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1.
Virchows Arch ; 484(5): 777-788, 2024 May.
Article in English | MEDLINE | ID: mdl-38168015

ABSTRACT

Pulmonary large cell carcinoma (LCC) is an undifferentiated neoplasm lacking morphological, histochemical, and immunohistochemical features of small cell lung cancer, adenocarcinoma (ADC), or squamous cell carcinoma (SCC). The available molecular information on this rare disease is limited. This study aimed to provide an integrated molecular overview of 16 cases evaluating the mutational asset of 409 genes and the transcriptomic profiles of 20,815 genes. Our data showed that TP53 was the most frequently inactivated gene (15/16; 93.7%) followed by RB1 (5/16; 31.3%) and KEAP1 (4/16; 25%), while CRKL and MYB genes were each amplified in 4/16 (25%) cases and MYC in 3/16 (18.8%) cases; transcriptomic analysis identified two molecular subtypes including a Pure-LCC and an adenocarcinoma like-LCC (ADLike-LCC) characterized by different activated pathways and cell of origin. In the Pure-LCC group, POU2F3 and FOXI1 were distinctive overexpressed markers. A tuft cell-like profile and the enrichment of a replication stress signature, particularly involving ATR, was related to this profile. Differently, the ADLike-LCC were characterized by an alveolar-cell transcriptomic profile and association with AIM2 inflammasome complex signature. In conclusion, our study split the histological marker-null LCC into two different transcriptomic entities, with POU2F3, FOXI1, and AIM2 genes as differential expression markers that might be probed by immunohistochemistry for the differential diagnosis between Pure-LCC and ADLike-LCC. Finally, the identification of several signatures linked to replication stress in Pure-LCC and inflammasome complex in ADLike-LCC could be useful for designing new potential therapeutic approaches for these subtypes.


Subject(s)
Biomarkers, Tumor , Carcinoma, Large Cell , Lung Neoplasms , Transcriptome , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Biomarkers, Tumor/genetics , Biomarkers, Tumor/analysis , Aged , Middle Aged , Female , Carcinoma, Large Cell/genetics , Carcinoma, Large Cell/pathology , Carcinoma, Large Cell/therapy , Gene Expression Profiling , Mutation , Aged, 80 and over
2.
J Environ Manage ; 350: 119651, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38039704

ABSTRACT

Tropical forests provide ecosystem services to around 2.7 billion people. Yet they are reaching tipping points due to social, economic, and environmental pressures. Technology is increasingly being leveraged to expand Community Forest Management (CFM) monitoring capabilities and to potentially increase its effectiveness, but a systematic accounting of this is lacking in the scientific literature. This study employed a mixed-methods approach combining a systematic literature review (SLR) with semi-structured interviews of technology-enhanced CFM (tech-CFM) case studies in tropical forests. From the SLR, evaluation criteria were identified and applied to 23 case studies that employed one or more novel technologies, 8 on the African continent, 9 in the Asia Pacific region, 5 in Latin America, and 1 in multiple regions. The results include classifying 22 monitoring technologies, with satellite remote sensing technology being the most common (17 case studies), followed by mobile devices (10 case studies), which are often integrated with geographic information system (8 case studies) analysis and data platforms. These technologies tend to be deployed in packages that augment each technology's capabilities, beyond their individual uses. Nonetheless, they are limited by poor internet coverage in remote regions, impeding the ability to develop real-time integrated monitoring systems. Tech-CFM shows potential for complementing and integrating with national monitoring system when adequate data collection protocols are in place. Practical social-cultural, technical, and project design recommendations are made for the integration of technology into CFM. Finally, a multi-criteria decision-making framework is developed from the literature-based evaluation criteria to assist practitioners in selecting appropriate technology suites.


Subject(s)
Conservation of Natural Resources , Ecosystem , Humans , Conservation of Natural Resources/methods , Forests , Remote Sensing Technology/methods , Geographic Information Systems
3.
J Immunother Cancer ; 11(6)2023 06.
Article in English | MEDLINE | ID: mdl-37286305

