Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 66
Filtrar
1.
Magy Onkol ; 68(1): 77-85, 2024 Mar 14.
Artículo en Húngaro | MEDLINE | ID: mdl-38484378

RESUMEN

During the care of brain tumor patients, supportive care and palliation are carried out in an individualized manner, accompanied by adequate communication, in a multidisciplinary professional environment. In the case of brain tumor patients, the burden of symptoms resulting from the progression of the disease and the complications of treatments occur in a particularly high proportion. The supportive care of patients in a modern approach covers the targeted treatment of physical and psychosocial problems and also includes integrated palliation. Palliative care is a form of care that can be used in addition to curative therapies, and it is advisable and necessary to introduce it as early as possible among brain tumor patients due to the significant deterioration of the quality of life. Dealing with seriously ill patients on a daily basis is also an emotional burden for the professional staff, and carries the risk of burnout. The support of the staff and family members, as well as the issues of adequate communication, are also part of the scope of the supportive care approach.


Asunto(s)
Neoplasias Encefálicas , Cuidados Paliativos , Humanos , Cuidados Paliativos/métodos , Calidad de Vida/psicología , Neoplasias Encefálicas/terapia
2.
Front Immunol ; 15: 1374581, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38524140

RESUMEN

Introduction: Psoriasis is a T-cell mediated autoimmune skin disease. HLA-C*06:02 is the main psoriasis-specific risk gene. Using a Vα3S1/Vß13S1 T-cell receptor (TCR) from a lesional psoriatic CD8+ T-cell clone we had discovered that, as an underlying pathomechanism, HLA-C*06:02 mediates an autoimmune response against melanocytes in psoriasis, and we had identified an epitope from ADAMTS-like protein 5 (ADAMTSL5) as a melanocyte autoantigen. The conditions activating the psoriatic autoimmune response in genetically predisposed individuals throughout life remain incompletely understood. Here, we aimed to identify environmental antigens that might trigger autoimmunity in psoriasis because of TCR polyspecificity. Methods: We screened databases with the peptide recognition motif of the Vα3S1/Vß13S1 TCR for environmental proteins containing peptides activating this TCR. We investigated the immunogenicity of these peptides for psoriasis patients and healthy controls by lymphocyte stimulation experiments and peptide-loaded HLA-C*06:02 tetramers. Results: We identified peptides from wheat, Saccharomyces cerevisiae, microbiota, tobacco, and pathogens that activated both the Vα3S1/Vß13S1 TCR and CD8+ T cells from psoriasis patients. Using fluorescent HLA-C*06:02 tetramers loaded with ADAMTSL5 or wheat peptides, we find that the same CD8+ T cells may recognize both autoantigen and environmental antigens. A wheat-free diet could alleviate psoriasis in several patients. Discussion: Our results show that due to TCR polyspecificity, several environmental antigens corresponding to previously suspected psoriasis risk conditions converge in the reactivity of a pathogenic psoriatic TCR and might thus be able to stimulate the psoriatic autoimmune response against melanocytes. Avoiding the corresponding environmental risk factors could contribute to the management of psoriasis.


Asunto(s)
Autoinmunidad , Psoriasis , Humanos , Linfocitos T CD8-positivos , Antígenos HLA-C , Autoantígenos , Péptidos , Receptores de Antígenos de Linfocitos T , Proteínas ADAMTS
3.
Br J Dermatol ; 190(5): 657-667, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38133541

