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1.
Nat Commun ; 14(1): 3804, 2023 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-37365163

RESUMO

The interleukin-1 family members, IL-1ß and IL-18, are processed into their biologically active forms by multi-protein complexes, known as inflammasomes. Although the inflammasome pathways that mediate IL-1ß processing in myeloid cells have been defined, those involved in IL-18 processing, particularly in non-myeloid cells, are still not well understood. Here we report that the host defence molecule NOD1 regulates IL-18 processing in mouse epithelial cells in response to the mucosal pathogen, Helicobacter pylori. Specifically, NOD1 in epithelial cells mediates IL-18 processing and maturation via interactions with caspase-1, instead of the canonical inflammasome pathway involving RIPK2, NF-κB, NLRP3 and ASC. NOD1 activation and IL-18 then help maintain epithelial homoeostasis to mediate protection against pre-neoplastic changes induced by gastric H. pylori infection in vivo. Our findings thus demonstrate a function for NOD1 in epithelial cell production of bioactive IL-18 and protection against H. pylori-induced pathology.


Assuntos
Células Epiteliais , Infecções por Helicobacter , Interleucina-18 , Proteína Adaptadora de Sinalização NOD1 , Animais , Camundongos , Células Epiteliais/metabolismo , Infecções por Helicobacter/metabolismo , Helicobacter pylori , Inflamassomos/metabolismo , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Transdução de Sinais , Proteína Adaptadora de Sinalização NOD1/metabolismo
2.
J Int Soc Sports Nutr ; 18(1): 62, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34530857

RESUMO

BACKGROUND: A ketogenic diet (KD) is a nutritional approach, usually adopted for weight loss, that restricts daily carbohydrates under 30 g/day. KD showed contradictory results on sport performance, whilst no data are available on team sports. We sought to investigate the influence of a KD on different parameters in semi-professional soccer players. METHODS: Subjects were randomly assigned to a iso-protein (1.8 g/Kg body weight/day) ketogenic diet (KD) or western diet (WD) for 30 days. Body weight and body composition, resting energy expenditure (REE), respiratory exchange ratio (RER), cross sectional area (CSA) and isometric muscle strength of quadriceps, counter movement jump (CMJ) and yoyo intermittent recovery test time were measured. RESULTS: There was a significantly higher decrease of body fat (p = 0.0359), visceral adipose tissue (VAT) (p = 0.0018), waist circumference (p = 0.0185) and extra-cellular water (p = 0.0060) in KD compared to WD group. Lean soft tissue, quadriceps muscle area, maximal strength and REE showed no changes in both groups. RER decreased significantly in KD (p = 0.0008). Yo-yo intermittent test improved significantly (p < 0.0001) in both groups without significant differences between groups. CMJ significantly improved (p = 0.0021) only in KD. CONCLUSIONS: This is the first study investigating the effects of a KD on semi-professional soccer players. In our study KD athletes lost fat mass without any detrimental effects on strength, power and muscle mass. When the goal is a rapid weight reduction in such athletes, the use of a KD should be taken into account. TRIAL REGISTRATION: registered retrospectively on Clinical Trial registration number NCT04078971 .


Assuntos
Composição Corporal , Dieta Cetogênica , Força Muscular , Músculo Esquelético/fisiologia , Fenômenos Fisiológicos da Nutrição Esportiva , Adulto , Atletas , Dieta Ocidental , Humanos , Masculino , Estudos Prospectivos , Adulto Jovem
4.
J Endocrinol Invest ; 44(8): 1679-1688, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33460012