ABSTRACT

BACKGROUND: Chemoimmunotherapy represents the standard of care for patients with advanced non-small cell lung cancer (NSCLC) and programmed death-ligand 1 (PD-L1) <50%. Although single-agent pembrolizumab has also demonstrated some activity in this setting, no reliable biomarkers yet exist for selecting patients likely to respond to single-agent immunotherapy. The main purpose of the study was to identify potential new biomarkers associated with progression-free-survival (PFS) within a multiomics analysis. METHODS: PEOPLE (NTC03447678) was a prospective phase II trial evaluating first-line pembrolizumab in patients with advanced EGFR and ALK wild type treatment-naïve NSCLC with PD-L1 <50%. Circulating immune profiling was performed by determination of absolute cell counts with multiparametric flow cytometry on freshly isolated whole blood samples at baseline and at first radiological evaluation. Gene expression profiling was performed using nCounter PanCancer IO 360 Panel (NanoString) on baseline tissue. Gut bacterial taxonomic abundance was obtained by shotgun metagenomic sequencing of stool samples at baseline. Omics data were analyzed with sequential univariate Cox proportional hazards regression predicting PFS, with Benjamini-Hochberg multiple comparisons correction. Biological features significant with univariate analysis were analyzed with multivariate least absolute shrinkage and selection operator (LASSO). RESULTS: From May 2018 to October 2020, 65 patients were enrolled. Median follow-up and PFS were 26.4 and 2.9 months, respectively. LASSO integration analysis, with an optimal lambda of 0.28, showed that peripheral blood natural killer cells/CD56dimCD16+ (HR 0.56, 0.41-0.76, p=0.006) abundance at baseline and non-classical CD14dimCD16+monocytes (HR 0.52, 0.36-0.75, p=0.004), eosinophils (CD15+CD16-) (HR 0.62, 0.44-0.89, p=0.03) and lymphocytes (HR 0.32, 0.19-0.56, p=0.001) after first radiologic evaluation correlated with favorable PFS as well as high baseline expression levels of CD244 (HR 0.74, 0.62-0.87, p=0.05) protein tyrosine phosphatase receptor type C (HR 0.55, 0.38-0.81, p=0.098) and killer cell lectin like receptor B1 (HR 0.76, 0.66-0.89, p=0.05). Interferon-responsive factor 9 and cartilage oligomeric matrix protein genes correlated with unfavorable PFS (HR 3.03, 1.52-6.02, p 0.08 and HR 1.22, 1.08-1.37, p=0.06, corrected). No microbiome features were selected. CONCLUSIONS: This multiomics approach was able to identify immune cell subsets and expression levels of genes associated to PFS in patients with PD-L1 <50% NSCLC treated with first-line pembrolizumab. These preliminary data will be confirmed in the larger multicentric international I3LUNG trial (NCT05537922). TRIAL REGISTRATION NUMBER: 2017-002841-31.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , B7-H1 Antigen/metabolism , Multiomics , Prospective Studies , Biomarkers
4.
Histopathology ; 82(2): 324-339, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36239545

ABSTRACT

WHO classification of Thoracic Tumours defines lung carcinoid tumours (LCTs) as well-differentiated neuroendocrine neoplasms (NENs) classified in low grade typical (TC) and intermediate grade atypical carcinoids (AC). Limited data exist concerning protein expression and morphologic factors able to predict disease aggressiveness. Though Ki-67 has proved to be a powerful diagnostic and prognostic factor for Gastro-entero-pancreatic NENs, its role in lung NENs is still debated. A retrospective series of 370 LCT from two oncology centers was centrally reviewed. Morphology and immunohistochemical markers (Ki-67, TTF-1, CD44, OTP, SSTR-2A, Ascl1, and p53) were studied and correlated with Overall Survival (OS), Cancer-specific survival (CSS) and Disease-free survival (DFS). Carcinoid histology was confirmed in 355 patients: 297 (83.7%) TC and 58 (16.3%) AC. Ki-67 at 3% was the best value in predicting DFS. Ki-67 ≥ 3% tumours were significantly associated with AC histology, stage III-IV, smoking, vascular invasion, tumour spread through air spaces OTP negativity, and TTF-1, Ascl1 and p53 positivity. After adjustment for center and period of diagnosis, both Ki-67 (≥3 versus <3) and histology (AC versus TC) alone significantly added prognostic information to OS and CSS multivariable model with age, stage and OTP; addition of both variables did not provide further prognostic information. Conversely, an improved significance of the DFS prediction model at multivariate analysis was seen by adding Ki-67 (≥3 versus <3, P adj = 0.01) to TC and AC histological distinction, age, lymph node involvement, residual tumour and OTP. Ki-67 ≥ 3% plays a potentially pivotal role in LCT prognosis, irrespective of histological grade.


Subject(s)
Carcinoid Tumor , Tumor Suppressor Protein p53 , Humans , Ki-67 Antigen , Retrospective Studies , Lung
5.
Tumori ; 109(1): 86-96, 2023 Feb.
Article in English | MEDLINE | ID: mdl-34719290

ABSTRACT

BACKGROUND: Implant-based breast reconstruction in the setting of radiotherapy often leads to higher complications rates (mainly capsular contracture and wound dehiscence) and poor cosmetic outcomes. We hypothesized that the combination of pulsed-electron avalanche knife (PEAK) PlasmaBlade (a pulsed radiofrequency electrosurgery) and acellular dermal matrix Veritas® in postmastectomy radiotherapy implant-based breast reconstruction could result in lower complications rate, better reconstructive results, and patient satisfaction. METHODS: A prospective observational study focused on the use of PEAK PlasmaBlade in implant-based breast reconstruction and radiotherapy was carried out in the Plastic Reconstructive Surgery Unit at Fondazione IRCCS Istituto Nazionale Tumori Milano between December 2017 and 2019 (2017-2018: enrollment; 2018-2019: follow-up). Patient demographics were queried and complication rates and patient and surgeon satisfaction were assessed. RESULTS: A total of 88 patients were enrolled; 2 patients received bilateral reconstruction, leading to a total of 90 procedures. Sixty-two women received contralateral symmetrization. Seroma was the most frequent minor complication (8.8%); implant exposure was the most recorded among major complications (5.5%). Preoperative lipofilling was the most substantial protective factor for preventing complications (p < 0.001). A significant association between capsular thermal damage thickness and the type of electrosurgery used (traditional electrosurgery vs PEAK PlasmaBlade) was observed, with lower values with PEAK PlasmaBlade (p < 0.0001). CONCLUSIONS: Our protocol results in low rates of surgical complications and a high level of patient and surgeon satisfaction although longer follow-up is needed.