RESUMEN

BACKGROUND: Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are potentially life-threatening autoimmune blistering diseases. Treatment is based on long-term immunosuppression with high doses of glucocorticosteroids in combination with potentially corticosteroid-sparing agents and/or rituximab. Immunoadsorption (IA) has emerged as a fast-acting adjuvant treatment option. OBJECTIVES: To assess the clinical efficacy of IA in addition to best medical treatment (BMT). METHODS: We conducted a multicentre (26 centres from Germany and Austria) randomized controlled trial in 72 patients with newly diagnosed, relapsed or chronic active PV or PF (34 female patients and 38 male patients, aged 42-72 years) comparing BMT (prednisolone 1.0 mg kg-1 per day plus azathioprine or mycophenolate) with adjuvant IA (BMT + IA). Central 1 : 1 randomization was done at the coordinating centre for clinical trials (KKS Marburg). The primary endpoint was analysed using Kaplan-Meier and Cox regression methods. RESULTS: The study was ended prematurely owing to safety concerns after random allocation of 72 patients to BMT + IA (n = 34) or BMT (n = 38). The primary endpoint, time to complete remission on therapy, was not significantly different for the two groups [hazard ratio (HR) 1.35, 95% confidence interval (CI) 0.68-2.69; P = 0.39]. The cumulative dose of prednisolone was significantly lower in the BMT + IA group compared with BMT alone (difference -1214, 95% CI -2225 to -70; P = 0.03). In a post hoc analysis, patients with more extensive PV/PF showed a tendency towards a shorter time to remission in the BMT + IA group compared with the BMT group (HR 1.87, P = 0.17 in patients with baseline Pemphigus Disease Area Index ≥ 15). While more adverse events were observed in patients in the BMT group (29 vs. 25), severe adverse events were more frequent in patients in the BMT + IA group (17 events in 10 patients vs. 11 events in 8 patients). CONCLUSIONS: In this study, adjuvant IA did not demonstrate a shorter time to clinical remission, but a corticosteroid-sparing effect was observed. In patients with extensive PV/PF, post hoc analysis suggests that adjuvant IA may lead to earlier remission, but potential adverse events must be carefully weighed against the expected benefits.


Pemphigus vulgaris and pemphigus foliaceus are potentially life-threatening autoantibody-driven blistering diseases, which present with erosions or blisters on skin and/or mucous membranes. Treatment is based on long-term immunosuppressive agents. Immunoadsorption (IA) is a procedure that removes autoantibodies from the blood and has emerged as a fast-acting treatment option for pemphigus.We conducted a trial comparing best medical treatment (BMT) (prednisolone 1.0 mg kg per day plus azathioprine or mycophenolate) with best medical treatment plus IA (BMT + IA). A total of 26 centres from Germany and Austria recruited 72 patients with active pemphigus (34 women and 38 men, aged 42­72 years) who were randomly allocated in a ratio of 1 : 1 to the treatment groups.Following inclusion of 72 patients in the BMT + IA (n = 34) or BMT (n = 38) groups, the study ended prematurely owing to safety concerns. The main outcome, time to complete remission (relief of all symptoms) while still receiving therapy, was not significantly different for the two groups. In contrast, the cumulative dose of prednisolone was significantly lower in the BMT + IA compared with BMT alone. In an additional analysis, patients with more extensive pemphigus showed a tendency towards a shorter time to remission in the BMT + IA group compared with the BMT group. While more adverse events were observed in the BMT group (29 vs. 25), severe adverse events were more frequent in the BMT + IA group (17 vs. 11). In this study, IA did not show a shorter time to clinical remission, but a prednisolone-sparing effect was observed. In patients with extensive pemphigus, adjuvant IA may possibly lead to earlier remission, but potential adverse events must be carefully weighed against the expected benefits.


Asunto(s)
Pénfigo , Humanos , Masculino , Femenino , Inmunosupresores/uso terapéutico , Prednisolona/uso terapéutico , Rituximab/uso terapéutico , Adyuvantes Inmunológicos/uso terapéutico , Corticoesteroides/uso terapéutico
4.
Sci Rep ; 13(1): 17378, 2023 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-37833455

RESUMEN

Clinical trials revealed significant antitumor activity for immune checkpoint inhibitors (ICI) in metastatic urothelial carcinoma (mUC). Due to their strict eligibility criteria, clinical trials include selected patient cohorts, and thus do not necessarily represent real-world population outcomes. In this multicentric, retrospective study, we investigated real-world data to assess the effectiveness of pembrolizumab and atezolizumab and to evaluate the prognostic value of routinely available clinicopathological and laboratory parameters. Clinical and follow-up data from mUC patients who received ICIs (01/2017-12/2021) were evaluated. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and duration of response (DOR) were used as endpoints. Patients' (n = 210, n = 76 atezolizumab and 134 pembrolizumab) median OS and PFS were 13.6 and 5.9 months, respectively. Impaired ECOG-PS, the presence of visceral, liver or bone metastases, and hemoglobin levels were independently associated with poor OS and DCR. Furthermore, Bellmunt risk factors and the enhanced Bellmunt-CRP score were shown to be prognostic for OS, PFS and DCR. In conclusion, ICIs are effective treatments for a broad range of mUC patients. Our results confirmed the prognostic value of numerous risk factors and showed that Bellmunt risk scores can further be improved when adding CRP to the model.


