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1.
J Endocrinol Invest ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38488977

RESUMO

PURPOSE: Graves' ophthalmopathy (GO) is an autoimmune disease that affects orbital soft tissues and represents the most common extrathyroidal manifestation of Graves' disease (GD). The European Group of Graves' Ophthalmopathy (EUGOGO) has attempted to shed light on the European epidemiological picture of GO, suggesting that GO in newly diagnosed patients in recent years has a trend towards a less severe clinical presentation. There are no studies that focus this issue on the population of our area; we aimed to evaluate the trend of GO clinical presentation in our outpatient clinic through an observation period of 10 years. METHODS: We compared 55 consecutive patients, 11 males (F) and 44 females (M), who came to our observation from January 2005 to December 2006 [Group 1 (G1)], with 56 patients, 15 males, and 41 females, who were referred to us from 2015 to 2016 [Group 2 (G2)]. We studied the following putative predictors of GO presentation and severity: thyroid function, smoking, diabetes, hypercholesterolemia, time from GO diagnosis to referral to our thyroid centre (TGOD), sex and age. RESULTS: GO severity was significantly reduced in G2 vs. G1 (p = 0.04). TGOD ≥ 3 months was related to clinical characteristics of GO (severity and Clinical Activity Score ≥ 4) and was an independent predictor of GO severity (p = 0.01). The other variables evaluated had no independent effects. CONCLUSIONS: We found that GO severity at presentation was significantly reduced over a ten-year observation period (2005-2006 vs. 2015-2016) in GO patients referred to our tertiary thyroid centre. TGOD ≥ 3 months was an independent predictor of GO severity.

2.
J Endocrinol Invest ; 47(7): 1691-1700, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38526837

RESUMO

PURPOSE: Patients with beta-thalassemia major (BTM) often develop several endocrine disorders due to chronic iron overload. They are also prone to osteoporosis and vertebral fractures. Plasmatic insulin-like growth factor-1 (IGF-1) levels are often low in subjects with BTM, which origin is multifactorial. The aim of this study was to evaluate a possible relationship between serum IGF-1 levels and the presence of osteoporosis and/or vertebral fractures. METHODS: We retrospectively evaluated the occurrence of vertebral fractures in 30 adult male patients affected by BTM (mean age 43.3 ± 7.9 years) with low serum IGF-1 (median value 52.4 ng/ml, 38.5-83.4). Only 6 of them (20.0%) were diagnosed with GH deficiency (GHD) after GHRH/arginine stimulation test, while 23 (76.7%) had osteoporosis and 12 (40.0%) had known vertebral fractures. All patients except one also showed at least one endocrine disorder. RESULTS: Serum IGF-1 was significantly lower in BTM patients with vertebral fractures compared to patients without vertebral fractures (U = 41.0, p = 0.005) while it was not significantly different between patients with low bone mass compared to patients without low bone mass. The diagnosis of GHD was significantly associated with lower serum IGF-1 (p = 0.001) and vertebral fractures (p = 0.002) but not with low bone mass. After ROC analysis, we found that very low IGF-1 (≤ 50.0 ng/dl) was associated with vertebral fractures (sensitivity 83.3%, specificity 75.0%) and was also predictive of GHD (sensitivity 75.0%, specificity 100.0%). CONCLUSION: Our study shows that, in male patients with BTM, serum IGF-1 ≤ 50.0 ng/dl is a marker of vertebral fractures and it is predictive of a diagnosis of GHD.


