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1.
J Clin Med ; 13(3)2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38337429

RESUMO

The article aims to find potential biomarker for the detection of tubular damage in pediatric neurogenic bladder (NB) by investigating urinary levels of liver-type fatty acid-binding protein (uL-FABP). This prospective analysis was conducted on two groups: 42 children with NB and 18 healthy children. The uL-FABP concentrations were measured using ELISA methods. The medical charts of the children were examined to determine age, sex, anthropometric measurements, activity assessment using Hoffer's scale, and renal function parameters. The results revealed that the uL-FABP/creatinine ratio was higher in the study group compared with the reference group, but the difference was not statistically significant (p = 0.52, p > 0.05). However, the uL-FABP/creatinine ratio exhibited a wider range in NB patients compared to the reference group. NB children with proteinuria and the history of high-grade vesicoureteral reflux (VUR) tended to have the highest uL-FABP concentrations. In conclusion, uL-FABP may be considered a potential tubular damage biomarker in children with NB. Proteinuria and the history of VUR may be the factors influencing the uL-FABP.

2.
Cancer Immunol Immunother ; 73(1): 17, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38236249

RESUMO

BACKGROUND: Vascular endothelial growth factor is associated with reduced immune response and impaired anti-tumor activity. Combining antiangiogenic agents with immune checkpoint inhibition can overcome this immune suppression and enhance treatment efficacy. METHODS: This study investigated the combination of ziv-aflibercept anti-angiogenic therapy with pembrolizumab in patients with advanced melanoma resistant to anti-PD-1 treatment. Baseline and on-treatment plasma and PBMC samples were analyzed by multiplex protein assay and mass cytometry, respectively. RESULTS: In this Phase 1B study (NCT02298959), ten patients with advanced PD-1-resistant melanoma were treated with a combination of ziv-aflibercept (at 2-4 mg/kg) plus pembrolizumab (at 2 mg/kg), administered intravenously every 2 weeks. Two patients (20%) achieved a partial response, and two patients (20%) experienced stable disease (SD) as the best response. The two responders had mucosal melanoma, while both patients with SD had ocular melanoma. The combination therapy demonstrated clinical activity and acceptable safety, despite the occurrence of adverse events. Changes in plasma analytes such as platelet-derived growth factor and PD-L1 were explored, indicating potential alterations in myeloid cell function. Higher levels of circulating CXCL10 in non-responding patients may reflect pro-tumor activity. Specific subsets of γδ T cells were associated with poor clinical outcomes, suggesting impaired γδ T-cell function in non-responding patients. CONCLUSIONS: Although limited by sample size and follow-up, these findings highlight the potential of the combination of ziv-aflibercept antiangiogenic therapy with pembrolizumab in patients with advanced melanoma resistant to anti-PD-1 treatment and the need for further research to improve outcomes in anti-PD-1-resistant melanoma. TRIAL REGISTRATION NUMBER: NCT02298959.


Assuntos
Anticorpos Monoclonais Humanizados , Melanoma , Receptores de Fatores de Crescimento do Endotélio Vascular , Proteínas Recombinantes de Fusão , Humanos , Melanoma/tratamento farmacológico , Leucócitos Mononucleares , Fator A de Crescimento do Endotélio Vascular
3.
Clin Cancer Res ; 30(7): 1281-1292, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38236580

