Dendritic Cell Subpopulations Are Associated with Prognostic Characteristics of Breast Cancer after Neoadjuvant Chemotherapy-An Observational Study.

Breast cancer (BC) is the most prevalent malignancy in women and researchers have strived to develop optimal strategies for its diagnosis and management. Neoadjuvant chemotherapy (NAC), which reduces tumor size, risk of metastasis and patient mortality, often also allows for a de-escalation of breast and axillary surgery. Nonetheless, complete pathological response (pCR) is achieved in no more than 40% of patients who underwent NAC. Dendritic cells (DCs) are professional antigen-presenting cells present in the tumor microenvironment. The multitude of their subtypes was shown to be associated with the pathological and clinical characteristics of BC, but it was not evaluated in BC tissue after NAC. We found that highe r densities of CD123+ plasmacytoid DCs (pDCs) were present in tumors that did not show pCR and had a higher residual cancer burden (RCB) score and class. They were of higher stage and grade and more frequently HER2-negative. The density of CD123+ pCDs was an independent predictor of pCR in the studied group. DC-LAMP+ mature DCs (mDCs) were also related to characteristics of clinical relevance (i.e., pCR, RCB, and nuclear grade), although no clear trends were identified. We conclude that CD123+ pDCs are candidates for a novel biomarker of BC response to NAC.

Clinical characteristics of elderly patients with atopic dermatitis - a retrospective observational study.

Atopic dermatitis (AD) is a chronic, recurrent inflammatory dermatosis. The most characteristic symptoms of the disease include itch, eczematous eruptions and excessive dryness of the skin. Elderly patients with AD represent a poorly characterized population because the physiological ageing, possible comorbidity and polypharmacy modify the clinical presentation typically observed in the younger age groups. The aim of the study is to comprehensively assess the clinical characteristics of elderly patients (>60 years old) with AD. Data were collected from 26 AD patients treated in the Department of Dermatology of the University Hospital in Krakow. Late-onset AD with generalized/prurigo lesions was the most predominant phenotype. Skin biopsy was required in 15 (58%) patients in the differential diagnosis process. Allergic rhinitis, a positive family history of atopy and xerosis were associated with a higher number of hospitalizations during the year prior to the last admission (p = 0.034, p = 0.046 and p = 0.036, respectively). Xerosis was more prevalent among subjects with polypharmacy (p = 0.046) and higher serum total IgE concentration (p = 0.048). AD in elderly patients is a new phenotype of the disease that requires careful differential diagnosis. Aged patients with an individual or family history of atopy, due to the increased incidence of severe exacerbations of AD, may benefit from the introduction of proactive therapy.

Immediate Response to Brentuximab Vedotin in a Patient with Localized MF-LCT.

The large cell transformation of mycosis fungoides (MF-LCT) is a phenomenon observed in the advanced stages of mycosis fungoides (MF), which is the most common primary cutaneous lymphoma. The diagnostic criteria of MF-LCT are a minimum of 25% of large cells or a formation of microscopic nodules of them in the histological examination of skin samples. The clinical outcomes for MF-LCT are poor, as less than 20% of patients survive 5 years after diagnosis, but the expression of the CD30 antigen is generally considered to be associated with a better prognosis. We present a case of a patient with the diagnosis of MF with LCT, with an ulcerated tumor lesion approximately 30 × 20 cm in size on the right lateral abdominal wall. Brentuximab vedotin (BV) treatment was started due to the presence of the CD30 antigen, with a quick and impressive regression of the cutaneous lesion and tumor mass and good treatment tolerance. After follow-up of 20 months, patient remains in complete remission. A schedule of treatment for MF-LCT is directed mainly by the clinical stage of the disease and the comorbidities; the more severe clinical course of the disease requires systemic treatment. If at least 5% of the cells found in the skin lesions biopsy sample express the CD30 antigen, a beneficial effect of BV treatment could be expected. It may seem that the use of BV is one of the optimal therapeutic options in patients with advanced MF-LCT showing expression of CD30.

Clinical aspects of the treatment of atopic dermatitis with topical glucocorticoids and calcineurin inhibitors - a pilot questionnaire study.