Assuntos
Biomarcadores , Fator de Crescimento Insulin-Like I , Fraturas da Coluna Vertebral , Talassemia beta , Humanos , Masculino , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/metabolismo , Adulto , Fraturas da Coluna Vertebral/sangue , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/diagnóstico , Estudos Retrospectivos , Talassemia beta/sangue , Talassemia beta/complicações , Talassemia beta/diagnóstico , Biomarcadores/sangue , Osteoporose/sangue , Osteoporose/etiologia , Osteoporose/diagnóstico , Pessoa de Meia-Idade , Prognóstico
3.
J Biol Regul Homeost Agents ; 35(2): 441-456, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33940790

RESUMO

Good fundamentals of posture and balance are essential for the efficient performance of both simple daily tasks and more complex movement patterns. In particular, postural balance is the ability to keep the body in equilibrium and to regain balance after the shift of body segments: postural control mechanisms of integration of the visual, vestibular and foot afferential channels contribute to this. This document provides recommendations based on scientific evidence, clinical practice, and consensus between experts concerning the prevention, diagnosis, and treatment of postural dysfunction at the three stages of life as the developmental age, adult age, and old age > 65 years and follows the "National Guidelines on Classification and Measuring of Posture and its Dysfunctions" per the Italian Ministry of Health (December 2017). The paper answers four main questions: i) "Which measures can be adopted to prevent postural dysfunctions?" ii) "What can we do in order to make a correct diagnosis of postural dysfunction?" iii) "What are the correct treatment programs for postural dysfunctions?" iv) Which professional competencies and experiences are useful for preventing, diagnosing and treating postural dysfunctions? By the Consensus of the Experts and the scientific evidence, emerge that the approach to postural dysfunctions requires a multidisciplinary and interdisciplinary team. Furthermore, rehabilitation treatment interventions must be specific to the age groups that have been indicated, to consider the integration of the main systems and subsystems of postural control that change with age.


Assuntos
Equilíbrio Postural , Postura , Consenso ,
4.
Public Health ; 186: 52-56, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32771661

RESUMO

OBJECTIVES: Lockdown measures in response to the coronavirus disease 2019 (COVID-19) pandemic can have serious mental health effects on the population, especially in vulnerable groups, such as those living in poor socio-economic conditions, those who are homeless, migrant workers and asylum seekers/refugees. In addition, these vulnerable groups frequently have greater difficulty accessing health services and in treatment adherence. The aim of this study is to estimate the impact of the COVID-19-related lockdown on service utilisation and follow-up adherence in an Italian mental health outpatient service for migrants and individuals in socio-economic difficulties. STUDY DESIGN: The design of this study is a retrospective cross-sectional study. METHODS: All patients who visited the mental health outpatient service in the months of February and March in the years 2017-2020 were included in the study. To compare service utilisation before and after the lockdown, the number of patients who visited the mental health outpatient service for psychiatric interview were recorded. Follow-up adherence was calculated as the percentage of patients who visited in February and subsequently attended a follow-up visit in March of the same year. RESULTS: The number of patients who visited the outpatient service between February 2017 and February 2020 was continuously increasing. In March 2020, fewer patients visited the service for psychiatric interview, in line with the introduction of lockdown measures. In addition, the number of the patients who visited in February 2020 and returned for their follow-up visits in March 2020 declined from approximately 30% over the same months in 2017-2019 to 17.53% in March 2020. CONCLUSIONS: The lockdown-related reduction in numbers of patients accessing the mental health service makes it difficult to help vulnerable populations during a period of time in which their mental health needs are expected to increase. Moreover, the reduction seen in follow-up compliance increases the risk of treatment discontinuation and possible relapse. Proactive alternative strategies need to be developed to reach these vulnerable populations.


Assuntos
Infecções por Coronavirus/prevenção & controle , Emigrantes e Imigrantes/psicologia , Utilização de Instalações e Serviços/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Serviços de Saúde Mental/estatística & dados numéricos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pobreza , Cooperação e Adesão ao Tratamento/estatística & dados numéricos , Adulto , COVID-19 , Infecções por Coronavirus/epidemiologia , Estudos Transversais , Emigrantes e Imigrantes/estatística & dados numéricos , Feminino , Pessoas Mal Alojadas/psicologia , Pessoas Mal Alojadas/estatística & dados numéricos , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/epidemiologia , Refugiados/psicologia , Refugiados/estatística & dados numéricos , Estudos Retrospectivos , Populações Vulneráveis , Adulto Jovem
5.
Ann Oncol ; 29(5): 1286-1291, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29509837

