74 results on '"Cossa M."'
Search Results
2. Drones and machine-learning for monitoring dugong feeding grounds and gillnet fishing
- Author
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Cossa, D, primary, Cossa, M, additional, Timba, I, additional, Nhaca, J, additional, Macia, A, additional, and Infantes, E, additional
- Published
- 2023
- Full Text
- View/download PDF
3. Study protocol: a pragmatic, cluster-randomized controlled trial to evaluate the effect of implementation of the Truenat platform/MTB assays at primary health care clinics in Mozambique and Tanzania (TB-CAPT CORE).
- Author
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Leukes, V. N., Hella, J., Sabi, I., Cossa, M., Khosa, C., Erkosar, B., Mangu, C., Siyame, E., Mtafya, B., Lwilla, A., Viegas, S., Madeira, C., Machiana, A., Ribeiro, J., Garcia-Basteiro, A. L., Riess, F., Elísio, D., Sasamalo, M., Mhalu, G., and Denkinger, C. M.
- Subjects
SPUTUM examination ,PRIMARY health care ,MYCOBACTERIUM tuberculosis ,RESEARCH protocols ,TUBERCULOSIS - Abstract
Background: In 2020, the WHO-approved Molbio Truenat platform and MTB assays to detect Mycobacterium tuberculosis complex (MTB) and resistance to rifampicin directly on sputum specimens. This primary health care center-based trial in Mozambique and Tanzania investigates the effect of Truenat platform/MTB assays (intervention arm) combined with rapid communication of results compared to standard of care on TB diagnosis and treatment initiation for microbiologically confirmed TB at 7 days from enrolment. Methods: The Tuberculosis Close the Gap, Increase Access, and Provide Adequate Therapy (TB-CAPT) CORE trial employs a pragmatic cluster randomized controlled design to evaluate the impact of a streamlined strategy for delivery of Truenat platform/MTB assays testing at primary health centers. Twenty-nine centers equipped with TB microscopy units were selected to participate in the trial. Among them, fifteen health centers were randomized to the intervention arm (which involves onsite molecular testing using Truenat platform/MTB assays, process process optimization to enable same-day TB diagnosis and treatment initiation, and feedback on Molbio platform performance) or the control arm (which follows routine care, including on-site sputum smear microscopy and the referral of sputum samples to off-site Xpert testing sites). The primary outcome of the study is the absolute number and proportion of participants with TB microbiological confirmation starting TB treatment within 7 days of their first visit. Secondary outcomes include time to bacteriological confirmation, health outcomes up to 60 days from first visit, as well as user preferences, direct cost, and productivity analyses. Ethics and dissemination: TB-CAPT CORE trial has been approved by regulatory and ethical committees in Mozambique and Tanzania, as well as by each partner organization. Consent is informed and voluntary, and confidentiality of participants is maintained throughout. Study findings will be presented at scientific conferences and published in peer-reviewed international journals. Trial Registration: US National Institutes of Health's ClinicalTrials.gov, NCT04568954. Registered 23 September 2020. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
4. Scaling up shorter TB preventive treatment is long overdue
- Author
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Nguenha, D., primary, Cossa, M., additional, Acácio, S., additional, and Garcia-Basteiro, A. L., additional
- Published
- 2022
- Full Text
- View/download PDF
5. miR-146a-5p impairs melanoma resistance to kinase inhibitors by targeting COX2 and regulating NFkB-mediated inflammatory mediators
- Author
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Vergani, E, Dugo, M, Cossa, M, Frigerio, S, Di Guardo, L, Gallino, G, Mattavelli, I, Vergani, B, Lalli, L, Tamborini, E, Valeri, B, Gargiuli, C, Shahaj, E, Ferrarini, M, Ferrero, E, Gomez Lira, M, Huber, V, Vecchio, M, Sensi, M, Leone, B, Santinami, M, Rivoltini, L, Rodolfo, M, Vallacchi, V, Vergani E., Dugo M., Cossa M., Frigerio S., Di Guardo L., Gallino G., Mattavelli I., Vergani B., Lalli L., Tamborini E., Valeri B., Gargiuli C., Shahaj E., Ferrarini M., Ferrero E., Gomez Lira M., Huber V., Vecchio M. D., Sensi M., Leone B. E., Santinami M., Rivoltini L., Rodolfo M., Vallacchi V., Vergani, E, Dugo, M, Cossa, M, Frigerio, S, Di Guardo, L, Gallino, G, Mattavelli, I, Vergani, B, Lalli, L, Tamborini, E, Valeri, B, Gargiuli, C, Shahaj, E, Ferrarini, M, Ferrero, E, Gomez Lira, M, Huber, V, Vecchio, M, Sensi, M, Leone, B, Santinami, M, Rivoltini, L, Rodolfo, M, Vallacchi, V, Vergani E., Dugo M., Cossa M., Frigerio S., Di Guardo L., Gallino G., Mattavelli I., Vergani B., Lalli L., Tamborini E., Valeri B., Gargiuli C., Shahaj E., Ferrarini M., Ferrero E., Gomez Lira M., Huber V., Vecchio M. D., Sensi M., Leone B. E., Santinami M., Rivoltini L., Rodolfo M., and Vallacchi V.
- Abstract
Background: Targeted therapy with BRAF and MEK inhibitors has improved the survival of patients with BRAF-mutated metastatic melanoma, but most patients relapse upon the onset of drug resistance induced by mechanisms including genetic and epigenetic events. Among the epigenetic alterations, microRNA perturbation is associated with the development of kinase inhibitor resistance. Here, we identified and studied the role of miR-146a-5p dysregulation in melanoma drug resistance. Methods: The miR-146a-5p-regulated NFkB signaling network was identified in drug-resistant cell lines and melanoma tumor samples by expression profiling and knock-in and knock-out studies. A bioinformatic data analysis identified COX2 as a central gene regulated by miR-146a-5p and NFkB. The effects of miR-146a-5p/COX2 manipulation were studied in vitro in cell lines and with 3D cultures of treatment-resistant tumor explants from patients progressing during therapy. Results: miR-146a-5p expression was inversely correlated with drug sensitivity and COX2 expression and was reduced in BRAF and MEK inhibitor-resistant melanoma cells and tissues. Forced miR-146a-5p expression reduced COX2 activity and significantly increased drug sensitivity by hampering prosurvival NFkB signaling, leading to reduced proliferation and enhanced apoptosis. Similar effects were obtained by inhibiting COX2 by celecoxib, a clinically approved COX2 inhibitor. Conclusions: Deregulation of the miR-146a-5p/COX2 axis occurs in the development of melanoma resistance to targeted drugs in melanoma patients. This finding reveals novel targets for more effective combination treatment. [MediaObject not available: see fulltext.] Graphical Abstract: [Figure not available: see fulltext.]
- Published
- 2020
6. 3D tumor explant as a novel platform to investigate therapeutic pathways and predictive biomarkers in cancer patients
- Author
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Rodolfo, M, Huber, V, Cossa, M, Gallino, G, Leone, B, Vallacchi, V, Rivoltini, L, Vergani, E, Rodolfo, Monica, Huber, Veronica, Cossa, Mara, Gallino, Gianfrancesco, Leone, Biagio E, Vallacchi, Viviana, Rivoltini, Licia, Vergani, Elisabetta, Rodolfo, M, Huber, V, Cossa, M, Gallino, G, Leone, B, Vallacchi, V, Rivoltini, L, Vergani, E, Rodolfo, Monica, Huber, Veronica, Cossa, Mara, Gallino, Gianfrancesco, Leone, Biagio E, Vallacchi, Viviana, Rivoltini, Licia, and Vergani, Elisabetta
- Abstract
Immunotherapy with immune checkpoint inhibitors can induce durable clinical responses in different human malignancies but the number of responding patients remains globally modest. The limited therapeutic efficacy of ICI depends on multiple factors, among which the immune suppressive features of the tumor microenvironment play a key role. For this reason, experimental models that enable dissection of the immune-hostile tumor milieu components are required to unravel how to overcome resistance and obtain full-fledged anti-tumor immunity. Recent evidence supports the usefulness of 3D ex vivo systems in retaining features of tumor microenvironment to elucidate molecular and immunologic mechanisms of response and resistance to immune checkpoint blockade. In this perspective article we discuss the recent advances in patient-derived 3D tumor models and their potential in support of treatment decision making in clinical setting. We will also share our experience with dynamic bioreactor tumor explant culture of samples from melanoma and sarcoma patients as a reliable and promising platform to unravel immune responses to immune checkpoint inhibitors.
- Published
- 2022
7. Performance of Xpert MTB/RIF Ultra for tuberculosis diagnosis in the context of passive and active case finding
- Author
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Saavedra, B, Mambuque, E, Nguenha, D, Gomes, N, Munguambe, S, Garcia, JI, Izco, S, Acacio, S, Murias-Closas, A, Cossa, M, Losada, I, Pernas-Pardavila, H, Oliveras, L, Theron, G, and Garcia-Basteiro, AL
- Abstract
Aims We present a field evaluation of the diagnostic accuracy of Xpert MTB/RIF ("Xpert") and Xpert MTB/RIF Ultra ("Ultra") using two cohorts in a high tuberculosis/HIV burden setting in Southern Mozambique. Methods Single respiratory specimens from symptomatic adults accessing healthcare services (passive case finding (PCF) cohort) and from household and community close contacts (active case finding (ACF) cohort) were tested by smear microscopy, culture, Xpert and Ultra. Liquid and solid culture served as a composite reference standard. We explored the impact of trace results on specificity via their recategorisation to negative (in all and just among those previously treated individuals). Results 1419 and 252 participants were enrolled in the PCF and ACF cohorts, respectively. For the PCF cohort, Ultra showed higher sensitivity than Xpert overall (0.95 (95% CI 0.90-0.98) versus 0.88 (96% CI 0.82-0.93); p
- Published
- 2021
8. The prognostic impact of the extent of ulceration in clinical stage I-II melanoma patients: A multicenter study of the Italian Melanoma Intergroup (IMI)
- Author
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Portelli, F, Galli, F, Cattaneo, L, Cossa, M, De Giorgi, V, Forte, G, Fraternali Orcioni, G, Gianatti, A, Indini, A, Labianca, A, Maurichi, A, Merelli, B, Montesco, Mc, Occelli, M, Patuzzo, R, Piazzalunga, D, Pigozzo, J, Quaglino, P, Ribero, S, Salvatori, R, Saraggi, D, Sena, P, Senetta, R, Valeri, B, Tanaka, M, Fukayama, M, Palmieri, G, Mandala', M, Massi, D, and Italian Melanoma Intergroup (IMI)
- Published
- 2020
9. Thymus neuroendocrine tumors with CTNNB1 gene mutations, disarrayed ß-catenin expression, and dual intra-tumor Ki-67 labeling index compartmentalization challenge the concept of secondary high-grade neuroendocrine tumor: a paradigm shift
- Author
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Fabbri, A, Cossa, M, Sonzogni, A, Bidoli, P, Canova, S, Cortinovis, D, Abbate, M, Calabrese, F, Nannini, N, Lunardi, F, Rossi, G, La Rosa, S, Capella, C, Tamborini, E, Perrone, F, Busico, A, Capone, I, Valeri, B, Pastorino, U, Albini, A, Pelosi, G, Fabbri A, Cossa M, Sonzogni A, Bidoli P, Canova S, Cortinovis D, Abbate MI, Calabrese F, Nannini N, Lunardi F, Rossi G, La Rosa S, Capella C, Tamborini E, Perrone F, Busico A, Capone I, Valeri B, Pastorino U, Albini A, Pelosi G., Fabbri, A, Cossa, M, Sonzogni, A, Bidoli, P, Canova, S, Cortinovis, D, Abbate, M, Calabrese, F, Nannini, N, Lunardi, F, Rossi, G, La Rosa, S, Capella, C, Tamborini, E, Perrone, F, Busico, A, Capone, I, Valeri, B, Pastorino, U, Albini, A, Pelosi, G, Fabbri A, Cossa M, Sonzogni A, Bidoli P, Canova S, Cortinovis D, Abbate MI, Calabrese F, Nannini N, Lunardi F, Rossi G, La Rosa S, Capella C, Tamborini E, Perrone F, Busico A, Capone I, Valeri B, Pastorino U, Albini A, and Pelosi G.