Atopic dermatitis (AD) is the most common inflammatory skin disease. However, recent reports concerning the simple clinical aspects of treatment with topical glucocorticosteroids (TCS) and calcineurin inhibitors (TCI) are lacking. The objective of this study is providing an update on these characteristics of AD management. A group of 150 adults suffering from AD treated with TCS during last year was asked to fill an anonymous questionnaire. The course of topical treatment was analyzed in the context of the severity of symptoms and the knowledge of the patients about therapy. During the last year, the majority of patients (66%) were treated with class IV TCS; however, in the last two weeks, class I TCS was used the most frequently (35%). Only 11% were familiar with the concept of intermittent therapy and 4% used the fingertip unit (FTU). In total, 77% of them used TCI. Most of the patients used the same class of TCS permanently. Unfortunately, patients are unaware of simple approaches (like intermittent therapy or FTU) that increase both the effectiveness and safety of the treatment. Practicians should be aware of these problems to identify and eliminate them, primarily through the education of patients.

Neoductgenesis in Ductal Carcinoma In Situ Coexists with Morphological Abnormalities Characteristic for More Aggressive Tumor Biology.

Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer that is generally indolent, however, could advance to invasive carcinoma in more than one-third of cases if left untreated. Thus, there is continuous research to find DCIS characteristics that would enable clinicians to decide if it could be left without intensive treatment. Neoductgenesis (i.e., formation of the new duct of improper morphology) is a promising, but still not sufficiently evaluated indicator of future tumor invasiveness. We gathered data from 96 cases of DCIS (histopathological, clinical, and radiological) to assess the relationship between the neoductgenesis and well-established features of high-risk tumor behavior. Furthermore, our intention was to determine which degree of neoductgenesis should be considered clinically significant. Our major finding was that neoductgenesis is strictly related to other characteristics that indicate the invasive potential of the tumor and, to achieve more accurate prediction, neoductgenesis should be accordingly recognized to less strict criteria. Therefore, we conclude that neoductgenesis is another important revelator of tumor malignancy and that it requires further investigation during prospective controlled trials.

Prognostic Factors in Patients with Sudden Cardiac Arrest and Acute Myocardial Infarction Undergoing Percutaneous Interventions with the LUCAS-2 System for Mechanical Cardiopulmonary Resuscitation.

Sudden cardiac arrest (SCA) is one of the most perilous complications of acute myocardial infarction (AMI). For years, the return of spontaneous circulation (ROSC) has had to be achieved before the patient could be treated at the catheterization laboratory, as simultaneous manual chest compression and angiography were mutually exclusive. Mechanical chest compression devices enabled simultaneous resuscitation and invasive percutaneous procedures. The aim was to characterize the poorer responders that would allow one to predict the positive outcome of such a treatment. We retrospectively analyzed the medical charts of 94 patients with SCA due to AMI, who underwent mechanical cardiopulmonary resuscitation during angiography. In total, 48 patients, 8 (17%) of which survived the event, were included in the final analysis, which revealed that 83% of the survivors had mild to moderate hyperkalemia (potassium 5.0−6.0 mmol/L), in comparison to 15% of non-survivors (p = 0.002). In the age- and sex-adjusted model, patients with serum potassium > 5.0 mmol/L had 4.61-times higher odds of survival until discharge from the hospital (95% CI: 1.41−15.05, p = 0.01). Using the highest Youden index, we identified the potassium concentration of 5.1 mmol/L to be the optimal cut-off value for prediction of survival until hospital discharge (83.3% sensitivity and 87.9% specificity). The practical implications of these findings are that patients with potassium levels between 5.0 and 6.0 mmol/L may actually benefit most from percutaneous coronary interventions with ongoing mechanical chest compressions and that they do not need immediate correction for this electrolyte abnormality.

Analysis of Peripheral Blood Mononuclear Cells Gene Expression Highlights the Role of Extracellular Vesicles in the Immune Response following Hematopoietic Stem Cell Transplantation in Children.