Asunto(s)
Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Estudios Retrospectivos , Radioinmunoterapia
5.
Clin Exp Dermatol ; 49(1): 53-57, 2023 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-37793183

RESUMEN

BACKGROUND: Dermatitis herpetiformis (DH) is a rare gluten-induced skin disorder characterized predominantly by IgA autoantibodies against endomysium, tissue transglutaminase (TG2/tTG), epidermal transglutaminase (TG3/eTG) and deamidated gliadin. To date, circulating autoantibody reactivity has not been systematically described. OBJECTIVES: Characterization of serum reactivities in DH. METHODS: This multicentre international study analysed sera from 242 patients with DH taken at the time of initial diagnosis. DH-specific IgA and IgG serum autoantibodies were analysed by indirect immunofluorescence (IF) on monkey oesophagus, and by enzyme-linked immunosorbent assay (ELISA) based on recombinant TG2/tTG, TG3/eTG and deamidated gliadin (GAF3X). RESULTS: IgA indirect IF microscopy on monkey oesophagus revealed the highest reactivity (84.3%; specificity 100%) followed by IgA TG2/tTG ELISA (78.5%, specificity 99.0%), IgA TG3/eTG ELISA (72.7%, specificity 95.0%) and IgA GAF3X ELISA (69.0%, specificity 98.5%). CONCLUSIONS: Serum IgA and IgG autoantibodies against endomysium, TG2/tTG, TG3/eTG and deamidated gliadin are highly prevalent in DH. Indirect IF microscopy on monkey oesophagus (IgA) provides the highest diagnostic accuracy that can be further enhanced by 4.5% when combined with IgA TG2/tTG ELISA.


Asunto(s)
Dermatitis Herpetiforme , Humanos , Animales , Dermatitis Herpetiforme/diagnóstico , Gliadina , Inmunoglobulina A , Autoanticuerpos , Transglutaminasas , Ensayo de Inmunoadsorción Enzimática , Inmunoglobulina G , Haplorrinos
6.
Int J Mol Sci ; 24(18)2023 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-37762692

RESUMEN

The recent classification of pediatric thrombotic microangiopathies (TMA) takes into consideration mechanisms of disease for guidance to targeted therapies. We present our experience with seven patients with antibody mediated atypical hemolytic uremic syndrome (aHUS) and thrombotic thrombocytopenic purpura (TTP). Five children had aHUS with antibodies against complement factor H (CFH-ab) and two with TTP with antibodies against metalloproteinase ADAMTS13. In the aHUS cases diagnosed and treated before the eculizumab era, CFH-ab was detected using the ELISA assay. Mutational analysis of selected complement genes was performed. TTP was diagnosed if, in addition to microangiopathic hemolytic anemia and thrombocytopenia, ischemic organ involvement and severe deficiency in ADAMTS13 activity were present. Treatment protocol consisted of plasma exchanges (PE) and steroid pulses, followed by the combination of cyclophosphamide and rituximab to achieve long-term immunosuppression. Four patients with CFH-ab and the TTP patients with ADAMTS13 antibodies came into sustained remission. After a median follow-up of 11.7 (range 7.7-12.9) years without maintenance therapy, no disease recurrence was observed; nevertheless, six patients, two had hypertension and two had proteinuria as a late consequence. One patient, with late diagnosis of CFH-ab and additional genetic risk factors who was treated only with PE and plasma substitution, reached end-stage renal disease and was later successfully transplanted using eculizumab prophylaxis. In the cases of antibody-mediated TMAs, PE and early immunosuppressive treatment may result in sustained remission with preserved kidney function. Further data are needed to establish optimal treatment of anti-FH antibody-associated HUS.

7.
Exp Dermatol ; 32(9): 1412-1419, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37260420

RESUMEN

Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are two major autoimmune blistering skin diseases. Unlike PV, BP is accompanied by intense pruritus, suggesting possible involvement of the pruritogenic cytokine IL-31. However, the underlying mechanisms of the clinical difference between BP and PV in terms of pruritus are not fully understood. To compare the expression levels of IL-31 and its receptor IL-31RA in the lesional skin, including peripheral nerves in BP and PV patients, immunohistochemical staining for IL-31 and IL-31RA was performed in skin samples of BP and PV patients and healthy controls (HC). The IL-31RA-expressing area in epidermis and peripheral nerves was analysed using ImageJ and the percentage of positive cells for IL-31/IL-31RA in dermal infiltrating cells was manually quantified. Quantitative analyses revealed that IL-31/IL-31RA expressions in the epidermis and dermal infiltrate were significantly increased in BP compared to PV and HC. The difference between BP and PV became more obvious when advanced bullous lesions were compared. Peripheral nerves in BP lesions presented significantly higher IL-31RA expression compared to PV lesions. In conclusion, we found significantly augmented expressions of IL-31/IL-31RA in BP lesions, including peripheral nerves, in comparison to PV. These results suggest a possible contribution of IL-31/IL-31RA signalling to the difference between BP and PV in the facilitation of pruritus and local skin inflammation, raising the possibility of therapeutic targeting of the IL-31/IL-31RA pathway in BP patients.