RESUMO

Background: Hepatocellular carcinomas (HCCs) are not routinely biopsied, resulting in a lack of tumor materials for molecular profiling. Here we sought to determine whether plasma-derived cell-free DNA (cfDNA) captures the genetic alterations of HCC in patients who have not undergone systemic therapy. Patients and methods: Frozen biopsies from the primary tumor and plasma were synchronously collected from 30 prospectively recruited, systemic treatment-naïve HCC patients. Deep sequencing of the DNA from the biopsies, plasma-derived cfDNA and matched germline was carried out using a panel targeting 46 coding and non-coding genes frequently altered in HCCs. Results: In 26/30 patients, at least one somatic mutation was detected in biopsy and/or cfDNA. Somatic mutations in HCC-associated genes were present in the cfDNA of 63% (19/30) of the patients and could be detected 'de novo' without prior knowledge of the mutations present in the biopsy in 27% (8/30) of the patients. Mutational load and the variant allele fraction of the mutations detected in the cfDNA positively correlated with tumor size and Edmondson grade. Crucially, among the seven patients in whom the largest tumor was ≥5 cm or was associated with metastasis, at least one mutation was detected 'de novo' in the cfDNA of 86% (6/7) of the cases. In these patients, cfDNA and tumor DNA captured 87% (80/92) and 95% (87/92) of the mutations, suggesting that cfDNA and tumor DNA captured similar proportions of somatic mutations. Conclusion: In patients with high disease burden, the use of cfDNA for genetic profiling when biopsy is unavailable may be feasible. Our results support further investigations into the clinical utility of cfDNA in a larger cohort of patients.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , DNA Tumoral Circulante/genética , Neoplasias Hepáticas/genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Biópsia/métodos , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , DNA Tumoral Circulante/sangue , Análise Mutacional de DNA/métodos , Estudos de Viabilidade , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Fígado/patologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Projetos Piloto , Carga Tumoral/genética
6.
Opt Lett ; 40(2): 131-4, 2015 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-25679826

RESUMO

It is known that temperature variations and acoustic noise affect ultrastable frequency dissemination along optical fiber. Active stabilization techniques are adopted to compensate for the fiber-induced phase noise. However, despite this compensation, the ultimate link performances are limited by the delay-unsuppressed noise that is related to the propagation delay of the light in the fiber. We demonstrate a post-processing approach which enables us to overcome this limit. We implement a subtraction algorithm between the optical signal delivered at the remote link end and the round-trip signal. In this way, a 6 dB improvement beyond the delay-unsuppressed noise is obtained. We confirm the prediction with experimental data obtained on a 47 km metropolitan fiber link and propose how to extend this method for frequency dissemination.

7.
Opt Lett ; 39(5): 1177-80, 2014 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-24690700

RESUMO

We performed a two-way remote optical phase comparison on optical fiber. Two optical frequency signals were launched in opposite directions in an optical fiber and their phases were simultaneously measured at the other end. In this technique, the fiber noise is passively canceled, and we compared two optical frequencies at the ultimate 10(-21) stability level. The experiment was performed on a 47 km fiber that is part of the metropolitan network for Internet traffic. The technique relies on the synchronous measurement of the optical phases at the two ends of the link, which is here performed by digital electronics. This scheme offers some advantages with respect to active noise cancellation schemes, as the light travels only once in the fiber.

8.
Phys Rev Lett ; 112(5): 050801, 2014 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-24580583

RESUMO

We report a high-accuracy direct measurement of the blackbody radiation shift of the 133Cs ground-state hyperfine transition. This frequency shift is one of the largest systematic frequency biases encountered in realizing the current definition of the International System of Units (SI) second. Uncertainty in the blackbody radiation frequency shift correction has led to its being the focus of intense theoretical effort by a variety of research groups. Our experimental measurement of the shift used three primary frequency standards operating at different temperatures. We achieved an uncertainty a factor of five smaller than the previous best direct measurement. These results tend to validate the claimed accuracy of the recently calculated values.

