Autoimmunity, New Potential Biomarkers and the Thyroid Gland-The Perspective of Hashimoto's Thyroiditis and Its Treatment.

Autoimmune thyroid disease (AITD) is the most common organic specific illness of the thyroid gland. It may manifest as the overproduction or the decline of thyroxine and triiodothyronine. Hyperthyroidism develops due to the overproduction of hormones as an answer to the presence of stimulatory antibodies against the TSH receptor. Hashimoto's thyroiditis (HT) is generally characterized by the presence of thyroid peroxidase and thyroglobulin antibodies, with a concomitant infiltration of lymphocytes in the thyroid. Due to the progressive destruction of cells, AITD can lead to subclinical or overt hypothyroidism. Pathophysiology of AITD is extremely complicated and still not fully understood, with genetic, environmental and epigenetic factors involved in its development. Due to increasing incidence and social awareness of this pathology, there is an urgent need to expand the background concerning AITD. A growing body of evidence suggests possible ways of treatment apart from traditional approaches. Simultaneously, the role of potential new biomarkers in the diagnosis and monitoring of AITD has been highlighted recently, too. Therefore, we decided to review therapeutic trends in the course of AITD based on its pathophysiological mechanisms, mainly focusing on HT. Another aim was to summarize the state of knowledge regarding the role of new biomarkers in this condition.

Vascular Access Perception and Quality of Life of Haemodialysis Patients.

Background: Patient quality of life is widely used as a non-clinical determinant of care. For patients undergoing hemodialysis, vascular access is vital to the delivery of hemodialysis and its function may affect not only the clinical outcome of treatment but also the overall quality of life of the patient, highlighting the need for increased efforts to improve the quality of hemodialysis vascular access care. The objective of this study was to evaluate the correlation between vascular access perception and quality of life in patients undergoing hemodialysis. Methods: A total of 202 patients with active hemodialysis vascular access were included in the study. Quality of life was assessed using the Kidney Disease Quality of Life Instrument (KDQOL™) questionnaire, while vascular access perception was evaluated using the Vascular Access Questionnaire (VAQ). Results: The study presented evidence on the influence of vascular access for hemodialysis patients on their quality of life. This impact is related to factors directly associated with vascular access, such as the type of access and the patient's subjective evaluation of the access. Conclusions: The perception of vascular access is one of the factors that determines the quality of life of hemodialysis patients. The quality of life of hemodialysis patients decreases as the number of vascular access-related problems increases.

The Occurrence of Stress, Illness Acceptance and the Quality of Life of Patients after Pacemaker Implantation.

Pacemaker implantation improves the quality of life of most patients, especially in the initial period after implantation. It is necessary to measure the long-term quality of life and factors that can affect it-stress and illness acceptance. The aim of the study was to assess the impact of stress and illness acceptance on the quality of life of patients after pacemaker implantation. To obtain final conclusions, we performed a survey on a group of 100 patients with implanted pacemakers. Our survey consists of standardized research tools to check the quality of life (WHOQOL-BREF), perceived stress and ways to cope with it (PSS-10, mini-COPE) and acceptance of illness (AIS). The results of the study were summarized in a statistical analysis. At least a good quality of life was declared by more than half of the respondents [Me = 4; 95% PU (4, 4)]. The average result obtained by the respondents when converted to the STEN scale was six. The respondents were characterized by a moderate level of stress compared to the PSS-10 norms and it was related to the quality of life. Similar, statistically significant correlations were presented as mini-COPE and AIS results. Respondents were most likely to use acceptance strategies, active coping methods, when dealing with something else and planning. The rarest strategies were doing nothing and taking pharmaceuticals. The average score on the acceptance of illness scale was (M = 22.14; SD = 6.05), which is more than the result obtained by patients from the AIS normalization group. It shows that assessed patients after pacemaker implantation declare the general quality of life as good or higher. Additionally, this quality of life is closely related to stress levels, coping strategies and acceptance of illness, which shows us the importance of research in this area.

Assessment of Mood and Hope in Critically-Ill Patients as a Basis for the Improvement for the Palliative and Hospice Care.