Asunto(s)
Enfermedades Autoinmunes , Penfigoide Ampolloso , Pénfigo , Humanos , Vesícula , Citocinas , Prurito
8.
Children (Basel) ; 10(4)2023 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-37189924

RESUMEN

Background: Autosomal recessive osteopetrosis (ARO) is a rare genetic disorder of bone metabolism, primarily affecting the remodelling function of osteoclasts. Haematopoietic stem cell transplantation (HSCT) is the first-line treatment for ARO. Traditional tools for the assessment of therapeutic response, such as measuring donor chimerism, do not provide information on bone remodelling. The use of bone turnover markers (BTMs) might be ideal. Here, we report a case of a paediatric ARO patient undergoing successful HSCT. Methods: For the evaluation of donor-derived osteoclast activity and skeletal remodelling throughout the transplantation, the bone resorption marker ß-CTX (ß-C-terminal telopeptide) was used. Results: The low baseline level of ß-CTX markedly increased after transplantation and remained in the elevated range even after 3 months. Donor-derived osteoclast activity reached its new baseline level around the 50th percentile range after 5 months and proved to be stable during the 15-month follow-up time. The apparent increase of the baseline osteoclast activity after HSCT was in consonance with the radiographic improvement of the disease phenotype and the correction of bone metabolic parameters. Despite the successful donor-derived osteoclast recovery, craniosynostosis developed, and reconstructive surgery had to be performed. Conclusions: The use of ß-CTX may be of aid in assessing osteoclast activity throughout the transplantation. Further studies could help to establish the extended BTM profile of ARO patients using the available osteoclast- and osteoblast-specific markers.

10.
Pediatr Nephrol ; 38(8): 2549-2562, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36260163

RESUMEN

Given the wide diversity of causes of hematuria, ranging from simple urinary tract infections with rapid recovery to severe glomerulonephritis with fast decline in kidney function, it is essential to recognize the underlying disease. The first objective of the assessment is to determine whether the cause of the hematuria is medically significant. The combination of hematuria with proteinuria, the presence of hypertension, or worsening kidney function can represent signs of progressive kidney disease. Differentiating the various causes of hematuria is often simple and obvious based on the clinical signs and gross appearance of the urine. However, in some instances, additional non-invasive investigations, such as ultrasound imaging, urinary red cell morphology, measurement of calcium and other solutes in the urine, evaluation of kidney function, and protein excretion, are needed to elucidate the nature of the hematuria. Taking a detailed family history can help in establishing the underlying cause in cases of familial hematuria. On the other hand, the decision to perform a kidney biopsy in children with asymptomatic hematuria remains a challenging issue for clinicians. Ultimately, the frequency of diagnosis of glomerular involvement causing hematuria may depend on the threshold for performing a kidney biopsy. The following review will focus on the diagnostics of hematuria, starting with difficulties regarding its definition, followed by various means to differentiate between urinary, glomerular, and other causes, and finally reviewing the most common diseases that, due to their frequency or their effect on kidney function, present a diagnostic challenge in everyday practice.


Asunto(s)
Glomerulonefritis , Enfermedades Renales , Niño , Humanos , Hematuria/diagnóstico , Hematuria/etiología , Hematuria/orina , Riñón/diagnóstico por imagen , Riñón/patología , Enfermedades Renales/diagnóstico , Glomerulonefritis/complicaciones , Glomerulonefritis/diagnóstico , Glomerulonefritis/terapia , Glomérulos Renales/patología
11.
J Adv Res ; 44: 71-79, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-35581140

