role of wild-type GG genotype and wild-type G allele of SLC19A1 (rs3788200) polymorphism in osteopenia development.

It is estimated that 56–94% of the adult population have been stung by a hymenopterous insect at least once in their lifetime, with one third of these cases being stung by a bee [1]. The prevalence of systemic reactions in the adult general population is 0.3–8.9% in Europe [2]. In beekeepers, this prevalence increases to 14–32% [3]. It is important to prevent any future allergic reactions based on correct diagnosis and management, including the prescription of an autoinjector with adrenaline, and specific venom immunotherapy in confirmed venom allergy [2]. Diagnosis is based on the clinical history with the classification of the type of the reaction, identification of the stinging insect and confirmation of the specific IgE-mechanism of the systemic reaction [4]. It is recommended to perform skin tests and to detect serum sIgE to insect venoms at least 2 weeks after the sting after the refractory period [1]. Although the sensitivity of serological tests with recombinant allergens is lower than traditional methods with extract allergens, molecular diagnostic approaches may improve the diagnosis accuracy in some patients excluding “false-positive” test results due to IgE directed against cross-reactive carbohydrate determinants (CCD). Furthermore, it has been recently published that negative skin test results with the Apis mellifera extract may be due to the lack of some allergens in the diagnostic and therapeutic extract [5]. Patients with a bee venom allergy often have a broad sensitisation profile with the most relevant being Api m 1, which could not be sensitised in up to 43% of cases [1, 6]. The combination of 2 allergens (Api m 1 and Api m 10) enables the diagnosis of 86.6% of cases; the combination of 6 allergens (Api m 1–5, Api m 10) has a sensitivity of 94.4% [3, 6].

International audience; Primary and secondary mast cell activation syndromes (MCAS) can occur in patients with mastocytosis. During the past few years our knowledge about the pathogenesis and disease-triggering mechanisms in MCAS and mastocytosis have increased substantially. Whereas mastocytosis is characterized by an accumulation of neoplastic (clonal) mast cells (MC) in various organ systems, MCAS is defined by a massive and systemic activation of these cells. Mast cells are crucial effector cells in allergic diseases, thus their elevated number and activation can cause severe anaphylactic reactions and MCAS in patients with mastocytosis. However, these cells may also degranulate spontaneously or degranulate in response to non-allergic triggers leading to clinical symptoms. In mastocytosis patients, such symptoms may lead to the diagnosis of a primary MCAS. The diagnosis of a concomitant allergy in mastocytosis patients is challenging. In these patients, a mixed form (primary and secondary) of MCAS may be diagnosed. These patients may also suffer from life-threatening anaphylactic reactions when exposed to allergens. In these cases, the possibility of severe side effects of in vivo provocations can sometimes also limit diagnostic evaluations. In the current article, we discuss the diagnosis and management of patients suffering from mastocytosis and concomitant MCAS, with special emphasis on novel diagnostic tests and management, including allergen microarrays, recombinant allergen analysis, basophil activation tests, optimal prophylaxis, and specific therapies

Theranostics 11(1), 292-303 (2021). doi:10.7150/thno.51872, Published by Ivyspring, Wyoming, NSW