10.
J Public Health (Oxf) ; 36(1): 22-7, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23559596

RESUMO

BACKGROUND: In the last few years, Malta has witnessed increasing immigration flows from the Libyan coasts. Public health policies are focused on screening migrants for tuberculosis, whereas no systematic actions against STIs are implemented. The aim of this study is to define the epidemiological profile of asylum seekers in Malta as regards syphilis, hepatitis B, C and latent tuberculosis, thus supporting screening policies. METHODS: Five hundred migrants living in open centres were screened between December 2010 and June 2011. RESULTS: 83.2% of people was from Somalia, 81.2% males, average age 26.5 years. The tuberculin skin test (TST) was positive in 225 migrants (45%). Latent syphilis was diagnosed in 11 migrants, hepatitis C in 3 and 31 migrants were HBsAg positive. CONCLUSION: Systematic screening for asymptomatic migrants in Malta is not recommended for hepatitis C and syphilis, given the low prevalence observed. On the contrary, it should be considered for hepatitis B. TST could be indicated as the first step of a two step screening for migrants from countries with high TB incidence. Efficacy and cost-effectiveness could be achieved by further targeting screening to specific subgroups at higher risk of reactivation, such as people living with HIV and subjects affected by chronic diseases.


Assuntos
Hepatite B/epidemiologia , Hepatite C/epidemiologia , Tuberculose Latente/epidemiologia , Sífilis/epidemiologia , Adulto , África Ocidental/etnologia , Eritreia/etnologia , Etiópia/etnologia , Feminino , Humanos , Masculino , Malta/epidemiologia , Programas de Rastreamento , Prevalência , Somália/etnologia , Sífilis Latente/epidemiologia , Migrantes/estatística & dados numéricos , Teste Tuberculínico
11.
Am J Transplant ; 13(2): 348-52, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23137160

RESUMO

Life-long hepatitis B immunoglobulin (HBIG) administration is a main component of prophylactic strategy to prevent hepatitis B virus (HBV) reinfection after liver transplantation (LT). Long-term effects of HBIG treatment are known only for intravenous (IV) and intramuscular formulations. To evaluate safety and efficacy of self-administered SC HBIG, 135 LT patients receiving a 48-week treatment were analyzed. The dose of HBIG was 500 IU or 1000 IU if body weight was <75 kg or ≥75 kg, respectively. Patients were switched from the monthly IV HBIG treatment to weekly SC HBIG 2-3 weeks after the last IV dosage. All patients were able to SC self-injection after a single training. The treatment was effective in maintaining trough anti-HBs levels >100 IU/L. No severe drug-related side effects occurred. Fifteen injection-site small hematomas and four cases of mild itch occurred. At the end of the study, anti-HBs median titer was 232 IU/L (115-566 IU/L) and 97.8% of patients had an anti-HBs level >150 IU/L. Due to high mean level of anti-HBs titers observed during this study, individualized treatment schedules should be further investigated. In conclusion, SC HBIG for long-term prophylaxis of post-LT HBV reinfection resulted safe, well accepted, and effective in maintaining adequate anti-HBs levels.


Assuntos
Hepatite B/prevenção & controle , Imunoglobulinas/uso terapêutico , Transplante de Fígado/métodos , Adulto , Idoso , Antivirais/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Injeções Subcutâneas , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Autoadministração , Resultado do Tratamento
12.
Osteoporos Int ; 24(5): 1677-82, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23160916

