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1.
Future Oncol ; 20(22): 1565-1573, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38861296

RESUMO

Aim: There is little consensus on salvage management of glioblastoma after recurrence, for lack of evidence.Materials & methods: A retrospective study of treatments in patients with recurrent glioblastoma.Results: Surgery at recurrence was related to better overall survival (OS) and progression-free survival (PFS). Surgery at recurrence, Karnofsky index, MGMT methylation status, younger age at diagnosis and number of chemotherapy cycles were positive factors for OS and PFS. The benefit of OS was relevant for a second surgery performed at least 9 months after the first one. Systemic treatments after the second surgery were linked to an improved PFS.Conclusion: Younger age, Karnofsky index, MGMT methylation status and a median time between surgeries ≥9 months may be criteria for eligibility for surgery at recurrence.


[Box: see text].


Assuntos
Neoplasias Encefálicas , Glioblastoma , Recidiva Local de Neoplasia , Seleção de Pacientes , Humanos , Glioblastoma/cirurgia , Glioblastoma/mortalidade , Glioblastoma/patologia , Glioblastoma/genética , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Estudos Retrospectivos , Idoso , Adulto , Terapia de Salvação , Reoperação/estatística & dados numéricos , Intervalo Livre de Progressão , Metilases de Modificação do DNA/genética , Proteínas Supressoras de Tumor , Enzimas Reparadoras do DNA
2.
Genes Chromosomes Cancer ; 62(8): 483-488, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36849873

RESUMO

Soft tissue neoplasms displaying CD34 and S100 positivity with immunohistochemistry are rare with a wide morphological range and frequent neurotrophic tyrosine receptor kinase (NTRK) alterations. Recent reports describe fusions in other kinases besides NTRK in these tumors. In the present article, we report a case of a young male suffering from a soft tissue neoplasm in the lumbar region. At microscopic examination, it was a CD34 and S100-positive soft tissue tumor showing a multilobulated growth pattern composed of cells with pale cytoplasm and abundant normal smooth muscle stroma. The genetic profile showed two alterations affecting EGFR gene represented by a novel MYH9::EGFR fusion transcript and a p.K714N mutation.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Humanos , Masculino , Biomarcadores Tumorais/genética , Receptores ErbB/genética , Fusão Gênica , Imuno-Histoquímica , Cadeias Pesadas de Miosina/genética , Receptores Proteína Tirosina Quinases/genética , Sarcoma/genética , Neoplasias de Tecidos Moles/genética
3.
J Transl Med ; 21(1): 215, 2023 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-36959606

RESUMO

BACKGROUND: This study aimed to characterize the genetic profile of patients with glioma and discuss the impact of next-generation sequencing in glioma diagnosis and treatment. METHODS: Between 2019 and 2022, we analyzed the genetic profile of 99 patients with glioma through the Oncomine Focus Assay. The assay enables the detection of mutations in 52 driver genes, including single nucleotide variants (SNVs), copy number variants (CNVs), and gene fusions. We also collected and analyzed patients' clinic characteristics and treatment outcomes. RESULTS: Over a period of 35 months, 700 patients with glioma followed by our neuro-oncology unit were screened, and 99 were enrolled in the study; most of the patients were excluded for inadequate non-morphological MRI or lack/inadequacy of the tissue samples. Based on our findings, most patients with glioma present mutations, such as SNVs, CNVs or gene fusions. Our data were similar to those reported by The Cancer Genome Atlas Program in terms of frequency of SNVs and CNVs, while we observed more cases of gene fusions. Median overall survival, progression-free survival, and time to progression were significantly lower for patients with grade VI glioblastoma than those with other gliomas. Only four patients were offered a targeted treatment based on the mutation detected; however, only one received treatment, the others could not receive the selected treatment because of worsening clinical status. CONCLUSION: Routine timely molecular profiling in patients with glioma should be implemented to offer patients an individualized diagnostic approach and provide them with advanced targeted therapy options if available.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Glioma/diagnóstico , Glioma/genética , Glioma/terapia , Mutação/genética , Sequenciamento de Nucleotídeos em Larga Escala , Variações do Número de Cópias de DNA/genética , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia
4.
J Transl Med ; 21(1): 725, 2023 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-37845764