Subject(s)
Breast Neoplasms , Mammaplasty , Humans , Female , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Electrons , Mastectomy/adverse effects , Retrospective Studies , Mammaplasty/adverse effects , Mammaplasty/methods , Postoperative Complications/etiology , Follow-Up Studies
6.
Cancers (Basel) ; 14(19)2022 Sep 24.
Article in English | MEDLINE | ID: mdl-36230576

ABSTRACT

BACKGROUND: Combined large cell neuroendocrine carcinoma (CoLCNEC) is given by the association of LCNEC with adeno or squamous or any non-neuroendocrine carcinoma. Molecular bases of CoLCNEC pathogenesis are scant and no standardized therapies are defined. METHODS: 44 CoLCNECs: 26 with adenocarcinoma (CoADC), 7 with squamous cell carcinoma (CoSQC), 3 with small cell carcinoma (CoSCLC), 4 with atypical carcinoid (CoAC) and 4 napsin-A positive LCNEC (NapA+), were assessed for alterations in 409 genes and transcriptomic profiling of 20,815 genes. RESULTS: Genes altered included TP53 (n = 30), RB1 (n = 14) and KRAS (n = 13). Targetable alterations included six KRAS G12C mutations and ALK-EML4 fusion gene. Comparison of CoLCNEC transcriptomes with 86 lung cancers of pure histology (8 AC, 19 ADC, 19 LCNEC, 11 SCLC and 29 SQC) identified CoLCNEC as a separate entity of neuroendocrine tumours with three different molecular profiles, two of which showed a non-neuroendocrine lineage. Hypomethylation, activation of MAPK signalling and association to immunotherapy signature specifically characterized each of three CoLCNEC molecular clusters. Prognostic stratification was also provided. CONCLUSIONS: CoLCNECs are an independent histologic category. Our findings support the extension of routine evaluation of KRAS mutations, fusion genes and immune-related markers to offer new perspectives in the therapeutic management of CoLCNEC.

7.
Clin Lung Cancer ; 23(1): e17-e28, 2022 01.
Article in English | MEDLINE | ID: mdl-34334296

ABSTRACT

BACKGROUND: Immune-checkpoint inhibitors (ICIs) have significantly improved outcome of advanced non-small cell lung cancer (aNSCLC) patients. However, their efficacy remains uncertain in uncommon histologies (UH). MATERIALS AND METHODS: Data from ICI treated aNSCLC patients (April,2013-January,2021) in one Institution were retrospectively collected. Univariate and multivariate survival analyses were estimated by Kaplan-Meier and Cox proportional hazards regression model, respectively. Objective response rate (ORR) and disease control rate (DCR) were assessed. RESULTS: Of 375 patients, 79 (21.1%) had UH: 19 (24.1%) sarcomatoid carcinoma, 15 (19.0%) mucinous adenocarcinoma, 10 (12.6%) enteric adenocarcinoma, 8 (10.1%) adenocarcinoma not otherwise specified, 7 (8.9%) large-cell neuroendocrine carcinoma, 6 (7.6%) mixed histology non-adenosquamous, 5 (6.3%) adenosquamous carcinoma, 9 (11.4%) other UH. In UH group, programmed death-ligand 1 (PD-L1) <1%, 1-49%, ≥50% and unknown expression were reported in 27.8%, 22.8%, 31.7% and 17.7% patients respectively and ICI was the second/further-line in the majority of patients. After a median follow-up of 35.64 months (m), median progression-free survival (mPFS) was 2.5 m in UH [95% CI 2.2-2.9 m] versus (vs.) 2.7 m in CH [95% CI 2.3-3.2 m, P-value = .584]; median overall survival (mOS) was 8.8 m [95% CI 4.9-12.6 m] vs. 9.7 m [95% CI 8.0-11.3 m, P-value = .653]. At multivariate analyses only ECOG PS was a confirmed prognostic factor in UH. ORR and DCR were 25.3% and 40.5% in UH vs. 21.6% and 49.5% in CH [P-value = .493 and .155 respectively]. CONCLUSIONS: No significant differences were detected between UH and CH groups. Prospective trials are needed to understand ICIs role in UH population.


Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Immune Checkpoint Inhibitors/pharmacology , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Survival Analysis
8.
Clin Nutr ; 41(12): 2980-2987, 2022 12.
Article in English | MEDLINE | ID: mdl-34353669

ABSTRACT

BACKGROUND & AIMS: To investigate the association between the parameters used in nutritional screening assessment (body mass index [BMI], unintentional weight loss [WL] and reduced food intake) and clinical outcomes in non-critically ill, hospitalized coronavirus disease 2019 (COVID-19) patients. METHODS: This was a prospective multicenter real-life study carried out during the first pandemic wave in 11 Italian Hospitals. In total, 1391 patients were included. The primary end-point was a composite of in-hospital mortality or admission to ICU, whichever came first. The key secondary end-point was in-hospital mortality. RESULTS: Multivariable models were based on 1183 patients with complete data. Reduced self-reported food intake before hospitalization and/or expected by physicians in the next days since admission was found to have a negative prognostic impact for both the primary and secondary end-point (P < .001 for both). No association with BMI and WL was observed. Other predictors of outcomes were age and presence of multiple comorbidities. A significant interaction between obesity and multi-morbidity (≥2) was detected. Obesity was found to be a risk factor for composite end-point (HR = 1.36 [95%CI, 1.03-1.80]; P = .031) and a protective factor against in-hospital mortality (HR = 0.32 [95%CI, 0.20-0.51]; P < .001) in patients with and without multiple comorbidities, respectively. Secondary analysis (patients, N = 829), further adjusted for high C-reactive protein (>21 mg/dL) and LDH (>430 mU/mL) levels yielded consistent findings. CONCLUSIONS: Reduced self-reported food intake before hospitalization and/or expected by physicians in the next days since admission was associated with negative clinical outcomes in non-critically ill, hospitalized COVID-19 patients. This simple and easily obtainable parameter may be useful to identify patients at highest risk of poor prognosis, who may benefit from prompt nutritional support. The presence of comorbidities could be the key factor, which may determine the protective or harmful role of a high body mass index in COVID-19.


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , Prospective Studies , Nutritional Status , Nutrition Assessment , Obesity/complications , Hospitalization , Prognosis
9.
Sci Rep ; 11(1): 22892, 2021 11 24.
Article in English | MEDLINE | ID: mdl-34819555

ABSTRACT

Clinical and prognostic differences between symptomatic and asymptomatic older patients with COVID-19 are of great interest since frail patients often show atypical presentation of illness. Lung Ultrasound (LUS) has been proven to be a reliable tool for detecting early-phase COVID-19 pneumonic alterations. The current prospective bicentric study aimed to compare LUS score and 3-month overall mortality between asymptomatic and symptomatic older patients with COVID-19, according to frailty status. Patients were stratified according to LUS score tertiles and Clinical Frailty Scale categories. Survival rate was assessed by telephone interviews 3 months after discharge. 64 symptomatic (24 women, aged 80.0 ± 10.8 years) and 46 asymptomatic (31 women, aged 84.3 ± 8.8 years) were consecutively enrolled. LUS score resulted an independent predictor of 3-month mortality [OR 2.27 (CI95% 1.09-4.8), p = 0.03], and the highest mortality rate was observed in symptomatic and asymptomatic pre-frail and frail patients (70.6% and 66.7%, respectively) with greater LUS abnormalities (3rd tertile). In conclusion, LUS identified an acute interstitial lung involvement in most of the older asymptomatic patients. Mortality rate progressively increased according to clinical frailty and LUS score degree, resulting a reliable prognostic tool in both symptomatic and asymptomatic patients.


Subject(s)
COVID-19/diagnostic imaging , COVID-19/mortality , Pneumonia/diagnostic imaging , Aged , Aged, 80 and over , Asymptomatic Diseases/epidemiology , COVID-19/complications , Female , Hospitalization , Humans , Lung/diagnostic imaging , Lung/pathology , Male , Pneumonia/immunology , Prognosis , Prospective Studies , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Tomography, X-Ray Computed/methods , Ultrasonography/methods
10.
Transl Lung Cancer Res ; 9(5): 1940-1951, 2020 Oct.
Article in English | MEDLINE | ID: mdl-33209614

ABSTRACT

BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive tumor but approximately 12% of patients survive more than 3 years. The biological differences underlying better outcomes are not known. Several targeted agents and immunotherapy have been ineffective. Hedgehog (Hh) is one emerging pathway. We compared the biological profiles of patients with different survival, investigating the most frequently altered genes, including the Hh pathway. METHODS: We analyzed 56 MPM. A 36-month overall survival (OS) cut-off divided patients into 32 normo (NS) and 24 long (LS) survivors. We used next generation sequencing to test 21 genes, immunohistochemistry to evaluate SMO expression. Mutation differences between NS and LS and their associations with clinical features were analysed by Fisher's test, OS with the Kaplan-Meier method and its association with mutations by univariate and multivariate Cox proportional hazard models. RESULTS: Clinical features were similar in both groups. Eighteen out of 56 patients (32%) were wild-type for the genes analysed. At least five had mutations in BAP1, NF2, TP53, SMO and PTCH1 with no significant differences between the groups except for SMO. SMO, a member of the Hh pathway, was mutated only in NS (15.6%) and only SMO mutations were significantly associated with poor prognosis at univariate (HR =4.36, 95% CI: 2.32-8.18, P<0.0001) and multivariate (HR =9.2, 95% CI: 3.0-28.4, P=0.0001) analysis. All SMO mutated patients expressed high protein levels. CONCLUSIONS: SMO mutations were clearly associated with worse prognosis. SMO may be a therapeutic target but this needs to be confirmed in a prospective trial.