The aim of the research is to present a level of hope in people in the terminal phase of cancer who differ in terms of mood: cheerful vs. sad. The study group consisted of 246 patients. Their average age was 59.5. The youngest respondent was 18 and the oldest was 90. The Personal Card tests by T. Witkowski (KI) and B.L. Block (NCN-36), designed for people struggling with serious life-threatening diseases, were used. The test consists of four scales distinguished by factor analysis. Each scale comprises of eight items. The following are used to study hope: the situational dimension-health; the telek-temporal dimension-goals; the spiritual dimension-religious beliefs; and the emotional-affective dimension-motivations. In the global view, the hope of the subjects was moderate. In the situational dimension-health, the telek-temporal dimension-goals, and the spiritual dimension-religious beliefs, people with a generally cheerful mood had stronger hope, in comparison to people with a sad mood. Only in the emotional-affective dimension-motivations, did people with a sad mood manifest stronger hope in comparison to people with a cheerful mood. The conducted research allowed us to conclude that mood is one of the determinants of hope in terminally ill cancer patients.

Methodological Aspects of Indirect Calorimetry in Patients with Sepsis-Possibilities and Limitations.

The aim of the review was to analyse the challenges of using indirect calorimetry in patients with sepsis, including the limitations of this method. A systematic review of the literature was carried out. The analysis concerned the methodology and presentation of research results. In most studies assessing energy expenditure, energy expenditure was expressed in kcal per day (n = 9) and as the mean and standard deviation (n = 7). Most authors provided a detailed measurement protocol, including measurement duration (n = 10) and device calibration information (n = 7). Ten papers provided information on the day of hospitalisation when the measurements were obtained, nine on patient nutrition, and twelve on the criteria for inclusion and exclusion of participants from the study. Small study group sizes and study at a single centre were among the most cited limitations. Studies assessing energy expenditure in patients with sepsis by indirect calorimetry differ in the methodology and presentation of results, and their collective analysis is difficult. A meta-analysis of the results could enable multi-site and large patient evaluation. Standardisation of protocols and presentation of all collected data would enable their meta-analysis, which would help to achieve greater knowledge about metabolism in sepsis.

Do endocrine adverse events predict longer progression-free survival among patients with non-small-cell lung cancer receiving nivolumab?

The aim of the study was to assess the occurrence and nature of immune-related endocrine adverse events (irAEs) among patients with non-small-cell lung cancer (NSCLC) treated with nivolumab. METHODS: The study group included 35 patients (15 women, 20 men, 65.8 ± 7.1 years) with NSCLC in stage IIIB (n = 16, 45.7%) and IV (n = 19,54.3%) who were treated with nivolumab. RESULTS: Of the studied patients, 34.3% (n = 12) developed endocrine irAEs (irAE group): 22.9% (n = 8) hyperthyroidism and 8.6% (n = 3) hypothyroidism, and in one case, hypophysitis was observed. The median irAEs onset time was 2 months. In the group of patients with thyroid disorders, permanent hypothyroidism eventually developed in 58.3%. The severity of the analyzed irAEs ranged from mild to moderate (Grade 1-2); the case of hypophysitis was estimated as Grade 3. The comparison of progression-free survival time (PFS) between the two groups showed longer PFS in patients in the irAE group (p = 0.021). Patients with irAE were treated significantly longer with nivolumab and they received more doses of nivolumab, however in Cox analysis we did not find patients with irAE to experience progression later than patients without them. CONCLUSIONS: Nivolumab therapy is associated with an increased risk of endocrine adverse effects, particularly thyroid dysfunction. Endocrine adverse effects can be successfully treated pharmacologically and usually do not require discontinuation of immunotherapy. The relationship between a better cancer prognosis in patients who developed endocrine irAE has not been found.

Heart Metabolism in Sepsis-Induced Cardiomyopathy-Unusual Metabolic Dysfunction of the Heart.