RESUMO

BACKGROUND: Molecular Tumor Boards (MTB) operating in real-world have generated limited consensus on good practices for accrual, actionable alteration mapping, and outcome metrics. These topics are addressed herein in 124 MTB patients, all real-world accrued at progression, and lacking approved therapy options. METHODS: Actionable genomic alterations identified by tumor DNA (tDNA) and circulating tumor DNA (ctDNA) profiling were mapped by customized OncoKB criteria to reflect diagnostic/therapeutic indications as approved in Europe. Alterations were considered non-SoC when mapped at either OncoKB level 3, regardless of tDNA/ctDNA origin, or at OncoKB levels 1/2, provided they were undetectable in matched tDNA, and had not been exploited in previous therapy lines. RESULTS: Altogether, actionable alterations were detected in 54/124 (43.5%) MTB patients, but only in 39 cases (31%) were these alterations (25 from tDNA, 14 from ctDNA) actionable/unexploited, e.g. they had not resulted in the assignment of pre-MTB treatments. Interestingly, actionable and actionable/unexploited alterations both decreased (37.5% and 22.7% respectively) in a subset of 88 MTB patients profiled by tDNA-only, but increased considerably (77.7% and 66.7%) in 18 distinct patients undergoing combined tDNA/ctDNA testing, approaching the potential treatment opportunities (76.9%) in 147 treatment-naïve patients undergoing routine tDNA profiling for the first time. Non-SoC therapy was MTB-recommended to all 39 patients with actionable/unexploited alterations, but only 22 (56%) accessed the applicable drug, mainly due to clinical deterioration, lengthy drug-gathering procedures, and geographical distance from recruiting clinical trials. Partial response and stable disease were recorded in 8 and 7 of 19 evaluable patients, respectively. The time to progression (TTP) ratio (MTB-recommended treatment vs last pre-MTB treatment) exceeded the conventional Von Hoff 1.3 cut-off in 9/19 cases, high absolute TTP and Von Hoff values coinciding in 3 cases. Retrospectively, 8 patients receiving post-MTB treatment(s) as per physician's choice were noted to have a much longer overall survival from MTB accrual than 11 patients who had received no further treatment (35.09 vs 6.67 months, p = 0.006). CONCLUSIONS: MTB-recommended/non-SoC treatments are effective, including those assigned by ctDNA-only alterations. However, real-world MTBs may inadvertently recruit patients electively susceptible to diverse and/or multiple treatments.


Assuntos
Neoplasias , Estados Unidos , Humanos , National Cancer Institute (U.S.) , Estudos Retrospectivos , Mutação , Neoplasias/genética , DNA de Neoplasias/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Biomarcadores Tumorais/genética
5.
J Biomed Inform ; 142: 104394, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37209976

RESUMO

The Biomedical Research field is currently advancing to develop Clinical Trials and translational projects based on Real World Evidence. To make this transition feasible, clinical centers need to work toward Data Accessibility and Interoperability. This task is particularly challenging when applied to Genomics, that entered in routinary screening in the last years via mostly amplicon-based Next-Generation Sequencing panels. Said experiments produce up to hundreds of features per patient, and their summarized results are often stored in static clinical reports, making critical information inaccessible to automated access and Federated Search consortia. In this study, we present a reanalysis of 4620 solid tumor sequencing samples in five different histology settings. Furthermore, we describe all the Bioinformatics and Data Engineering processes that were put in place in order to create a Somatic Variant Registry able to deal with the large biotechnological variability of routinary Genomics Profiling.