International audience; Mast cell activation (MCA) is seen in a variety of clinical contexts and pathologies, including IgE-dependent allergic inflammation, other immunologic and inflammatory reactions, primary mast cell (MC) disorders, and hereditary alpha tryptasemia (HAT). MCA-related symptoms range from mild to severe to life-threatening. The severity of MCA-related symptoms depends on a number of factors, including genetic predisposition, the number and releasability of MCs, organs affected, and the type and consequences of comorbid conditions. In severe systemic reactions, MCA is demonstrable by a substantial increase of basal serum tryptase levels above the individual's baseline. When, in addition, the symptoms are recurrent, involve more than one organ system, and are responsive to therapy with MC-stabilizing or mediator-targeting drugs, the consensus criteria for the diagnosis of MCA syndrome (MCAS) are met. Based on the etiology of MCA, patients can further be classified as having i) primary MCAS where KIT-mutated, clonal, MCs are detected; ii) secondary MCAS where an underlying IgE-dependent allergy or other reactive MCA-triggering pathology is found; or iii) idiopathic MCAS, where neither a triggering reactive state nor KIT-mutated MCs are identified. Most severe MCA events occur in combined forms of MCAS, where KIT-mutated MCs, IgE-dependent allergies and sometimes HAT are detected. These patients may suffer from life-threatening anaphylaxis and are candidates for combined treatment with various types of drugs, including IgE-blocking antibodies, anti-mediator-type drugs and MC-targeting therapy. In conclusion, detailed knowledge about the etiology, underlying pathologies and co-morbidities is important to establish the diagnosis and develop an optimal management plan for MCAS, following the principles of personalized medicine.

Atherosclerosis and type II diabetes can be classified as lifestyle diseases. Unbalanced diet (highly processed food, excess salt food), a sedentary lifestyle and the use of stimulants (cigarettes, alcohol) can contribute to the emergence of both diseases. Both these diseases can coexist simultaneously. The development of type 2 diabetes may accelerate the development of atherosclerotic plaque, which in turn leads to many organ complications as well as death. People with slightly elevated glucose and cholesterol levels can be advised to take natural plant ingredients such as garlic and ginger along with changing their diet and increasing physical activity. garlic and ginger can be consumed alone as well as an addition to many dishes. In vitro and in vivo and clinical tests indicate the possibility of supporting the regulation of blood glucose and cholesterol levels by adding garlic and ginger to the diet.

Dietary supplements are a wide group of products belonging to the food category. Their sales are still growing. The composition, appearance and the intended use of these products make them resemble drugs. Dietary supplements are designed to meet the specific requirements of different consumer groups. Many dietary supplements contain herbal substances or their preparations. The safety of the herbal material is particularly affected by its proper identification, the part of the plant used as well as the standardization of the extract for a specific biologically active compound. Regardless of the group of consumers for which these products are intended, the risks associated with taking dietary supplements may relate to their contamination with heavy metals, pesticide residues or pathogenic microorganisms. There may also be adulterated dietary supplements on the market, the real composition of which differs from the composition presented on the original packing. Furthermore, the presence of restricted hazardous substances, or limited substances on the product is undoubtedly dangerous to health.

Objectives: Osteoporosis is a multifactorial disease that causes a loss of bone density. However, genetic factors play an increasingly important role in its development. To thoroughly understand the molecular mechanisms, polymorphic variants of genes candidate for osteoporosis are still being sought. The aim of our study was to investigate the influence of NFκB1 gene rs4648068 (A>G) and RUNX2 gene rs7771980 (-1025T>C) polymorphisms on the risk of osteoporosis. Material and methods: A group of 675 postmenopausal Caucasian women (109 women with osteopenia, 333 with osteoporosis and 233 with normal T-score) were examined. The bone mineral density (BMD) at the lumbar spine (L1-L4) was measured by dual energy x-ray absorptiometry (DXA). The analysis of NFκB1 and RUNX2 polymorphisms was performed using real-time PCR method. Results: Analysis of NFκB1 gene rs4648068 polymorphism showed that the GG genotype was slightly more frequent in the study groups compared to the control group. In the osteoporosis group, patients with the G allele in the genotype have lower bone mineral density values. For the RUNX2 rs7771980 polymorphism, in women with osteopenia we observed an increased incidence of TC heterozygotes compared to the control group (29.40% vs 24.90%, p > 0.05), and in women with osteoporosis, the TT genotype was more common (78.70% vs 73.80%, p > 0.05). No correlation was observed between the genotypes and the clinical parameters. Conclusions: The analysis showed no significant relationship between the genotypic distribution and the individual clinical parameters. However, it is suggested an association between the rs4648068 polymorphism of the NFκB1 gene and an increased risk of developing osteoporosis.