Due to the need for continuous work, the heart uses up to 8% of the total energy expenditure. Due to the relatively low adenosine triphosphate (ATP) storage capacity, the heart's work is dependent on its production. This is possible due to the metabolic flexibility of the heart, which allows it to use numerous substrates as a source of energy. Under normal conditions, a healthy heart obtains approximately 95% of its ATP by oxidative phosphorylation in the mitochondria. The primary source of energy is fatty acid oxidation, the rest of the energy comes from the oxidation of pyruvate. A failed heart is characterised by a disturbance in these proportions, with the contribution of individual components as a source of energy depending on the aetiology and stage of heart failure. A unique form of cardiac dysfunction is sepsis-induced cardiomyopathy, characterised by a significant reduction in energy production and impairment of cardiac oxidation of both fatty acids and glucose. Metabolic disorders appear to contribute to the pathogenesis of cardiac dysfunction and therefore are a promising target for future therapies. However, as many aspects of the metabolism of the failing heart remain unexplained, this issue requires further research.

Sepsis as a Pan-Endocrine Illness-Endocrine Disorders in Septic Patients.

Sepsis is defined as "life-threatening organ dysfunction caused by a dysregulated host response to infection". One of the elements of dysregulated host response is an endocrine system disorder. Changes in its functioning in the course of sepsis affect almost all hormonal axes. In sepsis, a function disturbance of the hypothalamic-pituitary-adrenal axis has been described, in the range of which the most important seems to be hypercortisolemia in the acute phase. Imbalance in the hypothalamic-pituitary-thyroid axis is also described. The most typical manifestation is a triiodothyronine concentration decrease and reverse triiodothyronine concentration increase. In the somatotropic axis, a change in the secretion pattern of growth hormone and peripheral resistance to this hormone has been described. In the hypothalamic-pituitary-gonadal axis, the reduction in testosterone concentration in men and the stress-induced "hypothalamic amenorrhea" in women have been described. Catecholamine and ß-adrenergic stimulation disorders have also been reported. Disorders in the endocrine system are part of the "dysregulated host response to infection". They may also affect other components of this dysregulated response, such as metabolism. Hormonal changes occurring in the course of sepsis require further research, not only in order to explore their potential significance in therapy, but also due to their promising prognostic value.

Metabolic Alterations in Sepsis.

Sepsis is defined as "life-threatening organ dysfunction caused by a dysregulated host response to infection". Contrary to the older definitions, the current one not only focuses on inflammation, but points to systemic disturbances in homeostasis, including metabolism. Sepsis leads to sepsis-induced dysfunction and mitochondrial damage, which is suggested as a major cause of cell metabolism disorders in these patients. The changes affect the metabolism of all macronutrients. The metabolism of all macronutrients is altered. A characteristic change in carbohydrate metabolism is the intensification of glycolysis, which in combination with the failure of entering pyruvate to the tricarboxylic acid cycle increases the formation of lactate. Sepsis also affects lipid metabolism-lipolysis in adipose tissue is upregulated, which leads to an increase in the level of fatty acids and triglycerides in the blood. At the same time, their use is disturbed, which may result in the accumulation of lipids and their toxic metabolites. Changes in the metabolism of ketone bodies and amino acids have also been described. Metabolic disorders in sepsis are an important area of research, both for their potential role as a target for future therapies (metabolic resuscitation) and for optimizing the current treatment, such as clinical nutrition.

PARP Inhibitors: An Innovative Approach to the Treatment of Inflammation and Metabolic Disorders in Sepsis.

