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1.
Int J Mol Sci ; 25(9)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38731922

RESUMO

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.


Assuntos
Autoimunidade , Biomarcadores , Doença de Hashimoto , Glândula Tireoide , Humanos , Doença de Hashimoto/imunologia , Doença de Hashimoto/terapia , Doença de Hashimoto/metabolismo , Doença de Hashimoto/diagnóstico , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Autoanticorpos/imunologia , Animais
2.
Int J Mol Sci ; 22(4)2021 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-33670025

RESUMO

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.


Assuntos
Arildialquilfosfatase/genética , Aterosclerose/enzimologia , Aterosclerose/genética , DNA Intergênico/genética , Família Multigênica , Animais , Aterosclerose/sangue , Humanos , Lipídeos/sangue , Polimorfismo Genético
3.
Ginekol Pol ; 89(9): 522-527, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30318581

RESUMO

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.


Assuntos
Adipocinas/metabolismo , Tecido Adiposo/metabolismo , Citocinas/metabolismo , Diabetes Gestacional/metabolismo , Células Secretoras de Insulina/metabolismo , Tecido Adiposo/fisiopatologia , Animais , Glicemia/metabolismo , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/fisiopatologia , Feminino , Humanos , Insulina/sangue , Gravidez , Transdução de Sinais
4.
Neurochem Res ; 42(4): 1038-1043, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28083847

RESUMO

Although the role of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in neuronal excitability and synaptic transmission is still unclear, it is postulated that the HCN channels may be involved in seizure activity. The aim of this study was to assess the effects of ivabradine (an HCN channel inhibitor) on the protective action of four classical antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) against maximal electroshock-induced seizures in mice. Tonic seizures (maximal electroconvulsions) were evoked in adult male albino Swiss mice by an electric current (sine-wave, 25 mA, 0.2 s stimulus duration) delivered via auricular electrodes. Acute adverse-effect profiles of the combinations of ivabradine with classical antiepileptic drugs were measured in mice along with total brain antiepileptic drug concentrations. Results indicate that ivabradine (10 mg/kg, i.p.) significantly enhanced the anticonvulsant activity of valproate and considerably reduced that of phenytoin in the mouse maximal electroshock-induced seizure model. Ivabradine (10 mg/kg) had no impact on the anticonvulsant potency of carbamazepine and phenobarbital in the maximal electroshock-induced seizure test in mice. Ivabradine (10 mg/kg) significantly diminished total brain concentration of phenytoin and had no effect on total brain valproate concentration in mice. In conclusion, the enhanced anticonvulsant action of valproate by ivabradine in the mouse maximal electroshock-induced seizure model was pharmacodynamic in nature. A special attention is required when combining ivabradine with phenytoin due to a pharmacokinetic interaction and reduction of the anticonvulsant action of phenytoin in mice. The combinations of ivabradine with carbamazepine and phenobarbital were neutral from a preclinical viewpoint.


Assuntos
Anticonvulsivantes/metabolismo , Anticonvulsivantes/uso terapêutico , Benzazepinas/metabolismo , Benzazepinas/uso terapêutico , Eletrochoque/efeitos adversos , Convulsões/metabolismo , Animais , Relação Dose-Resposta a Droga , Interações Medicamentosas/fisiologia , Quimioterapia Combinada , Ivabradina , Masculino , Camundongos , Distribuição Aleatória , Convulsões/tratamento farmacológico , Convulsões/etiologia
5.
Ann Hepatol ; 15(6): 862-869, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27740519