RESUMO

UNLABELLED: We found an association between the presence of Chlamydia pneumoniae DNA both in osteoporotic bone tissue and peripheral blood mononuclear cells (PBMCs) and the increase in circulating resorptive cytokines. INTRODUCTION: Our study was designed to determine whether C. pneumoniae infection may be involved in osteoporosis-associated bone loss. METHODS: The study included 59 women undergoing hip joint replacement surgery for femoral neck fracture: 32 with osteoporosis and 27 with osteoarthritis. A total of 118 tissue specimens (59 bone tissues, 59 PBMCs) were examined for C. pneumoniae DNA by real-time polymerase chain reaction (PCR). Serum levels of soluble receptor activator of nuclear factor kappa B ligand (sRANKL), osteoprotegerin (OPG), interleukin (IL)-1ß, tumor necrosis factor-α, and IL-6 were also measured. RESULTS: C. pneumoniae DNA was detected in osteoporotic bone tissue whereas it was not found in non-osteoporotic bone tissue (p < 0.05). A significantly higher rate of C. pneumoniae DNA (p < 0.05) was found in PBMCs of osteoporotic patients than in those of osteoarthritis patients. Among osteoporotic patients, serum sRANKL, IL-1, and IL-6 concentrations as well as sRANKL/OPG ratio significantly differ between patients with bone tissue and PBMCs positive to C. pneumoniae and C. pneumoniae-negative patients. CONCLUSION: The association between the presence of C. pneumoniae DNA, both in bone tissue and PBMCs, and the increase in sRANKL/OPG ratio as well as in IL-1ß and IL-6 levels observed in osteoporotic patients suggests C. pneumoniae infection as a new risk factor for osteoporosis.


Assuntos
Infecções por Chlamydophila/complicações , Chlamydophila pneumoniae/isolamento & purificação , Osteoporose Pós-Menopausa/microbiologia , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril , Estudos de Casos e Controles , Infecções por Chlamydophila/sangue , Chlamydophila pneumoniae/genética , Citocinas/sangue , DNA Bacteriano/análise , Feminino , Fraturas do Colo Femoral/cirurgia , Cabeça do Fêmur/microbiologia , Humanos , Mediadores da Inflamação/sangue , Leucócitos Mononucleares/microbiologia , Osteoartrite do Quadril/cirurgia , Osteoporose Pós-Menopausa/sangue , Fraturas por Osteoporose/cirurgia , Fatores de Risco
13.
Opt Lett ; 38(7): 1092-4, 2013 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-23546254

RESUMO

We describe a fiber-optic gyroscope based on the Sagnac effect, realized on a multiplexed telecom fiber network. Our loop encloses an area of 20 km² and coexists with Internet data traffic. This Sagnac interferometer is capable of detecting signals that are larger than 10(-8) (rad/s)/√Hz, thus approaching ring laser gyroscopes without using a narrow-linewidth laser or sophisticated optics. The proposed gyroscope could be useful for seismic applications, opening new possibilities for this kind of optical fiber sensor.

14.
Rev Sci Instrum ; 94(7)2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37417900

RESUMO

The Advanced Ion Source for Hadrontherapy (AISHa) is an electron cyclotron resonance ion source operating at 18 GHz, developed at the Istituto Nazionale di Fisica Nucleare-Laboratori Nazionali del Sud, with the aim of producing high intensity and low emittance highly charged ion beams for hadrontherapy purposes. Moreover, thanks to its unique peculiarities, AISHa is a suitable choice for industrial and scientific applications. In the framework of the INSpIRIT and IRPT projects, in collaboration with the Centro Nazionale di Adroterapia Oncologica, new candidates for cancer treatment are being developed. In particular, the paper presents the results of the commissioning of four ion beams of interest for hadrontherapy: H+, C4+, He2+, and O6+. Their charge state distribution in the best experimental conditions, their emittance, and brightness will be critically discussed, along with the role of ion source tuning and space charge effects in beam transport. Perspectives for further developments will also be presented.