RESUMO

PURPOSE: Evidence of an increased diagnostic pressure on thyroid has emerged over the past decades. This study aimed to provide estimates of a wide spectrum of surveillance indicators for thyroid dysfunctions and diseases in Italy. METHODS: A population-based study was conducted in North-eastern Italy, including 11.7 million residents (20% of the total Italian population). Prescriptions for TSH testing, neck ultrasound or thyroid fine needle aspiration (FNA), surgical procedures, and drugs for hypo- or hyperthyroidism were extracted from regional health databases. Proportions and rates of selected examinations were calculated from 2010 to 2017, overall and by sex, calendar years, age, and region. RESULTS: Between 2010 and 2017 in North-eastern Italy, 24.5% of women and 9.8% of men received at least one TSH test yearly. In 2017, 7.1% of women and 1.5% of men were prescribed drugs for thyroid dysfunction, 94.6% of whom for hypothyroidism. Neck ultrasound examinations were performed yearly in 6.9% of women and 4.6% of men, with a nearly two-fold variation between areas. Thyroid FNA and thyroidectomies were three-fold more frequent in women (394 and 85 per 100,000) than in men (128 and 29 per 100,000) with a marked variation between areas. Both procedures decreased consistently after 2013. CONCLUSIONS: The results of this population-based study describe recent variations over time and between surrounding areas of indicators of 'diagnostic pressure' on thyroid in North-eastern Italy. These results emphasize the need to harmonize practices and to reduce some procedures (e.g., neck ultrasound and total thyroidectomies) in certain areas.


Assuntos
Biópsia por Agulha Fina , Doenças da Glândula Tireoide , Testes de Função Tireóidea , Glândula Tireoide , Tireoidectomia , Ultrassonografia , Adulto , Idoso , Biópsia por Agulha Fina/métodos , Biópsia por Agulha Fina/tendências , Feminino , Humanos , Itália/epidemiologia , Masculino , Uso Excessivo dos Serviços de Saúde/prevenção & controle , Uso Excessivo dos Serviços de Saúde/tendências , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Vigilância da População , Fatores Sexuais , Doenças da Glândula Tireoide/diagnóstico , Doenças da Glândula Tireoide/epidemiologia , Doenças da Glândula Tireoide/cirurgia , Testes de Função Tireóidea/métodos , Testes de Função Tireóidea/tendências , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/patologia , Tireoidectomia/métodos , Tireoidectomia/tendências , Ultrassonografia/métodos , Ultrassonografia/tendências
5.
Eur J Surg Oncol ; 46(8): 1415-1422, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32402509

RESUMO

OBJECTIVE: Aim of the manuscript is to discuss how to improve margins in sacral chordoma. BACKGROUND: Chordoma is a rare neoplasm, arising in half cases from the sacrum, with reported local failure in >50% after surgery. METHODS: A multidisciplinary meeting of the "Chordoma Global Consensus Group" was held in Milan in 2017, focusing on challenges in defining and achieving optimal margins in chordoma with respect to surgery, definitive particle radiation therapy (RT) and medical therapies. This review aims to report on the outcome of the consensus meeting and to provide a summary of the most recent evidence in this field. Possible new ways forward, including on-going international clinical studies, are discussed. RESULTS: En-bloc tumor-sacrum resection is the cornerstone of treatment of primary sacral chordoma, aiming to achieve negative microscopic margins. Radical definitive particle therapy seems to offer a similar outcome compared to surgery, although confirmation in comparative trials is lacking; besides there is still a certain degree of technical variability across institutions, corresponding to different fields of treatment and different tumor coverage. To address some of these questions, a prospective, randomized international study comparing surgery versus definitive high-dose RT is ongoing. Available data do not support the routine use of any medical therapy as (neo)adjuvant/cytoreductive treatment. CONCLUSION: Given the significant influence of margins status on local control in patients with primary localized sacral chordoma, the clear definition of adequate margins and a standard local approach across institutions for both surgery and particle RT is vital for improving the management of these patients.


Assuntos
Cordoma/radioterapia , Cordoma/cirurgia , Margens de Excisão , Sacro/cirurgia , Humanos , Terapia com Prótons/efeitos adversos , Dosagem Radioterapêutica
6.
Eur J Intern Med ; 77: 79-85, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32151490