Hematopoietic stem cell transplantation (HSCT) is an effective treatment method used in many neoplastic and non-neoplastic diseases that affect the bone marrow, blood cells, and immune system. The procedure is associated with a risk of adverse events, mostly related to the immune response after transplantation. The aim of our research was to identify genes, processes and cellular entities involved in the variety of changes occurring after allogeneic HSCT in children by performing a whole genome expression assessment together with pathway enrichment analysis. We conducted a prospective study of 27 patients (aged 1.5-18 years) qualified for allogenic HSCT. Blood samples were obtained before HSCT and 6 months after the procedure. Microarrays were used to analyze gene expressions in peripheral blood mononuclear cells. This was followed by Gene Ontology (GO) functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) analysis using bioinformatic tools. We found 139 differentially expressed genes (DEGs) of which 91 were upregulated and 48 were downregulated. "Blood microparticle", "extracellular exosome", "B-cell receptor signaling pathway", "complement activation" and "antigen binding" were among GO terms found to be significantly enriched. The PPI analysis identified 16 hub genes. Our results provide insight into a broad spectrum of epigenetic changes that occur after HSCT. In particular, they further highlight the importance of extracellular vesicles (exosomes and microparticles) in the post-HSCT immune response.

Concentrations of Insulin-like Growth Factors and Insulin-like Growth Factor-Binding Proteins and Respective Gene Expressions in Children before and after Hematopoietic Stem Cell Transplantation.

Insulin-like growth factors (IGF-1 and IGF-2) and insulin-like growth factor-binding proteins (IGFBP-1 to -7) are involved in the regulation of cell proliferation and differentiation and may be associated with various metabolic parameters. The aim of our study was to compare levels of IGFs and IGFBPs and the expressions of their genes in children before and after hematopoietic stem cell transplantation (HSCT) to assess their potential as markers of late metabolic complications of HSCT. We also conducted additional comparisons with healthy controls and of correlations of IGF and IGFBP levels with anthropometric and biochemical parameters. We analyzed 19 children treated with HSCT and 21 healthy controls. We found no significant differences in the levels of IGFs and IGFBPs and expressions of their genes before and after HSCT, while IGF and IGFBP levels were significantly lower in children treated with HSCT compared with controls. We conclude that our results did not reveal significant differences between the levels of IGFs and IGFBPs before and after HSCT, which would make them obvious candidates for markers of late complications of the procedure in children. However, due to the very low number of patients this conclusion must be taken with caution and may be altered by further research.

Synthetic Retinoids as Potential Therapeutics in Prostate Cancer-An Update of the Last Decade of Research: A Review.

Prostate cancer (PC) is the second most common tumor in males. The search for appropriate therapeutic options against advanced PC has been in process for several decades. Especially after cessation of the effectiveness of hormonal therapy (i.e., emergence of castration-resistant PC), PC management options have become scarce and the prognosis is poor. To overcome this stage of disease, an array of natural and synthetic substances underwent investigation. An interesting and promising class of compounds constitutes the derivatives of natural retinoids. Synthesized on the basis of the structure of retinoic acid, they present unique and remarkable properties that warrant their investigation as antitumor drugs. However, there is no up-to-date compilation that consecutively summarizes the current state of knowledge about synthetic retinoids with regard to PC. Therefore, in this review, we present the results of the experimental studies on synthetic retinoids conducted within the last decade. Our primary aim is to highlight the molecular targets of these compounds and to identify their potential promise in the treatment of PC.

Melatonin as an Antioxidant and Immunomodulator in Atopic Dermatitis-A New Look on an Old Story: A Review.

Atopic dermatitis (AD) is common inflammatory dermatosis, typically with chronic and recurrent course, which significantly reduces the quality of life. Sleep disturbances are considered to be remarkably burdensome ailments in patients with AD, and are routinely included during assessment of disease severity. Therefore, endogenous substances engaged in the control of circadian rhythms might be important in pathogenesis of AD and, possibly, be used as biomarkers of disease severity or even in development of novel therapies. Melatonin (MT), the indoleamine produced by pineal gland (but also by multiple other tissues, including skin), plays a pivotal role in maintaining the sleep/wake homeostasis. Additionally, it possesses strong antioxidant and anti-inflammatory properties, which might directly link chronic skin inflammation and sleep abnormalities characteristic of AD. The objective of this work is to systematically present and summarize the results of studies (both experimental and clinical) that investigated the role of MT in the AD, with a focus on the antioxidant and immunomodulatory effects of MT.