RESUMEN

INTRODUCTION: Bullous pemphigoid (BP) is the most common autoimmune blistering disease. It predominately afflicts the elderly and is significantly associated with increased mortality. The observation of age-dependent changes in the skin microbiota as well as its involvement in other inflammatory skin disorders suggests that skin microbiota may play a role in the emergence of BP blistering. We hypothesize that changes in microbial diversity associated with BP might occur before the emergence of disease lesions, and thus could represent an early indicator of blistering risk. OBJECTIVES: The present study aims to investigate potential relationships between skin microbiota and BP and elaborate on important changes in microbial diversity associated with blistering in BP. METHODS: The study consisted of an extensive sampling effort of the skin microbiota in patients with BP and age- and sex-matched controls to analyze whether intra-individual, body site, and/or geographical variation correlate with changes in skin microbial composition in BP and/or blistering status. RESULTS: We find significant differences in the skin microbiota of patients with BP compared to that of controls, and moreover that disease status rather than skin biogeography (body site) governs skin microbiota composition in patients with BP. Our data reveal a discernible transition between normal skin and the skin surrounding BP lesions, which is characterized by a loss of protective microbiota and an increase in sequences matching Staphylococcus aureus, a known inflammation-promoting species. Notably, Staphylococcus aureus is ubiquitously associated with BP disease status, regardless of the presence of blisters. CONCLUSION: The present study suggests Staphylococcus aureus may be a key taxon associated with BP disease status. Importantly, we however find contrasting patterns in the relative abundances of Staphylococcus hominis and Staphylococcus aureus reliably discriminate between patients with BP and matched controls. This may serve as valuable information for assessing blistering risk and treatment outcomes in a clinical setting.


Asunto(s)
Enfermedades Autoinmunes , Microbiota , Penfigoide Ampolloso , Humanos , Anciano , Penfigoide Ampolloso/patología , Penfigoide Ampolloso/terapia , Piel , Vesícula/patología , Enfermedades Autoinmunes/patología
12.
Children (Basel) ; 9(12)2022 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-36553362

RESUMEN

The present case report features a highly uncommon form of a paediatric TCF3-HLF positive acute lymphoblastic leukaemia (ALL) relapse, an extramedullary, peripheral bone manifestation. Following complete remission, during the conditioning for haematopoietic stem cell transplantation (HSCT), our sixteen-year-old male patient complained of fever, pain and swelling of the right forearm. Radiography suggested acute osteomyelitis in the right ulna with subsequent surgical confirmation. Intraoperatively obtained debris culture grew Staphylococcus aureus and Acinetobacter pittii. Measures taken to control the infection were deemed to be successful. However, after the completion of the otherwise uneventful HSCT, a very early medullary relapse was diagnosed. Revising the original surgical samples from the ulna, bone relapse of ALL was immunohistochemically confirmed. Reviewing the previous cases found in the literature, it is advised to consider uncommon forms of ALL relapse when encountering ambiguous cases of osteomyelitis or arthritis during haematological remission.

13.
Transl Psychiatry ; 12(1): 497, 2022 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-36450713

RESUMEN

Epidemiological studies indicate a bidirectional association between metabolic disturbances, including obesity and related pathological states, and mood disorders, most prominently major depression. However, the biological mechanisms mediating the comorbid relationship between the deranged metabolic and mood states remain incompletely understood. Here, we tested the hypothesis that the enhanced activation of brown fat tissue (BAT), known to beneficially regulate obesity and accompanying dysfunctional metabolic states, is also paralleled by an alteration of affective behaviour. We used upstream stimulatory factor 1 (USF-1) knock-out (KO) mice as a genetic model of constitutively activated BAT and positive cardiometabolic traits and found a reduction of depression-like and anxiety-like behaviours associated with USF-1 deficiency. Surgical removal of interscapular BAT did not impact the behavioural phenotype of USF-1 KO mice. Further, the absence of USF-1 did not lead to alterations of adult hippocampal neural progenitor cell proliferation, differentiation, or survival. RNA-seq analysis characterised the molecular signature of USF-1 deficiency in the hippocampus and revealed a significant increase in the expression of several members of the X-linked lymphocyte-regulated (xlr) genes, including xlr3b and xlr4b. Xlr genes are the mouse orthologues of the human FAM9 gene family and are implicated in the regulation of dendritic branching, dendritic spine number and morphology. The transcriptional changes were associated with morphological alterations in hippocampal neurons, manifested in reduced dendritic length and complexity in USF-1 KO mice. Collectively these data suggest that the metabolic regulator USF-1 is involved in the control of affective behaviour in mice and that this modulation of mood states is unrelated to USF-1-dependent BAT activation, but reflected in structural changes in the brain.