RESUMO

BACKGROUND: An abnormal ankle-brachial pressure index (ABI) is a marker of the risk for increased total and cardiovascular (CV) mortality. However, it is not clear whether it is associated with an even worse prognosis in patients with previous CV events or with cancer mortality. MATERIALS AND METHODS: Consecutive subjects undergoing ABI assessment for suspected peripheral artery disease or for stratification of CV risk in ten centers in the Veneto Region (northeast Italy), between 2011 and 2014 were enrolled. The ABI was expressed as normal ≥0.9 to ≤1.3, and abnormal <0.9 or >1.3. All-cause mortality and CV or cancer mortality and hospitalizations for CV disease were collected from administrative databases up to December 2018. RESULTS: The study enrolled 1,177 patients. ABI was abnormal in 57.2%. Median follow-up was 61.6 months (53.4-70.1). All-cause, CV and cancer mortality were higher in patients with abnormal than normal ABI, with hazard ratios (HR) respectively 2.0 (95% CI 1.48-2.69), 1.98 (95% CI 1.24-3.17) and 1.85 (95% CI 1.09-3.15). Among subjects with abnormal ABI, the risk of overall mortality, HR 1.57 (95% CI 1.17-2.12), and CV mortality, HR 2.39 (95% CI 1.43-3.99), was higher in those with previous CV events. These latter also had a higher risk of hospitalization for myocardial infarction and stroke: HR 1.85 (95% CI 1.023.37) and 2.17 (95% CI 1.10-4.28). CONCLUSIONS: The co-existence of abnormal ABI and a history of CV events identifies subjects at higher risk, who call for a more aggressive approach. Abnormal ABI is also a predictor of cancer mortality.


Assuntos
Doenças Cardiovasculares , Neoplasias , Índice Tornozelo-Braço , Fatores de Risco de Doenças Cardíacas , Humanos , Itália/epidemiologia , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco
7.
Cancer Radiother ; 23(5): 378-384, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31178272

RESUMO

PURPOSE: To apply the German Hodgkin Study Group (GHSG) risk model in patients with recurrent/refractory Hodgkin lymphoma receiving involved-field radiotherapy after autologous stem cell transplantation. MATERIAL AND METHODS: The study consisted in the retrospective analysis of 30 consecutive patients with recurrent/refractory Hodgkin lymphoma who received involved-field radiotherapy after autologous stem cell transplantation. Our policy was of adding involved-field radiotherapy for patients with positive PET scan before autologous stem cell transplantation (23 out of 30 patients, 77%), and/or irradiating sites of bulky disease at relapse (11 out of 30 patients, 37%). Patients were stratified into four risk groups according to the presence of the five clinical risk factors identified by the GHSG; (1) stage IV disease; (2) time to relapse≤3 months; (3) ECOG-PS≥1; (4) bulk≥5cm; and (5) inadequate response to salvage chemotherapy. RESULTS: The median interval from autologous stem cell transplantation to involved-field radiotherapy was 3 months (range, 1-7 months), and the median involved-field radiotherapy dose was 35Gy (range, 12-40Gy). At a median follow-up of 35 months (range, 1-132 months), the 2-year progression-free survival in the entire series was 60%. When examining the four different GHSG risk groups, the progression-free survival rate at 2 years was 86%, 83%, 50%, and 36% for patients with score=0, score=1, score=2, and score=3 to 5, respectively (P=0,01). Among the 12 patients havingat leastthree risk factors who underwent thoracic involved-field radiotherapy, three (25%) developed pneumonitis. CONCLUSION: The adoption of the GHSG risk model at the time of recurrence/progression is a useful prognostic tool to select patients with Hodgkin lymphoma for consolidative involved-field radiotherapy after autologous stem cell transplantation.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/radioterapia , Modelos Teóricos , Radioterapia Adjuvante , Medição de Risco/métodos , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Feminino , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Prognóstico , Intervalo Livre de Progressão , Pneumonite por Radiação/epidemiologia , Pneumonite por Radiação/etiologia , Estudos Retrospectivos , Fatores de Risco , Terapia de Salvação , Taxa de Sobrevida , Condicionamento Pré-Transplante , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
9.
Cancer Radiother ; 23(1): 46-49, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30642779

RESUMO

A 25-year-old female with high-grade spindle cell sarcoma of the thyroid persistent after thyroidectomy performed at another hospital was referred to our institute. Chemotherapy followed by surgery with intraoperative radiotherapy and postoperative intensity-modulated radiotherapy were planned within the sarcoma board. Chemotherapy was discontinued after two cycles because of local disease progression and surgery with intraoperative radiotherapy, was anticipated. The treatment was completed with postoperative radiotherapy. After 36 months off-therapy, the patient was free of disease without significant late effects. Thyroid sarcomas are very rare and there is no consensus on their clinical management. Hence, case reports are useful to share treatment options. In this patient case, the histotype and the high-grade disease required a combined therapy program, managed in a multidisciplinary setting.