RESUMO

PURPOSE: Eribulin modulates the tumor-immune microenvironment via cGAS-STING signaling in preclinical models. This non-randomized phase II trial evaluated the combination of eribulin and pembrolizumab in patients with soft-tissue sarcomas (STS). PATIENTS AND METHODS: Patients enrolled in one of three cohorts: leiomyosarcoma (LMS), liposarcomas (LPS), or other STS that may benefit from PD-1 inhibitors, including undifferentiated pleomorphic sarcoma (UPS). Eribulin was administered at 1.4 mg/m2 i.v. (days 1 and 8) with fixed-dose pembrolizumab 200 mg i.v. (day 1) of each 21-day cycle, until progression, unacceptable toxicity, or completion of 2 years of treatment. The primary endpoint was the 12-week progression-free survival rate (PFS-12) in each cohort. Secondary endpoints included the objective response rate, median PFS, safety profile, and overall survival (OS). Pretreatment and on-treatment blood specimens were evaluated in patients who achieved durable disease control (DDC) or progression within 12 weeks [early progression (EP)]. Multiplexed immunofluorescence was performed on archival LPS samples from patients with DDC or EP. RESULTS: Fifty-seven patients enrolled (LMS, n = 19; LPS, n = 20; UPS/Other, n = 18). The PFS-12 was 36.8% (90% confidence interval: 22.5-60.4) for LMS, 69.6% (54.5-89.0) for LPS, and 52.6% (36.8-75.3) for UPS/Other cohorts. All 3 patients in the UPS/Other cohort with angiosarcoma achieved RECIST responses. Toxicity was manageable. Higher IFNα and IL4 serum levels were associated with clinical benefit. Immune aggregates expressing PD-1 and PD-L1 were observed in a patient that completed 2 years of treatment. CONCLUSIONS: The combination of eribulin and pembrolizumab demonstrated promising activity in LPS and angiosarcoma.


Assuntos
Anticorpos Monoclonais Humanizados , Furanos , Hemangiossarcoma , Cetonas , Leiomiossarcoma , Lipossarcoma , Policetídeos de Poliéter , Sarcoma , Humanos , Resultado do Tratamento , Lipopolissacarídeos/uso terapêutico , Sarcoma/patologia , Lipossarcoma/tratamento farmacológico , Microambiente Tumoral
4.
Clin Oral Investig ; 28(1): 59, 2023 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-38157091

RESUMO

OBJECTIVES: Periodontitis (PD) can cause systematic inflammation and is associated with various metabolic processes in the body. However, robust serum markers for these relationships are still lacking. This study aims to identify novel circulating inflammation-related proteins associated with PD using targeted proteomics. MATERIALS AND METHODS: We used population-based, cross-sectional data from 619 participants of the Polish Longitudinal University Study (Bialystok PLUS). Mean pocket probing depth (mPPD) and proportion of bleeding on probing (pBOP) served as exposure variables. Fifty-two inflammation-related proteins were measured using the Olink Target 96 Cardiovascular III and the Olink Target 96 Immune Response panels. Associations between periodontal measures and proteins were tested using covariate-adjusted linear regression models. RESULTS: At a false discovery rate of < 0.05, we identified associations of mPPD and pBOP with platelet-endothelial cell adhesion molecule-1 (PECAM-1) and tripartite motif-containing protein 21 (TRIM21). CONCLUSION: This study revealed novel associations between PD and serum levels of PECAM-1 and TRIM21. Our results suggest that these proteins might be affected by molecular processes that take place in the inflamed periodontium. CLINICAL RELEVANCE: Novel associations of PECAM-1 and TRIM21 with PD indicate promising serum markers for understanding the disease's pathophysiological processes and call for further biomedical investigations.


Assuntos
Periodontite , Proteômica , Humanos , Molécula-1 de Adesão Celular Endotelial a Plaquetas , Estudos Transversais , Proteína C-Reativa/análise , Inflamação , Periodontite/complicações , Biomarcadores
5.
J Proteome Res ; 22(7): 2509-2515, 2023 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-37269315