- Abstract
We herein report an uncommon association of intimately admixed atypical carcinoid (AC) and large cell neuroendocrine (NE) carcinoma (LCNEC) of the thymus, occurring in two 20- and 39-year-old Caucasian males. Both tumors were treated by maximal thymectomy. The younger patient presented with a synchronous lesion and died of disease after 9 months, while the other patient was associated with a recurrent ectopic adrenocorticotropic hormone Cushing’s syndrome and is alive with disease at the 2-year follow-up. MEN1 syndrome was excluded in either case. Immunohistochemically, disarrayed cytoplasmic and nuclear ß-catenin expression was seen alongside an intra-tumor Ki-67 antigen labeling index (LI) ranging from 2 to 80% in the younger patient’s tumor and from 3 to 45% in the other. Both exhibited upregulated cyclin D1 and retinoblastoma, while vimentin was overexpressed in the recurrent LCNEC only. Next-generation sequencing revealed CTNNB1, TP53, and JAK3 mutations in the synchronous tumor and CTNNB1 mutation alone in the metachronous tumor (the latter with the same mutation as the first tumor of 17 years prior). None of the 23 T-NET controls exhibited this hallmarking triple alteration (p = 0.003). These findings suggested that LCNEC components developed from pre-existing CTNNB1-mutated AC upon loss-of-function TP53 and gain-of-function JAK3 mutations in one case and an epithelial-mesenchymal transition upon vimentin overexpression in the other case. Both tumors maintained intact cyclin D1–retinoblastoma machinery. Our report challenges the concept of secondary LCNEC as an entity that develops from pre-existing AC as a result of tumor progression, suggesting a paradigm shift to the current pathogenesis of NET
- Published
- 2017
10. The density and spatial tissue distribution of CD8(+) and CD163(+) immune cells predict response and outcome in melanoma patients receiving MAPK inhibitors
- Author
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Massi, D., Rulli, E., Cossa, M., Valeri, B., Rodolfo, M., Merelli, B., De Logu, F., Nassini, R., Del Vecchio, M., Di Guardo, L., De Penni, R., Guida, M., Sileni, V. C., Di Giacomo, A. M., Tucci, M., Occelli, M., Portelli, F., Vallacchi, V., Consoli, F., Quaglino, P., Queirolo, P., Baroni, G., Carnevale-Schianca, F., Cattaneo, L., Minisini, A., Palmieri, G., Rivoltini, L., Mandala, M., Simi, S., and Galli, F.
- Subjects
Male ,0301 basic medicine ,Oncology ,Cancer Research ,Kaplan-Meier Estimate ,B7-H1 Antigen ,0302 clinical medicine ,Receptors ,Tumor Microenvironment ,Immunology and Allergy ,Melanoma ,beta Catenin ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,MAP Kinase Kinase Kinases ,CD ,3. Good health ,Differentiation ,030220 oncology & carcinogenesis ,Cell Surface ,Myeloid cells ,Melanoma prognosis ,Microenvironment ,T lymphocytes ,Aged ,Antigens, CD ,Antigens, Differentiation, Myelomonocytic ,CD8 Antigens ,Female ,Humans ,Programmed Cell Death 1 Ligand 2 Protein ,Protein Kinase Inhibitors ,Proto-Oncogene Proteins B-raf ,Receptors, Cell Surface ,Molecular Medicine ,Research Article ,medicine.medical_specialty ,Immunology ,lcsh:RC254-282 ,03 medical and health sciences ,Immune system ,Immunity ,Internal medicine ,medicine ,Progression-free survival ,Antigens ,Pharmacology ,Tumor microenvironment ,Performance status ,business.industry ,Myelomonocytic ,medicine.disease ,030104 developmental biology ,business ,CD163 ,CD8 - Abstract
Background Clinical response to MAPK inhibitors in metastatic melanoma patients is heterogeneous for reasons still needing to be elucidated. As the patient immune activity contributes to treatment clinical benefit, the pre-existing level of immunity at tumor site may provide biomarkers of disease outcome to therapy. Here we investigated whether assessing the density and spatial tissue distribution of key immune cells in the tumor microenvironment could identify patients predisposed to respond to MAPK inhibitors. Methods Pretreatment tumor biopsies from a total of 213 patients (158 for the training set and 55 for the validation set) treated with BRAF or BRAF/MEK inhibitors within the Italian Melanoma Intergroup were stained with selected immune markers (CD8, CD163, beta-catenin, PD-L1, PD-L2). Results, obtained by blinded immunohistochemical scoring and digital image analysis, were correlated with clinical response and outcome by multivariate logistic models on response to treatment and clinical outcome, adjusted for American Joint Committee on Cancer stage, performance status, lactate dehydrogenase and treatment received. Results Patients with high intratumoral, but not peritumoral, CD8(+) T cells and concomitantly low CD163(+) myeloid cells displayed higher probability of response (OR 9.91, 95% CI 2.23-44.0, p = 0.003) and longer overall survival (HR 0.34, 95% CI 0.16-0.72, p = 0.005) compared to those with intratumoral low CD8(+) T cells and high CD163(+) myeloid cells. The latter phenotype was instead associated with a shorter progression free survival (p = 0.010). In contrast, PD-L1 and PD-L2 did not correlate with clinical outcome while tumor beta-catenin overexpression showed association with lower probability of response (OR 0.48, 95% CI 0.21-1.06, p = 0.068). Conclusions Analysis of the spatially constrained distribution of CD8(+) and CD163(+) cells, representative of the opposite circuits of antitumor vs protumor immunity, respectively, may assist in identifying melanoma patients with improved response and better outcome upon treatment with MAPK inhibitors. These data underline the role of endogenous immune microenvironment in predisposing metastatic melanoma patients to benefit from therapies targeting driver-oncogenic pathways.
- Published
- 2019
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- View/download PDF
11. The prognostic impact of the extent of ulceration in patients with clinical stage I–II melanoma: a multicentre study of the Italian Melanoma Intergroup (IMI).
- Author
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Portelli, F., Galli, F., Cattaneo, L., Cossa, M., De Giorgi, V., Forte, G., Fraternali Orcioni, G., Gianatti, A., Indini, A., Labianca, A., Maurichi, A., Merelli, B., Montesco, M.C., Occelli, M., Patuzzo, R., Piazzalunga, D., Pigozzo, J., Quaglino, P., Ribero, S., and Salvatori, R.
- Subjects
SENTINEL lymph nodes ,PROPORTIONAL hazards models ,PROGNOSIS ,MELANOMA - Abstract
Summary: Background: The presence of ulceration has been recognized as an adverse prognostic factor in primary cutaneous melanoma (PCM). Objectives: To investigate whether the extent of ulceration (EoU) predicts relapse‐free survival (RFS) and overall survival (OS) in PCM. Materials and methods: We retrieved data for 477 patients with ulcerated PCM from databases of the Italian Melanoma Intergroup. Univariate and multivariable Cox proportional hazard models were used to assess the independent prognostic impact of EoU. Results: A significant interaction emerged between Breslow thickness (BT) and EoU, considering both RFS (P < 0·0001) and OS (P = 0·0006). At multivariable analysis, a significant negative impact of EoU on RFS [hazard ratio (HR) (1‐mm increase) 1·26, 95% confidence interval (CI) 1·08–1·48, P = 0·0047] and OS [HR (1‐mm increase) 1·25, 95% CI 1·05–1·48, P = 0·0120] was found in patients with BT ≤ 2 mm, after adjusting for BT, age, tumour‐infiltrating lymphocytes, sentinel lymph node status and mitotic rate. No impact of EoU was found in patients with 2·01–4 mm and > 4 mm BT. Conclusions: This study demonstrates that EoU has an independent prognostic impact in PCM and should be recorded as a required element in pathology reports. What is already known about this topic? Ulceration is a well‐known prognostic factor in melanoma.There are conflicting results on the prognostic value of the extent of ulceration. What does this study add? The extent of ulceration is an independent prognostic factor in primary cutaneous melanoma with Breslow thickness (BT) ≤ 2 mm.The extent of ulceration should be incorporated into the pathology report as a required, core element.Patients with extensive ulceration with a BT ≤ 2 mm are at high risk of recurrence and should be included in prospective adjuvant trials. Linked Comment: Wilkinson and Gyorki. Br J Dermatol 2021; 184:192–193. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
12. A novel computational method for automatic segmentation, quantification and comparative analysis of immunohistochemically labeled tissue sections
- Author
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Casiraghi, E, Huber, V, Frasca, M, Cossa, M, Tozzi, M, Rivoltini, L, Leone, B, Villa, A, Vergani, B, Leone, BE, Casiraghi, E, Huber, V, Frasca, M, Cossa, M, Tozzi, M, Rivoltini, L, Leone, B, Villa, A, Vergani, B, and Leone, BE
- Abstract
Background: In the clinical practice, the objective quantification of histological results is essential not only to define objective and well-established protocols for diagnosis, treatment, and assessment, but also to ameliorate disease comprehension. Software: The software MIAQuant_Learn presented in this work segments, quantifies and analyzes markers in histochemical and immunohistochemical images obtained by different biological procedures and imaging tools. MIAQuant_Learn employs supervised learning techniques to customize the marker segmentation process with respect to any marker color appearance. Our software expresses the location of the segmented markers with respect to regions of interest by mean-distance histograms, which are numerically compared by measuring their intersection. When contiguous tissue sections stained by different markers are available, MIAQuant_Learn aligns them and overlaps the segmented markers in a unique image enabling a visual comparative analysis of the spatial distribution of each marker (markers' relative location). Additionally, it computes novel measures of markers' co-existence in tissue volumes depending on their density. Conclusions: Applications of MIAQuant_Learn in clinical research studies have proven its effectiveness as a fast and efficient tool for the automatic extraction, quantification and analysis of histological sections. It is robust with respect to several deficits caused by image acquisition systems and produces objective and reproducible results. Thanks to its flexibility, MIAQuant_Learn represents an important tool to be exploited in basic research where needs are constantly changing.
- Published
- 2018
13. Miaquant, a novel system for automatic segmentation, measurement, and localization comparison of different biomarkers from serialized histological slices
- Author
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Casiraghi, E, Cossa, M, Huber, V, Tozzi, M, Rivoltini, L, Villa, A, Vergani, B, CASIRAGHI, ELENA, Cossa, Mara, Huber, Veronica, Tozzi, Matteo, Rivoltini, Licia, Villa, Antonello, Vergani, Barbara, Casiraghi, E, Cossa, M, Huber, V, Tozzi, M, Rivoltini, L, Villa, A, Vergani, B, CASIRAGHI, ELENA, Cossa, Mara, Huber, Veronica, Tozzi, Matteo, Rivoltini, Licia, Villa, Antonello, and Vergani, Barbara
- Abstract
In the clinical practice, automatic image analysis methods quickly quantizing histological results by objective and replicable methods are getting more and more necessary and widespread. Despite several commercial software products are available for this task, they are very little flexible, and provided as black boxes without modifiable source code. To overcome the aforementioned problems, we employed the commonly used MATLAB platform to develop an automatic method, MIAQuant, for the analysis of histochemical and immunohistochemical images, stained with various methods and acquired by different tools. It automatically extracts and quantifies markers characterized by various colors and shapes; furthermore, it aligns contiguous tissue slices stained by different markers and overlaps them with differing colors for visual comparison of their localization. Application of MIAQuant for clinical research fields, such as oncology and cardiovascular disease studies, has proven its efficacy, robustness and flexibility with respect to various problems; we highlight that, the flexibility of MIAQuant makes it an important tool to be exploited for basic researches where needs are constantly changing. MIAQuant software and its user manual are freely available for clinical studies, pathological research, and diagnosis.
- Published
- 2017
14. Global Surgery 2030:A roadmap for high income country actors
- Author
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Ng-Kamstra, JS, SLM, Greenberg, Abdullah, F, Amado, V, Anderson, GA, Cossa, M, and Leather, Andrew John Moffat
- Abstract
The Millennium Development Goals have ended and the Sustainable Development Goals have begun, marking a shift in the global health landscape. The frame of reference has changed from a focus on 8 development priorities to an expansive set of 17 interrelated goals intended to improve the well-being of all people. In this time of change, several groups, including the Lancet Commission on Global Surgery, have brought a critical problem to the fore: 5 billion people lack access to safe, affordable surgical and anaesthesia care when needed. The magnitude of this problem and the world's new focus on strengthening health systems mandate reimagined roles for and renewed commitments from high income country actors in global surgery. To discuss the way forward, on 6 May 2015, the Commission held its North American launch event in Boston, Massachusetts. Panels of experts outlined the current state of knowledge and agreed on the roles of surgical colleges and academic medical centres; trainees and training programmes; academia; global health funders; the biomedical devices industry, and news media and advocacy organisations in building sustainable, resilient surgical systems. This paper summarises these discussions and serves as a consensus statement providing practical advice to these groups. It traces a common policy agenda between major actors and provides a roadmap for maximising benefit to surgical patients worldwide. To close the access gap by 2030, individuals and organisations must work collectively, interprofessionally and globally. High income country actors must abandon colonial narratives and work alongside low and middle income country partners to build the surgical systems of the future.