The Expression of Genes Related to Lipid Metabolism and Metabolic Disorders in Children before and after Hematopoietic Stem Cell Transplantation-A Prospective Observational Study.

Metabolic disorders in children after hematopoietic stem cell transplantation (HSCT) are poorly characterized. However, it is known that dyslipidemia and insulin resistance are particularly common in these patients. We conducted a prospective study of 27 patients treated with HSCT to assess the possibility of predicting these abnormalities. We measured gene expressions using a microarray technique to identify differences in expression of genes associated with lipid metabolism before and after HSCT. In patients treated with HSCT, total cholesterol levels were significantly higher after the procedure compared with the values before HSCT. Microarray analysis revealed statistically significant differences in expressions of three genes, DPP4, PLAG1, and SCD, after applying the Benjamini-Hochberg procedure (pBH < 0.05). In multiple logistic regression, the increase of DPP4 gene expression before HCST (as well as its change between pre- and post-HSCT status) was associated with dyslipidemia. In children treated with HSCT, the burden of lipid disorders in short-term follow-up seems to be lower than before the procedure. The expression pattern of DPP4 is linked with dyslipidemia after the transplantation.

Methylation and Expression of FTO and PLAG1 Genes in Childhood Obesity: Insight into Anthropometric Parameters and Glucose-Lipid Metabolism.

The occurrence of childhood obesity is influenced by both genetic and epigenetic factors. FTO (FTO alpha-ketoglutarate dependent dioxygenase) is a gene of well-established connection with adiposity, while a protooncogene PLAG1 (PLAG1 zinc finger) has been only recently linked to this condition. We performed a cross-sectional study on a cohort of 16 obese (aged 6.6-17.7) and 10 healthy (aged 11.4-16.9) children. The aim was to evaluate the relationship between methylation and expression of the aforementioned genes and the presence of obesity as well as alterations in anthropometric measurements (including waist circumference (WC), body fat (BF_kg) and body fat percent (BF_%)), metabolic parameters (lipid profile, blood glucose and insulin levels, presence of insulin resistance) and blood pressure. Expression and methylation were measured in peripheral blood mononuclear cells using a microarray technique and a method based on restriction enzymes, respectively. Multiple regression models were constructed to adjust for the possible influence of age and sex on the investigated associations. We showed significantly increased expression of the FTO gene in obese children and in patients with documented insulin resistance. Higher FTO expression was also associated with an increase in WC, BF_kg, and BF_% as well as higher fasting concentration of free fatty acids (FFA). FTO methylation correlated positively with WC and BF_kg. Increase in PLAG1 expression was associated with higher BF%. Our results indicate that the FTO gene is likely to play an important role in the development of childhood adiposity together with coexisting impairment of glucose-lipid metabolism.

Recent Progress in Discovering the Role of Carotenoids and Their Metabolites in Prostatic Physiology and Pathology with a Focus on Prostate Cancer-A Review-Part I: Molecular Mechanisms of Carotenoid Action.

Among the vast variety of plant-derived phytochemicals, the group of carotenoids has continuously been investigated in order to optimize their potential application in the area of dietary intervention and medicine. One organ which has been especially targeted in many of these studies and clinical trials is the human prostate. Without doubt, carotenoids (and their endogenous derivatives-retinoids and other apo-carotenoids) are involved in intra- and intercellular signaling, cell growth and differentiation of prostate tissue. Due to the accumulation of new data on the role of different carotenoids such as lycopene (LC) and ß-carotene (BC) in prostatic physiology and pathology, the present review aims to cover the past ten years of research in this area. Data from experimental studies are presented in the first part of the review, while epidemiological studies are disclosed and discussed in the second part. The objective of this compilation is to emphasize the present state of knowledge regarding the most potent molecular targets of carotenoids and their main metabolites, as well as to propose promising carotenoid agents for the prevention and treatment of prostatic diseases.