RESUMO

Periodontitis (PD), a widespread chronic infectious disease, compromises oral health and is associated with various systemic conditions and hematological alterations. Yet, to date, it is not clear whether serum protein profiling improves the assessment of PD. We collected general health data, performed dental examinations, and generated serum protein profiles using novel Proximity Extension Assay technology for 654 participants of the Bialystok PLUS study. To evaluate the incremental benefit of proteomics, we constructed two logistic regression models assessing the risk of having PD according to the CDC/AAP definition; the first one contained established PD predictors, and in addition, the second one was enhanced by extensive protein information. We then compared both models in terms of overall fit, discrimination, and calibration. For internal model validation, we performed bootstrap resampling (n = 2000). We identified 14 proteins, which improved the global fit and discrimination of a model of established PD risk factors, while maintaining reasonable calibration (area under the curve 0.82 vs 0.86; P < 0.001). Our results suggest that proteomic technologies offer an interesting advancement in the goal of finding easy-to-use and scalable diagnostic applications for PD that do not require direct examination of the periodontium.


Assuntos
Periodontite , Proteômica , Humanos , Proteômica/métodos , Periodontite/diagnóstico , Fatores de Risco , Proteínas Sanguíneas
6.
Lab Invest ; 103(8): 100174, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37169083

RESUMO

We developed a comprehensive method for functional assessment of the changes in immune populations and killing activity of peripheral blood mononuclear cells after cocultures with cancer cells using mass cytometry. In this study, a 43-marker mass cytometry panel was applied to a coculture of immune cells from healthy donors' peripheral blood mononuclear cells with diverse cancer cell lines. DNA content combined with classical CD45 surface staining was used as gating parameters for cocultures of immune cells (CD45high/DNAlow) with hematological (CD45low/DNAhigh) and solid cancer cell lines (CD45neg/DNAhigh). This strategy allows for universal discrimination of cancer cells from immune populations without the need for a specific cancer cell marker and simultaneous assessment of phenotypical changes in both populations. The use of mass cytometry allows for simultaneous detection of changes in natural killer, natural killer T cell, and T cell phenotypes and degranulation of immune populations upon target recognition, analysis of target cells for cytotoxic protein granzyme B content, and cancer cell death. These findings have broad applicability in research and clinical settings with the aim to phenotype and assess functional changes following not only NK-cancer cell interactions but also the effect of those interactions on other immune populations.


Assuntos
Citotoxicidade Imunológica , Neoplasias , Leucócitos Mononucleares , Células Matadoras Naturais , Linfócitos T , Técnicas de Cocultura , Citometria de Fluxo , Neoplasias/metabolismo
7.
Cancer Cell ; 40(11): 1358-1373.e8, 2022 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-36379208

RESUMO

Patients with smoldering multiple myeloma (SMM) are observed until progression, but early treatment may improve outcomes. We conducted a phase II trial of elotuzumab, lenalidomide, and dexamethasone (EloLenDex) in patients with high-risk SMM and performed single-cell RNA and T cell receptor (TCR) sequencing on 149 bone marrow (BM) and peripheral blood (PB) samples from patients and healthy donors (HDs). We find that early treatment with EloLenDex is safe and effective and provide a comprehensive characterization of alterations in immune cell composition and TCR repertoire diversity in patients. We show that the similarity of a patient's immune cell composition to that of HDs may have prognostic relevance at diagnosis and after treatment and that the abundance of granzyme K (GZMK)+ CD8+ effector memory T (TEM) cells may be associated with treatment response. Last, we uncover similarities between immune alterations observed in the BM and PB, suggesting that PB-based immune profiling may have diagnostic and prognostic utility.


Assuntos
Mieloma Múltiplo , Mieloma Múltiplo Latente , Humanos , Biomarcadores , Progressão da Doença , Fatores Imunológicos , Imunoterapia , Lenalidomida/efeitos adversos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo Latente/terapia , Ensaios Clínicos Fase II como Assunto
8.
Proc Natl Acad Sci U S A ; 119(25): e2122379119, 2022 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-35696582