Sepsis is not only a threat to the health of individual patients but also presents a serious epidemiological problem. Despite intensive research, modern sepsis therapy remains based primarily on antimicrobial treatment and supporting the functions of failing organs. Finding a cure for sepsis represents a great and as yet unfulfilled need in modern medicine. Research results indicate that the activity of poly (adenosine diphosphate (ADP)-ribose) polymerase (PARP) may play an important role in the inflammatory response and the cellular metabolic disorders found in sepsis. Mechanisms by which PARP-1 may contribute to inflammation and metabolic disorders include effects on the regulation of gene expression, impaired metabolism, cell death, and the release of alarmins. These findings suggest that inhibition of this enzyme may be a promising solution for the treatment of sepsis. In studies using experimental sepsis models, inhibition of PARP-1 has been shown to ameliorate the inflammatory response and increase survival. This action was described, among others, for olaparib, a PARP-1 inhibitor approved for use in oncology. While the results of current research are promising, the use of PARP inhibitors in non-oncological diseases raises some concerns, mainly related to the enzyme's role in deoxyribonucleic acid (DNA) repair. However, the results of studies on experimental models indicate the effectiveness of even short-term PARP-1 inhibition and do not confirm concerns regarding its impact on the integrity of nuclear DNA. Current research presents PARP inhibition as a potential solution for the treatment of sepsis and indicates the need for further research.

The Relevance of Noncoding DNA Variations of Paraoxonase Gene Cluster in Atherosclerosis-Related Diseases.

The human paraoxonase (PON) gene cluster is comprised of three contiguous genes (PON1, PON2 and PON3) of presumably common origin coding three lactonases of highly similar structure and substrate specificity. The catalytic activity of PON proteins is directed toward artificial organophosphates and in physiological conditions toward thiolactones and oxidized phospholipids. Consequently, PON enzymes are regarded as an effective defense against oxidative stress and, as a result, against atherosclerosis development. Additionally, both PON's serum activity and its concentration are influenced by several polymorphic variations in coding and noncoding DNA regions of the PON gene cluster remaining in linkage disequilibrium. Hence, the genetic polymorphism of the PON gene cluster may contribute to atherosclerotic process progression or deceleration. In this review the authors analyzed the relevance of noncoding DNA polymorphic variations of PON genes in atherosclerosis-related diseases involving coronary and peripheral artery disease, stroke, diabetes mellitus, dementia and renal disease and concluded that the effect of PON gene cluster' polymorphism has a considerable impact on the course and outcome in these conditions. The following PON genetic variations may serve as additional predictors of the risk of atherosclerosis in selected populations and individuals.

Hope in Advanced Cancer Patients in the Terminal Phase of Neoplastic Disease and Stability of Basic Mood.

The aim of this research is to compare the hope experienced by advanced cancer patients in the terminal phase of neoplastic disease in relation to the stability of their basic mood. The study group consisted of 246 patients, average age 59.5. The youngest respondent was 18 and the oldest was 90. The diagnostic tools used in the work comprised the Personal Card designed by T. Witkowski (PC) and an NCN-36 test (Block's Hope test), designed by B.L. Block to measure the strength of hope in people struggling with serious life-threatening diseases. The test consists of 4 subscales distinguished by factor analysis. Each subscale consists of 8 items. The test allows an evaluation of hope in the following dimensions: situational dimension (health, thelic-temporal dimension), goals to be achieved in the future, spiritual dimension (spirituality), religious beliefs, and emotional-motivational (affective) dimension (motivations). In cheerful patients who are in the terminal phase of cancer, mood stability does not constitute a major differentiating factor for experiencing hope. In sad people, on the other hand, mood stability affects the intensity of hope-those with an unstable mood are more likely to have a stronger emotional-motivational dimension of hope than sad people with a balanced mood.

Hope of Recovery in Patients in the Terminal Phase of Cancer under Palliative and Hospice Care in Poland.

INTRODUCTION: The objective of the presented research is to characterize hope in the situational dimension, i.e., health, in the patients with cancer in the terminal phase of the disease, being treated in hospices and palliative care centers. Hope is very important for all the patients, especially for patients with cancer in various phases of the disease. Giving up on oncologic therapy and causal treatment is often associated with a transition into palliative care. When death and a loss of values become a threat, the individual has got hope to rely on. Material and Methods. The study relies on the Test to Measure Hope in the Health Context (NCN-36) by B.L. Block. 246 patients in the terminal phase of cancer participated in the study. RESULTS: The internal structure of hope of recovery in the patients' group was varied. The patients showed low levels of hope of recovery since they do not believe in the effectiveness of treatment. They were also not convinced of the effectiveness of modifications in dieting, lifestyle, or the use of nonconventional medicine. They trusted the doctor in charge and were moderately satisfied with the therapy in use. The intensity of hope of recovery was on the low level in the patients in the terminal phase of cancer. Age, sex, place of living, and marital status had a significant influence on the level of hope of recovery. Variables such as living on one's own or living with one's family, socioeconomic status, education, or profession did not affect the level of hope of recovery. CONCLUSIONS: The presented results allowed as to conclude that the assessment of hope in terminally ill cancer patients can be considered as one of the important tools enabling the personalization and the improvement of palliative care.