Mastocytosis is a unique hematologic neoplasm with complex biology and pathology and a variable clinical course. The disease can essentially be divided into cutaneous mastocytosis (CM) and systemic mastocytosis (SM). In adults, SM is diagnosed in most cases and manifests as either indolent or advanced disease. Patients with advanced SM have an unfavorable prognosis with reduced survival. However, so far, little is known about the prevalence of various categories of SM and about prognostic factors. In an attempt to learn more about the behavior and evolution of various forms of CM and SM, the European Competence Network on Mastocytosis (ECNM) initiated a mastocytosis registry in 2012. In this article, the set up and start phase of this registry are described. Until 2018, more than 3000 patients from 12 countries and 25 centers have been enrolled. In a majority of all patients, robust follow-up data and relevant clinical end points are available. Using this data set, a series of registry projects have been launched, with the aim to validate previously identified diagnostic and prognostic variables and to identify new disease-related and patient-related parameters in various forms of mastocytosis. Moreover, the core data set of the registry will be useful to establish multiparametric scoring systems through which prognostication and individualized management of patients with mastocytosis should improve in the foreseeable future. (C) 2019 American Academy of Allergy, Asthma & Immunology

Mastocytosis is a rare neoplasm characterized by the expansion and accumulation of mast cells in various organ systems. Systemic mastocytosis (SM) may or may not present with cutaneous lesions. To examine the frequency and clinical impact of cutaneous involvement, data on 1,510 patients with mastocytosis collected in the registry of the European Competence Network on Mastocytosis were analyzed. Cutaneous involvement was found in 1,195 of 1,510 patients (79.1%). Of these, 286 had cutaneous mastocytosis, and 721 had SM with skin involvement. Adult patients with skin involvement who did not have a bone marrow examination (n = 188) were defined as having mastocytosis in the skin. In 315 patients, SM without skin involvement was found. The percentage of cases with cutaneous involvement was higher in indolent SM (100%) and smoldering SM (87.9%) compared to aggressive SM (46.8%) or mast cell leukemia (38.5%). After a median follow-up of 5.6 years, no patient with cutaneous masto-cytosis had died, but 2.6% of the patients with mastocytosis in the skin, 5.7% of the patients with SM with skin involvement, and 28.95% of the patients with SM without skin involvement had died. Overall survival was longer in patients with skin involvement (cutaneous mastocytosis and/or mastocytosis in the skin and/or SM with skin involvement) than in patients with SM without skin involvement (P < 0.0001). These data argue for a thorough examination of both the skin and bone marrow in adult patients with mastocytosis.

Genes encoding insulin receptor substrates IRS-1 and IRS-2 perform key functions in the insulin pathway. Numerous authors have suggested that single-nucleotide polymorphism (SNP) changes in the DNA sequence may be associated with the development of obesity, insulin resistance and type 2 diabetes. The Gly972Arg polymorphism of the IRS-1 gene and the Gly1057Asp polymorphism of the IRS-2 gene are believed to be associated with the occurrence of insulin resistance and obesity according to many sources. The aim of our study was to investigate the influence of these polymorphisms on the clinical parameters and to assess their correlations in obese Polish pregnant women. A total of 154 pregnant Caucasian women from the Wielkopolska region were analyzed: 78 diagnosed with overweight or obesity (study group) and 76 with normal body mass (controls). The analysis of the polymorphisms was performed using the PCR-restriction fragment length polymorphism (PCR-RFLP) method. The IRS-2 Gly1057Asp polymorphism revealed no significant correlations with excessive weight gain during pregnancy. The analysis of the IRS-1 Gly972Arg polymorphism showed an association with obesity between the study and control groups (GG-80.77%, GR-17.95%, RR-1.28% vs GG-94.74%, GR-5.26%; p = 0.023). We also observed slightly increased BMI values ​​and higher values ​​of the waist and hip circumference before pregnancy in the case of the IRS-1 Gly972Arg polymorphism. The analysis of the clinical and anthropometric parameters demonstrated no significant relationships between the genotypes of the polymorphic variants of the IRS-1 and IRS-2 genes but suggested an association between the IRS-1 Gly972Arg polymorphism and the risk for obesity.