RESUMO

 Background. Chemerin and retinol binding protein-4 (RBP-4) are adipokines which may play a role in the progression of NAFLD. It has been also suggested that cytokeratin-18 (CK-18) could be a marker of hepatocyte caspase-directed death while transgelin-2 production could reflect stage of liver fibrosis. The aim of this study was to evaluate the level of the above adipokines in sera of patients with NAFLD and determine the relation between the level of transgelin-2 and fibrosis-4 index (FIB-4). MATERIAL AND METHODS: Ninety-five subjects included initially to the study were divided into four groups: (I) prediabetics, obese with NAFLD and metabolic syndrome (MS), (II) lean with NAFLD and without MS, (III) obese without NAFLD and MS, and (IV) healthy individuals. We determined the levels of chemerin, RBP-4, transgelin-2 and CK-18 fragments in sera of patients with NAFLD. Moreover, we examined if the levels of CK-18 fragments and transgelin-2 correlates with FIB4 value. RESULTS: Chemerin and RBP-4 were highly expressed in sera of all NAFLD, especially in obese individuals. Chemerin level was also linked to MS. High level of serum CK-18 fragments and transgelin-2 did not correlate with obesity and MS, but seemed to correlate with progression of NAFLD to liver fibrosis. CONCLUSIONS: In conclusion, the production of the two adipokines, chemerin and RBP-4, is strongly associated with obesity in patients with NAFLD. Serum concentrations of CK-18 fragments and transgelin-2 correlate with the severity of NAFLD, but no with obesity.


Assuntos
Quimiocinas/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Queratina-18/sangue , Proteínas dos Microfilamentos/sangue , Proteínas Musculares/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Proteínas Plasmáticas de Ligação ao Retinol/análise , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Obesidade/sangue , Obesidade/diagnóstico , Estado Pré-Diabético/sangue , Estado Pré-Diabético/diagnóstico , Valor Preditivo dos Testes , Prognóstico , Índice de Gravidade de Doença
6.
Ginekol Pol ; 87(3): 194-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27306128

RESUMO

OBJECTIVES: The aim of the study was to estimate whether diabetes was an independent risk factor for perioperative complications in patients undergoing gynecologic surgery. MATERIAL AND METHODS: The study population consisted of 182 women (diabetics and controls) who underwent elective gynecologic surgery. Each patient without diabetes from the control group and matched for age and body mass index diabetic patient were admitted with the same gynecologic diagnosis, underwent the same gynecologic procedure, were operated on in the same operating room and were hospitalized within the same time interval. The following parameters of the perioperative period were compared between every matched pair of patients (diabetic vs. non-diabetic patient): number and characteristics of intra- and postoperative complications, length of postoperative hospitalization, decrease in hemoglobin level, increase in body temperature, and postoperative use of antibiotics. RESULTS: The study revealed no statistically significant differences between the diabetic patients and pair-matched controls in terms of the examined parameters of the perioperative period. CONCLUSIONS: Diabetes was not an independent risk factor for early postoperative complications after gynecologic procedures in the examined population. Good pre-operative glycemic control and strict cooperation of the diabetologist with the surgeon in the perioperative period resulted in reduction of the complication rate to the level typical for non-diabetic patients.


Assuntos
Complicações do Diabetes/complicações , Diabetes Mellitus , Procedimentos Cirúrgicos em Ginecologia/métodos , Período Perioperatório , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco
7.
J Clin Med ; 13(8)2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38673698

RESUMO

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.