Assuntos
Sarcoma/terapia , Neoplasias da Glândula Tireoide/terapia , Adulto , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Terapia Neoadjuvante , Equipe de Assistência ao Paciente , Radioterapia Adjuvante , Sarcoma/patologia , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia
10.
Hum Mov Sci ; 60: 175-182, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29936337

RESUMO

Strength, power and muscular endurance tests have been developed as means of assessing people's physical abilities. However, testing may be expensive or time consuming. A method to reduce the time of physical assessment could be to use predictive algorithms for indirect assessment. The aim of this study will be to determine a relationship between strength, power and muscular endurance in order to identify predictors for an easier and faster assessment. 33 male strength-trained participants (22.8 ±â€¯4.6 years, 172.5 ±â€¯6.7 cm, 68.0 ±â€¯10.6 kg) performed a single pull-up (SPU) and a single push-up (SPH) and a set of pull-ups (EPU) and push-ups (EPH) to exhaustion. The participants were divided into three sub-groups according to their training experience. Force(F), Power(P), Velocity(V) and relative power(R-P), extracted from an accelerometer (500 Hz), were compared between groups (ANOVA) and a subsequent linear regression analysis was performed to identify predictors of the performance measures. The regression models were able to explain 61% of the variance with the EPU as dependent variable and the V of the SPU as independent variable and 68% of the variance with the EPH as dependent variable and EPU as independent variable. In addition, increased performance measures were found according to training experience, in particular regarding muscular endurance of both the EPU and EPH (p < 0.001 and p < 0.01, respectively). A significant effect of training experience was also present for the V of the SPU (p < 0.001). The results indicate that a relation between muscular endurance and velocity is present. The generated equations allow to estimate both the number of EPH and EPU from a SPU. The equations may be helpful to reduce the time of assessment for upper body physical evaluation.


Assuntos
Músculo Esquelético/fisiologia , Resistência Física/fisiologia , Acelerometria , Adulto , Algoritmos , Antropometria , Humanos , Masculino , Força Muscular/fisiologia , Educação Física e Treinamento , Treinamento Resistido , Levantamento de Peso , Adulto Jovem
11.
Ann Surg Oncol ; 24(13): 3872-3879, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29043525

RESUMO

BACKGROUND: This study was designed to assess patterns of recurrence and long-term outcomes of patients undergoing surgery for localized retroperitoneal sarcoma (RPS) after neoadjuvant high dose long-infusion ifosfamide (HLI) and radiotherapy (RT). METHODS: Patients received three cycles of HLI (14 g/m2). RT was started in combination with II cycle up to a total dose of 50.4 Gy. Surgery was scheduled 4-6 weeks after the end of RT. The primary endpoint was relapse-free survival (RFS) after surgery. Secondary endpoints were overall survival (OS), crude cumulative incidence of local recurrence (CCI-LR), and distant metastases (CCI-DM). For patients who relapsed, progression-free survival (PFS) and post-relapse OS were estimated. The trial was registered with ITASARC_*II_2004_003. RESULTS: Between 2003 and 2010, 83 patients were recruited. At a median follow-up of 91.7 months, 42 (56%) of 75 operated patients developed LR (n = 27) or DM (n = 10) or both LR and DM (n = 5) relapse. Seven-year RFS was 46.6% [95% confidence interval (CI) 29.6-52.4]. Thirty-two patients died. Seven-year OS rate was 63.2% (95% CI 42.7-66.0). The corresponding CCI of LR and DM were 37.4% [standard error (SE) 5.5%] and 20.0% (SE 12.6%), respectively. The only factor significantly associated with LR was FNCLCC grading, whereas histological subtype resulted associated with DM. At recurrence, 24 patients (57%) underwent surgery. Two-year post-relapse PFS and OS rates for patients developing LR or DM were 14.8, 41.0, 27.3, and 63.6%, respectively. CONCLUSIONS: LR after neoadjuvant CT-RT for RPS were predominantly infield. While almost one half of relapsed patients underwent further surgery, prognosis was poor.