Assuntos
Pesquisa Biomédica , Neoplasias , Humanos , Genômica , Biologia Computacional/métodos , Sistema de Registros , Neoplasias/diagnóstico , Neoplasias/genética
6.
Pathologica ; 115(2): 97-100, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37114626

RESUMO

CIC-rearranged sarcomas are rare mesenchymal neoplasms belonging to the family of undifferentiated small round cell sarcomas. This report details the case of a 45-year-old man presenting with symptoms of mediastinal compression, radiological diagnosis of a mediastinal mass and rapid evolution to full-blown superior vena cava syndrome. The emergency was successfully managed with a pharmacological approach. Formulation of a pathological diagnosis of CIC-rearranged sarcoma was initially supported by fluorescence in situ hybridisation findings and later validated by next-generation sequencing, which showed CIC-DUX4 gene fusion. A chemotherapy regimen was started with immediate benefits for the patient. The spectrum of pathological entities able to cause superior vena cava syndrome is wide, and recognition of rare causes is important to tailor the therapeutic approach to the specific disease. This is, to the best of our knowledge, the first report of CIC-rearranged sarcoma presenting with superior vena cava syndrome.


Assuntos
Sarcoma de Células Pequenas , Sarcoma , Síndrome da Veia Cava Superior , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Proteínas de Fusão Oncogênica/genética , Sarcoma/complicações , Sarcoma/diagnóstico , Sarcoma/genética , Sarcoma de Células Pequenas/diagnóstico , Sarcoma de Células Pequenas/genética , Sarcoma de Células Pequenas/patologia , Síndrome da Veia Cava Superior/genética
7.
Int J Mol Sci ; 23(18)2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36142631

RESUMO

Giant cell tumour of bone (GCTB) is a benign, locally aggressive primary bone neoplasm that represents 5% of all bone tumours. The principal treatment approach is surgery. Although generally GCTB is considered only a locally aggressive disease, it can metastasise, and lung metastases occur in 1-9% of patients. To date, only the use of denosumab has been approved as medical treatment for GCTB. Even more rarely, GCTB undergoes sarcomatous transformation into a malignant tumour (4% of all GCTB), but history of this malignant transformation is unclear and unpredictable. Considering the rarity of the event, the data in the literature are few. In this review, we summarise published data of GCTB malignant transformation and we analyse three cases of malignant transformation of GCTB, evaluating histopathology, genetics, and radiological aspects. Despite the rarity of this event, we conclude that a strict follow up is recommended to detect early malignant transformation.


Assuntos
Neoplasias Ósseas , Tumor de Células Gigantes do Osso , Neoplasias Ósseas/patologia , Transformação Celular Neoplásica/genética , Denosumab , Tumor de Células Gigantes do Osso/diagnóstico , Tumor de Células Gigantes do Osso/genética , Tumor de Células Gigantes do Osso/patologia , Humanos , Encaminhamento e Consulta
8.
Perfusion ; 35(3): 190-196, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31470766

RESUMO

Since 2011, invasive infections due to Mycobacterium chimaera have been diagnosed in patients with previous cardiac surgery. The use of heating/cooling devices (heater-cooler units), necessary to regulate the blood temperature in extra-corporeal circulation, has been identified as a source of contaminated aerosol. Adhering to a strict maintenance program according to the manufacturer's instructions for use including sanitizing is essential to reduce the risk. Current manufacturer guidelines and national recommendations for detection and decontamination of Mycobacterium chimaera and other non-tuberculosis mycobacteria should organically update units' policies and protocols as they are published.


Assuntos
Ponte Cardiopulmonar/efeitos adversos , Contaminação de Equipamentos/estatística & dados numéricos , Mycobacterium/patogenicidade , Guias como Assunto , Humanos
9.
J Neurooncol ; 144(1): 211-216, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31273578

RESUMO

PURPOSE: Patients with relapse of recurrent glioma have a poor outcome and limited treatment options. The aim of this study is to investigate the clinical benefit and tolerability of weekly intravenous administration of carboplatin-based monotherapy in adult glioma patients who had progressed from previous chemotherapy lines based on temozolomide and nitrosoureas. METHODS: This was a single-arm, phase II study. Eligibility criteria included progressive or recurrent glioma after radiotherapy and chemotherapy-based treatments and Karnofsky performance status (KPS) > 60. RESULTS: Thirty-two patients (median age 43.5 years) were enrolled to receive weekly carboplatin monotherapy in an intravenous method of administration. The median duration of response was 7.3 months with an overall disease control rate of 31.3%. Median progression-free survival was 2.3 months while overall survival was 5.5 months. Pre-treatment with corticosteroids (i.e. dexamethasone) was associated to clinical benefit in 43.8% of patients. Patients achieving clinical benefit exhibited a longer progression-free survival (4.6 vs. 1.5 months; p > 0.001) and overall survival (7.9 vs. 3.2 months; p = 0.041) compared with those not achieving clinical benefit. CONCLUSIONS: Our findings show that single agent, weekly, intravenous administration of carboplatin may have a role in patients with recurrent glioma and suggest that pre-treatment with corticosteroids may confer survival benefit.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Carboplatina/uso terapêutico , Glioma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Terapia de Salvação , Adulto , Idoso , Neoplasias Encefálicas/patologia , Feminino , Seguimentos , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Taxa de Sobrevida , Adulto Jovem
10.
J Neurooncol ; 145(1): 189, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31502041