Assuntos
Terapia com Prótons , Ciclotrons
15.
ESMO Open ; 7(6): 100591, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36208496

RESUMO

BACKGROUND: A growing body of evidence suggests that non-viral hepatocellular carcinoma (HCC) might benefit less from immunotherapy. MATERIALS AND METHODS: We carried out a retrospective analysis of prospectively collected data from consecutive patients with non-viral advanced HCC, treated with atezolizumab plus bevacizumab, lenvatinib, or sorafenib, in 36 centers in 4 countries (Italy, Japan, Republic of Korea, and UK). The primary endpoint was overall survival (OS) with atezolizumab plus bevacizumab versus lenvatinib. Secondary endpoints were progression-free survival (PFS) with atezolizumab plus bevacizumab versus lenvatinib, and OS and PFS with atezolizumab plus bevacizumab versus sorafenib. For the primary and secondary endpoints, we carried out the analysis on the whole population first, and then we divided the cohort into two groups: non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) population and non-NAFLD/NASH population. RESULTS: One hundred and ninety patients received atezolizumab plus bevacizumab, 569 patients received lenvatinib, and 210 patients received sorafenib. In the whole population, multivariate analysis showed that treatment with lenvatinib was associated with a longer OS [hazard ratio (HR) 0.65; 95% confidence interval (CI) 0.44-0.95; P = 0.0268] and PFS (HR 0.67; 95% CI 0.51-0.86; P = 0.002) compared to atezolizumab plus bevacizumab. In the NAFLD/NASH population, multivariate analysis confirmed that lenvatinib treatment was associated with a longer OS (HR 0.46; 95% CI 0.26-0.84; P = 0.0110) and PFS (HR 0.55; 95% CI 0.38-0.82; P = 0.031) compared to atezolizumab plus bevacizumab. In the subgroup of non-NAFLD/NASH patients, no difference in OS or PFS was observed between patients treated with lenvatinib and those treated with atezolizumab plus bevacizumab. All these results were confirmed following propensity score matching analysis. By comparing patients receiving atezolizumab plus bevacizumab versus sorafenib, no statistically significant difference in survival was observed. CONCLUSIONS: The present analysis conducted on a large number of advanced non-viral HCC patients showed for the first time that treatment with lenvatinib is associated with a significant survival benefit compared to atezolizumab plus bevacizumab, in particular in patients with NAFLD/NASH-related HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Humanos , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Bevacizumab/farmacologia , Bevacizumab/uso terapêutico , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Hepáticas/tratamento farmacológico
16.
BMC Cancer ; 11: 411, 2011 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-21943074

RESUMO

BACKGROUND: The Aurora kinase family members, Aurora-A, -B and -C, are involved in the regulation of mitosis, and alterations in their expression are associated with cell malignant transformation. To date no information on the expression of these proteins in medullary thyroid carcinoma (MTC) are available. We here investigated the expression of the Aurora kinases in human MTC tissues and their potential use as therapeutic targets. METHODS: The expression of the Aurora kinases in 26 MTC tissues at different TNM stages was analyzed at the mRNA level by quantitative RT-PCR. We then evaluated the effects of the Aurora kinase inhibitor MK-0457 on the MTC derived TT cell line proliferation, apoptosis, soft agar colony formation, cell cycle and ploidy. RESULTS: The results showed the absence of correlation between tumor tissue levels of any Aurora kinase and tumor stage indicating the lack of prognostic value for these proteins. Treatment with MK-0457 inhibited TT cell proliferation in a time- and dose-dependent manner with IC50 = 49.8 ± 6.6 nM, as well as Aurora kinases phosphorylation of substrates relevant to the mitotic progression. Time-lapse experiments demonstrated that MK-0457-treated cells entered mitosis but were unable to complete it. Cytofluorimetric analysis confirmed that MK-0457 induced accumulation of cells with ≥ 4N DNA content without inducing apoptosis. Finally, MK-0457 prevented the capability of the TT cells to form colonies in soft agar. CONCLUSIONS: We demonstrate that Aurora kinases inhibition hampered growth and tumorigenicity of TT cells, suggesting its potential therapeutic value for MTC treatment.