Assuntos
Quimiorradioterapia , Ifosfamida/uso terapêutico , Terapia Neoadjuvante , Recidiva Local de Neoplasia/patologia , Neoplasias Retroperitoneais/patologia , Sarcoma/patologia , Adulto , Idoso , Antineoplásicos Alquilantes/uso terapêutico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Prognóstico , Neoplasias Retroperitoneais/terapia , Sarcoma/terapia , Taxa de Sobrevida
12.
Tech Coloproctol ; 21(8): 633-640, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28755256

RESUMO

BACKGROUND: Rectum-sparing approaches appear to be appropriate in rectal cancer patients with a major (mCR) or complete clinical response (cCR) after neoadjuvant therapy. The aim of the present study is to evaluate the effectiveness of rectum-sparing approaches at 2 years after the completion of neoadjuvant treatment. STUDY DESIGN: Patients with rectal adenocarcinoma eligible to receive neoadjuvant therapy will be prospectively enrolled. Patients will be restaged 7-8 weeks after the completion of neoadjuvant therapy and those with mCR (defined as absence of mass, small mucosal irregularity no more than 2 cm in diameter at endoscopy and no metastatic nodes at MRI) or cCR will be enrolled in the trial. Patients with mCR will undergo local excision, while patients with cCR will either undergo local excision or watch and wait policy. The main end point of the study is to determine the percentage of rectum preservation at 2 years in the enrolled patients. CONCLUSION: This protocol is the first prospective trial that investigates the role of both local excision and watch and wait approaches in patients treated with neoadjuvant therapy for rectal cancer. The trial is registered at clinicaltrials.gov (NCT02710812).


Assuntos
Adenocarcinoma/terapia , Neoplasias Retais/terapia , Conduta Expectante , Adenocarcinoma/cirurgia , Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , Humanos , Terapia Neoadjuvante , Tratamentos com Preservação do Órgão , Período Pré-Operatório , Radioterapia Adjuvante , Neoplasias Retais/cirurgia , Reto , Projetos de Pesquisa
13.
Int J Numer Method Biomed Eng ; 33(8): e2839, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-27704706

RESUMO

Transparent and removable aligners represent an effective solution to correct various orthodontic malocclusions through minimally invasive procedures. An aligner-based treatment requires patients to sequentially wear dentition-mating shells obtained by thermoforming polymeric disks on reference dental models. An aligner is shaped introducing a geometrical mismatch with respect to the actual tooth positions to induce a loading system, which moves the target teeth toward the correct positions. The common practice is based on selecting the aligner features (material, thickness, and auxiliary elements) by only considering clinician's subjective assessments. In this article, a computational design and engineering methodology has been developed to reconstruct anatomical tissues, to model parametric aligner shapes, to simulate orthodontic movements, and to enhance the aligner design. The proposed approach integrates computer-aided technologies, from tomographic imaging to optical scanning, from parametric modeling to finite element analyses, within a 3-dimensional digital framework. The anatomical modeling provides anatomies, including teeth (roots and crowns), jaw bones, and periodontal ligaments, which are the references for the down streaming parametric aligner shaping. The biomechanical interactions between anatomical models and aligner geometries are virtually reproduced using a finite element analysis software. The methodology allows numerical simulations of patient-specific conditions and the comparative analyses of different aligner configurations. In this article, the digital framework has been used to study the influence of various auxiliary elements on the loading system delivered to a maxillary and a mandibular central incisor during an orthodontic tipping movement. Numerical simulations have shown a high dependency of the orthodontic tooth movement on the auxiliary element configuration, which should then be accurately selected to maximize the aligner's effectiveness.


Assuntos
Simulação por Computador , Ortodontia/instrumentação , Software , Técnicas de Movimentação Dentária/instrumentação , Análise de Elementos Finitos , Humanos , Imageamento Tridimensional , Incisivo , Modelos Dentários , Modelos Teóricos , Polímeros
14.
Br J Surg ; 104(1): 138-147, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27706805