During the past few years many scientific investigations regarding the status of enteroanastomoses after surgical resections have been performed all over the world. General surgery wards perform intestinal resections on patients with neoplastic processes or with advanced nonspecific intestinal inflammation. Partial resections of the intestines are also performed on patients with necrotic changes caused by intestinal torsion or embolism of the branches of the mesenteric artery. These types of surgeries often require additional treatment which should cause a minimal strain for the patient in the postoperative period in order to obtain the highest percentage of recoveries. In proliferative diseases chemo- and radiotherapy are the most commonly used methods of treatment whereas general and local steroid therapy are used in inflammatory diseases. Additionally, immunomodulating agents are used with conventional therapy to improve the therapeutic effect. In a few studies, the influence of drugs on the local status of the intestine and wound healing status after surgeries was examined. The influence of selected agents on the status of experimental enteroanastomoses performed on the large intestine of rats was evaluated based on physical and morphometric tests. The study was performed on 60 Wistar rats, all of whom were male, of a similar body weight (250-350 grams) and the same age (2 months old). The rats were operated on to create an experimental anastomosis of the ascending colon. Then we administered selected drugs to evaluate their effect on the status of the newly created intestinal anastomosis. Selected parameters were evaluated after 4, 7 and 14 days after the surgery. In our experimental cycle animals were divided into 4 groups with 15 individuals in each group. The first group (I) was given physiological saline intraperitoneally (control group). Animals in the second group (II) were given the immuno-modulating drug interferon (Intron A) (45.000 IU/kg of b.w./day) after the surgery. Animals in the third group (III) were given the steroid Dexaven (0.5 mg/day) after the surgery. Animals in the fourth group (IV) were given a cytostatic agent (5-fluoroauracil) after the surgery (20 mg/kg/day). All of the drugs were administered in the same form as intra-peritoneal injections with the same amount of fluid. The study was planned for 5 cycles. 12 animals participated in one experimental cycle: 3 animals each from groups I, II, III and IV were operated on. The drugs were given for 5 days starting from the second day after the surgery. The rats were dissected after the 4th, 7th and 14th days of the experimental cycle to evaluate the status of the enteroanastomosis and the skin, according to previously mentioned parameters. Macroscopic changes of the enteroanastomosis were examined. Swabs were taken from all individuals with features of inflammation around this location. Next, the tightness of the anastomosis was evaluated by examining the appearance of air in the area of the anastomosis. The most important and last part of the experiment was amorphometric analysis of the large intestine with the anastomosis. In preparations stained with hematoxylin and eosin the following parameters were evaluated: amount of active intestinal crypts/mm, amount of non-active intestinal crypts/mm, total amount of intestinal crypts/mm, thickness of the mucous membrane, thickness of the submucous membrane, thickness of the muscular layer, fractal dimension of the mucosal membrane, fractal dimension of conjunctive tissue. Under the influence of steroid agents tightness disorders of the anastomosis were observed. Evaluation of the influence of the used substances on the morphometry of the enteroanastomosis revealed evident changes in the later days of the trial. In the days following the dissection of the animals from the control group histological changes were also observed that can suggest that the surgical intervention in itself influenced the morphometric parameters and caused disorders in the activity of intestinal crypts, decreased the dimension of the submucous membrane and altered the regeneration of the mucous membrane of the large intestine. Generally, agents used in the study caused disorders in the healing of the anastomosis, which significantly decreased particular dimensions of analyzed parameters. The substances examined influenced the thickness of the submucous membrane by making it thinner. Steroid and immunotherapy changed the reconstruction of conjunctive tissue which significantly affected the status and the resistance of the anastomosis. Intraperitoneal administration of selected therapeutical substances, especially Dexaven and Intron A have influenced the complete healing process of the anastomosis by disturbing the regenerative processes.