8.
Cancer Med ; 13(18): e70162, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39300954

RESUMO

OBJECTIVE: The article aims to assess the role of stress and anxiety in relation to the level of emotional control among cancer patients. Currently cancer ranks second, after cardiovascular disease, as the most common cause of death. Moreover, it is predicted that in the coming years, cancer will become the leading cause of death worldwide. This is due to the extended lifespan of the population and also to the presence of carcinogenic factors in the surrounding environment. The emergence of cancer is a significant stressor that affects individuals in diverse ways, leading to cognitive, behavioral, and emotional consequences. In line with the adopted aim, emotional issues are the chosen area of exploration in this article. METHODS: The study included 102 patients. The differences between the patients' results according to various scales and the results produced by the validation group data were examined using one-sample t-tests. The relationships between the quantitative variables were determined using Spearman's rho coefficients, and the relationships between the quantitative and qualitative variables were verified using Kruskal-Wallis tests. RESULTS: The participants exhibited higher anxiety suppression levels than individuals in the normalization group. They sought emotional support more frequently than the average person in the population, turned to religion, engaged in other such activities, lived in denial more often, discontinued activities, and displayed a sense of humor less frequently. The more frequently they controlled their anger, the less they sought emotional and instrumental support, catharsis, and attempted to accept the situation and cease being active. Additionally, controlling anxiety, sadness, and depression coexisted with self-blame, denial, and compensatory actions. CONCLUSIONS: Cancer patients face intense anxiety. Emotional and instrumental support, along with the ability to express and manage emotions, are crucial for these patients, especially within the context of facing the challenge of cancer. Finding constructive ways to express strong and difficult emotions prevents their accumulation and reduces the need for emotional suppression. Preventive actions should be oriented toward supporting the emotional competencies of patients.


Assuntos
Ansiedade , Regulação Emocional , Neoplasias , Estresse Psicológico , Humanos , Neoplasias/psicologia , Feminino , Masculino , Ansiedade/psicologia , Estresse Psicológico/psicologia , Pessoa de Meia-Idade , Idoso , Adulto , Emoções , Inquéritos e Questionários
9.
Nutrients ; 14(5)2022 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-35267903

RESUMO

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.


Assuntos
Sepse , Calorimetria Indireta/métodos , Metabolismo Energético , Humanos , Estado Nutricional , Sepse/metabolismo
10.
Artigo em Inglês | MEDLINE | ID: mdl-36361008

RESUMO

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.


Assuntos
Marca-Passo Artificial , Qualidade de Vida , Humanos , Inquéritos e Questionários , Adaptação Psicológica
11.
Artigo em Inglês | MEDLINE | ID: mdl-36011622

RESUMO

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.


Assuntos
Cuidados Paliativos na Terminalidade da Vida , Neoplasias , Afeto , Estado Terminal , Humanos , Pessoa de Meia-Idade , Neoplasias/psicologia , Neoplasias/terapia , Cuidados Paliativos
12.
J Inflamm Res ; 14: 1827-1844, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33986609

RESUMO

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.

13.
J Clin Med ; 10(11)2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34072402

RESUMO

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.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34300048

RESUMO

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.


Assuntos
Cardiomiopatias , Insuficiência Cardíaca , Sepse , Trifosfato de Adenosina , Cardiomiopatias/etiologia , Cardiomiopatias/metabolismo , Metabolismo Energético , Ácidos Graxos/metabolismo , Glucose/metabolismo , Coração , Insuficiência Cardíaca/etiologia , Humanos , Miocárdio/metabolismo , Oxirredução
15.
J Clin Med ; 10(10)2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-34066289

RESUMO

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.

16.
PLoS One ; 16(9): e0257484, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34587185

RESUMO

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.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/uso terapêutico , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Hipertireoidismo/etiologia , Hipotireoidismo/etiologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Imunoterapia/efeitos adversos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nivolumabe/efeitos adversos , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Risco
17.
Endokrynol Pol ; 71(3): 256-259, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32797472

RESUMO

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.


Assuntos
Tumores Neuroendócrinos/complicações , Tumores Neuroendócrinos/terapia , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/terapia , Doença de von Hippel-Lindau/terapia , Feminino , Humanos , Masculino , Tumores Neuroendócrinos/genética , Neoplasias Pancreáticas/genética , Prognóstico , Doença de von Hippel-Lindau/genética , Doença de von Hippel-Lindau/patologia
18.
Cancers (Basel) ; 12(8)2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32824462

RESUMO

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.

19.
J Clin Med ; 9(11)2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33158136

RESUMO

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.

20.
Biomed Res Int ; 2020: 7529718, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32884944

RESUMO

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.


Assuntos
Esperança , Cuidados Paliativos na Terminalidade da Vida , Neoplasias/psicologia , Neoplasias/terapia , Cuidados Paliativos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polônia
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