RESUMO

BACKGROUND: Local excision for rectal cancer is expected to offer a better functional outcome than conventional surgery. The aim of the present study was to compare quality of life and bowel function in patients with rectal cancer who underwent either local excision or conventional surgery after chemoradiotherapy. METHODS: This was a retrospective multicentre study. Patients who underwent local excision were compared with those who had mesorectal excision. Quality of life and bowel function were investigated using validated questionnaires (European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-CR29 and Memorial Sloan-Kettering Cancer Center Bowel Function Instrument) at a median follow-up of 49 (range 13-95) months. Further analysis was undertaken of data from patients who underwent local excision alone compared with those requiring subsequent radical surgery. Statistical significance was set at P < 0·010. RESULTS: The mean constipation score was significantly better in the local excision group than in the mesorectal excision group (3·8 (95 per cent c.i. 0·3 to 7·2) versus 19·8 (12·1 to 27·4); P < 0·001). Compared with patients who underwent mesorectal excision, those who had local excision had less sensation of incomplete emptying (mean score 3·7 (3·4 to 4·0) versus 2·8 (2·5 to 3·1); P < 0·001) and second bowel movements within 15 min (mean score 3·6 (3·3 to 3·9) versus 3·0 (2·7 to 3·3); P = 0·006). Patients who underwent local excision alone scored better than those who had mesorectal excision, particularly for bowel function, who, in turn, scored better than patients requiring subsequent radical surgery following local excision. CONCLUSION: Patients who underwent local excision had a better quality of life and bowel function than those who underwent mesorectal excision.


Assuntos
Quimiorradioterapia Adjuvante , Terapia Neoadjuvante , Qualidade de Vida , Neoplasias Retais/terapia , Adenocarcinoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Constipação Intestinal/complicações , Defecação , Incontinência Fecal/complicações , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Inquéritos e Questionários
15.
Ann Oncol ; 27(12): 2283-2288, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27733375

RESUMO

BACKGROUND: To report on long-term results of a phase 3 trial comparing three versus five cycles of adjuvant chemotherapy (CT) with full-dose epirubicin+ifosfamide in high-risk soft tissue sarcomas (STS). METHODS: Patients (pts) were randomized to receive three preoperative cycles of epirubicin 120 mg/m2 and ifosfamide 9 g/m2 (Arm A) or to receive the same three preoperative cycles plus two postoperative cycles (Arm B). Radiotherapy could be either delivered in the preoperative or in the postoperative setting. Non-inferiority of the primary end point, OS, was assessed by the confidence interval of the hazard ratio (HR; Arm A/Arm B) derived from Cox model. RESULTS: Between January 2002 and April 2007, 164 pts were assigned to arm A and 164 to arm B. At a median follow-up (FU) of 117 months (IQ range 103-135 months), 123 deaths were recorded: 58 in Arm A and 65 in Arm B. Ten-year OS was 61% for the entire group of patients: 64% in Arm A and 59% in Arm B. The intention-to-treat analysis confirmed that three cycles were not inferior to five cycles (one-sided 95% upper confidence limit was 1.24). A per protocol analysis was consistent with these results. Pts with leiomyosarcoma and undifferentiated pleomorphic sarcoma (UPS) had the lowest, and the highest response rates, respectively. Consistently, Leiomyosarcoma and UPS had the worse and the best prognosis, respectively. CONCLUSIONS: At a longer FU, the non-inferiority of three cycles of a full-dose conventional CT in comparison to five is confirmed. Response to therapy is also confirmed to be associated with better survival. This regimen is currently tested within an ongoing international trial against three cycles of a neoadjuvant histology-tailored CT (ClinicalTrials.gov Identifier: NCT01710176).


Assuntos
Quimioterapia Adjuvante , Leiomiossarcoma/tratamento farmacológico , Prognóstico , Sarcoma/tratamento farmacológico , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Leiomiossarcoma/patologia , Leiomiossarcoma/radioterapia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Sarcoma/patologia , Sarcoma/radioterapia , Resultado do Tratamento
16.
Eur J Surg Oncol ; 42(12): 1914-1923, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27424789