Endocrine Adverse Events of Nivolumab in Non-Small Cell Lung Cancer Patients-Literature Review.

In recent years, we have observed significant progress in cancer treatment associated with the development of immunotherapy. A programmed cell death 1 molecule (PD-1) on the surface of T lymphocytes may be stimulated via a specific PD-ligand 1 (PD-L1), which inhibits lymphocyte activation and leads to apoptosis. Some malignant cells are characterized by high PD-L1 expression. Nivolumab, an anti-PD-1 antibody, blocks the interaction between PD-1 and its ligands and inhibits the signaling pathway by preventing the tumor-derived PD-L1 from blocking T lymphocytes. In patients with non-small cell lung cancer (NSCLC), it is used either in monotherapy or in combination with other drugs. Immunotherapy is associated with the possibility of immune-related adverse effects (irAE) including endocrinopathies (3-23%). Thyroid disorders are the most common, with severity rarely exceeding grade 2. Hypophysitis, adrenal insufficiency and diabetes are possible complications which require immediate treatment. Individuals with autoimmune diseases diagnosed prior to immunotherapy are at risk of its exacerbation. In the management of patients receiving immunotherapy, evaluation of history of autoimmune diseases, awareness and early diagnosis of irAE are crucial and may affect treatment outcomes.

Pancreatic neuroendocrine tumours in patients with von Hippel-Lindau disease.

Von Hippel-Lindau disease is a highly penetrant autosomal genetic disorder caused by a germline mutation in the tumour suppressor gene, manifesting with the formation of various tumours, including neuroendocrine tumours of the pancreas. The incidence of the latter is not very high, varying from 5% to 18%. To compare, haemangioblastomas and clear cell renal carcinoma are present in 70% of von Hippel-Lindau patients and are considered the main prognostic factors, with renal cancer being the most common cause of death. However, pancreatic neuroendocrine tumours should not be neglected, considering their malignant potential (different to sporadic cases), natural history, and treatment protocol. This paper aims to review the literature on the epidemiology, natural history, treatment, and surveillance of individuals affected by pancreatic neuroendocrine tumours in von Hippel-Lindau disease.

Hope of patients in the terminal phase of cancer and place of residence.

OBJECTIVE: The aim of the study is to compare the hope of rural and urban inhabitants in the terminal stage of a neoplastic disease covered by stationary hospice care. MATERIAL AND METHODS: The study was carried out among patients in the terminal phase of a neoplastic disease. They were patients of both 24-hour and daily palliative and hospice care units throughout the country. The study group consisted of 246 patients, average age - 59.5, the youngest respondent was 18 and the oldest - 90. The B. L. Block (NCN-36) test, prepared for people struggling with serious life-threatening diseases, was used. Comparison of the results with regard to the place of residence was based on the test Friedman ANOVA and Kendall compatibility factor. The general comparison of hope in individual dimensions and globally with the division into the degree of urbanization, was based on the Kruskal-Wallis test. RESULTS: On the basis of factor analysis, 4 scales constructed from 8 items branch were distinguished. The following scales are used to study hope in the situational dimension - health, the telek-temporal dimension - goals, the spiritual dimension - religious beliefs and in the emotional-affective (affective) dimension - motivations. CONCLUSIONS: The strength of hope in people in the terminal phase of cancer, residing in villages, settlements, small, medium and large cities, was similar and depended on its magnitude. Of all the manifestations of hope, the greatest variation in results occurred in the subjects when they encountered serious problems and difficulties. The inhabitants of medium-sized cities were characterized by a higher hope at that time.