RESUMO

Acute myeloid leukemia (AML) remains a therapeutic challenge, and a paucity of tumor-specific targets has significantly hampered the development of effective immune-based therapies. Recent paradigm-changing studies have shown that natural killer (NK) cells exhibit innate memory upon brief activation with IL-12 and IL-18, leading to cytokine-induced memory-like (CIML) NK cell differentiation. CIML NK cells have enhanced antitumor activity and have shown promising results in early phase clinical trials in patients with relapsed/refractory AML. Here, we show that arming CIML NK cells with a neoepitope-specific chimeric antigen receptor (CAR) significantly enhances their antitumor responses to nucleophosphmin-1 (NPM1)-mutated AML while avoiding off-target toxicity. CIML NK cells differentiated from peripheral blood NK cells were efficiently transduced to express a TCR-like CAR that specifically recognizes a neoepitope derived from the cytosolic oncogenic NPM1-mutated protein presented by HLA-A2. These CAR CIML NK cells displayed enhanced activity against NPM1-mutated AML cell lines and patient-derived leukemic blast cells. CAR CIML NK cells persisted in vivo and significantly improved AML outcomes in xenograft models. Single-cell RNA sequencing and mass cytometry analyses identified up-regulation of cell proliferation, protein folding, immune responses, and major metabolic pathways in CAR-transduced CIML NK cells, resulting in tumor-specific, CAR-dependent activation and function in response to AML target cells. Thus, efficient arming of CIML NK cells with an NPM1-mutation-specific TCR-like CAR substantially improves their innate antitumor responses against an otherwise intracellular mutant protein. These preclinical findings justify evaluating this approach in clinical trials in HLA-A2+ AML patients with NPM1c mutations.


Assuntos
Memória Imunológica , Células de Memória Imunológica , Imunoterapia Adotiva , Células Matadoras Naturais , Leucemia Mieloide Aguda , Nucleofosmina , Receptores de Antígenos Quiméricos , Antígeno HLA-A2/imunologia , Humanos , Células de Memória Imunológica/imunologia , Células de Memória Imunológica/transplante , Imunoterapia Adotiva/métodos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/transplante , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Mutação , Nucleofosmina/genética , Nucleofosmina/imunologia , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/imunologia
9.
Immunotherapy ; 14(11): 843-850, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35695027

RESUMO

We report a case of multiple high-grade and rare immune-related adverse events (irAEs) in a patient with microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). A middle-aged MSI-H mCRC patient with metastases to the lungs and lymph nodes received several lines of chemotherapy and immunotherapy and developed five different high-grade irAEs during immunotherapy, including lymphadenitis, pneumonitis, hypophysitis, thyroiditis and transverse myelitis. Genomic profiling revealed high tumor mutational burden of 43 Muts/Mb. Cytokine profiling showed a threefold increase in MMP-9 shortly prior to the onset of lymphadenitis and a fourfold increase of Ang-1 1 week after the resolution of lymphadenitis. Further studies are warranted to investigate the association of MSI-H mCRC with irAEs and the role of cytokines in predicting irAEs.


Immune-related adverse events (irAEs) are a potential side effect of taking immunotherapy treatment for cancer. We report a case of a patient with a highly mutated form of metastatic colon cancer who developed five unique and severe irAEs while receiving immunotherapy. The patient developed inflammation of the lymph nodes, lungs, pituitary gland, thyroid and spinal cord. Genetic testing showed that the tumor was highly mutated (43 Muts/Mb). Analysis of cell signaling proteins called cytokines revealed that MMP-9 sharply increased before the onset of lymphadenitis and Ang-1 sharply increased after its resolution. Further research is needed to understand the relationship between highly mutated colon cancer and irAEs as well as the role of cytokines in predicting the onset and resolution of irAEs.