11.
J Clin Med ; 9(8)2020 Jul 30.
Article in English | MEDLINE | ID: mdl-32751518

ABSTRACT

Clinical data suggest that only a subgroup of non-small cell lung cancer (NSCLC) patients has long-term benefits after front-line platinum-based therapy. We prospectively investigate whether KRAS status and DNA polymerase ß expression could help identify patients responding to platinum compounds. Prospectively enrolled, advanced NSCLC patients treated with a first-line regimen containing platinum were genotyped for KRAS and centrally evaluated for DNA polymerase ß expression. Overall survival (OS), progression-free survival (PFS), and the objective response rate (ORR) were recorded. Patients with KRAS mutations had worse OS (hazard ratio (HR): 1.37, 95% confidence interval (95% CI): 0.70-2.27). Negative DNA polymerase ß staining identified a subgroup with worse OS than patients expressing the protein (HR: 1.43, 95% CI: 0.57-3.57). The addition of KRAS to the analyses further worsened the prognosis of patients with negative DNA polymerase ß staining (HR: 1.67, 95% CI: 0.52-5.56). DNA polymerase ß did not influence PFS and ORR. KRAS may have a negative role in platinum-based therapy responses in NSCLC, but its impact is limited. DNA polymerase ß, when not expressed, might indicate a group of patients with poor outcomes. KRAS mutations in tumors not expressing DNA polymerase ß further worsens survival. Therefore, these two biomarkers together might well identify patients for whom alternatives to platinum-based chemotherapy should be used.

12.
Lung Cancer ; 146: 66-69, 2020 08.
Article in English | MEDLINE | ID: mdl-32516667

ABSTRACT

Objectives - Rare tumors are diagnostic challenges for pathologists. Consultation or referral to Centers with expertise is crucial for the right diagnosis. This is particularly true for Thymic Epithelial Tumors (TETs), whose treatment strategies vary according to histological subgroup. We aimed at evaluating the accuracy of TET pathologic characterization in an Italian reference Center. Materials and methods - All the cases with diagnosis or suspicion of TETs, which underwent a pathological second opinion at Istituto Nazionale dei Tumori (INT), Milan, between 2015 and 2019 were retrospectively reviewed. All cases had been pathologically characterized through immunohistochemistry (IHC). Descriptive statistics were used for qualitative variables. Concordance was estimated through Cohen's kappa (k). Results - Out of 278 cases of TETs diagnosed in INT, 72 were referred to INT for a pathologic revision. The INT revision changed the diagnosis in 41 cases (56.9%), with a potential therapeutic shift in 32 (44.4%). In particular, 20 cases of thymoma were reviewed as a different subtype of thymoma (19/20) or lymphoma (1/20); nine cases of thymic carcinoma were reviewed as thymoma. On the other hand, three cases of lung carcinoma were reviewed as thymic carcinoma (2/3) or thymoma (1); eight cases of carcinoma Not Otherwise Specified were reviewed as thymic carcinoma; one case of lymphoma was reviewed as thymoma. Concordance between pathologists was moderate for thymoma (74.7%, k 0.447), inferior for thymic carcinoma (60.5%, k 0.139). Conclusion - A significant proportion of cases referred to INT for a presumptive TET received a different characterization. A potential shift in therapeutic indication was not rare. This underlines the importance for TETs to get a second pathological diagnosis by an expert pathologist and supports the need for networks on rare cancers.


Subject(s)
Lung Neoplasms , Neoplasms, Glandular and Epithelial , Thymus Neoplasms , Humans , Italy/epidemiology , Lung Neoplasms/diagnosis , Neoplasms, Glandular and Epithelial/diagnosis , Retrospective Studies , Thymus Neoplasms/diagnosis
13.
JMIR Mhealth Uhealth ; 8(6): e16165, 2020 06 08.
Article in English | MEDLINE | ID: mdl-32357123