BACKGROUND: Mastocytosis in adults often presents with skin lesions. A bone marrow biopsy is necessary to confirm or exclude the presence of systemic mastocytosis (SM) in these cases. When a bone marrow biopsy is not performed, the provisional diagnosis is mastocytosis in the skin (MIS). No generally accepted scoring system has been established to estimate the risk of SM in these patients.OBJECTIVE: To develop a risk score to predict SM in adults with MIS.METHODS: We examined 1145 patients with MIS from the European Competence Network on Mastocytosis Registry who underwent a bone marrow biopsy. A total of 944 patients had SM and 201 patients had cutaneous mastocytosis; 63.7% were female, and 36.3% were male. Median age was 44 +/- 13.3 years. The median serum tryptase level amounted to 29.3 +/- 81.9 ng/mL. We established a multivariate regression model using the whole population of patients as a training and validation set (bootstrapping). A risk score was developed and validated with receiver-operating curves.RESULTS: In the multivariate model, the tryptase level (P < .001), constitutional/cardiovascular symptoms (P = .014), and bone symptoms/osteoporosis (P < .001) were independent predictors of SM (P < .001; sensitivity, 90.7%; specificity, 69.1%). A 6-point risk score was established (risk, 10.7%-98.0%) and validated.CONCLUSIONS: Using a large data set of the European Competence Network on Mastocytosis Registry, we created a risk score to predict the presence of SM in patients with MIS. Although the score will need further validation in independent cohorts, our score seems to discriminate safely between patients with SM and with pure cutaneous mastocytosis. (C) 2020 American Academy of Allergy, Asthma & Immunology

Mast cells (MCs) are an important component of the immune system. Their physiological function is involved in multiple areas of human physiology, thus symptoms of their increased activation vary greatly from severe allergic reactions, such as anaphylaxis, to chronic symptoms, such as depression or osteoporosis. Studies on mastocytosis revealed a subgroup of patients presenting symptoms of increased MC degranulation, defined as mast cell activation syndrome (MCAS). This population includes patients with primary MCAS with clonal abnormal MCs, who do not fulfill the criteria for mastocytosis. These symptoms often overlap with comorbidities, which makes the diagnosis and treatment of MCAS difficult. The syndrome is diagnosed on the basis of 3 criteria: 1) the presence of typical symptoms; 2) elevation of serum tryptase levels; and 3) response to anti-mediator treatment. The diagnosis of MCAS is important especially in patients with anaphylaxis or osteoporosis who require the use of an epinephrine emergency kit and insect venom immunotherapy. In this review, genetic mechanisms and typical symptoms of MCAS as well as its diagnostic criteria and implications were discussed, with a special emphasis on practical guidance with the aim to improve patient care.

Background: In indolent systemic mastocytosis (ISM), several risk factors of disease progression have been identified. Previous studies, performed with limited patient numbers, have also shown that the clinical course in ISM is stable and comparable to that of cutaneous mastocytosis (CM). The aim of this project was to compare the prognosis of patients with ISM with that of patients with CM.Methods: We employed a dataset of 1993 patients from the registry of the European Competence Network on Mastocytosis (ECNM) to compare outcomes of ISM and CM.Results: We found that overall survival (OS) is worse in ISM compared to CM. Moreover, in patients with typical ISM, bone marrow mastocytosis (BMM), and smoldering SM (SSM), 4.1% of disease progressions have been observed (4.9% of progressions in typical ISM group, 1.7% in BMM, and 9.4% in SSM). Progressions to advanced SM were observed in 2.9% of these patients. In contrast, six patients with CM (1.7%) converted to ISM and no definitive progression to advanced SM was found. No significant differences in OS and event-free survival (EFS) were found when comparing ISM, BMM, and SSM. Higher risk of both progression and death was significantly associated with male gender, worse performance status, and organomegaly.Conclusion: Our data confirm the clinical impact of the WHO classification that separates ISM from CM and from other SM variants.