Assuntos
Antineoplásicos Imunológicos , Neoplasias do Colo , Doenças do Sistema Imunitário , Linfadenite , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias do Colo/tratamento farmacológico , Citocinas , Genômica , Humanos , Imunoterapia/efeitos adversos , Linfadenite/induzido quimicamente , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1 , Estudos Retrospectivos
10.
STAR Protoc ; 3(2): 101362, 2022 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-35573480

RESUMO

With the increasing use of mass cytometry in clinical research, a simplified and standardized protocol for immunophenotyping human peripheral blood mononuclear cells (PBMCs) in clinical trials is needed. We present a simplified in-plate staining protocol for up to 80 samples, for laboratories of all mass cytometry expertise levels, aimed to generate reproducible datasets for large clinical cohorts. In this protocol, we provide details on the requirements to obtain meaningful results, spanning from sample quality, barcoding, and batch-freezing of stained samples.


Assuntos
Criopreservação , Leucócitos Mononucleares , Criopreservação/métodos , Citometria de Fluxo/métodos , Humanos , Imunofenotipagem , Coloração e Rotulagem
11.
J Clin Invest ; 132(11)2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35349491

RESUMO

BackgroundResponses to conventional donor lymphocyte infusion for postallogeneic hematopoietic cell transplantation (HCT) relapse are typically poor. Natural killer (NK) cell-based therapy is a promising modality to treat post-HCT relapse.MethodsWe initiated this ongoing phase I trial of adoptively transferred cytokine-induced memory-like (CIML) NK cells in patients with myeloid malignancies who relapsed after haploidentical HCT. All patients received a donor-derived NK cell dose of 5 to 10 million cells/kg after lymphodepleting chemotherapy, followed by systemic IL-2 for 7 doses. High-resolution profiling with mass cytometry and single-cell RNA sequencing characterized the expanding and persistent NK cell subpopulations in a longitudinal manner after infusion.ResultsIn the first 6 enrolled patients on the trial, infusion of CIML NK cells led to a rapid 10- to 50-fold in vivo expansion that was sustained over months. The infusion was well tolerated, with fever and pancytopenia as the most common adverse events. Expansion of NK cells was distinct from IL-2 effects on endogenous post-HCT NK cells, and not dependent on CMV viremia. Immunophenotypic and transcriptional profiling revealed a dynamic evolution of the activated CIML NK cell phenotype, superimposed on the natural variation in donor NK cell repertoires.ConclusionGiven their rapid expansion and long-term persistence in an immune-compatible environment, CIML NK cells serve as a promising platform for the treatment of posttransplant relapse of myeloid disease. Further characterization of their unique in vivo biology and interaction with both T cells and tumor targets will lead to improvements in cell-based immunotherapies.Trial RegistrationClinicalTrials.gov NCT04024761.FundingDunkin' Donuts, NIH/National Cancer Institute, and the Leukemia and Lymphoma Society.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Interleucina-2 , Humanos , Células Matadoras Naturais , Recidiva , Transplante Homólogo
12.
STAR Protoc ; 3(1): 101163, 2022 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-35243367

RESUMO

This protocol details a staining technique optimized for immunophenotyping of human bone marrow immune populations using mass cytometry. The protocol accounts for the limitations of working with human bone marrow, such as reduced viability, low cell counts, and fragile cell pellets, to successfully acquire single viable cells ready for downstream analysis. This assay can be used to characterize the activation, exhaustion, and cytotoxicity of immune populations and ensure comprehensive immunophenotyping of human bone marrow clinical samples.


Assuntos
Células da Medula Óssea , Medula Óssea , Citometria de Fluxo/métodos , Humanos , Imunofenotipagem , Coloração e Rotulagem
13.
Artigo em Inglês | MEDLINE | ID: mdl-35206557