RESUMO

In the original article, the names of authors Mariantonia Carosi and Tatiana Koudriavtseva were incorrectly captured, and author Francesco Cognetti's affiliation was incorrect. The information is correctly shown here.

11.
Future Oncol ; 15(8): 841-850, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30656982

RESUMO

AIM: This single-center study evaluated the effect of comorbidities on progression-free and overall survival in elderly patients with glioblastoma multiforme (GBM). PATIENTS & METHODS: Comorbid conditions were identified in each patient with the modified version of the cumulative illness rating scale (CIRS). RESULTS:  Total of 118 patients with GBM were enrolled. An age of >75 years at diagnosis, high CIRS, comorbidity index and performance status play a predictive role on survival. CONCLUSION: Comorbidities play an important prognostic role in elderly patients with GBM, a factor too often neglected in clinical practice. If the prognostic role of comorbidity measured by CIRS on outcome will be confirmed, it would be interesting to add it in the algorithm for treatment choice in elderly GBM patients.


Assuntos
Neoplasias Encefálicas/epidemiologia , Glioblastoma/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/terapia , Comorbidade , Feminino , Glioblastoma/terapia , Humanos , Masculino , Prognóstico , Intervalo Livre de Progressão , Análise de Sobrevida
12.
J Water Health ; 17(3): 490-498, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31095523

RESUMO

Although in Europe the quality of swimming pools (SPs) is dictated by regulations, microbiological and chemical hazards are described in the literature. Environmental bacteria or toxic disinfection by-product (DBP) compounds may indeed be recovered in waters even after disinfection. We evaluated the water quality from 26 outdoor seasonal SPs of the Versilia district, according to requirements of Regional Decree 54R/2015. In spring 2017, supply and reinstatement waters were collected after shock hyperchlorination (10 mg/L) while in summertime, a second sampling of waters before entering the pools, as well as in the pools, was performed after SPs were open to the public. In all samples, microbiological and chemical parameters were determined as defined by Directive 98/83/EC and the Italian Health Ministry. Microbiological data were within suggested limits. The first chemical analyses showed that in 35% of the feeding-pool seawater samples, the halogenated organic compounds were higher than the maximum permissible concentrations (30 µg/L). Pool waters were then dechlorinated and re-treated with hydrogen peroxide (10 mg/L) to ensure the abatement of DBPs (from 164 ± 107 to 0.9 ± 0.8 µg/L; p = 0.002). Results highlighted the need of self-controlled procedures for the SPs waters to prevent waterborne diseases and suggested hydrogen peroxide as the most appropriate disinfection method.


Assuntos
Desinfetantes/análise , Piscinas/estatística & dados numéricos , Poluentes Químicos da Água/análise , Desinfecção , Itália , Estações do Ano
13.
J Transl Med ; 16(1): 22, 2018 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-29402328