ABSTRACT

BACKGROUND: Childhood obesity prevention is a public health priority in industrialized countries. The Reggio Emilia Local Health Authority has implemented a program involving primary and secondary prevention as well as the care of obese children. There are many health-promoting mobile apps, but few are targeted to children and very few are sponsored by public health agencies. OBJECTIVE: The goal of the research was to describe the process and tools adopted to cocreate a mobile app sponsored by the Reggio Emilia Local Health Authority to be installed in parents' phones aimed at promoting child health and preventing obesity. METHODS: After stakeholder mapping, a consulting committee including relevant actors, stakeholders, and users was formed. Key persons for childhood obesity prevention were interviewed, focus groups with parents and pediatricians were conducted, and community reporting storytelling was collected. The results of these activities were presented to the consulting committee in order to define the functionalities and contents of the mobile app. RESULTS: Three key trends emerged from community reporting: being active, playing, and being outdoors; time for oneself, family, and friends; and the pressures of life and work and not having time to be active and socialize. In focus groups, interviews, and labs, mothers showed a positive attitude toward using an app to manage their children's weight, while pediatricians expressed concerns that the app could increase their workload. When these findings were explored by the consulting committee, four key themes were extracted: strong relationships with peers, family members, and the community; access to safe outdoor spaces; children's need for age-appropriate independence; and professional support should be nonjudgmental and stigma-free. It should be a dialogue that promotes family autonomy. The app functions related to these needs include the following: (1) newsletter with anticipatory guidance, recipes, and vaccination and well-child visit reminders; (2) regional map indicating where physical activity can be done; (3) information on how to manage emergencies (eg, falls, burns, fever); (4) module for reinforcing the counseling intervention conducted by pediatricians for overweight children; and (5) a function to build a balanced daily diet. CONCLUSIONS: The pilot study we conducted showed that cocreation in health promotion is feasible, with the consulting committee being the key co-governance and cocreation tool. The involvement of stakeholders in this committee made it possible to expand the number of persons and institutions actively contributing to the project.


Subject(s)
Mobile Applications , Child , Female , Humans , Obesity , Pilot Projects , Research Design , Smartphone
14.
Nutrients ; 12(2)2020 Jan 21.
Article in English | MEDLINE | ID: mdl-31973152

ABSTRACT

BACKGROUND AND AIM: Excess sodium intake is a recognised causal factor of hypertension and its cardiovascular complications; there is however a lack of practical instruments to assess and monitor the level of knowledge and behaviour about dietary salt intake and to relate these factors to the population general dietary habits. METHODS AND RESULTS: A self-administered questionnaire was developed to assess the salt and health related knowledge and behaviour of the Italian population through an online survey. A sample of 11,618 Italian participants completed the questionnaire. The degree of knowledge and the reported behaviour about salt intake were both found to be related to age, gender, home region, level of education and occupation. There was a significant interrelation between salt knowledge and behaviour and both were significantly and directly related to the degree of adherence to a Mediterranean-like dietary pattern. A hierarchical evaluation was also made of the relevance of any single question to the overall assessment of knowledge and behaviour about salt intake. CONCLUSIONS: The study population overall appeared to have a decent level of knowledge about salt, but a less satisfactory behaviour. Our findings point to social inequalities and young age as the main factors having a negative impact on knowledge and behaviour about salt intake as part of generally inadequate dietary habits. The degrees of knowledge and behaviour were significantly and directly interrelated, confirming that improving knowledge is a key step for behavioural changes, and suggesting that educational campaigns are crucial for the implementation of good practices in nutrition.


Subject(s)
Diet, Healthy/psychology , Feeding Behavior/psychology , Health Knowledge, Attitudes, Practice , Sodium Chloride, Dietary/adverse effects , Adolescent , Adult , Aged , Female , Humans , Italy , Male , Middle Aged , Surveys and Questionnaires , Young Adult
15.
Ann Thorac Surg ; 109(3): e199-e201, 2020 03.
Article in English | MEDLINE | ID: mdl-31400331

ABSTRACT

A 71-year-old male former smoker was referred for worsening hemoptysis from a hilar left tumor without radiologic or bronchoscopic identification of the bleeding source. He underwent an urgent upper lobectomy extended to the pericardium and left phrenic nerve to control active bleeding. Histologic analysis revealed a malignant triton tumor, a rare aggressive subtype of malignant peripheral nerve sheath tumors. This is a case report of unusual pulmonary involvement associated with hemoptysis. Despite radical surgery and multimodal treatment with adjuvant chemotherapy the patient died of systemic dissemination 10 months after surgery, with a disease-free survival of 3 months.


Subject(s)
Lung Neoplasms/pathology , Neurofibrosarcoma/pathology , Aged , Diagnosis, Differential , Fatal Outcome , Hemoptysis/etiology , Humans , Lung Neoplasms/complications , Male , Neurofibrosarcoma/complications , Symptom Flare Up
16.
Epidemiol Prev ; 44(5-6 Suppl 1): 153-162, 2020.
Article in English | MEDLINE | ID: mdl-33415958