RESUMO

BACKGROUND: The aim of this study was to assess risk factors for tooth loss in the population of the city of Bialystok, in north-eastern Poland, taking into account the entire population and different age groups. The study included 1138 subjects divided into three subgroups: 20-44 years, 45-64 years, and 65-79 years. Participants were classified according to the number of teeth lost (0-8 vs. 9-28). Socio-economic variables, smoking history, and dental habits were collected through a questionnaire. Medical examinations provided data on the body mass index and the fasting blood glucose level. Data were statistically analysed using Mann-Whitney U, Student's t, chi2 tests, and binary logistic regression, p < 0.05. RESULTS: For the general population, being female (OR 1.38, 1.07-1.79, p = 0.015), having secondary education (OR 4.18, Cl 2.97-5.87, p < 0.000), higher body mass index (OR 1.13, Cl 1.10-1.17, p < 0.000), higher fasting blood glucose level (OR 1.03 1.03-1.04, p < 0.000), being former smoker (OR 1.72, Cl 1.29-2.31, p < 0.000), ever smoker (OR 1.69, Cl 1.29-2.20, p < 0.000), current smoker (OR 1.62, Cl 1.15-2.29, p < 0.006), longer smoking period (OR 1.11, Cl 1.09-1.14, p < 0.000), last visit to the dentist over a year ago (OR 1.92, Cl 0.44-2.58, p < 0.000) and tooth brushing less than two times a day (OR 1.6, Cl 1.14-2.23, p < 0.006) were associated with losing more than 8 teeth. In the subgroup aged 20-44 years, only smoking duration was a risk factor for tooth loss (p = 0.02). For the middle-aged and oldest groups, education level (respectively p < 0.001, and p = 0.001), body mass index (respectively, p < 0.001, and p = 0.037), smoking status ever/former/current (respectively p < 0.001 and p = 0.002), smoking status never/ever (respectively p < 0.001 and p = 0.009), smoking duration (p < 0.001) were related to tooth loss. Additionally, in the elderly group, fasting blood glucose level (p = 0.044) and frequency of dental visits (p = 0.007) were related to tooth loss. We concluded that in the evaluated population, tooth loss was associated with socio-demographic, medical, and behavioural factors.


Assuntos
Abandono do Hábito de Fumar , Perda de Dente , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Polônia/epidemiologia , Fatores de Risco , Fumar/efeitos adversos , Fumar/epidemiologia , Perda de Dente/epidemiologia , Adulto Jovem
14.
Artigo em Inglês | MEDLINE | ID: mdl-35206665

RESUMO

Educating the general population about dental trauma is of public health interest. The aim of this scoping review was to map research on traumatic dental injuries (TDIs) education in the general population and to identify the most relevant methods of knowledge transfer. PubMed, Scopus, Web of Science All Databases, reference lists, and grey literature were searched. Articles in English published between 2000 and 2020 were included. A total of 32 articles fulfilled inclusion criteria. The most frequently tested modality was lecture/seminar/workshop. Studies focused mainly on teachers and medical staff as target groups. Post-intervention evaluation showed an increase in knowledge. In long-term follow-up, a decrease in knowledge was found. The effectiveness of different modalities varied. Studies comparing single-modal and multimodal approaches did not confirm the effect of combined methods. Printed materials are a practical mode for laypeople. Lectures should be reserved for professions with high probability of coming into contact with a TDI victim. The Internet can be a promising tool to educate people. Educators have to choose the method of communication most appropriate for the target population. The education should include topics related to dental trauma prevention. Further research is needed to investigate the effectiveness of multimodal TDI education.


Assuntos
Atenção à Saúde , Projetos de Pesquisa , Escolaridade , Humanos
15.
Artigo em Inglês | MEDLINE | ID: mdl-35162649

RESUMO

The aim of the study was to determine oral health-related quality of life (OHRQoL) using the measures Geriatric/General Oral Health Assessment (GOHAI) and Oral Health Impact Profile (OHIP-14) in relation to missing teeth in the Polish population aged 20-79. This was a cross-sectional study carried out among 1112 randomly selected participants. The mean age was 48.72 and mean number of teeth was 20.12. Altogether, in the GOHAI, the percentage that gave a positive response to each question ranged from 3.3% to 48.0%; in the OHIP-14, these answers ranged from 2.4% to 25.1%. The GOHAI measure was statistically significant, with more grouping variables than the OHIP-14 measure. Both measures showed significant associations with gender, age, dry mouth, education, professional status, number of teeth, and upper and lower total dentures. We detected a significant relationship between oral health-related quality of life and the factors influencing the presence or absence of dentition. Missing teeth were statistically associated with GOHAI, OHIP-14, advanced age, self-reported dry mouth, lower education, higher Body Mass Index (BMI), lower professional status, diabetes, myocardial infraction, and total dentures in upper or/and lower jaws. However, edentulous individuals had two times higher risk of having an OHIP-14 score above the median. This suggests that oral health practitioners should work to prevent oral diseases that lead to tooth loss in their patients, starting from an early age.