- Published
- 2016
15. Global Surgery 2030: a roadmap for high income country actors
- Author
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Ng-Kamstra, JS, Greenberg, SLM, Abdullah, F, Amado, V, Anderson, GA, Cossa, M, Costas-Chavarri, A, Davies, J, Debas, HT, Dyer, GSM, Erdene, S, Farmer, PE, Gaumnitz, A, Hagander, L, Haider, A, Leather, AJM, Lin, Y, Marten, R, Marvin, JT, McClain, CD, Meara, JG, Mehes, M, Mock, C, Mukhopadhyay, S, Orgoi, S, Prestero, T, Price, RR, Raykar, NP, Riesel, JN, Riviello, R, Rudy, SM, Saluja, S, Sullivan, R, Tarpley, JL, Taylor, RH, Telemaque, L-F, Toma, G, Varghese, A, Walker, M, Yamey, G, Shrime, MG, Ng-Kamstra, JS, Greenberg, SLM, Abdullah, F, Amado, V, Anderson, GA, Cossa, M, Costas-Chavarri, A, Davies, J, Debas, HT, Dyer, GSM, Erdene, S, Farmer, PE, Gaumnitz, A, Hagander, L, Haider, A, Leather, AJM, Lin, Y, Marten, R, Marvin, JT, McClain, CD, Meara, JG, Mehes, M, Mock, C, Mukhopadhyay, S, Orgoi, S, Prestero, T, Price, RR, Raykar, NP, Riesel, JN, Riviello, R, Rudy, SM, Saluja, S, Sullivan, R, Tarpley, JL, Taylor, RH, Telemaque, L-F, Toma, G, Varghese, A, Walker, M, Yamey, G, and Shrime, MG
- Abstract
The Millennium Development Goals have ended and the Sustainable Development Goals have begun, marking a shift in the global health landscape. The frame of reference has changed from a focus on 8 development priorities to an expansive set of 17 interrelated goals intended to improve the well-being of all people. In this time of change, several groups, including the Lancet Commission on Global Surgery, have brought a critical problem to the fore: 5 billion people lack access to safe, affordable surgical and anaesthesia care when needed. The magnitude of this problem and the world's new focus on strengthening health systems mandate reimagined roles for and renewed commitments from high income country actors in global surgery. To discuss the way forward, on 6 May 2015, the Commission held its North American launch event in Boston, Massachusetts. Panels of experts outlined the current state of knowledge and agreed on the roles of surgical colleges and academic medical centres; trainees and training programmes; academia; global health funders; the biomedical devices industry, and news media and advocacy organisations in building sustainable, resilient surgical systems. This paper summarises these discussions and serves as a consensus statement providing practical advice to these groups. It traces a common policy agenda between major actors and provides a roadmap for maximising benefit to surgical patients worldwide. To close the access gap by 2030, individuals and organisations must work collectively, interprofessionally and globally. High income country actors must abandon colonial narratives and work alongside low and middle income country partners to build the surgical systems of the future.
- Published
- 2016
16. 1019 ANALYSIS OF HISTOLOGICAL AND IMMUNOHISTOCHEMICAL PATTERN OF HEPATOCELLULAR CARCINOMA EXPRESSING CYTOKERATIN 7 BY COMPUTERIZED MORPHOMETRY
- Author
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Vertemati, M., primary, Minóla, E., additional, Moscheni, C., additional, Petrella, D., additional, Cossa, M., additional, Goffredi, M., additional, and Vizzotto, L., additional
- Published
- 2011
- Full Text
- View/download PDF
17. 379 QUANTITATIVE ASSESSMENT OF STEATOSIS IN LIVER TRANSPLANTATION BY MORPHOMETRIC ANALYSIS
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Vertemati, M., primary, Goffredi, M., additional, Aseni, P., additional, Lamperti, L., additional, Cossa, M., additional, Minola, E., additional, De Carlis, L., additional, and Vizzotto, L., additional
- Published
- 2010
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18. The 'preliminary neuropsychological battery'. An instrument to grade the cognitive level of minimally responsive patients
- Author
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COSSA, M. FABIANI, A. FARINATO, M., F. M., primary
- Published
- 1999
- Full Text
- View/download PDF
19. 3D tumor explant as a novel platform to investigate therapeutic pathways and predictive biomarkers in cancer patients
- Author
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Rodolfo, Monica, Huber, Veronica, Cossa, Mara, Gallino, Gianfrancesco, Leone, Biagio E., Vallacchi, Viviana, Rivoltini, Licia, Vergani, Elisabetta, Rodolfo, M, Huber, V, Cossa, M, Gallino, G, Leone, B, Vallacchi, V, Rivoltini, L, and Vergani, E
- Subjects
bioreactor ,sarcoma ,Immunology ,melanoma ,Immunology and Allergy ,immunotherapy ,patient-derived 3D tumor explant - Abstract
Immunotherapy with immune checkpoint inhibitors can induce durable clinical responses in different human malignancies but the number of responding patients remains globally modest. The limited therapeutic efficacy of ICI depends on multiple factors, among which the immune suppressive features of the tumor microenvironment play a key role. For this reason, experimental models that enable dissection of the immune-hostile tumor milieu components are required to unravel how to overcome resistance and obtain full-fledged anti-tumor immunity. Recent evidence supports the usefulness of 3D ex vivo systems in retaining features of tumor microenvironment to elucidate molecular and immunologic mechanisms of response and resistance to immune checkpoint blockade. In this perspective article we discuss the recent advances in patient-derived 3D tumor models and their potential in support of treatment decision making in clinical setting. We will also share our experience with dynamic bioreactor tumor explant culture of samples from melanoma and sarcoma patients as a reliable and promising platform to unravel immune responses to immune checkpoint inhibitors.
- Published
- 2022
20. miR-146a-5p impairs melanoma resistance to kinase inhibitors by targeting COX2 and regulating NFkB-mediated inflammatory mediators
- Author
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Elisabetta Ferrero, Marina Ferrarini, Chiara Gargiuli, Viviana Vallacchi, Michele Del Vecchio, Macarena Gomez Lira, Eriomina Shahaj, Mara Cossa, Elena Tamborini, Barbara Vergani, Luca Lalli, Mario Santinami, Barbara Valeri, Monica Rodolfo, Gianfrancesco Gallino, Simona Frigerio, Veronica Huber, Marialuisa Sensi, Licia Rivoltini, Elisabetta Vergani, Lorenza Di Guardo, Matteo Dugo, Ilaria Mattavelli, Biagio Eugenio Leone, Vergani, E, Dugo, M, Cossa, M, Frigerio, S, Di Guardo, L, Gallino, G, Mattavelli, I, Vergani, B, Lalli, L, Tamborini, E, Valeri, B, Gargiuli, C, Shahaj, E, Ferrarini, M, Ferrero, E, Gomez Lira, M, Huber, V, Vecchio, M, Sensi, M, Leone, B, Santinami, M, Rivoltini, L, Rodolfo, M, and Vallacchi, V
- Subjects
Proto-Oncogene Proteins B-raf ,BRAF/MEK inhibitors ,medicine.medical_treatment ,lcsh:Medicine ,Drug resistance ,Models, Biological ,Biochemistry ,Targeted therapy ,03 medical and health sciences ,0302 clinical medicine ,miR-146a-5p ,Cell Line, Tumor ,microRNA ,medicine ,Humans ,Epigenetics ,BRAF/MEK inhibitor ,lcsh:QH573-671 ,Extracellular Signal-Regulated MAP Kinases ,Melanoma ,Protein Kinase Inhibitors ,Molecular Biology ,030304 developmental biology ,Mitogen-Activated Protein Kinase Kinases ,0303 health sciences ,Kinase ,business.industry ,lcsh:Cytology ,Research ,lcsh:R ,NF-kappa B ,Cell Biology ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Gene expression profiling ,MicroRNAs ,Cyclooxygenase 2 ,Drug Resistance, Neoplasm ,Apoptosis ,030220 oncology & carcinogenesis ,Cancer research ,Inflammation Mediators ,Melanoma resistance ,business ,Proto-Oncogene Proteins c-akt ,COX2 ,Signal Transduction - Abstract
Background Targeted therapy with BRAF and MEK inhibitors has improved the survival of patients with BRAF-mutated metastatic melanoma, but most patients relapse upon the onset of drug resistance induced by mechanisms including genetic and epigenetic events. Among the epigenetic alterations, microRNA perturbation is associated with the development of kinase inhibitor resistance. Here, we identified and studied the role of miR-146a-5p dysregulation in melanoma drug resistance. Methods The miR-146a-5p-regulated NFkB signaling network was identified in drug-resistant cell lines and melanoma tumor samples by expression profiling and knock-in and knock-out studies. A bioinformatic data analysis identified COX2 as a central gene regulated by miR-146a-5p and NFkB. The effects of miR-146a-5p/COX2 manipulation were studied in vitro in cell lines and with 3D cultures of treatment-resistant tumor explants from patients progressing during therapy. Results miR-146a-5p expression was inversely correlated with drug sensitivity and COX2 expression and was reduced in BRAF and MEK inhibitor-resistant melanoma cells and tissues. Forced miR-146a-5p expression reduced COX2 activity and significantly increased drug sensitivity by hampering prosurvival NFkB signaling, leading to reduced proliferation and enhanced apoptosis. Similar effects were obtained by inhibiting COX2 by celecoxib, a clinically approved COX2 inhibitor. Conclusions Deregulation of the miR-146a-5p/COX2 axis occurs in the development of melanoma resistance to targeted drugs in melanoma patients. This finding reveals novel targets for more effective combination treatment. Graphical Abstract
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- 2020
21. A novel computational method for automatic segmentation, quantification and comparative analysis of immunohistochemically labeled tissue sections
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Antonello Villa, Elena Casiraghi, Matteo Tozzi, Licia Rivoltini, Barbara Vergani, Biagio Eugenio Leone, Marco Frasca, Mara Cossa, Veronica Huber, Casiraghi, E, Huber, V, Frasca, M, Cossa, M, Tozzi, M, Rivoltini, L, Leone, B, Villa, A, and Vergani, B
- Subjects
0301 basic medicine ,Support Vector Machine ,Computer science ,Image Processing ,Biochemistry ,030218 nuclear medicine & medical imaging ,0302 clinical medicine ,Computer-Assisted ,Structural Biology ,Histochemical and immunohistochemical image analysis ,Digital image processing ,Image Processing, Computer-Assisted ,Segmentation ,lcsh:QH301-705.5 ,Tumor ,Comparative analysi ,Applied Mathematics ,Comparative analysis ,Computer Science Applications1707 Computer Vision and Pattern Recognition ,Immunohistochemistry ,Histochemical and immunohistochemical image analysi ,Computer Science Applications ,Algorithm ,Statistical analysis ,lcsh:R858-859.7 ,Algorithms ,Human ,Supervised learning methods ,Decision Tree ,Statistical analysi ,lcsh:Computer applications to medicine. Medical informatics ,Intersection (Euclidean geometry) ,03 medical and health sciences ,Histogram ,Biomarkers, Tumor ,Humans ,Computational Biology ,Decision Trees ,Software ,Staining and Labeling ,Molecular Biology ,business.industry ,Supervised learning ,Pattern recognition ,Support vector machine ,030104 developmental biology ,Tissue sections ,lcsh:Biology (General) ,Artificial intelligence ,business ,Supervised learning method ,Biomarkers - Abstract
Background In the clinical practice, the objective quantification of histological results is essential not only to define objective and well-established protocols for diagnosis, treatment, and assessment, but also to ameliorate disease comprehension. Software The software MIAQuant_Learn presented in this work segments, quantifies and analyzes markers in histochemical and immunohistochemical images obtained by different biological procedures and imaging tools. MIAQuant_Learn employs supervised learning techniques to customize the marker segmentation process with respect to any marker color appearance. Our software expresses the location of the segmented markers with respect to regions of interest by mean-distance histograms, which are numerically compared by measuring their intersection. When contiguous tissue sections stained by different markers are available, MIAQuant_Learn aligns them and overlaps the segmented markers in a unique image enabling a visual comparative analysis of the spatial distribution of each marker (markers’ relative location). Additionally, it computes novel measures of markers’ co-existence in tissue volumes depending on their density. Conclusions Applications of MIAQuant_Learn in clinical research studies have proven its effectiveness as a fast and efficient tool for the automatic extraction, quantification and analysis of histological sections. It is robust with respect to several deficits caused by image acquisition systems and produces objective and reproducible results. Thanks to its flexibility, MIAQuant_Learn represents an important tool to be exploited in basic research where needs are constantly changing.
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- 2018
22. MIAQuant, a novel system for automatic segmentation, measurement, and localization comparison of different biomarkers from serialized histological slices
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Matteo Tozzi, Veronica Huber, Mara Cossa, Antonello Villa, Elena Casiraghi, Barbara Vergani, Licia Rivoltini, Casiraghi, E, Cossa, M, Huber, V, Tozzi, M, Rivoltini, L, Villa, A, and Vergani, B
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0301 basic medicine ,Histology ,Source code ,Computer science ,media_common.quotation_subject ,Statistical analysi ,Biophysics ,Bioinformatics ,digital image processing ,03 medical and health sciences ,Automation ,Software ,statistical analysis ,Robustness (computer science) ,Histochemical and immunohistochemical image analysis ,Digital image processing ,Humans ,MATLAB ,Artificial intelligence ,Statistical analysis ,Cell Biology ,lcsh:QH301-705.5 ,computer.programming_language ,media_common ,Commercial software ,Original Paper ,Staining and Labeling ,business.industry ,Visual comparison ,Pattern recognition ,artificial intelligence ,Histochemical and immunohistochemical image analysi ,030104 developmental biology ,Biophysic ,lcsh:Biology (General) ,Chromogenic Compounds ,business ,computer ,Biomarkers - Abstract
In the clinical practice, automatic image analysis methods quickly quantizing histological results by objective and replicable methods are getting more and more necessary and widespread. Despite several commercial software products are available for this task, they are very little flexible, and provided as black boxes without modifiable source code. To overcome the aforementioned problems, we employed the commonly used MATLAB platform to develop an automatic method, MIAQuant, for the analysis of histochemical and immunohistochemical images, stained with various methods and acquired by different tools. It automatically extracts and quantifies markers characterized by various colors and shapes; furthermore, it aligns contiguous tissue slices stained by different markers and overlaps them with differing colors for visual comparison of their localization. Application of MIAQuant for clinical research fields, such as oncology and cardiovascular disease studies, has proven its efficacy, robustness and flexibility with respect to various problems; we highlight that, the flexibility of MIAQuant makes it an important tool to be exploited for basic researches where needs are constantly changing. MIAQuant software and its user manual are freely available for clinical studies, pathological research, and diagnosis.