Asunto(s)
Encéfalo , Trastorno Depresivo Mayor , Adulto , Humanos , Animales , Ratones , Ratones Noqueados , Trastornos de Ansiedad , Hipocampo
14.
J Neurosci ; 42(40): 7659-7672, 2022 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-36194650

RESUMEN

A strong bidirectional link between metabolic and psychiatric disorders exists; yet, the molecular basis underlying this interaction remains unresolved. Here we explored the role of the brown adipose tissue (BAT) as modulatory interface, focusing on the involvement of uncoupling protein 1 (UCP-1), a key metabolic regulator highly expressed in BAT, in the control of emotional behavior. Male and female constitutive UCP-1 knock-out (KO) mice were used to investigate the consequences of UCP-1 deficiency on anxiety-related and depression-related behaviors under mild thermogenic (23°C) and thermoneutral (29°C) conditions. UCP-1 KO mice displayed a selective enhancement of anxiety-related behavior exclusively under thermogenic conditions, but not at thermoneutrality. Neural and endocrine stress mediators were not affected in UCP-1 KO mice, which showed an activation of the integrated stress response alongside enhanced fibroblast-growth factor-21 (FGF-21) levels. However, viral-mediated overexpression of FGF-21 did not phenocopy the behavioral alterations of UCP-1 KO mice and blocking FGF-21 activity did not rescue the anxiogenic phenotype of UCP-1 KO mice. No effects of surgical removal of the intrascapular BAT on anxiety-like behavior or FGF-21 levels were observed in either UCP-1 KO or WT mice. We provide evidence for a novel role of UCP-1 in the regulation of emotions that manifests as inhibitory constraint on anxiety-related behavior, exclusively under thermogenic conditions. We propose this function of UCP-1 to be independent of its activity in the BAT and likely mediated through a central role of UCP-1 in brain regions with converging involvement in energy and emotional control.SIGNIFICANCE STATEMENT In this first description of a temperature-dependent phenotype of emotional behavior, we propose uncoupling protein-1 (UCP-1), the key component of the thermogenic function of the brown adipose tissue, as molecular break controlling anxiety-related behavior in mice. We suggest the involvement of UCP-1 in fear regulation to be mediated through its expression in brain regions with converging roles in energy and emotional control. These data are important and relevant in light of the largely unexplored bidirectional link between metabolic and psychiatric disorders, which has the potential for providing insight into novel therapeutic strategies for the management of both conditions.


Asunto(s)
Canales Iónicos , Proteínas Mitocondriales , Ratones , Masculino , Femenino , Animales , Temperatura , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo , Canales Iónicos/genética , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Tejido Adiposo Pardo/metabolismo , Ratones Noqueados , Ansiedad
15.
Biomedicines ; 10(10)2022 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-36289821

RESUMEN

Programmed death ligand-1 (PD-L1) is an immune checkpoint molecule and a widely used therapeutic target in urothelial cancer. Its circulating, soluble levels (sPD-L1) were recently suggested to be associated with the presence and prognosis of various malignancies but have not yet been investigated in upper tract urothelial carcinoma (UTUC). In this study, we assessed sPD-L1 levels in 97 prospectively collected serum samples from 61 UTUC patients who underwent radical nephroureterectomy (RNU), chemotherapy (CTX), or immune checkpoint inhibitor (ICI) therapy. In addition to pretreatment samples, postoperative and on-treatment sPD-L1 levels were determined in some patients by using ELISA. In the RNU group, elevated preoperative sPD-L1 was associated with a higher tumor grade (p = 0.019), stage (p < 0.001) and the presence of metastasis (p = 0.002). High sPD-L1 levels were significantly associated with worse survival in both the RNU and CTX cohorts. sPD-L1 levels were significantly elevated in postoperative samples (p = 0.011), while they remained unchanged during CTX. Interestingly, ICI treatment caused a strong, 25-fold increase in sPD-L1 (p < 0.001). Our results suggest that elevated preoperative sPD-L1 level is a predictor of higher pathological tumor stage and worse survival in UTUC, which therefore may help to optimize therapeutic decision-making. The observed characteristic sPD-L1 flare during immune checkpoint inhibitor therapy may have clinical significance.