RESUMO

BACKGROUND: An extensive crosstalk co-regulates the Hippo and Wnt pathway. Preclinical studies revealed that the Hippo transducers YAP/TAZ mediate a number of oncogenic functions in gastric cancer (GC). Moreover, comprehensive characterization of GC demonstrated that the Wnt pathway is targeted by oncogenic mutations. On this ground, we hypothesized that YAP/TAZ- and Wnt-related biomarkers may predict clinical outcomes in GC patients treated with chemotherapy. METHODS: In the present study, we included 86 patients with advanced GC treated with first-line chemotherapy in prospective phase II trials or in routine clinical practice. Tissue samples were immunostained to evaluate the expression of YAP/TAZ. Mutational status of key Wnt pathway genes (CTNNB1, APC and FBXW7) was assessed by targeted DNA next-generation sequencing (NGS). Survival curves were estimated and compared by the Kaplan-Meier product-limit method and the log-rank test, respectively. Variables potentially affecting progression-free survival (PFS) were verified in univariate Cox proportional hazard models. The final multivariate Cox models were obtained with variables testing significant at the univariate analysis, and by adjusting for all plausible predictors of the outcome of interest (PFS). RESULTS: We observed a significant association between TAZ expression and Wnt mutations (Chi-squared p = 0.008). Combined TAZ expression and Wnt mutations (TAZpos/WNTmut) was more frequently observed in patients with the shortest progression-free survival (negative outliers) (Fisher p = 0.021). Uni-and multivariate Cox regression analyses revealed that patients whose tumors harbored the TAZpos/WNTmut signature had an increased risk of disease progression (univariate Cox: HR 2.27, 95% CI 1.27-4.05, p = 0.006; multivariate Cox: HR 2.73, 95% CI 1.41-5.29, p = 0.003). Finally, the TAZpos/WNTmut signature negatively impacted overall survival. CONCLUSIONS: Collectively, our findings indicate that the oncogenic YAP/TAZ-Wnt crosstalk may be active in GC, conferring chemoresistant traits that translate into adverse survival outcomes.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Mutação/genética , Proteínas Serina-Treonina Quinases/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Via de Sinalização Wnt/genética , Idoso , Biomarcadores Tumorais/metabolismo , Feminino , Via de Sinalização Hippo , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Análise de Sobrevida , Transativadores , Fatores de Transcrição , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional , Resultado do Tratamento
14.
J Transl Med ; 16(1): 247, 2018 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-30180862

RESUMO

We have previously reported that nuclear expression of the Hippo transducer TAZ in association with Wnt pathway mutations negatively impacts survival outcomes in advanced gastric cancer (GC) patients. Here, we extended these previous findings by investigating another oncogenic cooperation, namely, the interplay between YAP, the TAZ paralogue, and p53. The molecular output of the YAP-p53 cooperation is dependent on TP53 mutational status. In the absence of mutations, the YAP-p53 crosstalk elicits a pro-apoptotic response, whereas in the presence of TP53 mutations it activates a pro-proliferative transcriptional program. In order to study this phenomenon, we re-analyzed data from 83 advanced GC patients treated with chemotherapy whose tissue samples had been characterized for YAP expression (immunohistochemistry, IHC) and TP53 mutations (deep sequencing). In doing so, we generated a molecular model combining nuclear YAP expression in association with TP53 missense variants (YAP+/TP53mut(mv)). Surprisingly, this signature was associated with a decreased risk of disease progression (multivariate Cox for progression-free survival: HR 0.53, 95% CI 0.30-0.91, p = 0.022). The YAP+/TP53mut(mv) model was also associated with better OS in the subgroup of patients who received chemotherapy beyond the first-line setting (multivariate Cox: HR 0.36, 95% CI 0.16-0.81, p = 0.013). Collectively, our findings suggest that the oncogenic cooperation between YAP and mutant p53 may translate into better survival outcomes. This apparent paradox can be explained by the pro-proliferative program triggered by YAP and mutant p53, that supposedly renders cancer cells more vulnerable to cytotoxic therapies.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Mutação de Sentido Incorreto , Fosfoproteínas/genética , Neoplasias Gástricas/genética , Proteína Supressora de Tumor p53/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adulto , Idoso , Antineoplásicos/uso terapêutico , Proliferação de Células , Progressão da Doença , Intervalo Livre de Doença , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Fosfoproteínas/metabolismo , Modelos de Riscos Proporcionais , Análise de Regressão , Neoplasias Gástricas/mortalidade , Fatores de Transcrição , Resultado do Tratamento , Proteína Supressora de Tumor p53/metabolismo , Proteínas de Sinalização YAP
15.
J Neurooncol ; 138(3): 527-535, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29594657