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- 2017
23. Thymus neuroendocrine tumors with CTNNB1 gene mutations, disarrayed ß-catenin expression, and dual intra-tumor Ki-67 labeling index compartmentalization challenge the concept of secondary high-grade neuroendocrine tumor: a paradigm shift
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Adele Busico, Francesca Lunardi, Giulio Rossi, Maria Ida Abbate, Fiorella Calabrese, Stefania Canova, Alessandra Fabbri, Adriana Albini, Carlo Capella, Stefano La Rosa, Nazarena Nannini, Iolanda Capone, Elena Tamborini, Barbara Valeri, Angelica Sonzogni, Federica Perrone, Paolo Bidoli, Diego Cortinovis, Mara Cossa, Ugo Pastorino, Giuseppe Pelosi, Fabbri, A, Cossa, M, Sonzogni, A, Bidoli, P, Canova, S, Cortinovis, D, Abbate, M, Calabrese, F, Nannini, N, Lunardi, F, Rossi, G, La Rosa, S, Capella, C, Tamborini, E, Perrone, F, Busico, A, Capone, I, Valeri, B, Pastorino, U, Albini, A, and Pelosi, G
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Adult ,Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,medicine.medical_treatment ,Vimentin ,Neuroendocrine tumors ,Pathology and Forensic Medicine ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,MEN1 ,Molecular Biology ,beta Catenin ,biology ,Retinoblastoma ,Large cell neuroendocrine carcinoma ,Large cell ,Carcinoma ,High-Throughput Nucleotide Sequencing ,Thymus Neoplasms ,Cell Biology ,General Medicine ,Atypical carcinoid ,medicine.disease ,Immunohistochemistry ,Ã -catenin ,Carcinoma, Neuroendocrine ,Thymus ,Thymectomy ,Neuroendocrine ,Ki-67 Antigen ,030104 developmental biology ,Tumor progression ,Thymus neuroendocrine tumors, CTNNB1 gene mutations ,030220 oncology & carcinogenesis ,Ki-67 ,Mutation ,Next-generation sequencing ,Ã-catenin ,Disease Progression ,2734 ,biology.protein - Abstract
We herein report an uncommon association of intimately admixed atypical carcinoid (AC) and large cell neuroendocrine (NE) carcinoma (LCNEC) of the thymus, occurring in two 20- and 39-year-old Caucasian males. Both tumors were treated by maximal thymectomy. The younger patient presented with a synchronous lesion and died of disease after 9 months, while the other patient was associated with a recurrent ectopic adrenocorticotropic hormone Cushing's syndrome and is alive with disease at the 2-year follow-up. MEN1 syndrome was excluded in either case. Immunohistochemically, disarrayed cytoplasmic and nuclear ß-catenin expression was seen alongside an intra-tumor Ki-67 antigen labeling index (LI) ranging from 2 to 80% in the younger patient's tumor and from 3 to 45% in the other. Both exhibited upregulated cyclin D1 and retinoblastoma, while vimentin was overexpressed in the recurrent LCNEC only. Next-generation sequencing revealed CTNNB1, TP53, and JAK3 mutations in the synchronous tumor and CTNNB1 mutation alone in the metachronous tumor (the latter with the same mutation as the first tumor of 17 years prior). None of the 23 T-NET controls exhibited this hallmarking triple alteration (p = 0.003). These findings suggested that LCNEC components developed from pre-existing CTNNB1-mutated AC upon loss-of-function TP53 and gain-of-function JAK3 mutations in one case and an epithelial-mesenchymal transition upon vimentin overexpression in the other case. Both tumors maintained intact cyclin D1-retinoblastoma machinery. Our report challenges the concept of secondary LCNEC as an entity that develops from pre-existing AC as a result of tumor progression, suggesting a paradigm shift to the current pathogenesis of NET.
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- 2017
24. Expanding Xpert MTB/RIF Ultra® and LF-LAM testing for diagnosis of tuberculosis among HIV-positive adults admitted to hospitals in Tanzania and Mozambique: a randomized controlled trial (the EXULTANT trial).
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Mangu C, Cossa M, Ndege R, Khosa C, Leukes V, de la Torre-Pérez L, Machiana A, Kivuma B, Mnzava D, Zachariah C, Manjate P, Tagliani E, Schacht C, Buech J, Singh S, Ehrlich J, Riess F, Sanz S, Kranzer K, Cox H, Sabi I, Nguenha D, Meggi B, Weisser M, Ntinginya N, Schumacher S, Ruhwald M, Penn-Nicholson A, and Garcia-Basteiro AL
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- Humans, Mozambique, Tanzania, Adult, Male, Female, Sputum microbiology, Lipopolysaccharides urine, Mycobacterium tuberculosis genetics, Mycobacterium tuberculosis isolation & purification, Mycobacterium tuberculosis drug effects, Feces microbiology, Feces virology, Hospitalization, HIV Infections complications, Tuberculosis diagnosis, Tuberculosis complications, Tuberculosis drug therapy
- Abstract
Introduction: Tuberculosis (TB) is an important cause of morbidity and mortality among people living with HIV (PLHIV). Current WHO-recommended strategies for diagnosing TB among hospitalized PLHIV rely on symptom screening and disease severity to assess eligibility for urine lipoarabinomannan lateral flow (LF-LAM) and molecular testing. Despite these recommendations, autopsy studies show a large burden of undiagnosed TB among admitted PLHIV. The EXULTANT trial aims to assess the impact of an expanded screening strategy using three specimens (sputum, stool, and urine) for TB diagnosis among PLHIV admitted to hospitals in two high HIV and TB burden African countries., Methods: This is a multicenter, pragmatic, individually randomized controlled trial conducted across eleven hospitals in Tanzania and Mozambique. Participants in the intervention arm will be tested with Xpert MTB/RIF Ultra® from expectorated sputum, stool, and urine samples, with additional urine LF-LAM testing in the first 24 h after hospital admission, irrespective of the presence of the symptoms. The control arm will implement the WHO standard of care recommendations. Hospitalized adults (≥ 18 years) with a confirmed HIV-diagnosis, irrespective of antiretroviral (ART) therapy status or presence of TB symptoms will be assessed for eligibility at admission. Patients with a pre-existing TB diagnosis, those receiving anti-tuberculosis therapy or tuberculosis preventive treatment in the 6 months prior to enrolment, and those transferred from other hospitals will not be eligible. Also, participants admitted for traumatic reasons such as acute abdomen, maternal conditions, scheduled surgery, having a positive SARS-CoV2 test will be ineligible. The primary endpoint is the proportion of participants with microbiologically confirmed TB starting treatment within 3 days of enrolment., Discussion: The EXULTANT trial investigates rapid implementation after admission of a new diagnostic algorithm using Xpert MTB/RIF Ultra® in several non-invasive specimens, in addition to LF-LAM, in hospitalized PLHIV regardless of TB symptoms. This enhanced strategy is anticipated to detect frequently missed TB cases in this population and is being evaluated as an implementable and scalable intervention., Trial Registration: Trial reference number: NCT04568967 (ClinicalTrials.gov) registered on 2020-09-29., (© 2024. The Author(s).)
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- 2024
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25. Exploring the Gender and Age Demographics of Patients Treated by Emergency Medical Teams during Disasters.
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Shiroma N, Chimed-Ochir O, Yumiya Y, Cossa M, Ussene I, Toyokuni Y, Chishima K, Akahoshi K, Mimura S, Wakai A, Kondo H, Koido Y, Salio F, Kayano R, and Kubo T
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- Humans, Female, Japan, Mozambique, Male, Aged, Middle Aged, Adult, Adolescent, Young Adult, Child, Child, Preschool, Infant, Emergency Medical Services statistics & numerical data, Aged, 80 and over, Age Factors, Infant, Newborn, Sex Factors, Disasters
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Background: Standardized health-data collection enables effective disaster responses and patient care. Emergency medical teams use the Japan Surveillance in Post-Extreme Emergencies and Disasters (J-SPEED) reporting template to collect patient data. EMTs submit data on treated patients to an EMT coordination cell. The World Health Organization's (WHO) EMT minimum dataset (MDS) offers an international standard for disaster data collection., Goal: The goal of this study was to analyze age and gender distribution of medical consultations in EMT during disasters., Methods: Data collected from 2016 to 2020 using the J-SPEED/MDS tools during six disasters in Japan and Mozambique were analyzed. Linear regression with data smoothing via the moving average method was employed to identify trends in medical consultations based on age and gender., Results: 31,056 consultations were recorded: 13,958 in Japan and 17,098 in Mozambique. Women accounted for 56.3% and 55.7% of examinees in Japan and Mozambique, respectively. Children accounted for 6.8% of consultations in Japan and 28.1% in Mozambique. Elders accounted for 1.32 and 1.52 times more consultations than adults in Japan and Mozambique, respectively., Conclusions: Study findings highlight the importance of considering age-specific healthcare requirements in disaster planning. Real-time data collection tools such as J-SPEED and MDS, which generate both daily reports and raw data for in-depth analysis, facilitate the validation of equitable access to healthcare services, emphasize the specific needs of vulnerable groups, and enable the consideration of cultural preferences to improve healthcare provision by EMTs.
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- 2024
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26. Multistep tumor genetic evolution and changes in immunogenicity trigger immune-mediated disease eradication in stage IV melanoma: lessons from a single case.
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Vallacchi V, Vergani E, Cossa M, Gargiuli C, Busico A, Devecchi A, Dugo M, Bergamaschi L, De Cecco L, Cavalieri S, Valeri B, Tamborini E, Gallino G, Del Vecchio M, Santinami M, Sensi M, Rivoltini L, Di Guardo L, and Rodolfo M
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- Humans, Ipilimumab therapeutic use, Vemurafenib, T-Lymphocytes pathology, Receptors, Antigen, T-Cell therapeutic use, Tumor Microenvironment, Melanoma drug therapy, Melanoma genetics, Melanoma pathology
- Abstract
Durable remissions are observed in 10%-20% of treated patients with advanced metastatic melanoma but the factors associated with long-term complete clinical responses are largely unknown. Here, we report the molecular characteristics of tumor evolution during disease progression along a 9-year clinical course in a patient with advanced disseminated melanoma who received different treatments, including trametinib, ipilimumab, radiation, vemurafenib, surgical tumor debulking and a second ipilimumab course, ultimately achieving complete long-term disease remission.Longitudinal analyses of therapies-resistant metastatic tumors revealed the effects of different treatments on tumor's microenvironment and immunogenicity, ultimately creating a milieu favorable to immunotherapy response. Monitoring of the temporal dynamics of T cells by analysis of the T cell receptor (TCR) repertoire in the tumor and peripheral blood during disease evolution indicated that T-cell clones with common TCR rearrangements, present at low levels at baseline, were maintained and expanded after immunotherapy, and that TCR diversity increased. Analysis of genetic, molecular, and cellular components of the tumor depicted a multistep process in which treatment with kinase inhibitors strongly conditioned the immune microenvironment creating an inflamed milieu converting cold into hot tumors, while ipilimumab impacted and increased the TCR repertoire, a requirement for tumor rejection.Since the optimal sequencing of treatment with antibodies targeting immune checkpoints and kinase inhibitors for advanced melanoma is still clinically debated, this case indicates that immunotherapy success is possible even after progression on targeted therapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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27. Implementation of WHO guidelines on urine lateral flow LAM testing in high TB/HIV burden African countries.
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Aguiar Soares K, Ehrlich J, Camará M, Chaloub S, Emeka E, Gando HG, Ismail F, Mvusi L, Jele T, José B, Kgwaadira B, Kisonga R, Letta T, Liega AO, Lungu PS, Maama L, Mahoumbou J, Mbendera K, Ogoro J, Tollo DAD, Sandy C, Saye RG, Sheehama J, Musala S, Tugumisirize D, Carratala L, Cossa M, and Garcia-Basteiro AL
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- Humans, World Health Organization, Lipopolysaccharides, Sensitivity and Specificity, Tuberculosis diagnosis, Tuberculosis epidemiology, HIV Infections complications, HIV Infections diagnosis
- Abstract
Competing Interests: Conflict of interest: All authors have no potential conflicts of interest to disclose.
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- 2023
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28. Similar local recurrence and survival in patients with T1 radial growth phase melanoma on head and neck treated with 5 or 10 mm margins: A retrospective study.