ABSTRACT

OBJECTIVES: to explain differences in effectiveness of paediatrician-led motivational interviewing (MI) in decreasing body mass index (BMI) between children of mothers with low or high education level. DESIGN: secondary analysis of a randomised control trial. SETTING AND PARTICIPANTS: individually randomized controlled trial previously conducted from 2011 to 2013 in the province of Reggio Emilia (Emilia-Romagna Region, Northern Italy). Eligible participants included in the trial were 372 (187 in the MI group and 185 in the control group) overweight children (BMI percentile >= 85th and < 95th) aged between 4 and 7 years, residing in the province of Reggio Emilia and under the care of paediatrician for >= 12 months. The intervention included 5 MI sessions based on the transtheoretical model of addiction and behavioural change delivered at 1, 4, 7, and 12 months after the baseline visit, when families had to define specific goals in changing physical activity (PA) and diet behaviours. MAIN OUTCOME MEASURES: primary: BMI score variation (ΔBMI) from baseline to 12 months; secondary: percentage of changes in parent-reported PA and dietary behaviours. RESULTS: a significant effect of MI on ΔBMI in children whose mothers had high education level (ΔBMI = -0.62; 95%CI -0.92;-0.32) were observed. Children of women with high education level in MI group had more improvements in set unstructured PA, decreasing screen time and sweet snacks consumption, while children with less educated mothers had improvements in consuming more vegetable soup and less desserts, sweet snacks, and sugary beverages. Highly educated mothers chose for their children to drink fewer sugary beverages and to increase PA. Less educated mothers most frequently chose as goals having breakfast, eating more fruit and vegetables, eating fewer snacks, and having less screen time. Overall achievement was similar in the two strata for diet goals, but higher for PA goals in the high education level stratum. CONCLUSIONS: MI intervention was not effective in reducing BMI in children of mothers with low education level. This does appear to be weakly or not associated with goal choices and achievement within MI, it is rather an effect of unmeasured behaviours which possibly mediate association between MI and BMI reduction.


Subject(s)
Educational Status , Pediatric Obesity , Body Mass Index , Child , Diet , Female , Humans , Infant , Italy/epidemiology , Mothers , Overweight , Pediatric Obesity/epidemiology , Pediatric Obesity/prevention & control
17.
Clin Lung Cancer ; 20(3): e413-e417, 2019 05.
Article in English | MEDLINE | ID: mdl-30617039

ABSTRACT

Advanced lung adenocarcinoma with inactive liver kinase B1 (LKB1) tumor suppressor protein is associated with poor response to immune checkpoint inhibitors and molecularly targeted agents, and with dismal patient prognosis. LKB1 is a central orchestrator of cancer cell metabolism, and halts tumor growth/proliferation during metabolic stress. Recent preclinical evidence suggests that LKB1-inactive lung adenocarcinoma is highly sensitive to metformin, a safe and low-cost antidiabetic compound that inhibits mitochondrial oxidative phosphorylation. The effects of metformin can be enhanced by nutrient deprivation (ie, glucose, amino acids), which reduces intracellular levels of ATP and anabolic precursors and can be achieved by the fasting mimicking diet (FMD). Noticeably, metformin also prevents resistance to cisplatin in preclinical in vitro and in vivo models of LKB1-inactive lung adenocarcinoma. Based on such preclinical evidence, the phase II FAME trial was designed to test the hypothesis that the addition of metformin, with or without cyclic FMD, to standard platinum-based chemotherapy improves the progression-free survival of patients with advanced, LKB-1 inactive lung adenocarcinoma. Enrolled patients will be randomized in a 1:1 ratio to receive cisplatin/carboplatin and pemetrexed with the addition of metformin alone (Arm A) or metformin plus FMD (Arm B). The FAME study will use a "pick-the-winner" design with the aim of establishing which of the 2 experimental treatments is superior in terms of antitumor efficacy and safety. The primary assumption of the study is that the combination of the 2 experimental treatments shall improve median progression-free survival from 7.6 months (historical data with chemotherapy alone) to 12 months. Secondary study endpoints are: objective response rate, overall survival, treatment tolerability, and compliance to the experimental treatment.


Subject(s)
Adenocarcinoma of Lung/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Fasting , Lung Neoplasms/therapy , Metformin/administration & dosage , Pemetrexed/therapeutic use , Platinum Compounds/therapeutic use , AMP-Activated Protein Kinase Kinases , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/mortality , Adolescent , Adult , Aged , Diet Therapy , Female , Humans , Lung Neoplasms/genetics , Lung Neoplasms/mortality , Male , Middle Aged , Mutation/genetics , Neoplasm Staging , Protein Serine-Threonine Kinases/genetics , Survival Analysis , Young Adult
18.
Cancer Treat Rev ; 71: 76-87, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30366202

ABSTRACT

Thymic epithelial tumors (TETs) are a heterogenous group of rare tumors, with a complex histopatological classification. Furthermore, the recent introduction of the first TNM staging system, that is scheduled to replace the Masaoka-Koga system, may create further difficulties in TET management, that remains challenging. Several guidelines for treatment of TETs are available and provide recommendations based mainly on non randomized trials and retrospective or limited series. Often the lack of evidence leads to formulation of indications based on expert opinions. As for other rare cancers it is crucial to create networks to coordinate the work among centres involved in treatment of these diseases in order to offer the best diagnostic and therapeutic tools. For this purpose, in 2014 a network named TYME (ThYmic MalignanciEs), was founded in Italy with the aim of improving care and research in TETs. In September 2017 a panel of multidisciplinary experts from TYME network and from other Italian centres strongly involved in TET diagnosis and treatment convened a first Italian Expert meeting together with representatives of association for patients affected by rare thoracic cancers Tu.To.R, to explore how these tumors are managed in the different centres of Italy compared to ESMO guidelines. In this paper we summarize the issues discussed during that meeting and we propose recommandations based on Masaoka Koga and the new TNM staging system.