Assuntos
Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/genética , Neoplasias da Glândula Tireoide/enzimologia , Adulto , Idoso , Aurora Quinases , Carcinoma Neuroendócrino , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Histonas/metabolismo , Humanos , Espaço Intracelular/metabolismo , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Fosforilação/efeitos dos fármacos , Ploidias , Transporte Proteico/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-ret/genética , Fuso Acromático/efeitos dos fármacos , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Adulto Jovem
17.
ESMO Open ; 6(4): 100190, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34144271

RESUMO

BACKGROUND: After the advent of new treatment options for advanced hepatocellular carcinoma (HCC), the identification of prognostic factors is crucial for the selection of the most appropriate therapy for each patient. PATIENTS AND METHODS: With the aim to fill this gap, we applied recursive partitioning analysis (RPA) to a cohort of 404 patients treated with lenvatinib. RESULTS: The application of RPA resulted in a classification based on five variables that originated a new prognostic score, the lenvatinib prognostic index (LEP) index, identifying three groups: low risk [patients with prognostic nutritional index (PNI) >43.3 and previous trans-arterial chemoembolization (TACE)]; medium risk [patients with PNI >43.3 but without previous TACE and patients with PNI <43.3, albumin-bilirubin (ALBI) grade 1 and Barcelona Clinic Liver Cancer stage B (BCLC-B)]; high risk [patients with PNI <43.3 and ALBI grade 2 and patients with PNI <43.3, albumin-bilirubin (ALBI) grade 1 and Barcelona Clinic Liver Cancer stage C (BCLC-C)]. Median overall survival was 29.8 months [95% confidence interval (CI) 22.8-29.8 months] in low risk patients (n = 128), 17.0 months (95% CI 15.0-24.0 months) in medium risk (n = 162) and 8.9 months (95% CI 8.0-10.7 months) in high risk (n = 114); low risk hazard ratio (HR) 1 (reference group), medium risk HR 1.95 (95% CI 1.38-2.74), high risk HR 4.84 (95% CI 3.16-7.43); P < 0.0001. The LEP index was validated in a cohort of 127 Italian patients treated with lenvatinib. While the same classification did not show a prognostic value in a cohort of 311 patients treated with sorafenib, we also show a possible predictive role in favor of lenvatinib in the low risk group. CONCLUSIONS: LEP index is a promising, easy-to-use tool that may be used to stratify patients undergoing systemic treatment of advanced HCC.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia , Prognóstico , Quinolinas
18.
Radiol Med ; 115(8): 1208-18, 2010 Dec.
Artigo em Inglês, Italiano | MEDLINE | ID: mdl-20680498

RESUMO

PURPOSE: This paper reports our immediate and 12-month follow-up results in the treatment of arterial stenoses/occlusions of the femoropopliteal region with the use of the SilverHawk directional atherectomy device (EV3, USA). MATERIALS AND METHODS: In an 18-month period, we treated 18 patients (13 men, five women, age range 39-81 years) with the SilverHawk directional atherectomy device. Inclusion criteria were symptomatic femoropopliteal stenosis/insufficiency, nonresponsiveness to medical therapy, and Rutherford categories 3-5. Exclusion criteria were based on the preliminary colour Doppler ultrasound (US) assessment and were plaque with a calcified component >50% and inadequate upstream and/or downstream vascular bed. Patients with severe vascular impairment, classified as TransAtlantic Inter-Society Consensus (TASC) D, were also excluded. RESULTS: The procedure was successfully completed in all cases, with evident recanalisation and sufficient wall remodelling. No major complication was observed. At assessment immediately after the procedure and over the following days, an improvement in clinical symptoms and in the Rutherford scale was observed. Follow-up at 2 and 12 months identified one case of distal reocclusion subsequently treated with amputation, and two cases of restenosis (primary patency 79%) successfully treated with a repeat procedure (secondary patency 96%). CONCLUSIONS: The SilverHawk directional atherectomy device proved to be an effective and safe tool in all our patients treated for femoropopliteal stenosis/occlusion, with a significant improvement in both imaging findings and clinical signs and symptoms.