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Maurichi A, Barretta F, Patuzzo R, Miceli R, Gallino G, Mattavelli I, Leva A, Harwood C, Bergamaschi D, Borg TM, Shimonovitz-Moore M, Spadola G, Tolomio E, Barbieri C, Queirolo P, Manganoni AM, Pellacani G, Espeli V, Mangas C, Leoni-Parvex S, Cossa M, Belotti A, Valeri B, Cortinovis U, and Santinami M
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- Humans, Retrospective Studies, Margins of Excision, Neoplasm Recurrence, Local pathology, Hutchinson's Melanotic Freckle surgery, Melanoma pathology, Skin Neoplasms pathology
- Abstract
Background: Melanoma guidelines recommend surgical excision with 10 mm margins for T1 melanomas (invasive melanomas with Breslow thickness ≤1 mm), including those in radial growth phase, which are without metastatic potential; however, such margins may be problematic on head-and-neck., Objective: We compared outcomes of wide (10 mm margins) versus narrow (5 mm margins) excisions in patients with radial growth phase T1 melanoma on head-and-neck including face., Methods: We retrospectively examined 610 consecutive patients excised with wide versus narrow margins, from 2001 to 2018, at six European centres. In all cases, radial growth phase, and clear margins with 5 or 10 mm of clearance, were ascertained histologically. Multivariable models investigated associations of margins and other factors with overall survival and local recurrence., Results: Three hundred and sixteen (51.8%) patients received wide excision, 219 (69.3%) with primary wound closure, 97 (30.7%) with reconstruction; 294 (48.2%) patients received narrow excision, 264 (89.8%) with primary wound closure, 30 (10.2%) with reconstruction (p < 0.001). Median follow-ups were 88 months (wide) and 187 months (narrow) (inter-quartile ranges 43-133 and 79-206, respectively). Ten-year overall survival (95% confidence interval) was 96.7% (94.2%-99.3%) in wide and 98.2% (96.4%-100%) in narrow patients. Ten-year local recurrence incidence was 6.4% (4.1%-10.1%) in wide and 7.8% (5.3%-11.6%) in narrow groups. Lentigo maligna melanoma subtype appeared associated with increased risk of local recurrence in narrow versus wide patients (15.0% vs. 7.5%; p = 0.190)., Conclusions: Narrower excision margins for T1 radial growth phase melanoma are not associated with worse overall survival (hazard ratio 0.97, p = 0.996) or increased local recurrence (subdistribution hazard ratio: 0.87; p = 0.751) compared to wider margins, and may be safely applied to such lesions, although caution may be required in the presence of lentigo maligna melanoma., (© 2023 European Academy of Dermatology and Venereology.)
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- 2023
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29. Association of Excision Margin Size With Local Recurrence and Survival in Patients With T1a Melanoma at Critical Structures.
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Maurichi A, Barretta F, Patuzzo R, Sala L, Miceli R, Gallino G, Mattavelli I, Leva A, Simonotti N, Taglione B, Cossa M, Belotti A, Valeri B, Cortinovis U, and Santinami M
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- Humans, Male, Female, Middle Aged, Margins of Excision, Cohort Studies, Retrospective Studies, Homosexuality, Male, Neoplasm Recurrence, Local epidemiology, Melanoma, Cutaneous Malignant, Melanoma surgery, Skin Neoplasms surgery, Hutchinson's Melanotic Freckle, Sexual and Gender Minorities
- Abstract
Importance: Melanoma guidelines recommend surgical excision with 10-mm margins for T1 melanoma. However, this procedure may be problematic at sites close to critical structures such as the scalp, face, external genitalia, acral, periumbilical, and perineal areas., Objective: To compare outcomes of wide (10-mm margins) vs narrow (5-mm margins) excision in patients with T1a melanoma near critical structures., Design, Setting, and Participants: This cohort study was a retrospective comparison of 1341 consecutive patients aged 18 years or older from the National Cancer Institute of Milan, Italy, diagnosed between 2001 and 2020 with T1a cutaneous melanoma close to critical structures who accepted wide excision vs narrow excision., Exposures: Local recurrence and melanoma-specific mortality (MSM) rates with 5-mm vs 10-mm excision margins., Main Outcomes and Measures: The primary aim of the study was to ascertain whether a narrower (5-mm) vs wider (10-mm) excision margin was associated with local recurrence and MSM. The secondary aim was to compare the need for reconstructive surgery in the groups defined by excision margin width. Between April 28 and August 7, 2022, associations were assessed by weighted Cox and Fine-Gray univariable and multivariable models., Results: A total of 1179 patients met the inclusion criteria (median [IQR] age, 50.0 [39.5-63.0] years; female, 610 [51.7%]; male, 569 [49.3%]). Six hundred twenty-six patients (53.1%) received a wide excision (434 [69.3%] with linear repair and 192 [30.7%] with flap or graft reconstruction) and 553 (46.9%) received a narrow excision (491 [88.8%] with linear repair and 62 [11.2%] with flap or graft reconstruction). The weighted 10-year MSM was 1.8% (95% CI, 0.8%-4.2%) in the wide group and 4.2% (95% CI, 2.2%-7.9%) in the narrow group; the weighted 10-year local recurrence rate was 5.7% (95% CI, 3.9%-8.3%) in the wide group and 6.7% (95% CI, 4.7%-9.5%) in the narrow group. Breslow thickness greater than 0.4 mm (subdistribution hazard ratio [sHR] for 0.6 vs 0.4 mm, 2.42; 95% CI, 1.59-3.68; P < .001) and mitotic rate greater than 1/mm2 (sHR for a single increment, 3.35; 95% CI, 2.59-4.32; P < .001) were associated with worse MSM. Multivariable analysis showed that acral lentiginous melanoma, lentigo maligna melanoma, and increasing Breslow thickness were associated with a higher incidence of local recurrence., Conclusions and Relevance: The study's findings suggest that local excision with 5-mm margins for T1a melanoma may not be associated with an increased risk of local recurrence. Breslow thickness greater than 0.4 mm, mitotic rate greater than 1/mm2, and acral lentiginous melanoma and lentigo maligna melanoma subtypes were associated with a higher risk of recurrence. These findings may be useful for future melanoma treatment guidelines.
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- 2023
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30. First Activation of the WHO Emergency Medical Team Minimum Data Set in the 2019 Response to Tropical Cyclone Idai in Mozambique.
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Kubo T, Chimed-Ochir O, Cossa M, Ussene I, Toyokuni Y, Yumiya Y, Kayano R, and Salio F
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- Child, Humans, Mozambique, World Health Organization, Data Collection, Cyclonic Storms, Disasters
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Introduction: During a disaster, comprehensive, accurate, timely, and standardized health data collection is needed to improve patient care and support effective responses. In 2017, the World Health Organization (WHO) developed the Emergency Medical Team (EMT) Minimum Data Set (MDS) as an international standard for data collection in the context of disasters and public health emergencies. The EMT MDS was formally activated for the first time in 2019 during the response to Cyclone Idai in Mozambique., Study Objective: The aim of this study was to analyze data collected through the EMT MDS during Cyclone Idai of 2019 and to identify the benefits of and opportunities for its future use., Methods: The EMT MDS was used for data collection. All 13 international EMTs deployed from March 27 through July 12 reported data in accordance with the EMT MDS form. The collected data were analyzed descriptively., Results: A total of 18,468 consultations, including delivery of 94 live births, were recorded. For children under-five and those five-years and older, the top five reasons for consultation were minor injuries (4.5% and 10.8%, respectively), acute respiratory infections ([ARI] 12.6% and 4.8%, respectively), acute watery diarrhea (18.7% and 7.7%, respectively), malaria (9.2% and 6.1%, respectively), and skin diseases (5.1% and 3.1%, respectively). Non-disaster-related health events accounted for 84.7% of the total health problems recorded. Obstetric care was among the core services provided by EMTs during the response., Conclusion: Despite of challenges, the EMT MDS reporting system was found to support the responses and coordination of EMTs. The role of the Mozambican Ministry of Health (MOH), its cooperation with EMTs, and the dedicated technical support of international organizations enabled its successful implementation.
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- 2022
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31. Genetic Layout of Melanoma Lesions Is Associated with BRAF/MEK-Targeted Therapy Resistance and Transcriptional Profiles.
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Vergani E, Busico A, Dugo M, Devecchi A, Valeri B, Cossa M, Di Guardo L, De Cecco L, Feltrin E, Valle G, Deho P, Frigerio S, Lalli L, Gallino G, Del Vecchio M, Santinami M, Pruneri G, Tamborini E, Rivoltini L, Sensi M, Vallacchi V, and Rodolfo M
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- Humans, Vemurafenib therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, MAP Kinase Kinase Kinases genetics, MAP Kinase Kinase Kinases therapeutic use, Mutation, Chromatin, Mechanistic Target of Rapamycin Complex 1, Mitogen-Activated Protein Kinase Kinases, Protein Kinase Inhibitors pharmacology, Protein Kinase Inhibitors therapeutic use, Proto-Oncogene Proteins B-raf genetics, Melanoma drug therapy, Melanoma genetics, Melanoma pathology
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The genetic landscape of melanoma resistance to targeted therapy with small molecules inhibiting BRAF and MEK kinases is still largely undefined. In this study, we portrayed in detail the somatic alterations of resistant melanoma and explored the associated biological processes and their integration with transcriptional profiles. By targeted next-generation sequencing and whole-exome sequencing analyses, a list of 101 genes showing imbalance in metastatic tumors from patients with a complete/durable response or disease progression during therapy with vemurafenib or with dabrafenib and trametinib was defined. Classification of altered genes in functional categories indicated that the mutational pattern of both resistant tumors and melanoma cell lines was enriched in gene families involved in oncogenic signaling pathways and in DNA repair. Integration of genomic and transcriptomic features showed that the enrichment of mutations in gene sets associated with anabolic processes, chromatin alterations, and IFN-α response determined a significant positive modulation of the same gene signatures at the transcriptional level. In particular, MTORC1 signaling was enriched in tumors from poorly responsive patients and in resistant tumors excised from treated patients. Results indicate that genetic patterns are associated with melanoma resistance to targeted therapy and disclose the underlying key molecular pathways to define drug combinations for improved personalized therapies., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2022
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32. Prevalence and Severity of Burn Scars in Rural Mozambique.
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Barba P, Neubauer DC, Cossa M, Sieker J, Hornacek MW, Lance SH, Ewing E, Tsai C, Funzamo C, Amado V, Adamo F, Rose J, Bendix P, Vaz F, Noormahomed E, Bickler SW, and Gosman A
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- Adult, Cicatrix epidemiology, Cicatrix etiology, Cicatrix pathology, Female, Humans, Mozambique epidemiology, Prevalence, Rural Population, Burns complications, Burns epidemiology, Contracture epidemiology, Contracture etiology, Contracture surgery
- Abstract
Background: Burn injuries are common in low- and middle-income countries (LMICs) and their associated disability is tragic. This study is the first to explore burn scars in rural communities in Mozambique. This work also validated an innovate burn assessment tool, the Morphological African Scar Contractures Classification (MASCC), used to determine surgical need., Methods: Using a stratified, population-weighted survey, the team interviewed randomly selected households from September 2012 to June 2013. Three rural districts (Chókwè, Nhamatanda, and Ribáuè) were selected to represent the southern, central and northern regions of the country. Injuries were recorded, documented with photographs, and approach to care was gathered. A panel of residents and surgeons reviewed the burn scar images using both the Vancouver Scar Scale and the MASCC, a validated visual scale that categorizes patients into four categories corresponding to levels of surgical intervention., Results: Of the 6104 survey participants, 6% (n = 370) reported one or more burn injuries. Burn injuries were more common in females (57%) and most often occurred on the extremities. Individuals less than 25 years old had a significantly higher odds of reporting a burn scar compared to people older than 45 years. Based on the MASCC, 12% (n = 42) would benefit from surgery to treat contractures., Conclusion: Untreated burn injuries are prevalent in rural Mozambique. Our study reveals a lack of access to surgical care in rural communities and demonstrates how the MASCC scale can be used to extend the reach of surgical assessment beyond the hospital through community health workers., (© 2022. The Author(s).)
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- 2022
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33. Performance of Xpert MTB/RIF Ultra for tuberculosis diagnosis in the context of passive and active case finding.
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Saavedra B, Mambuque E, Nguenha D, Gomes N, Munguambe S, García JI, Izco S, Acacio S, Murias-Closas A, Cossa M, Losada I, Pernas-Pardavila H, Oliveras L, Theron G, and García-Basteiro AL
- Subjects
- Adult, Diagnostic Tests, Routine, Humans, Sensitivity and Specificity, Sputum, Mycobacterium tuberculosis, Tuberculosis, Tuberculosis, Pulmonary diagnosis
- Abstract
Aims: We present a field evaluation of the diagnostic accuracy of Xpert MTB/RIF ("Xpert") and Xpert MTB/RIF Ultra ("Ultra") using two cohorts in a high tuberculosis/HIV burden setting in Southern Mozambique., Methods: Single respiratory specimens from symptomatic adults accessing healthcare services (passive case finding (PCF) cohort) and from household and community close contacts (active case finding (ACF) cohort) were tested by smear microscopy, culture, Xpert and Ultra. Liquid and solid culture served as a composite reference standard. We explored the impact of trace results on specificity via their recategorisation to negative (in all and just among those previously treated individuals)., Results: 1419 and 252 participants were enrolled in the PCF and ACF cohorts, respectively. For the PCF cohort, Ultra showed higher sensitivity than Xpert overall (0.95 (95% CI 0.90-0.98) versus 0.88 (96% CI 0.82-0.93); p<0.001) and among smear-negative patients (0.84 (96% CI 0.71-0.93) versus 0.63 (96% CI 0.48-0.76)). Ultra's specificity was lower than Xpert's (0.96 (96% CI 0.95-0.97) versus 0.98 (96% CI 0.97-0.99); p=0.008). For ACF, sensitivities were the same (0.67 (95% CI 0.22-0.96) for both tests), although Ultra detected a higher number of microbiologically confirmed samples than Xpert (4.7% (12 out of 252) versus 2.7% (seven out of 252)). Conditional recategorisation of trace results among previously treated participants maintained differences in specificity in the PCF cohort., Conclusion: These results add evidence on the improved sensitivity of Ultra and support its use in different case finding scenarios., Competing Interests: Conflict of interest: B. Saavedra has nothing to disclose. Conflict of interest: E. Mambuque has nothing to disclose. Conflict of interest: D. Nguenha has nothing to disclose. Conflict of interest: N. Gomes has nothing to disclose. Conflict of interest: S. Munguambe has nothing to disclose. Conflict of interest: J.I. Garcia has nothing to disclose. Conflict of interest: S. Izco has nothing to disclose. Conflict of interest: S. Acacio has nothing to disclose. Conflict of interest: A. Murias-Closas has nothing to disclose. Conflict of interest: M. Cossa has nothing to disclose. Conflict of interest: I. Losada has nothing to disclose. Conflict of interest: H. Pernas-Pardavila has nothing to disclose. Conflict of interest: L. Oliveras has nothing to disclose. Conflict of interest: G. Theron has nothing to disclose. Conflict of interest: A.L. García-Basteiro has nothing to disclose., (Copyright ©The authors 2021. For reproduction rights and permissions contact permissions@ersnet.org.)