RESUMO

Bevacizumab (BV), a neutralizing monoclonal antibody against the vascular endothelial growth factor ligand, is recognized as a potent anti-angiogenic agent with antitumor activity. The aim of this single-center, retrospective, longitudinal study was to investigate the possible predictive value of baseline demographic, clinical and laboratory parameters for early 3-month response to BV therapy in patients with recurrent glioma. Forty-nine patients with recurrent glioma received BV at 10 mg/kg intravenously every 3 weeks alone or in association with chemotherapy were included in this study. Blood samples were collected from all patients before the first (baseline), the second and the third administration of BV. After 3 months of BV therapy, patients with partial response were defined as responders whereas patients with stable or progressive disease were defined as non-responders. The median overall follow-up was 8 months (range 1-73), the median overall survival (OS) was 8 months (95% CI 6-10) and the median progression free survival (PFS) was 4 months (95% CI 3-5). Thirty-five % of patients were responders and showed significantly lower von Willebrand factor (VWF) levels than non-responders at all sample times (p < .02 for all). Also, on multivariate analysis the baseline VWF value was the only predictor for an early response to BV therapy. Furthermore, D-dimer and prothrombin fragment 1+2 were predictive factors for OS while Karnofsky performance status resulted predictive for PFS. VWF antigen value is a possible predictive biomarker for an early 3-month response to BV therapy in recurrent glioma.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Fator de von Willebrand/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/sangue , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/mortalidade , Feminino , Seguimentos , Glioma/sangue , Glioma/mortalidade , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/mortalidade , Dados Preliminares , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo , Adulto Jovem
16.
Environ Res ; 166: 55-60, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29864633

RESUMO

Risk assessment, environmental monitoring, and the disinfection of water systems are the key elements in preventing legionellosis risk. The Italian Study Group of Hospital Hygiene of the Italian Society of Hygiene, Preventive Medicine, and Public Health and the Italian Multidisciplinary Society for the Prevention of Health Care-Associated Infections carried out a national cross-sectional survey to investigate the measures taken to prevent and control legionellosis in Italian hospitals. A multiple-choice questionnaire was developed, comprising 71 questions regarding hospital location, general characteristics, clinical and environmental surveillance, and control and preventive measures for legionellosis in 2015. Overall, 739 hospitals were enrolled from February to June 2017, and 178 anonymous questionnaires were correctly completed and evaluated (response rate: 24.1%). The survey was conducted using the SurveyMonkey® platform, and the data were analyzed using Stata 12 software. Of the participating hospitals, 63.2% reported at least one case of legionellosis, of which 28.2% were of proven nosocomial origin. The highest case numbers were reported in the Northern Italy, in hospitals with a pavilion structure or cooling towers, and in hospitals with higher numbers of beds, wards and operating theaters. Laboratory diagnosis was performed using urinary antigen testing alone (31.9%), both urinary antigen testing and single antibody titer (17.8%), or with seroconversion also added (21.5%). Culture-based or molecular investigations were performed in 28.8% and 22.1% of the clinical specimens, respectively. The water systems were routinely tested for Legionella in 97.4% of the hospitals, 62% of which detected a positive result (> 1000 cfu/L). Legionella pneumophila serogroup 2-15 was the most frequently isolated species (58.4%). The most common control measures were the disinfection of the water system (73.7%), mostly through thermal shock (37.4%) and chlorine dioxide (34.4%), and the replacement (69.7%) or cleaning (70.4%) of faucets and showerheads. A dedicated multidisciplinary team was present in 52.8% of the hospitals, and 73% of the hospitals performed risk assessment. Targeted training courses were organized in 36.5% of the hospitals, involving nurses (30.7%), physicians (28.8%), biologists (21.5%), technicians (26.4%), and cleaners (11%). Control and prevention measures for legionellosis are present in Italian hospitals, but some critical aspects should be improved. More appropriate risk assessment is necessary, especially in large facilities with a high number of hospitalizations. Moreover, more sensitive diagnostic tests should be used, and dedicated training courses should be implemented.