RESUMO

BACKGROUND: Cutaneous metastases represent a therapeutic challenge. An increasing body of experience suggests that electrochemotherapy (ECT) provides effective tumor control, although its evidence basis should be strengthened. METHODS: This prospective, multicenter, observational study enrolled patients with superficial metastases, who underwent ECT at 10 centers between 2008 and 2013. Outcomes included adherence to European Standard Operating Procedures of ECT (ESOPE), tumor response, local progression-free survival (LPFS), toxicity and patient-reported outcomes (PROs, EORTC QLQ-C30 plus an 8-item questionnaire). RESULTS: We enrolled 376 eligible patients. Tumor histotype distribution was as follows: melanoma, 56%; squamous cell carcinoma, 11%; Kaposi sarcoma, 11%; breast carcinoma, 8%; basal cell carcinoma, 6%; soft tissue sarcomas, 3%; others, 5%. We registered 1304 target tumors (median size 1 cm). Treatment adhered to ESOPE in 88% of patients as to the route of drug administration, and in 70% as to electrode application. The procedure was mainly performed under sedation (64.6%) and by using intravenous chemotherapy (93.4%). Tumor response rate at 60 days was 88% (complete, 50%). Small tumor size predicted complete response achievement (OR 2.24, p = 0.003), higher LPFS (HR 0.68, p = 0.004) and improved PROs (Global Health Status, p < 0.001; wound bleeding, p < 0.001; healing, p = 0.002; and aesthetics, p < 0.001). Skin toxicity (grade ≥3, 7.8%) was lower in patients with tumors <2 cm (p≤0.001). One-year LPFS was 73.7% (95%CI 68.4-78.3). CONCLUSIONS: ECT represents a valuable skin-directed therapy across a range of malignancies. The most frequently applied treatment modality is intravenous chemotherapy under sedation. Small tumor size predicts durable tumor control, fewer side-effects and better PROs.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma/terapia , Eletroquimioterapia/métodos , Melanoma/terapia , Sarcoma de Kaposi/terapia , Sarcoma/terapia , Neoplasias Cutâneas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bleomicina/uso terapêutico , Neoplasias da Mama/patologia , Carcinoma/secundário , Carcinoma Basocelular/secundário , Carcinoma Basocelular/terapia , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/terapia , Cisplatino/uso terapêutico , Feminino , Humanos , Injeções Intralesionais , Estimativa de Kaplan-Meier , Masculino , Melanoma/secundário , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Sarcoma/secundário , Sarcoma de Kaposi/secundário , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/secundário , Resultado do Tratamento , Adulto Jovem
17.
Cell Death Dis ; 6: e2047, 2016 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-26764573

RESUMO

Despite some success with certain hematological malignancies and in contrast with the strong pro-apoptotic effects measured in vitro, the overall response rate of acute lymphoblastic leukemia (ALL) to histone deacetylase inhibitors (HDACis) is low. With the aim to improve the understanding of how HDACis work in vivo, we investigated the therapeutic efficacy of the clinically approved HDACi Givinostat in a collection of nine pediatric human T-ALL engrafted systemically in NOD/SCID mice. We observed highly heterogeneous antileukemia responses to Givinostat, associated with reduction of the percentage of infiltrating blasts in target organs, induction of apoptosis and differentiation. These effects were not associated with the T-ALL cytogenetic subgroup. Transcriptome analysis disclosed an immediate transcriptional signature enriched in genes involved in cell-cycle regulation and DNA repair, which was validated by quantitative RT-PCR and was associated with in vivo response to this HDACi. Increased phospho-H2AX levels, a marker of DNA damage, were measured in T-ALL cells from Givinostat responders. These results indicate that the induction of the DNA damage response could be an early biomarker of the therapeutic effects of Givinostat in T-ALL models. This information should be considered in the design of future clinical trials with HDACis in acute leukemia.


Assuntos
Carbamatos/administração & dosagem , Diferenciação Celular/efeitos dos fármacos , Inibidores de Histona Desacetilases/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Dano ao DNA/efeitos dos fármacos , Humanos , Camundongos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Artigo em Inglês | MEDLINE | ID: mdl-26418417