- Published
- 2021
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34. Liquid Biopsy and Radiological Response Predict Outcomes Following Discontinuation of Targeted Therapy in Patients with BRAF Mutated Melanoma.
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Di Guardo L, Randon G, Corti F, Vallacchi V, Raimondi A, Fucà G, Bini M, Maurichi A, Patuzzo R, Gallino G, Mattavelli I, Ruggeri R, Angi M, Cossa M, Valeri B, Cimminiello C, Santinami M, Rivoltini L, de Braud F, Rodolfo M, and Vecchio MD
- Subjects
- Humans, Liquid Biopsy, Proto-Oncogene Proteins B-raf genetics, Retrospective Studies, Melanoma drug therapy, Melanoma genetics, Neoplasms, Second Primary
- Abstract
Background: Outcomes of patients with metastatic melanoma discontinuing BRAF-targeted therapy for cumulative toxicity after sustained response are unknown., Materials and Methods: This retrospective case series analysis conducted at a single Cancer Center in Italy included patients with BRAF mutated metastatic melanoma treated with a BRAF inhibitor as a single agent or in combination with a MEK inhibitor between June 1, 2011 and January 1, 2020 and interrupted treatment due to cumulative toxicity after achieving complete response (CR) or long-lasting partial response (PR; i.e. >12 months)., Results: We included 24 patients with a median treatment duration of 59.4 months (95% confidence interval [CI], 55.4-63.4; range, 12-88). CR and PR were achieved in 71% and 29% of patients, respectively. At a median follow-up after treatment discontinuation of 37.8 months (95% CI, 33.7-41.9), the 12-month progression-free survival after discontinuation (dPFS) rate was 70.8% (95% CI 54.8-91.6) and 24-month dPFS rate was 58.3% (95% CI, 41.6-81.8). Baseline patient and tumor characteristics as well as treatment duration and best response did not significantly impact on dPFS. Patients with CR and negative circulating tumor DNA (ctDNA) at time of discontinuation had a significantly improved dPFS compared with patients with either radiological residual disease or ctDNA positivity (p = .007). No patient in CR with undetectable ctDNA experienced progression., Conclusion: The risk of progression is high even in patients with sustained sensitivity to BRAF/MEK inhibitors. Integration of liquid biopsy in clinical trials investigating the optimal management of patients with sustained sensitivity to BRAF/MEK inhibitors is warranted., Implications for Practice: Outcomes of patients with metastatic melanoma discontinuing BRAF-targeted therapy for cumulative toxicity are unknown. This study analyzed patients with sustained responses (median treatment duration 59.4 months). Twelve- and 24-month progression-free survival following discontinuation were 70.8% and 58.3%, respectively. Complete response and negative circulating tumor DNA at time of discontinuation are promising prognostic biomarkers in this setting., (© 2021 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.)
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- 2021
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35. Genetic Variants and Somatic Alterations Associated with MITF-E318K Germline Mutation in Melanoma Patients.
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Vergani E, Frigerio S, Dugo M, Devecchi A, Feltrin E, De Cecco L, Vallacchi V, Cossa M, Di Guardo L, Manoukian S, Peissel B, Ferrari A, Gallino G, Maurichi A, Rivoltini L, Sensi M, and Rodolfo M
- Subjects
- Adult, Aged, Aged, 80 and over, Chromosomes, Human, Pair 9, Cyclin-Dependent Kinase Inhibitor p16 genetics, Female, Heterozygote, Humans, Male, Middle Aged, Proto-Oncogene Proteins B-raf genetics, Receptor, Melanocortin, Type 1 genetics, Exome Sequencing, Young Adult, Melanoma, Cutaneous Malignant, Germ-Line Mutation, Melanoma genetics, Microphthalmia-Associated Transcription Factor genetics, Skin Neoplasms genetics
- Abstract
The MITF-E318K variant has been implicated in genetic predisposition to cutaneous melanoma. We addressed the occurrence of MITF-E318K and its association with germline status of CDKN2A and MC1R genes in a hospital-based series of 248 melanoma patients including cohorts of multiple, familial, pediatric, sporadic and melanoma associated with other tumors. Seven MITF-E318K carriers were identified, spanning every group except the pediatric patients. Three carriers showed mutated CDKN2A, five displayed MC1R variants, while the sporadic carrier revealed no variants. Germline/tumor whole exome sequencing for this carrier revealed germline variants of unknown significance in ATM and FANCI genes and, in four BRAF-V600E metastases, somatic loss of the MITF wild-type allele, amplification of MITF-E318K and deletion of a 9p21.3 chromosomal region including CDKN2A and MTAP. In silico analysis of tumors from MITF-E318K melanoma carriers in the TCGA Pan-Cancer-Atlas dataset confirmed the association with BRAF mutation and 9p21.3 deletion revealing a common genetic pattern. MTAP was the gene deleted at homozygous level in the highest number of patients. These results support the utility of both germline and tumor genome analysis to define tumor groups providing enhanced information for clinical strategies and highlight the importance of melanoma prevention programs for MITF-E318K patients.
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- 2021
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36. Survival in Patients With Sentinel Node-Positive Melanoma With Extranodal Extension.
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Maurichi A, Barretta F, Patuzzo R, Miceli R, Gallino G, Mattavelli I, Barbieri C, Leva A, Angi M, Lanza FB, Spadola G, Cossa M, Nesa F, Cortinovis U, Sala L, Di Guardo L, Cimminiello C, Del Vecchio M, Valeri B, and Santinami M
- Subjects
- Extranodal Extension, Humans, Lymph Node Excision, Lymph Nodes pathology, Lymphatic Metastasis pathology, Prognosis, Retrospective Studies, Sentinel Lymph Node Biopsy, Melanoma pathology, Skin Neoplasms pathology
- Abstract
Background: Prognostic parameters in sentinel node (SN)-positive melanoma are important indicators to identify patients at high risk of recurrence who should be candidates for adjuvant therapy. We aimed to evaluate the presence of melanoma cells beyond the SN capsule-extranodal extension (ENE)-as a prognostic factor in patients with positive SNs., Methods: Data from 1,047 patients with melanoma and positive SNs treated from 2001 to 2020 at the Istituto Nazionale dei Tumori in Milano, Italy, were retrospectively investigated. Kaplan-Meier survival and crude cumulative incidence of recurrence curves were estimated. A multivariable logistic model was used to investigate the association between ENE and selected predictive factors. Cox models estimated the effect of the selected predictors on survival endpoints., Results: Median follow-up was 69 months. The 5-year overall survival rate was 62.5% and 71.7% for patients with positive SNs with and without ENE, respectively. The 5-year disease-free survival rate was 54.0% and 64.0% for patients with positive SNs with and without ENE, respectively. The multivariable logistic model showed that age, size of the main metastatic focus in the SN, and numbers of metastatic non-SNs were associated with ENE (all P<.0001). The multivariable Cox regression models showed the estimated prognostic effects of ENE associated with age, ulceration, size of the main metastatic focus in the SN, and number of metastatic non-SNs (all P<.0001) on disease-free survival and overall survival., Conclusions: ENE was a significant prognostic factor in patients with positive-SN melanoma. This parameter may be useful in clinical practice as a selection criterion for adjuvant treatment in patients with stage IIIA disease with a tumor burden <1 mm in the SN. We recommend its inclusion as an independent prognostic determinant in future updates of melanoma guidelines.
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- 2021
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37. Assessment of Surgical Care Provided in National Health Services Hospitals in Mozambique: The Importance of Subnational Metrics in Global Surgery.
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Cossa M, Rose J, Berndtson AE, Noormahomed E, and Bickler SW
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- Female, Hospitals, Humans, Mozambique epidemiology, Pregnancy, Prospective Studies, Benchmarking, State Medicine
- Abstract
Introduction: Surgery plays a critical role in sustainable healthcare systems. Validated metrics exist to guide implementation of surgical services, but low-income countries (LIC) struggle to report recommended metrics and this poses a critical barrier to addressing unmet need. We present a comprehensive national sample of surgical encounters from a LIC by assessing the National Health Services of Mozambique., Material and Methods: A prospective cohort of all surgical encounters from Mozambique's National Health Service was gathered for all provinces between July and December 2015. Primary outcomes were timely access, provider densities for surgery, anesthesiology, and obstetrics (SAO) per 100,000 population, annualized surgical procedure volume per 100,000, and postoperative mortality (POMR). Secondary outcomes include operating room density and efficiency., Results: Fifty-four hospitals had surgical capacity in 11 provinces with 47,189 surgeries. 44.9% of Mozambique's population lives in Districts without access to surgical services. National SAO density was 1.2/100,000, ranging from 0.4/100,000 in Manica Province to 9.8/100,000 in Maputo City. Annualized national surgical case volume was 367 procedures/100,000 population, ranging from 180/100,000 in Zambezia Province to 1,897/100,000 in Maputo City. National POMR was 0.74% and ranged from 0.23% in Maputo Province to 1.78% in Niassa Province., Discussion: Surgical delivery in Mozambique falls short of international targets. Subnational deficiencies and variations between provinces pose targets for quality improvement in advancing national surgical plans. This serves as a template for LICs to follow in gathering surgical metrics for the WHO and the World Bank and offers short- and long-term targets for surgery as a component of health systems strengthening.
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- 2021
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38. The role of sentinel lymph node status performed in melanoma patients with local recurrence or in transit metastasis.
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Mattavelli I, Maurichi A, Galeone C, Gallino G, Barbieri C, Leva A, Tolomio E, Valeri B, Cossa M, Patuzzo R, and Santinami M
- Subjects
- Aged, Female, Humans, Lymphatic Metastasis, Male, Prospective Studies, Melanoma pathology, Neoplasm Recurrence, Local pathology, Sentinel Lymph Node Biopsy, Skin Neoplasms pathology
- Abstract
Background: Sentinel Node Biopsy (SNB) is routinely performed for primary melanoma, but its role in the treatment of Local Recurrence (LR) and In-Transit metastasis (IT) is controversial. This study aims to assess the role of SNB in melanoma patients who developed first loco-regional recurrence., Methods: A series of consecutive melanoma patients who received SNB for a first IT or LR at the National Cancer Institute of Milan, Italy, from 2000 to 2015 were selected from a prospective database. Clinicopathological characteristics were analyzed., Results: Seventy-two patients met selection criteria. Forty-three patients (59.7%) received SNB for LR and 29 (40.3%) for IT. The average interval between treatment of primitive melanoma and first recurrence diagnosis was 19 months (interquartile range: 6.9-49.0). SN identification rate was 97.2%. SN positivity was detected in 26 (37.1%) patients. The SN-positive ratein melanoma patients who had LR or IT was significantly higher than reported for primary tumours. Of patients with nodal involvement 17 had LR and 9 IT lesions. Disease Free Survival (DFS) was slightly higher in SN negative patients, in the absence of statistically significant differences. Overall Survival (OS) analysis showed similar values in the two groups., Conclusion: Since DFS and OS do not show significant differences between SN negative and positive patients, our data do not give clear indications about performing SNB in case of first LR or IT. However, we suggest submitting patients with LR to this procedure to obtain a more accurate staging and eventually candidate these patients to adjuvant treatment., Competing Interests: Declaration of competing interest All authors have no conflicts of interest to disclose., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)
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- 2021
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39. Digital Immunophenotyping Predicts Disease Free and Overall Survival in Early Stage Melanoma Patients.