Hope in Hospitalized Patients with Terminal Cancer.

: Hope is of great importance for patients diagnosed with cancer, especially those that are terminally ill. The diagnosis often puts an end to the realization of personal, social, and professional goals. The aim of this study was to characterize the hope of hospitalized patients diagnosed with cancer in the terminal phase of the disease. The research tool used in the study was Block's hope test (NCN-36; NCN- Nadzieja Chorych Nowotworowych - Hope of Cancer Patients), designed for patients with life-threatening diseases. The results showed that the patients were characterized by a moderate level of global hope. The highest levels of hope were noted in the spiritual-religious area and the lowest levels of hope concerned curing the disease. Patients exhibited varied levels of hope and varied internal structures of hope. They presented four different types of hope: optimistic, moderate, religious, and weak. Optimistic hope was found most frequently in patients diagnosed with a terminal phase of cancer, while weak hope was represented by the smallest group of these patients.

Metformin inhibits both oleic acid-induced and CB1R receptor agonist-induced lipid accumulation in Hep3B cells: The preliminary report.

Fatty liver is characterized by excessive accumulation of triglycerides within hepatocytes. Recent findings indicate that natural history of nonalcoholic fatty liver is regulated, in part, by endogenous cannabinoids. Metformin is an oral hypoglycemic medication which inhibits gluconeogenesis and glycogenolysis in hepatocytes and limits lipid storage in the liver through the inhibition of free fatty acid formation via induction of activated protein kinase activity (AMPK). Both endocannabinoids and metformin may modulate hepatosteatosis; therefore, it was interesting to examine whether metformin may affect lipid accumulation in hepatocytes by acting on cannabinoid receptors, CB1 and CB2, in in vitro study. Hep3B cells were incubated with or without metformin (Met), phosphatidylcholine (PC), and oleic acid (OA). Cells without any of the examined substances served as negative control. Cells treated only with OA served as positive control. The quantity of intracellular lipids was assessed using Oil-Red-O staining. Selective CB1R agonist, arachidonyl-2-chloromethylamide (ACEA), and CB2R agonist, AM1241 (2-iodo-5-nitrophenyl)-[1-(methylpiperidin-2-ylmethyl)-1 H-indol-3-yl]methanone, were also used to treat Hep3B cells. In some experiments, antagonist for CB1R, AM6545, or SR144528 as selective antagonist of CB2R were used. In the study, Met decreased lipid accumulation in cells treated with OA and inhibited CB1R agonist-induced lipid accumulation in hepatocytes. The CB2R agonist-induced hepatic lipid accumulation was not inhibited by metformin. The results indicate that metformin may interact with endocannabinoid system in the liver by inhibiting CB1R agonist-stimulated fat accumulation in hepatocytes.

Gestational diabetes mellitus - literature review on selected cytokines and hormones of confirmed or possible role in its pathogenesis.

The incidence of gestational diabetes mellitus (GDM) increases globally, including Poland. Considering serious consequences of gestational diabetes for both mother and fetus, screening for this disorder is an obligatory element of managing pregnant woman. The pathogenesis of gestational diabetes is not yet thoroughly explained. However, it is insulin resistance and chronic subclinical inflammatory process which are considered to be major factors responsible for the development of GDM. These two states are triggered mainly by secretion of proinflammatory cytokines and by abnormal function of adipose tissue. The study reviews the literature on selected hormones and cytokines whose role in the GDM pathogenesis has been already confirmed as well as on those proteins whose role is either not yet fully understood or which may possibly participate in GDM development. Owing to the fact that underlying mechanisms of GDM are, in general, similar to the mechanisms responsible for metabolic disorders such as diabetes mellitus type 2 or obesity, in this review we focus first on the role these molecules play in pathogenesis of metabolic disorders and then present current state of knowledge on their action in gestational diabetes development. The review presents: TNF alpha, adipokines - adiponectin and leptin and relatively newly discovered proteins: fetuin A, periostin, angiopoietin-like protein 8 or high mobility group box.