Assuntos
Controle de Infecções/métodos , Legionella pneumophila/isolamento & purificação , Legionelose/prevenção & controle , Abastecimento de Água , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Estudos Transversais , Desinfecção , Humanos , Itália/epidemiologia , Legionelose/epidemiologia , Inquéritos e Questionários , Microbiologia da Água
17.
J Water Health ; 16(3): 425-434, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29952331

RESUMO

Italian Directives recommend the good quality of natural mineral waters but literature data assert a potential risk from microorganisms colonizing wellsprings and mineral water bottling plants. We evaluated the presence of microorganisms in spring waters (SW) and bottled mineral waters (BMW) samples. Routine microbiological indicators, additional microorganisms like Legionella spp., Nontuberculous mycobacteria (NTM) and amoebae (FLA) were assessed in 24 SW and 10 BMW samples performing cultural and molecular methods. In 33 out of 34 samples, no cultivable bacteria ≥10 CFU/L was found. Cultivable FLA were detected in 50% of water samples. qPCR showed the presence of Legionella qPCR units in 24% of samples (from 1.1 × 102 to 5.8 × 102 qPCR units/L) and NTM qPCR units in 18% of samples (from 1 × 102 to 1 × 105 qPCR units/L). Vermamoeba vermiformis and Acanthamoeba polyphaga were recovered respectively in 70% of BMW samples (counts from 1.3 × 103 to 1.2 × 105 qPCR units/L) and 42% of SW samples (from 1.1 × 103 to 1.3 × 104 qPCR units/L). Vahlkampfia spp. was detected in 42% of SW and 70% of BMW samples (from 1.2 × 103 to 1.2 × 105 qPCR units/L). Considering the presence of FLA, we underline the importance of a wider microbiological risk assessment in natural mineral waters despite the absence of cultivable bacteria.


Assuntos
Água Potável/microbiologia , Águas Minerais/microbiologia , Microbiologia da Água , Qualidade da Água/normas , Amoeba , Água Potável/parasitologia , Itália , Legionella , Águas Minerais/parasitologia , Micobactérias não Tuberculosas
18.
Int J Cancer ; 140(11): 2587-2595, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28233295

RESUMO

The DNA damage response (DDR) network is exploited by cancer cells to withstand chemotherapy. Gastric cancer (GC) carries deregulation of the DDR and harbors genetic defects that fuel its activation. The ATM-Chk2 and ATR-Chk1-Wee1 axes are deputed to initiate DNA repair. Overactivation of these pathways in cancer cells may represent an adaptive response for compensating genetic defects deregulating G1 -S transition (e.g., TP53) and ATM/ATR-initiated DNA repair (e.g., ARID1A). We hypothesized that DDR-linked biomarkers may predict clinical outcomes in GC patients treated with chemotherapy. Immunohistochemical assessment of DDR kinases (pATM, pChk2, pChk1 and pWee1) and DNA damage markers (γ-H2AX and pRPA32) was performed in biological samples from 110 advanced GC patients treated with first-line chemotherapy, either in phase II trials or in routine clinical practice. In 90 patients, this characterization was integrated with targeted ultra-deep sequencing for evaluating the mutational status of TP53 and ARID1A. We recorded a positive association between the investigated biomarkers. The combination of two biomarkers (γ-H2AXhigh /pATMhigh ) was an adverse factor for both progression-free survival (multivariate Cox: HR 2.23, 95%CI: 1.47-3.40) and overall survival (multivariate Cox: HR: 2.07, 95%CI: 1.20-3.58). The relationship between the γ-H2AXhigh /pATMhigh model and progression-free survival was consistent across the different TP53 backgrounds and was maintained in the ARID1A wild-type setting. Conversely, this association was no longer observed in an ARID1A-mutated subgroup. The γ-H2AXhigh /pATMhigh model negatively impacted survival outcomes in GC patients treated with chemotherapy. The mutational status of ARID1A, but apparently not TP53 mutations, affects its predictive significance.