Subject(s)
Neoplasms, Glandular and Epithelial/diagnosis , Neoplasms, Glandular and Epithelial/therapy , Thymus Neoplasms/diagnosis , Thymus Neoplasms/therapy , Autoimmune Diseases/etiology , Chemotherapy, Adjuvant/methods , Contrast Media , Female , Humans , Male , Neoplasm Recurrence, Local , Neoplasms, Glandular and Epithelial/diagnostic imaging , Neoplasms, Glandular and Epithelial/pathology , Thymus Neoplasms/diagnostic imaging , Thymus Neoplasms/pathology , Tomography, X-Ray Computed/methods
19.
Oncogene ; 37(50): 6463-6476, 2018 12.
Article in English | MEDLINE | ID: mdl-30076413

ABSTRACT

Although limited by severe side effects and development of resistance, platinum-based therapies still represent the most common first-line treatment for non-small cell lung cancer (NSCLC). However, a crucial need in the clinical management of NSCLC is represented by the identification of cases sensitive to DNA damage response (DDR)-targeting drugs, such as cisplatin or PARP inhibitors. Here, we provide a molecular rationale for the stratification of NSCLC patients potentially benefitting from platinum compounds based on the expression levels of RANBP9, a recently identified player of the cellular DDR. RANBP9 was found overexpressed by immunohistochemistry (IHC) in NSCLC compared to normal adjacent tissues (NATs) (n = 147). Moreover, a retrospective analysis of 132 platinum-treated patients from the multi-centric TAILOR trial showed that RANBP9 overexpression levels are associated with clinical response to platinum compounds [Progression Free Survival Hazard Ratio (RANBP9 high vs low) 1.73, 95% CI 1.15-2.59, p = 0.0084; Overall Survival HR (RANBP9 high vs low) 1.99, 95% CI 1.27-3.11, p = 0.003]. Accordingly, RANBP9 KO cells showed higher sensitivity to cisplatin in comparison with WT controls both in vitro and in vivo models. NSCLC RANBP9 KO cells were also more sensitive than control cells to the PARP inhibitor olaparib alone and in combination with cisplatin, due to defective ATM-dependent and hyper-activated PARP-dependent DDR. The current investigation paves the way to prospective studies to assess the clinical value of RANBP9 protein levels as prognostic and predictive biomarker of response to DDR-targeting drugs, leading to the development of new tools for the management of NSCLC patients.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Cytoskeletal Proteins/metabolism , DNA Damage/physiology , Drug Resistance, Neoplasm/physiology , Lung Neoplasms/pathology , Nuclear Proteins/metabolism , Animals , Antineoplastic Agents/pharmacology , Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/metabolism , Cisplatin/pharmacology , Female , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Male , Mice , Mice, Nude , Xenograft Model Antitumor Assays
20.
Clin Lung Cancer ; 19(5): e811-e814, 2018 09.
Article in English | MEDLINE | ID: mdl-30033090

ABSTRACT

Thymic epithelial tumors are rare malignancies. Thymic carcinoma represents about 20% of all thymic epithelial tumors and has aggressive behavior, with a greater tendency to metastatic spread. Thymic carcinoma is often diagnosed in advanced stages for which systemic treatment is the main therapeutic option. The association of chemotherapy and antiangiogenic agents in the first-line setting has never been investigated in this very rare cancer. However, preclinical and clinical evidence has suggested that inhibition of angiogenesis could be beneficial. The RELEVENT trial is a multicenter, open-label, single-arm, phase II study aimed at investigating the activity and safety of ramucirumab combined with paclitaxel and carboplatin in chemotherapy-naive patients affected by thymic carcinoma or B3 thymoma with area of carcinoma. The primary endpoint of the trial is the overall response rate. Progression-free survival, overall survival, and safety are secondary endpoints. Patient-reported outcomes will be collected at each visit. The mutational status of a subset of genes, polymorphisms, and selected micro-RNA expression will be evaluated.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Research Design , Thymoma/drug therapy , Thymus Neoplasms/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Humanized , Carboplatin/administration & dosage , Female , Follow-Up Studies , Humans , Male , Middle Aged , Paclitaxel/administration & dosage , Prognosis , Thymoma/pathology , Thymus Neoplasms/pathology , Young Adult , Ramucirumab
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