Assuntos
Arteriopatias Oclusivas/cirurgia , Aterectomia/instrumentação , Artéria Femoral , Doenças Vasculares Periféricas/cirurgia , Artéria Poplítea , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia , Arteriopatias Oclusivas/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Vasculares Periféricas/diagnóstico por imagem , Resultado do Tratamento , Ultrassonografia Doppler em Cores , Grau de Desobstrução Vascular
19.
Eur Rev Med Pharmacol Sci ; 24(7): 4040-4047, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32329881

RESUMO

OBJECTIVE: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2)-related pneumonia, referred to as COVID-19 (Coronavirus Disease 19), is a public health emergency as it carries high morbidity, mortality, and has no approved specific pharmacological treatments. In this case series, we aimed to report preliminary data obtained with anti-complement C5 therapy with eculizumab in COVID-19 patients admitted to intensive care unit (ICU) of ASL Napoli 2 Nord. PATIENTS AND METHODS: This is a case series of patients with a confirmed diagnosis of SARS-CoV2 infection and severe pneumonia or ARDS who were treated with up to 4 infusions of eculizumab as an off-label agent. Patients were also treated with anticoagulant therapy with Enoxaparin 4000 IU/day via subcutaneous injection, antiviral therapy with Lopinavir 800 mg/day + Ritonavir 200 mg/day, hydroxychloroquine 400 mg/day, ceftriaxone 2 g/day IV, vitamine C 6 g/day for 4 days, and were on Non-Invasive Ventilation (NIV). RESULTS: We treated four COVID-19 patients admitted to the intensive care unit because of severe pneumonia or ARDS. All patients successfully recovered after treatment with eculizumab. Eculizumab induced a drop in inflammatory markers. Mean C Reactive Protein levels dropped from 14.6 mg/dl to 3.5 mg/dl and the mean duration of the disease was 12.8 days. CONCLUSIONS: Eculizumab has the potential to be a key player in treatment of severe cases of COVID-19. Our results support eculizumab use as an off-label treatment of COVID-19, pending confirmation from the ongoing SOLID-C19 trial.


Assuntos
Coronavirus , Síndrome Respiratória Aguda Grave , Anticorpos Monoclonais Humanizados , Betacoronavirus , COVID-19 , Ativação do Complemento , Infecções por Coronavirus , Humanos , Pandemias , Pneumonia Viral , SARS-CoV-2
20.
Ann Oncol ; 20(5): 941-5, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19150944

RESUMO

BACKGROUND: Surveys carried out in Mediterranean countries demonstrated very low rates of awareness of both diagnosis and prognosis among cancer patients. In our institution, a long-term training program aimed at improving communication skills among all physicians interacting with cancer patients was conducted. We report here the results of an extensive assessment of patients' awareness conducted after the first training period. PATIENTS AND METHODS: In a 2-year period, after every first visit of patients with a histological diagnosis of cancer, oncologists elicited perception of the patients and completed a structured questionnaire focusing on the understanding of the diagnosis and prognosis. Our data are thus a photograph of the results of the informative process conducted during the diagnostic phase. RESULTS: Among the enrolled 649 patients, 79.3% were aware of their diagnosis; factors significantly associated with higher levels of awareness were age younger than 70 and referral from surgery (versus internal medicine). Knowledge about the palliative or curative aims of future treatments (a surrogate sign of prognostic consciousness) was evident in 55.2%. CONCLUSIONS: Compared with historical data, our results show a high level of comprehension of the diagnosis of malignancy, probably due to the extensive training effort together with the method chosen for assessment.


Assuntos
Atitude do Pessoal de Saúde , Conhecimentos, Atitudes e Prática em Saúde , Oncologia/educação , Neoplasias/diagnóstico , Neoplasias/terapia , Educação de Pacientes como Assunto , Relações Médico-Paciente , Revelação da Verdade , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Conscientização , Compreensão , Empatia , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Direitos do Paciente , Prognóstico , Avaliação de Programas e Projetos de Saúde , Encaminhamento e Consulta , Inquéritos e Questionários , Recursos Humanos , Adulto Jovem
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