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De Logu F, Galli F, Nassini R, Ugolini F, Simi S, Cossa M, Miracco C, Gianatti A, De Giorgi V, Rulli E, Cossu A, Massi D, and Mandalà M
- Subjects
- Adult, Biomarkers, Tumor analysis, Female, Humans, Male, Melanoma mortality, Middle Aged, Skin Neoplasms immunology, Skin Neoplasms mortality, Tumor Microenvironment immunology, CD8-Positive T-Lymphocytes immunology, Lymphocytes, Tumor-Infiltrating immunology, Melanoma pathology, Skin Neoplasms pathology
- Abstract
Background: the prognostic significance of tumor infiltrating lymphocytes (TILs) in intermediate/thick primary cutaneous melanoma (PCM) remains controversial, partially because conventional evaluation is not reliable, due to inter-observer variability and diverse scoring methods. We aimed to assess the prognostic impact of the density and spatial distribution of immune cells in early stage intermediate/thick PCM., Materials and Methods: digital image acquisition and quantitative analysis of tissue immune biomarkers (CD3, CD4, CD8, CD68, PD-L1, CD163, FOX-P3, and PD-1) was carried out in a training cohort, which included patients with primary PCM ≥ 2 mm diagnosed, treated, and followed-up prospectively in three Italian centers. Results were validated in an independent Italian cohort., Results: in the training cohort, 100 Stage II-III melanoma patients were valuable. At multivariable analysis, a longer disease free survival (DFS) was statistically associated with higher levels of CD4
+ intratumoral T-cells (aHR [100 cell/mm2 increase] 0.98, 95%CI 0.95-1.00, p = 0.041) and CD163+ inner peritumoral (aHR [high vs. low] 0.56, 95%CI 0.32-0.99, p = 0.047). A statistically significant longer DFS (aHR [high-high vs. low-low] 0.52, 95%CI 0.28-0.99, p = 0.047) and overall survival (OS) (aHR [high-high vs. low-low] 0.39, 95%CI 0.18-0.85, p = 0.018) was found in patients with a high density of both intratumoral CD8+ T-cells and CD68+ macrophages as compared to those with low density of both intratumoral CD8+ T-cells and CD68+ macrophages. Consistently, in the validation cohort, patients with high density of both intratumoral CD8+ and CD3+ T-cells were associated to a statistically better DFS (aHR[high-high vs. low-low] 0.24, 95%CI 0.10-0.56, p < 0.001) and those with high density of both intratumoral CD8+ and CD68+ were associated to a statistically longer OS (aHR[high-high vs. low-low] 0.28, 95%CI 0.09-0.86, p = 0.025)., Conclusion: our findings suggest that a specific preexisting profile of T cells and macrophages distribution in melanomas may predict the risk of recurrence and death with potential implications for the stratification of stage II-III melanoma patients.- Published
- 2021
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40. Surgical treatment of melanoma metastases to the small bowel: A single cancer referral center real-life experience.
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Gallino G, Maurichi A, Patuzzo R, Mattavelli I, Barbieri C, Leva A, Valeri B, Cossa M, Galeone C, Pelucchi C, and Santinami M
- Subjects
- Adult, Female, Follow-Up Studies, Humans, Intestinal Neoplasms diagnosis, Intestinal Neoplasms secondary, Intestine, Small, Italy epidemiology, Male, Melanoma diagnosis, Melanoma secondary, Middle Aged, Neoplasm Metastasis, Prognosis, Retrospective Studies, Skin Neoplasms diagnosis, Skin Neoplasms mortality, Survival Rate trends, Intestinal Neoplasms surgery, Melanoma surgery, Skin Neoplasms surgery
- Abstract
Introduction: Treatment of metastatic melanoma has rapidly changed during the last years, and patients often require a multidisciplinary approach to achieve effective results. We aimed to assess the survival benefit achieved through surgical approach to patients with small bowel (SB) metastases from cutaneous melanoma, to emphasize the potential role of surgery in association with novel therapies., Methods: Ninety consecutive patients with cutaneous melanoma diagnosed as having resectable SB metastases from 1995 to 2015 were retrospectively investigated., Results: Median age at surgery of melanoma metastases was 53.4 years. Among 30 patients who had a curative-intent resection, the 5- and 10-year survival rates were 61% and 54%, respectively, while among 60 patients treated with a palliative surgery the corresponding rates were both 4%. Among 29 patients, for whom the interval time between the occurrence of SB metastases and the previous surgical event on GI tract was ≥36 months, the 5-year overall survival rate was 42%; for 56 patients who had an interval time <36 months the corresponding survival rate was 14%. Within the whole series, an absence of any residual disease after surgery (R0) was a factor affecting better survival, regardless of the evidence of metastases in other organs., Conclusion: Our observational data showed that surgical treatment for patients with SB metastases from melanoma might increase survival, but further studies are needed to confirm this finding. In the age of novel available therapies, the increase in survival time given by surgery may offer important chances for patients to benefit from systemic therapies., Competing Interests: Declaration of competing interest All authors disclose that there are no financial and personal relationships with other people or organizations that could inappropriately influence their work., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)
- Published
- 2021
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41. Designing a National Curriculum to Advance Surgical Oncology in Mozambique: A Delphi Consensus Study.
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Morais A, Simão M, Cossa M, Come J, Selemane C, Tivane A, Tulsidás S, Lorenzoni C, Rodrigues J, Antunes L, Brito D, Costa MJ, Sidat M, Martins MDRO, and Santos LL
- Subjects
- Clinical Competence, Consensus, Curriculum, Delphi Technique, Humans, Mozambique, Surgical Oncology
- Abstract
Objective: Mozambique is currently experiencing an increase in chronic diseases including cancer. There is a large unmet need for cancer surgery in Mozambique. The aim of this study was to define the content and the design of a training program for practicing surgeons in surgical oncology that would be consensually regarded as adequate to care for oncological patients requiring surgical interventions., Design & Setting: A 3-round modified-Delphi approach was implemented to obtain consensus on surgical oncology training curriculum. The participants were purposefully selected experts in surgical oncology working in Mozambique. In round 1, participants answered a questionnaire with open-ended questions regarding the content of the curriculum and the timing and venue of training. In round 2, answers from the first round were presented to a purposeful selected sample of nationally recognized experts in oncology and surgical oncology, including members of the Mozambican College of Surgeons and leadership of the Ministry of Health. A final round was carried out to discuss the draft version of the training program aiming to achieve a predetermined consensus level of 80%., Participants: Fifteen of 23 experts (65.2%) responded to round one.The response rate for round 1 and 3 was 80% (12 of the 15 participants in round one)., Results: The responses collected in the first round were analyzed and revealed that basic principles of oncology and basic principles of surgical oncology should be included in the curriculum of surgical residency in Mozambique (80% of the experts agree; Cronbach α = 0.93); a 24-months fellowship in surgical oncology should take place after residency in the surgical field (86.6% of experts agree; Cronbach α = 0.97); and should occur at Maputo Central Hospital and at comprehensive cancer centers abroad (100% agree). In round 2 the proposal for the program of surgical oncology fellowship obtained a strong agreement amongst the experts (97.3%). The final proposal for the program was divided into the following structure: (1) theoretical components; (2) duration; (3) location; (4) methodology; (5) technical skills in oncology; and (6) competency and paid particular attention to the oncological diseases prevalent in Mozambique. The agreement amongst the experts was 97.3%., Conclusions: The experts reached a consensus regarding the general structure for a cancer surgery postgraduate training program in Mozambique, which should be a 24-months fellowship after residency in surgical disciplines. This fellowship should mostly take place in Mozambique, but it should also include dedicated internships in recognized cancer hospitals abroad. Such curricula embrace the Global Curriculum in Surgical Oncology including in particular the oncological nosology of Mozambique and should advance the quality of oncology surgical care provided in the country., (Copyright © 2020 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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42. Analysis of Sentinel Node Biopsy and Clinicopathologic Features as Prognostic Factors in Patients With Atypical Melanocytic Tumors.
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Maurichi A, Miceli R, Patuzzo R, Barretta F, Gallino G, Mattavelli I, Barbieri C, Leva A, Cortinovis U, Tolomio E, Sant M, Castelli G, Zichichi L, Pellacani G, Stanganelli I, Simonacci M, Manganoni A, Del Forno C, Caresana G, Harwood C, Bergamaschi D, Lasithiotakis K, Bennett D, Espeli V, Mangas C, Leoni Parvex S, Valeri B, Cossa M, Barisella M, Pellegrinelli A, Miranda C, Anichini A, Mortarini R, Zoras O, and Santinami M
- Subjects
- Adolescent, Adult, Child, Disease-Free Survival, Humans, Lymphatic Metastasis, Mitosis, Neoplasm Recurrence, Local, Prognosis, Retrospective Studies, Young Adult, Melanoma diagnosis, Sentinel Lymph Node Biopsy, Skin Neoplasms diagnosis
- Abstract
Background: Atypical melanocytic tumors (AMTs) include a wide spectrum of melanocytic neoplasms that represent a challenge for clinicians due to the lack of a definitive diagnosis and the related uncertainty about their management. This study analyzed clinicopathologic features and sentinel node status as potential prognostic factors in patients with AMTs., Patients and Methods: Clinicopathologic and follow-up data of 238 children, adolescents, and adults with histologically proved AMTs consecutively treated at 12 European centers from 2000 through 2010 were retrieved from prospectively maintained databases. The binary association between all investigated covariates was studied by evaluating the Spearman correlation coefficients, and the association between progression-free survival and all investigated covariates was evaluated using univariable Cox models. The overall survival and progression-free survival curves were established using the Kaplan-Meier method., Results: Median follow-up was 126 months (interquartile range, 104-157 months). All patients received an initial diagnostic biopsy followed by wide (1 cm) excision. Sentinel node biopsy was performed in 139 patients (58.4%), 37 (26.6%) of whom had sentinel node positivity. There were 4 local recurrences, 43 regional relapses, and 8 distant metastases as first events. Six patients (2.5%) died of disease progression. Five patients who were sentinel node-negative and 3 patients who were sentinel node-positive developed distant metastases. Ten-year overall and progression-free survival rates were 97% (95% CI, 94.9%-99.2%) and 82.2% (95% CI, 77.3%-87.3%), respectively. Age, mitotic rate/mm2, mitoses at the base of the lesion, lymphovascular invasion, and 9p21 loss were factors affecting prognosis in the whole series and the sentinel node biopsy subgroup., Conclusions: Age >20 years, mitotic rate >4/mm2, mitoses at the base of the lesion, lymphovascular invasion, and 9p21 loss proved to be worse prognostic factors in patients with ATMs. Sentinel node status was not a clear prognostic predictor.
- Published
- 2020
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43. miR-146a-5p impairs melanoma resistance to kinase inhibitors by targeting COX2 and regulating NFkB-mediated inflammatory mediators.
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Vergani E, Dugo M, Cossa M, Frigerio S, Di Guardo L, Gallino G, Mattavelli I, Vergani B, Lalli L, Tamborini E, Valeri B, Gargiuli C, Shahaj E, Ferrarini M, Ferrero E, Gomez Lira M, Huber V, Del Vecchio M, Sensi M, Leone BE, Santinami M, Rivoltini L, Rodolfo M, and Vallacchi V
- Subjects
- Cell Line, Tumor, Cyclooxygenase 2 genetics, Extracellular Signal-Regulated MAP Kinases metabolism, Gene Expression Regulation, Neoplastic drug effects, Humans, Melanoma pathology, MicroRNAs genetics, Mitogen-Activated Protein Kinase Kinases antagonists & inhibitors, Mitogen-Activated Protein Kinase Kinases metabolism, Models, Biological, Protein Kinase Inhibitors pharmacology, Proto-Oncogene Proteins B-raf antagonists & inhibitors, Proto-Oncogene Proteins B-raf metabolism, Proto-Oncogene Proteins c-akt metabolism, Signal Transduction drug effects, Cyclooxygenase 2 metabolism, Drug Resistance, Neoplasm drug effects, Drug Resistance, Neoplasm genetics, Inflammation Mediators metabolism, Melanoma drug therapy, Melanoma genetics, MicroRNAs metabolism, NF-kappa B metabolism, Protein Kinase Inhibitors therapeutic use
- Abstract
Background: Targeted therapy with BRAF and MEK inhibitors has improved the survival of patients with BRAF-mutated metastatic melanoma, but most patients relapse upon the onset of drug resistance induced by mechanisms including genetic and epigenetic events. Among the epigenetic alterations, microRNA perturbation is associated with the development of kinase inhibitor resistance. Here, we identified and studied the role of miR-146a-5p dysregulation in melanoma drug resistance., Methods: The miR-146a-5p-regulated NFkB signaling network was identified in drug-resistant cell lines and melanoma tumor samples by expression profiling and knock-in and knock-out studies. A bioinformatic data analysis identified COX2 as a central gene regulated by miR-146a-5p and NFkB. The effects of miR-146a-5p/COX2 manipulation were studied in vitro in cell lines and with 3D cultures of treatment-resistant tumor explants from patients progressing during therapy., Results: miR-146a-5p expression was inversely correlated with drug sensitivity and COX2 expression and was reduced in BRAF and MEK inhibitor-resistant melanoma cells and tissues. Forced miR-146a-5p expression reduced COX2 activity and significantly increased drug sensitivity by hampering prosurvival NFkB signaling, leading to reduced proliferation and enhanced apoptosis. Similar effects were obtained by inhibiting COX2 by celecoxib, a clinically approved COX2 inhibitor., Conclusions: Deregulation of the miR-146a-5p/COX2 axis occurs in the development of melanoma resistance to targeted drugs in melanoma patients. This finding reveals novel targets for more effective combination treatment. Video Abstract.
- Published
- 2020
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44. Reply to E. Hindié.