Assuntos
Qualidade de Vida , Perda de Dente , Adulto , Idoso , Estudos Transversais , Humanos , Pessoa de Meia-Idade , Saúde Bucal , Polônia/epidemiologia , Inquéritos e Questionários , Perda de Dente/epidemiologia , Adulto Jovem
16.
J Clin Med ; 10(14)2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34300322

RESUMO

This article aims to explore changes in urinary concentrations of selected neurotrophins in the course of TENS therapy in children with overactive bladder (OAB). A two-group open-label prospective study was conducted. The intervention group comprised 30 children aged between 5 and 12 years old with OAB refractory to conservative therapy. They received 12 weeks of TENS therapy in a home setting. The urinary neurotrophins, NGF, BDNF, NT3, NT4, were measured by ELISA at baseline and at the end of the TENS therapy. Total urinary neurotrophins levels were standardized to mg of creatinine (Cr). We compared the results with the reference group of 30 participants with no symptoms of bladder overactivity. The results revealed that children with OAB both before and after TENS therapy had higher NGF, BDNF, and NT4 concentrations in total and after normalization to Cr than the reference group in contrast to NT3. The response to the therapy expressed as a decrease of urinary neurotrophins after TENS depended on the age and the presenting symptoms. In conclusion, children older than 8 years of age with complaints of daytime incontinence responded better to TENS.

17.
J Clin Med ; 10(11)2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34071981

RESUMO

The lack of early biomarkers of renal damage in children with neurogenic bladder (NB) prompts us to investigate the role of promising proteins: neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). This prospective analysis was conducted on 58 children with NB and 25 healthy children. We assessed urinary levels of NGAL and KIM-1 in both groups. Age, sex, anthropometric measurements, activity assessment, renal function, and urodynamics parameters were analyzed. The differences between the median uNGAL and uKIM-1 in the NB group compared to control were recorded. However, only uNGAL levels were statistically significantly higher. Statistically significant correlation was found between gender, recurrent urinary tract infections, bladder trabeculation, its compliance, activity assessment, and uNGAL. To conclude, elevated levels of uNGAL may be considered a biomarker of tubular injury in children with NB due to MMC in contrast to uKIM-1.

18.
Adv Med Sci ; 66(1): 162-169, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33621833

RESUMO

Neurogenic bladder (NB) is one of the most challenging problems in nephro-urological management in pediatrics. It is an important risk factor of secondary upper urinary tract damage. A complete clinical evaluation is necessary and requires life-long extensive medical attention including invasive procedures that affect patients' quality of life. Potential non-invasive biomarkers would be desirable, especially in the pediatric population. The aim of this review was to analyze two decades of data regarding potential non-invasive biomarkers in the assessment and follow-up of children with NB. This paper summarizes and appraises the knowledge about both biochemical and imaging-based markers in 3 aspects: markers of urinary tract infections (UTIs), bladder and renal function, and this paper looks at their prospective application in everyday clinical care.