Assuntos
Antineoplásicos/uso terapêutico , Dano ao DNA/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Idoso , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Biomarcadores Tumorais/metabolismo , Proteínas de Ciclo Celular , Proteínas de Ligação a DNA/metabolismo , Intervalo Livre de Doença , Feminino , Mucosa Gástrica/metabolismo , Histonas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estômago/efeitos dos fármacos , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo
19.
BMC Public Health ; 17(1): 233, 2017 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-28264671

RESUMO

BACKGROUND: Lifestyles profoundly determine the quality of an individual's health and life since his childhood. Many diseases in adulthood are avoidable if health-risk behaviors are identified and improved at an early stage of life. The aim of the present research was to characterize a cohort of children aged 6-8 years selected in order to perform an epidemiological molecular study (the MAPEC_LIFE study), investigate lifestyles of the children that could have effect on their health status, and assess possible association between lifestyles and socio-cultural factors. METHODS: A questionnaire composed of 148 questions was administered in two different seasons to parents of children attending 18 primary schools in five Italian cities (Torino, Brescia, Pisa, Perugia and Lecce) to obtain information regarding the criteria for exclusion from the study, demographic, anthropometric and health information on the children, as well as some aspects on their lifestyles and parental characteristics. The results were analyzed in order to assess the frequency of specific conditions among the different seasons and cities and the association between lifestyles and socio-economic factors. RESULTS: The final cohort was composed of 1,164 children (50.9 boys, 95.4% born in Italy). Frequency of some factors appeared different in terms of the survey season (physical activity in the open air, the ways of cooking certain foods) and among the various cities (parents' level of education and rate of employment, sport, traffic near the home, type of heating, exposure to passive smoking, ways of cooking certain foods). Exposure to passive smoking and cooking fumes, obesity, residence in areas with heavy traffic, frequency of outdoor play and consumption of barbecued and fried foods were higher among children living in families with low educational and/or occupational level while children doing sports and consuming toasted bread were more frequent in families with high socio-economic level. CONCLUSIONS: The socio-economic level seems to affect the lifestyles of children enrolled in the study including those that could cause health effects. Many factors are linked to the geographical area and may depend on environmental, cultural and social aspects of the city of residence.


Assuntos
Cidades/estatística & dados numéricos , Características da Família , Nível de Saúde , Estilo de Vida , Fatores Socioeconômicos , Criança , Estudos de Coortes , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Itália , Masculino , Pais , Estações do Ano , Inquéritos e Questionários , Poluição por Fumaça de Tabaco
20.
BMC Public Health ; 14: 970, 2014 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-25236852

RESUMO

BACKGROUND: The Italian Study Group on Hospital Hygiene of the Italian Society of Hygiene, Preventive Medicine and Public Health conducted a multicentre survey aiming to evaluate undergraduate health care students' knowledge of tuberculosis and tuberculosis control measures in Italy. METHODS: In October 2012-June 2013, a sample of medical and nursing students from 15 Italian universities were enrolled on a voluntary basis and asked to complete an anonymous questionnaire investigating both general knowledge of tuberculosis (aetiology, clinical presentation, outcome, screening methods) and personal experiences and practices related to tuberculosis prevention. Data were analysed through multivariable regression using Stata software. RESULTS: The sample consisted of 2,220 students in nursing (72.6%) and medicine (27.4%) courses. Our findings clearly showed that medical students had a better knowledge of tuberculosis than did nursing students.Although the vast majority of the sample (up to 95%) answered questions about tuberculosis aetiology correctly, only 60% of the students gave the correct responses regarding clinical aspects and vaccine details. Overall, 66.9% of the students had been screened for tuberculosis, but less than 20% of those with a negative result on the tuberculin skin test were vaccinated. Multivariable regression analysis showed that age and type of study programme (nursing vs. medical course) were determinants of answering the questions correctly. CONCLUSIONS: Although our data showed sufficient knowledge on tuberculosis, this survey underlines the considerable need for improvement in knowledge about the disease, especially among nursing students. In light of the scientific recommendations concerning tuberculosis knowledge among students, progress of current health care curricula aimed to develop students' skills in this field is needed.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Estudantes de Medicina/estatística & dados numéricos , Estudantes de Enfermagem/estatística & dados numéricos , Tuberculose/psicologia , Adulto , Estudos Transversais , Feminino , Humanos , Itália , Masculino , Inquéritos e Questionários , Universidades , Adulto Jovem
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