16.
Orv Hetil ; 163(38): 1520-1527, 2022 Sep 18.
Artículo en Húngaro | MEDLINE | ID: mdl-36121725

RESUMEN

Introduction: Hospice movement began in Hungary in 1991, today home care and impatient care is accessable na-tionwide. However, despite the growing number of patients receving palliative care, according to the survey of the Hungarian Hospice Palliative Association, the average time they have spent receiving home hospice care was only 26,7 days in 2020, when the ideal would be 8,5 months. It has been proven by studies, that involving hospice -palli-ative care early on in the treatment of oncology patients has benefits for both the quality of life and treatment and cost-effectiveness. To make this possible, we have to make certain ways of health care which lead the patients in need to specialised palliative care. Objective and method: In this statement, we introduce two forms of treatment which have proven that the early inte-gration of palliative care is efficiently attainable throughout health care systems in Hungary today.Results: Starting September of 2019, the National Institute of Oncology Palliative Mobil Team has been helping the patients of the Institute receive optimal care through consultation. In the general medicine, general practice partner-ship of Szentendre, two family doctors with palliative licence examination have been organizing trainings for their colleagues in order to show a new approach and help more patients of the region receive palliative care in time. Conclusion: These examples further prove that by accessing the current financial and human resources, through edu-cation and a change of attitude, the improvement of palliative care in Hungary is possible.


Asunto(s)
Cuidados Paliativos al Final de la Vida , Hospitales para Enfermos Terminales , Neoplasias , Humanos , Oncología Médica , Neoplasias/terapia , Cuidados Paliativos , Calidad de Vida
20.
Orv Hetil ; 162(44): 1769-1775, 2021 10 31.
Artículo en Húngaro | MEDLINE | ID: mdl-34718229

RESUMEN

Összefoglaló. A palliatív ellátások korai bevonása az onkológiai betegek ellátásába elonnyel jár mind a beteg életminosége, mind a kezelés színvonala, mind a költséghatékonyság szempontjából. Szükség van egy olyan modellre, mely alapján a megfelelo idoben, a megfelelo beteg a megfelelo minoségu palliatív ellátásban részesül. Ebben a közleményben a palliatív ellátás korai integrációjának elonyei, szintjei és a speciális palliatív ellátás fogalmának ismertetése után a leginkább elterjedt beutalási modellek elonyeit és hátrányait mutatjuk be a nemzetközi szakirodalom alapján. A speciális palliatív ellátást igénylo betegek kiszurésére szolgáló, prognózisalapú modellek hátránya, hogy nincs elég kapacitás az ilyen módon beutalt nagyszámú beteg ellátására, ezért széles körben nem terjedtek el. A tüneteken alapuló modellek sokszor bonyolultak és a mindennapi klinikai gyakorlatban nem használatosak. Az új kutatások alapján egyszeru, gyakorlatias kérdéssorokat alkalmaznak, melyekkel könnyen kiemelhetok, akik profitálnak a speciális palliatív intervencióból. Ezek közül a Yale egyetemi és a PALLIA -10 modellt ismertetjük részletesen. Amennyiben az aktív onkológiai ellátást végzok a megfelelo palliatív beutalási kritériumokat ismerik és alkalmazzák, a betegek idoben jutnak a megfelelo komplex kezeléshez anélkül, hogy a palliatív ellátórendszer túlterhelodne. Orv Hetil. 2021; 162(44): 1769-1775. Summary. Early integration of palliative care into the trajectory of cancer care brings advantages into the patients' quality of life, the level of care and cost-efficiency, too. On the basis of a predefined model, the right patient may receive the right level of palliative care at the right time. Having defined the advantages, the levels of early integration of palliative care and the concept of special palliative care, we also aim to describe the advantages and disadvantages of the most common referral models on the basis of international literature in this article. The drawback of prognosis-based models to identify patients needing special palliative care is the lack of capacity to provide care for the large number of patients so recognised; therefore they have not become widespread. Needs-based models tend to be complicated and thus rarely applied in everyday clinical practice. On the basis of new researches, simple, pragmatic questionnaires are utilised through which the patients who could benefit from special palliative care interventions are easy to identify. Here we give a detailed report of the Yale University and PALLIA-10 models. On condition that appropriate palliative referral criteria are known and applied by active oncology care providers, patients may receive adequate complex care without the palliative care system being overloaded. Orv Hetil. 2021; 162(44): 1769-1775.


Asunto(s)
Ingestión de Alimentos , Calidad de Vida , Humanos , Encuestas y Cuestionarios
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...