RESUMO

Dedicated imaging methods are among the most important tools of modern computer-aided medical applications. In the last few years, cone beam computed tomography (CBCT) has gained popularity in digital dentistry for 3D imaging of jawbones and teeth. However, the anatomy of a maxillofacial region complicates the assessment of tooth geometry and anatomical location when using standard orthogonal views of the CT data set. In particular, a tooth is defined by a sub-region, which cannot be easily separated from surrounding tissues by only considering pixel grey-intensity values. For this reason, an image enhancement is usually necessary in order to properly segment tooth geometries. In this paper, an anatomy-driven methodology to reconstruct individual 3D tooth anatomies by processing CBCT data is presented. The main concept is to generate a small set of multi-planar reformation images along significant views for each target tooth, driven by the individual anatomical geometry of a specific patient. The reformation images greatly enhance the clearness of the target tooth contours. A set of meaningful 2D tooth contours is extracted and used to automatically model the overall 3D tooth shape through a B-spline representation. The effectiveness of the methodology has been verified by comparing some anatomy-driven reconstructions of anterior and premolar teeth with those obtained by using standard tooth segmentation tools. Copyright © 2015 John Wiley & Sons, Ltd.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Dente/diagnóstico por imagem , Humanos , Aumento da Imagem , Software
19.
J Sports Med Phys Fitness ; 55(7-8): 730-4, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-24921617

RESUMO

AIM: There are limited studies that indicate the effects of trampoline exercise on strength and other physiological parameters. This study aims to determine whether twelve weeks of trampoline exercise would have any effects on the physical and physiological parameters of male gymnasts. METHODS: A number of 20 intercollegiate competitive male gymnasts (as experimental group) and 20 non-athlete male (as control group) participated voluntarily. Their anthropometric characteristics and the anaerobic power were measured and their back strength, vertical jump, standing long jump and 20 meter sprint performances were measured. RESULTS: As a result; whereas 12 weeks of trampoline exercise improved standing long jump (before 242.35±3.40 cm; after 251.70±2.95 cm) and also vertical jump, 20 meter sprint speed and anaerobic power of subjects. We did not observe significant changes on back strength performances (before 148.32±5.73 kg; after 148.10±5.71). CONCLUSION: The trampoline exercise protocol improved significantly speed, jump and anaerobic performances of the experimental group, while did not induced any changes on back strength performances. More studies are necessary to confirm the interesting results coming from this pilot intervention.


Assuntos
Desempenho Atlético/fisiologia , Ginástica/fisiologia , Força Muscular/fisiologia , Antropometria , Estudos de Casos e Controles , Humanos , Masculino , Projetos Piloto , Adulto Jovem
20.
Ann Oncol ; 26(3): 567-72, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25488687

RESUMO

BACKGROUND: To report the results of the first European prospective nonrandomized trial dedicated to pediatric synovial sarcoma. PATIENTS AND METHODS: From August 2005 to August 2012, 138 patients <21 years old with nonmetastatic synovial sarcoma were registered in 9 different countries (and 60 centers). Patients were treated with a multimodal therapy including ifosfamide-doxorubicin chemotherapy and radiotherapy, according to a risk stratification based on surgical stage, tumor size and site, and nodal involvement. RESULTS: With a median follow-up of 52.1 months (range 13.8-104.4 months), event-free survival (EFS) was 81.9% and 80.7%, and overall survival (OS) was 97.2% and 90.7%, at 3 and 5 years, respectively. The only significant prognostic variable at univariate analysis was the risk group: 3-year EFS was 91.7% for low-risk, 91.2% for intermediate-risk, and 74.4% for high-risk cases. In 24 low-risk patients (completely resected tumor ≤5 cm in size) treated with surgery alone, there were two local relapses and no metastatic recurrences. Among 67 high-risk patients (unresected, or axial tumor or nodal involvement), 66 underwent surgery after neoadjuvant chemotherapy. Response to chemotherapy was 55.2%, including 22.4% cases with complete or major partial remissions, and 32.8% with minor partial remissions. CONCLUSION: This study demonstrates that collaborative prospective studies on rare pediatric sarcomas are feasible even on a European scale, with excellent treatment compliance. The overall results of treatment were satisfactory, with higher survival rates than those previously published by pediatric groups. Nonetheless, larger, international projects are needed, based on a cooperative effort of pediatric and adult oncologists. CLINICAL TRIALS NUMBER: European Union Drug Regulating Authorities Clinical Trials No. 2005-001139-31.


Assuntos
Sarcoma Sinovial/diagnóstico , Sarcoma Sinovial/epidemiologia , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/epidemiologia , Adolescente , Criança , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Estudos Prospectivos , Sarcoma Sinovial/terapia , Neoplasias de Tecidos Moles/terapia
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