Recent Progress in Discovering the Role of Carotenoids and Metabolites in Prostatic Physiology and Pathology-A Review-Part II: Carotenoids in the Human Studies.

Among the vast variety of plant-derived phytochemicals, the group of carotenoids has continuously been investigated in order to optimize their potential application in the area of dietary intervention related to chronic diseases. One organ that has been especially targeted in many of these studies and clinical trials is the human prostate. Without doubt, carotenoids (and their endogenous derivatives-retinoids and apo-carotenoids) are involved in a plethora of intra- and intercellular signaling, cell growth, and differentiation of prostate tissue. Due to the accumulation of new data on the role of different carotenoids, such as lycopene (LYC) and ß-carotene (BC), in prostatic physiology and pathology, the present review aimed to cover the past ten years of research in this regard. Data from experimental studies are presented in the first part of the review, while epidemiological studies are disclosed in this second part. The objective of this compilation was to emphasize the present state of knowledge about the most potent molecular targets of carotenoids, as well as to propose promising carotenoid agents for the prevention and possible treatment of prostatic diseases.

Adipokines as Biomarkers of Atopic Dermatitis in Adults.

Atopic dermatitis (AD) is characterized by chronic, relapsing, pruritic skin inflammation and does not have a well-understood pathogenesis. In this study, we addressed the contribution of adipokines to AD eczema based on the assessment of blood levels of adiponectin, resistin, leptin, lipocalin-2, and vaspin in adult non-obese patients suffering from chronic extrinsic childhood-onset AD. We investigated 49 AD patients with a median age of 37 years. The control group consisted of 30 age-matched healthy subjects. Adipokines were assessed in the serum by ELISA assays and the severity of AD with the SCORing Atopic Dermatitis (SCORAD) index. We found that adiponectin and resistin decreased and leptin appreciably increased in AD patients when compared to those in healthy subjects. Further, the levels of adiponectin and resistin were inversely related to the intensity of eczema. In conclusion, apart from the formerly investigated role of leptin in AD, this study points to adiponectin and resistin as the potential candidate adipokine biomarkers involved in shaping eczema intensity and severity, which may help predict disease exacerbations and enable the development of effective targeted therapeutic interventions.

Polymorphisms of SLC19A1 80 G>A, MTHFR 677 C>T, and Tandem TS Repeats Influence Pharmacokinetics, Acute Liver Toxicity, and Vomiting in Children With Acute Lymphoblastic Leukemia Treated With High Doses of Methotrexate.

Introduction: High dose methotrexate (HD-Mtx) is highly effective and significantly improves overall acute lymphoblastic leukemia (ALL) patients survival. The pharmacodynamics of Mtx depends on the polymorphism of genes encoding proteins engaged in the folate metabolism pathway. The aim of the current study is to determine the relationship between variants of folate metabolism-related genes and the frequency of acute toxicities of HD-Mtx. Material and Methods: A group of 133 patients aged 1.5-18.1 years (median: 6.3) was treated in accordance with the ALL-IC-2002 and ALL-IC-2009 protocols. The following polymorphisms were determined: 80 G>A SLC19A1 (solute carrier family 19 member 1; rs1051266) with direct DNA sequencing, as well as 677 C>T MTHFR (methylenetetrahydrofolate reductase; rs1801133) and the tandem repeats of the TS (thymidylate synthase) with PCR technique. HD-Mtx organ toxicities were evaluated based on the laboratory tests results and the National Cancer Institute criteria. Results: In patients with genotypes AA for SLC19A1 and CC or CT for MTHFR Mtx steady state concentrations (Css) and AUCinf were distinctly higher. In patients with genotype 3R/3R for TS initial elimination rate constant was significantly higher (P = 0.003). Patients receiving Mtx at the dose of 5 g/m2 had lower clearance (4.35 vs. 8.92 L/h/m2) as compared to the ones receiving 2 g/m2 that indicates non-linear Mtx elimination at the higher dose. Liver impairment was the most frequently observed toxicity. The homozygous genotype was associated with a significantly higher incidence of hepatic toxicity for both the SLC19A1 (P = 0.037) and TS (P = 0.002). Logistic regression analysis indicated an increased risk of vomiting for the 2R/3R genotype of the TS gene (OR 3.20, 95% CI 1.33-7.68, P = 0.009) and for vomiting and hepatic toxicity for the 3R/3R genotype (vomiting: OR 3.39, 95% CI 1.12-10.23, P = 0.031; liver toxicity: OR 2.28, 95% CI 1.05-4.95, P = 0.038). None of the acute toxicities differed between the analyzed dosing groups. Conclusions: Determination of polymorphisms of SLC19A1, MTHFR, and TS genes might allow for a better prior selection of patients with higher risk of elevated Mtx levels. Our study is the first one to report the increased risk of hepatotoxicity and vomiting in patients with TS polymorphisms.