Assuntos
Biomarcadores/metabolismo , Neoplasias Renais/patologia , Neoplasias da Bexiga Urinária/patologia , Bexiga Urinaria Neurogênica/patologia , Infecções Urinárias/patologia , Criança , Gerenciamento Clínico , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/terapia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/terapia , Bexiga Urinaria Neurogênica/metabolismo , Bexiga Urinaria Neurogênica/terapia , Infecções Urinárias/metabolismo , Infecções Urinárias/terapia
19.
Cancer Immunol Immunother ; 70(8): 2209-2221, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33481042

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) often cause immune-related adverse events (irAEs), most of which are treated with corticosteroids despite evidence suggesting that corticosteroids may blunt antitumor efficacy. We sought to identify cytokine changes that correlate with irAEs and study the impact of corticosteroid treatment on cytokine levels. METHODS: We analyzed expression of 34 cytokines in 52 melanoma patients who developed irAEs during therapy with ICIs. Luminex serum assay was performed at baseline, 1, 2, and 3 months after starting ICI. Baseline cytokine levels and longitudinal log2 fold-change was compared with incidence and grade of irAEs. Cytokine patterns were compared between patients based on development of irAEs and steroid treatment. RESULTS: There were no differences in baseline cytokine levels between patients who developed grade 1-2 irAEs (N = 28) vs. grade 3-4 irAEs (N = 24). Dermatitis patients (N = 8) had significantly higher baseline Ang-1 (p = 0.006) and CD40L (p = 0.005). Pneumonitis patients (N = 4) had significantly higher baseline IL-17 (p = 0.009). Colitis patients (N = 8) had a trend toward decreased GCSF (p = 0.08). Through Spearman's correlation analysis, patients who developed irAEs without receiving corticosteroids (N = 23) exhibited harmonization of cytokine fold-change, with 0/276 pairwise comparisons demonstrating significant divergence. In contrast, corticosteroid treatment in patients with irAEs (N = 15) altered fold-change to a discordant pattern (42/276 diverged, 15.2%). This discordant cytokine pattern in patients receiving corticosteroids is similar to the cytokine pattern in patients who did not develop irAEs (N = 8) during the longitudinal profiling period (41/276, 14.9%). CONCLUSIONS: Baseline levels of certain cytokines correlate with specific irAEs in melanoma patients receiving ICIs. irAEs drive a concordant pattern of cytokine fold-change, which is disrupted by corticosteroid treatment.


Assuntos
Corticosteroides/efeitos adversos , Corticosteroides/imunologia , Citocinas/imunologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/imunologia , Imunoterapia/efeitos adversos , Melanoma/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/imunologia , Estudos Retrospectivos
20.
Artigo em Inglês | MEDLINE | ID: mdl-33066192

RESUMO

The aim of the study was to perform preliminary research to compare the smoking prevalence, attitudes and behavior between dentistry students in two universities in Europe using the standardized Global Health Professions Student Survey (GHPSS) questionnaire. This was cross-sectional carried out among dentistry students from the Medical University in Bialystok, Poland and Sapienza University of Rome, Italy. There were 582 participants; 282 were Italians, 202 were smokers and 42% were Italians. The response rate was 79.9% of Italian students and 79.6% of Polish students. The prevalence of smoking was significantly higher among Italian students (42% vs. 28.0%). Attitudes and behaviour of smokers and non-smokers differed statistically. Polish and Italian dental students presented statistically different behavior regarding the time to smoke the first cigarette, the willingness to stop smoking and trying to stop smoking in the last year. The multiple logistic regression analysis revealed that two independent variables, exposure to second-hand smoke (SHS) both at home and in public places (OR = 3.26 and OR = 5.9, respectively), showed a significantly higher occurrence of smoking. There is a high use of tobacco among dental students, which is particularly high in Italian dental students. Students realizes the positive perception of their own tobacco counsellor role in a dental setting. Dental students should be role models to their peers and patients.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Fumar/epidemiologia , Estudantes de Odontologia/psicologia , Poluição por Fumaça de Tabaco , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Itália/epidemiologia , Masculino , Polônia/epidemiologia , Prevalência , Inquéritos e Questionários , Poluição por Fumaça de Tabaco/efeitos adversos
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