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Maurichi A, Miceli R, Eriksson H, Newton-Bishop J, Nsengimana J, Chan M, Hayes AJ, Heelan K, Adams D, Patuzzo R, Barretta F, Gallino G, Harwood C, Bergamaschi D, Bennett D, Lasithiotakis K, Ghiorzo P, Dalmasso B, Manganoni A, Consoli F, Mattavelli I, Barbieri C, Leva A, Cortinovis U, Espeli V, Mangas C, Quaglino P, Ribero S, Broganelli P, Pellacani G, Longo C, Del Forno C, Borgognoni L, Sestini S, Pimpinelli N, Fortunato S, Chiarugi A, Nardini P, Morittu E, Florita A, Cossa M, Valeri B, Milione M, Pruneri G, Zoras O, Anichini A, Mortarini R, and Santinami M
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- 2020
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45. Factors Affecting Sentinel Node Metastasis in Thin (T1) Cutaneous Melanomas: Development and External Validation of a Predictive Nomogram.
- Author
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Maurichi A, Miceli R, Eriksson H, Newton-Bishop J, Nsengimana J, Chan M, Hayes AJ, Heelan K, Adams D, Patuzzo R, Barretta F, Gallino G, Harwood C, Bergamaschi D, Bennett D, Lasithiotakis K, Ghiorzo P, Dalmasso B, Manganoni A, Consoli F, Mattavelli I, Barbieri C, Leva A, Cortinovis U, Espeli V, Mangas C, Quaglino P, Ribero S, Broganelli P, Pellacani G, Longo C, Del Forno C, Borgognoni L, Sestini S, Pimpinelli N, Fortunato S, Chiarugi A, Nardini P, Morittu E, Florita A, Cossa M, Valeri B, Milione M, Pruneri G, Zoras O, Anichini A, Mortarini R, and Santinami M
- Abstract
Purpose: Thin melanomas (T1; ≤ 1 mm) constitute 70% of newly diagnosed cutaneous melanomas. Regional node metastasis determined by sentinel node biopsy (SNB) is an important prognostic factor for T1 melanoma. However, current melanoma guidelines do not provide clear indications on when to perform SNB in T1 disease and stress an individualized approach to SNB that considers all clinicopathologic risk factors. We aimed to identify determinants of sentinel node (SN) status for incorporation into an externally validated nomogram to better select patients with T1 disease for SNB., Patients and Methods: The development cohort comprised 3,666 patients with T1 disease consecutively treated at the Istituto Nazionale Tumori (Milan, Italy) between 2001 and 2018; 4,227 patients with T1 disease treated at 13 other European centers over the same period formed the validation cohort. A random forest procedure was applied to the development data set to select characteristics associated with SN status for inclusion in a multiple binary logistic model from which a nomogram was elaborated. Decision curve analyses assessed the clinical utility of the nomogram., Results: Of patients in the development cohort, 1,635 underwent SNB; 108 patients (6.6%) were SN positive. By univariable analysis, age, growth phase, Breslow thickness, ulceration, mitotic rate, regression, and lymphovascular invasion were significantly associated with SN status. The random forest procedure selected 6 variables (not growth phase) for inclusion in the logistic model and nomogram. The nomogram proved well calibrated and had good discriminative ability in both cohorts. Decision curve analyses revealed the superior net benefit of the nomogram compared with each individual variable included in it as well as with variables suggested by current guidelines., Conclusion: We propose the nomogram as a decision aid in all patients with T1 melanoma being considered for SNB.
- Published
- 2020
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46. Unusual skin toxicity associated with sustained disease response induced by nivolumab in a patient with non-small cell lung cancer.
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Galli G, Proto C, Cossa M, Valeri B, Sdao S, Signorelli D, Imbimbo M, de Braud F, Garassino MC, and Lo Russo G
- Subjects
- Antineoplastic Agents, Immunological therapeutic use, Biopsy, Carcinoma, Non-Small-Cell Lung diagnosis, Carcinoma, Non-Small-Cell Lung drug therapy, Humans, Immunohistochemistry, Lung Neoplasms diagnosis, Lung Neoplasms drug therapy, Male, Middle Aged, Molecular Targeted Therapy adverse effects, Molecular Targeted Therapy methods, Nivolumab therapeutic use, Skin Diseases drug therapy, Steroids therapeutic use, Tomography, X-Ray Computed, Treatment Outcome, Antineoplastic Agents, Immunological adverse effects, Carcinoma, Non-Small-Cell Lung complications, Lung Neoplasms complications, Nivolumab adverse effects, Skin Diseases diagnosis, Skin Diseases etiology
- Abstract
Introduction: Immunotherapy has shown efficacy in the treatment of different malignancies. Nivolumab, an immune checkpoint inhibitor directed against programmed death-1, has been approved for non-small cell lung cancer (NSCLC) in pretreated patients. Although it is generally well-tolerated, immunotherapy may be complicated by a wide range of immune-mediated adverse events. We describe the case of an uncommon skin toxicity arising as alopecia universalis induced by nivolumab in a patient with NSCLC., Case Description: A 58-year-old man received nivolumab for metastatic NSCLC after progression to 3 lines of chemotherapy. The treatment was prescribed in June 2016, and induced a rapid and significant disease response. Nivolumab was well-tolerated until May 2017, when partial alopecia at hair and eyelashes appeared. In the next months, alopecia became complete and extended to the whole body surface. The dermatologic picture was compatible with alopecia areata. A topical steroid therapy was attempted, without benefit. The patient refused systemic treatments and is still undergoing nivolumab without new toxicities and with persistent disease response., Conclusions: This case suggests that alopecia areata may be a rare immune-related adverse event of immune checkpoint agents. Its late onset in our patient is uncommon and unexpected, underlining that the risk of nivolumab-induced toxicity is not limited to the beginning of treatment. Despite its rarity, alopecia areata should be considered in the range of adverse events potentially induced by immune checkpoint inhibitors even in the long term. Potential association between toxicity and efficacy of immunotherapy in NSCLC warrants further investigation.
- Published
- 2019
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47. Understanding the bricks to build better surgical oncology unit at Maputo Central Hospital: prevalent surgical cancers and residents knowledge.
- Author
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Morais A, Come J, Selemane C, Pires G, Tivane A, Cossa M, Tulsidás S, Antunes L, Costa MJ, Sidat M, Martins MDR, Carrilho C, and Santos LL
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Curriculum, Educational Measurement, Female, Health Knowledge, Attitudes, Practice, Hospitals, Humans, Male, Middle Aged, Mozambique, Neoplasm Staging, Neoplasms epidemiology, Neoplasms pathology, Prevalence, Registries, Retrospective Studies, Young Adult, Clinical Competence, Internship and Residency standards, Neoplasms surgery, Surgical Oncology education
- Abstract
Introduction: Cancer is a growing concern in Mozambique. However, the country has limited facilities and few oncologists. Surgical oncologists are an unmet need. The aim of this study was to assess residents' knowledge in prevalent cancer domains and to identify and characterize prevalent cancers treated by surgery at Maputo Central Hospital, the largest hospital in Mozambique. The expectations were that the findings shall inform the development of a comprehensive curriculum in surgical oncology fellowship fit for the Hospital., Methods: To identify and characterize prevalent cancers, we performed a retrospective analysis of individual cancer patient registries of Maputo Central Hospital (MCH), Mozambique. Information was recorded into data collection sheets and analyzed with SPSS
® 21. To assess MCH residents oncologic knowledge, we invited Twenty-six junior residents (49% of all residents) of different specialties to take a 30 item multiple choice written test used elsewhere in previous studies. The test focused on the domains of Basis of oncology, Radiotherapy, Pathology, Chemotherapy, Pain management, Surgical oncology and Clinical Pathway. The test was administered anonymously and without prior notice. We analyzed the overall test and topic performance of residents., Results: The study covered a period of 3 years and 203 patients. The most prevalent malignant tumors treated by general and thoracic surgery in MCH cancer registry were esophageal (7%), female breast (6.5%) and colorectal cancer (2.8%). Globally these malignancies were diagnosed at an advanced stage of the disease and required a multimodal treatment. The mean percent correct score of residents was 37.3%. The dimension with the highest percent correct score were clinical management (46%) and surgical oncology (28%) showed the lowest correct score., Conclusion: In Maputo, Mozambique esophageal, breast and colorectal cancer were the most prevalent malignancies treated, with surgery, by thoracic or general surgery in MCH. The test scores suggest that, among residents, the knowledge in oncology needs to be improved, rendering support to the need of a surgical oncology training tailored to suit the local needs. Specific training should take into account local cancer prevalence, resources, their quality and the support of surgical oncology services with volume and experience., Competing Interests: The authors declare no competing interests.- Published
- 2019
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48. Intrapericardial diaphragmatic hernia in a 6-month-old girl: A case report and review of the literature.
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Cossa M and Robinson TD
- Abstract
Introduction: Intrapericardial congenital diaphragmatic hernia (IPCDH) is extremely rare: only 18 cases in children have been reported in the literature since 1981. We report the 19th case of infantile IPCDH in a 6-month-old girl and compare with previous reports., Presentation of Case: Our patient initially presented with four days of dyspnea and was diagnosed with CDH by preoperative radiography. She was taken to the operating room, where an IPCDH was discovered, and successfully reduced., Discussion: CDH may present with cardiopulmonary compromise, but IPCDH directly compress the heart, leading to acute or subacute heart failure., Conclusion: Pediatric surgeons should be aware of and prepared for the possibility of IPCDH when making surgical plans to correct CDH., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2019
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49. Tumor-derived microRNAs induce myeloid suppressor cells and predict immunotherapy resistance in melanoma.
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Huber V, Vallacchi V, Fleming V, Hu X, Cova A, Dugo M, Shahaj E, Sulsenti R, Vergani E, Filipazzi P, De Laurentiis A, Lalli L, Di Guardo L, Patuzzo R, Vergani B, Casiraghi E, Cossa M, Gualeni A, Bollati V, Arienti F, De Braud F, Mariani L, Villa A, Altevogt P, Umansky V, Rodolfo M, and Rivoltini L
- Subjects
- Animals, Female, Humans, Leukocytes, Mononuclear pathology, Male, Melanoma, Experimental pathology, Melanoma, Experimental therapy, Mice, Myeloid-Derived Suppressor Cells pathology, Immunotherapy, Leukocytes, Mononuclear immunology, Melanoma, Experimental immunology, MicroRNAs metabolism, Myeloid-Derived Suppressor Cells immunology, RNA, Neoplasm immunology
- Abstract
The accrual of myeloid-derived suppressor cells (MDSCs) represents a major obstacle to effective immunotherapy in cancer patients, but the mechanisms underlying this process in the human setting remain elusive. Here, we describe a set of microRNAs (miR-146a, miR-155, miR-125b, miR-100, let-7e, miR-125a, miR-146b, miR-99b) that are associated with MDSCs and resistance to treatment with immune checkpoint inhibitors in melanoma patients. The miRs were identified by transcriptional analyses as being responsible for the conversion of monocytes into MDSCs (CD14+HLA-DRneg cells) mediated by melanoma extracellular vesicles (EVs) and were shown to recreate MDSC features upon transfection. In melanoma patients, these miRs were increased in circulating CD14+ monocytes, plasma, and tumor samples, where they correlated with the myeloid cell infiltrate. In plasma, their baseline levels clustered with the clinical efficacy of CTLA-4 or programmed cell death protein 1 (PD-1) blockade. Hence, MDSC-related miRs represent an indicator of MDSC activity in cancer patients and a potential blood marker of a poor immunotherapy outcome.
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- 2018
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50. Clinical and Pathologic Profiles of Esophageal Cancer in Mozambique: A Study of Consecutive Patients Admitted to Maputo Central Hospital.
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Come J, Castro C, Morais A, Cossa M, Modcoicar P, Tulsidâs S, Cunha L, Lobo V, Morais AG, Cotton S, Lunet N, Carrilho C, and Santos LL
- Subjects
- Adult, Aged, Aged, 80 and over, Esophageal Neoplasms mortality, Female, Hospitals, Humans, Male, Middle Aged, Mozambique, Survival Rate, Esophageal Neoplasms diagnosis, Esophageal Neoplasms pathology
- Abstract
Purpose: Eastern Africa was recently described as a high-incidence geographic area for esophageal cancer. Mozambique is included in this region. This study aimed to characterize this malignant disease at Maputo Central Hospital (MCH) to develop a global program for esophageal cancer management in Mozambique., Methods: MCH records from between 2012 and 2016 were used to assess the clinical, pathologic, and outcome profiles of esophageal tumors. A descriptive analysis of data collected was performed. Overall survival was evaluated using Kaplan-Meier curves., Results: In the study, 522 consecutive patient cases of esophageal cancer were recorded. The median patient age was 56.1 years (range, 27 to 97 years); 291 (55.7%) patients were women, and 230 (44.1%) were men. Regarding tumor site, 113 patients (21.6%) had a tumor in the lower third, 154 (29.5%) in the middle, and 50 (9.6%) in the upper third of the esophagus; in the remaining 196 (37.5%), tumor site was unknown. Squamous cell carcinoma comprised 94.4% of cases with documented histopathology (74.9% of the sample). Surgical treatment was possible in 32 patients (6.1%). Disease stage was documented only in these 32 surgical patients; 28.1%, 53.1%, and 18.8% had stage I, II, and III disease, respectively. The remaining patient cases seemed to involve clinically advanced tumors. The median follow-up time was of 1.6 months. The median survival time was of 3.5 months for all patients; for patients treated with curative intent, it was of 8.7 months., Conclusion: Esophageal carcinoma is a common malignant tumor at MCH and is diagnosed in the advanced stages resulting in poor prognosis. Therefore, implementation of an Esophageal Cancer Program in Mozambique is essential.
- Published
- 2018
- Full Text
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