Systemic mastocytosis (SM) is frequently associated with eosinophilia. To examine its prevalence and clinical impact in all WHO classification-based subcategories, we analyzed eosinophil counts in 2350 mastocytosis patients using the dataset of the European Competence Network on Mastocytosis. Ninety percent of patients had normal eosinophil counts, 6.8% mild eosinophilia (0.5-1.5 × 109/l), and 3.1% hypereosinophilia (HE; >1.5 × 109/l). Eosinophilia/HE were mainly present in patients with advanced SM (17%/19%), and only rarely recorded in patients with indolent and smoldering SM (5%/1%), and some patients with cutaneous mastocytosis. The eosinophil count correlated with organomegaly, dysmyelopoiesis, and the WHO classification, but not with mediator-related symptoms or allergy. Eosinophilia at diagnosis had a strong prognostic impact (p

Background: Del Nido (DN) cardioplegia is increasingly popular in adult cardiac surgery. It allegedly allows for up to 90 minutes of safe myocardial ischemia with a single dose. Aims: We aimed to evaluate the benefits of DN cardioplegia. Methods: Of the 2108 patients undergoing coronary or heart valve surgery with the use of cardiopulmonary bypass (CPB) between January 1, 2016, and September 30, 2017, 1236 (59%) received DN and 872 (41%) received cold blood cardioplegia. We retrospectively analyzed the collected data of all consecutive on‑pump patients to assess early mortality and postoperative troponin T release. A multivariable analysis of both outcomes adjusted for propensity to receive DN cardioplegia was performed. Results: Patients protected with DN cardioplegia had longer CPB and aortic cross‑clamp times (P < 0.001) but received fewer doses of cardioplegia. Median postoperative troponin T levels were higher in the DN‑cardioplegia than CB‑cardioplegia group: 0.324 ng/ml (interquartile range [IQR], 0.210–0.559 ng/ml) vs 0.285 ng/ml (IQR, 0.191–0.496 ng/ml); P = 0.01. However, when adjusted for the cross‑clamp time, propensity to receive DN cardioplegia, and other factors, DN cardioplegia was associated with lower postoperative troponin T levels. Early mortality rates did not differ between DN and CB cardioplegia (3.6% vs 3%; P = 0.54). Conclusions: Del Nido cardioplegia is a safe and effective method of myocardial protection in adults. It allows for a longer redosing interval with a safety profile and mortality comparable to those for CB cardioplegia, as shown by lower troponin T release when corrected for the time of myocardial ischemia.

Data on interleukin-31 (IL-31) involvement in the patho-genesis of mastocytosis, and its impact on pruritus development in the disease, are limited. The aim of this study was to analyse distinct IL-31 gene polymorphisms in 127 patients (age 0.5-76 years) with mastocytosis and their correlation with clinical presentation, pruritus and serum IL-31 levels. In patients with mastocytosis, the frequency of IL-31 IVS2+12AA genotype and IVS2+12A allele was higher than in control subjects and they were linked to an increased risk of development of mastocytosis. In adult patients, but not in children, -2057AA genotype was also associated with an increased risk of occurrence of mastocytosis. Pruritus affected 83.3% of 78 adult patients with mastocytosis, and a positive correlation between serum IL-31 levels and pruritus was found in these patients. In conclusion, distinct polymorphic variants of the IL-31 gene may be involved in the patho-genesis of mastocytosis, and IL-31 may be involved in the induction of pruritus in patients with mastocytosis.