Is vitamin D concentration an indicator of the severity of atopic dermatitis and chronic spontaneous urticaria in adults?

Atopic dermatitis (AD) and chronic spontaneous urticaria (CSU) are common chronic and recurrent dermatoses. The role of vitamin D in the immunological processes, including the development of inflammation, has been the subject of numerous studies. The feasible measurement of vitamin D serum concentration and possibly supplementation necessitates the assessment of its impact on the clinical severity of mentioned diseases. AIM: The aim of the study was to determine the relationship between blood serum vitamin D concentration and the severity of clinical symptoms in the group of adults suffering from AD or CSU. MATERIALS AND METHODS: The study was conducted in 2018 on groups of patients suffering from AD or CSU. Serum vitamin D concentration was determined by electrochemiluminescence assay. Student's t-test was adopted to compare vitamin D levels between groups. Spearman's rank correlation coefficient was used to assess the correlation between vitamin D concentration and the severity of AD (according to the SCORAD scale) and CSU (according to the UAS 7 scale). RESULTS: There was not found any statistically significant relationship between the severity of skin lesions scores in the course of AD and CSU and serum vitamin D concentration.

Low Ejection Fraction Predisposes to Contrast-Induced Nephropathy after the Second Step of Staged Coronary Revascularization for Acute Myocardial Infarction: A Retrospective Observational Study.

Patients who develop contrast-induced nephropathy (CIN) are at an increased short-term and long-term risk of adverse cardiovascular (CV) events. Our aim was to search for patient characteristics associated with changes in serum creatinine and CIN incidence after each step of two-stage coronary revascularization in patients with acute myocardial infarction (AMI) and multivessel coronary artery disease undergoing staged coronary angioplasty during hospitalization for AMI. We retrospectively analyzed medical records of 138 patients with acute myocardial infarction without hemodynamic instability, in whom two-stage coronary angioplasty was performed during the initial hospital stay. In-hospital serum creatinine levels were recorded before the 1st intervention (at admission), within 72 h after the 1st intervention (before the 2nd intervention), and within 72 h after the 2nd intervention. The incidence of CIN was 2% after the 1st intervention (i.e., primary angioplasty) and 8% after the 2nd intervention. Patients with significant left ventricular systolic dysfunction after the 1st intervention (ejection fraction (EF) ≤35%) exhibited higher relative rises in creatinine levels after the 2nd intervention (18 ± 29% vs. 2 ± 16% for EF ≤35% and >35%, respectively, p = 0.03), while respective creatinine changes after the 1st revascularization procedure were comparable (-1 ± 14% vs. 2 ± 13%, p = 0.4). CIN after the 2nd intervention was over five-fold more frequent in subjects with low EF (28% vs. 5%, p = 0.007). The association between low EF and CIN incidence or relative creatinine changes after the 2nd intervention was maintained upon adjustment for baseline renal function, major CV risk factors, and the use of renin-angiotensin axis antagonists prior to admission. In conclusion, low EF predisposes to CIN after second contrast exposure in patients undergoing two-stage coronary angioplasty during the initial hospitalization for AMI. Our findings suggest a need of extended preventive measures against CIN or even postponement of second coronary intervention in patients with significant left ventricular dysfunction scheduled for the second step of staged angioplasty.