Publications by authors named "Marchetti M"

1,131 Publications

Thrombocytopathies: Not Just Aggregation Defects-The Clinical Relevance of Procoagulant Platelets.

J Clin Med 2021 Feb 24;10(5). Epub 2021 Feb 24.

Hemostasis and Platelet Research Laboratory, Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), CH-1010 Lausanne, Switzerland.

Platelets are active key players in haemostasis. Qualitative platelet dysfunctions result in thrombocytopathies variously characterized by defects of their adhesive and procoagulant activation endpoints. In this review, we summarize the traditional platelet defects in adhesion, secretion, and aggregation. In addition, we review the current knowledge about procoagulant platelets, focusing on their role in bleeding or thrombotic pathologies and their pharmaceutical modulation. Procoagulant activity is an important feature of platelet activation, which should be specifically evaluated during the investigation of a suspected thrombocytopathy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10050894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956450PMC
February 2021

Emergence of dynamic vortex glasses in disordered polar active fluids.

Proc Natl Acad Sci U S A 2021 Mar;118(10)

Université de Lyon, École Normale Supérieure de Lyon, Université Claude Bernard, CNRS, Laboratoire de Physique, F-69342 Lyon, France;

In equilibrium, disorder conspires with topological defects to redefine the ordered states of matter in systems as diverse as crystals, superconductors, and liquid crystals. Far from equilibrium, however, the consequences of quenched disorder on active condensed matter remain virtually uncharted. Here, we reveal a state of strongly disordered active matter with no counterparts in equilibrium: a dynamical vortex glass. Combining microfluidic experiments and theory, we show how colloidal flocks collectively cruise through disordered environments without relaxing the topological singularities of their flows. The resulting state is highly dynamical but the flow patterns, shaped by a finite density of frozen vortices, are stationary and exponentially degenerated. Quenched isotropic disorder acts as a random gauge field turning active liquids into dynamical vortex glasses. We argue that this robust mechanism should shape the collective dynamics of a broad class of disordered active matter, from synthetic active nematics to collections of living cells exploring heterogeneous media.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2018218118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958234PMC
March 2021

Preexisting and treatment-emergent autoimmune cytopenias in patients with CLL treated with targeted drugs.

Blood 2021 Jun;137(25):3507-3517

Department of Molecular Biotechnology and Health Sciences, University of Torino-Division of Hematology, Azienda Ospedaliero-Universitaria (AOU) Città della Salute e della Scienza di Torino, Turin, Italy.

Autoimmune cytopenias (AICs) affect 5% to 9% of patients with chronic lymphocytic leukemia (CLL). Targeted drugs-ibrutinib, idelalisib, and venetoclax-have a prominent role in the treatment of CLL, but their impact on CLL-associated AICs is largely unknown. In this study, we evaluated the characteristics and outcome of preexisting AICs and described the incidence, quality, and management of treatment-emergent AICs during therapy with targeted drugs in patients with CLL. We collected data from 572 patients treated with ibrutinib (9% in combination with an anti-CD20 monoclonal antibody), 143 treated with idelalisib-rituximab, and 100 treated with venetoclax (12% in combination with an anti-CD20 monoclonal antibody). A history of preexisting AICs was reported in 104 (13%) of 815 patients. Interestingly, 80% of patients whose AICs had not resolved when treatment with a targeted drug was started experienced an improvement or a resolution during therapy. Treatment-emergent AICs occurred in 1% of patients during ibrutinib therapy, in 0.9% during idelalisib therapy, and in 7% during venetoclax therapy, with an estimated incidence rate of 5, 6, and 69 episodes per 1000 patients per year of exposure in the 3 treatment groups, respectively. The vast majority of patients who developed treatment-emergent AICs had unfavorable biological features such as an unmutated IGHV and a del(17p) and/or TP53 mutation. Notably, despite AICs, 83% of patients were able to continue the targeted drug, in some cases in combination with additional immunosuppressive agents. Overall, treatment with ibrutinib, idelalisib, or venetoclax seems to have a beneficial impact on CLL-associated AICs, inducing an improvement or even a resolution of preexisting AICs in most cases and eliciting treatment-emergent AICs in a negligible portion of patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood.2020008201DOI Listing
June 2021

Fluctuations can induce local nematic order and extensile stress in monolayers of motile cells.

Soft Matter 2021 Mar 17;17(11):3068-3073. Epub 2021 Feb 17.

Department of Physics, University of California Santa Barbara, Santa Barbara, CA 93106, USA.

Recent experiments in various cell types have shown that two-dimensional tissues often display local nematic order, with evidence of extensile stresses manifest in the dynamics of topological defects. Using a mesoscopic model where tissue flow is generated by fluctuating traction forces coupled to the nematic order parameter, we show that the resulting tissue dynamics can spontaneously produce local nematic order and an extensile internal stress. A key element of the model is the assumption that in the presence of local nematic alignment, cells preferentially crawl along the nematic axis, resulting in anisotropy of fluctuations. Our work shows that activity can drive either extensile or contractile stresses in tissue, depending on the relative strength of the contractility of the cortical cytoskeleton and tractions by cells on the extracellular matrix.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0sm02027cDOI Listing
March 2021

Prevention and Management of Thrombosis in BCR/ABL-Negative Myeloproliferative Neoplasms.

Hamostaseologie 2021 Feb 15;41(1):48-57. Epub 2021 Feb 15.

Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy.

Myeloproliferative neoplasms (MPNs) are clonal disorders of the hematopoietic stem cell. Classical BCR/ABL-negative MPNs include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Thrombotic events are a major cause of morbidity and mortality in these patients. Pathogenesis of blood clotting activation involves various abnormalities of platelets, erythrocytes, and leukocytes, as well as dysfunctions of endothelial cells. Patients with MPN can be stratified in "high risk" or "low risk" of thrombosis according to established risk factors. ET and PV clinical management is highly dependent on the patient's thrombotic risk, and a risk-oriented management strategy to treat these diseases is strongly recommended. In this review, we give an overview of risk factors, pathogenesis, and thrombosis prevention and treatment in MPN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1334-3259DOI Listing
February 2021

Validation of the Role of Thrombin Generation Potential by a Fully Automated System in the Identification of Breast Cancer Patients at High Risk of Disease Recurrence.

TH Open 2021 Jan 10;5(1):e56-e65. Epub 2021 Feb 10.

Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy.

 The measurement of thrombin generation (TG) potential by the calibrated automated thrombogram (CAT) assay provides a strong contribution in identifying patients at high risk of early disease recurrence (E-DR). However, CAT assay still needs standardization and clinical validation.  In this study, we aimed to validate the role of TG for E-DR prediction by means of the fully automated ST Genesia system.  A prospective cohort of 522 patients from the HYPERCAN study with newly diagnosed resected high-risk breast cancer was included. Fifty-two healthy women acted as controls. Plasma samples were tested for protein C, free-protein S, and TG by ST Genesia by using the STG-ThromboScreen reagent with and without thrombomodulin (TM).  In the absence of TM, patients showed significantly higher peak and ETP compared with controls. In the presence of TM, significantly lower inhibition of ETP and Peak were observed in patients compared with controls. E-DR occurred in 28 patients; these patients had significantly higher peak and endogenous thrombin potential (ETP) in the absence of TM compared with disease-free patients. Multivariable analysis identified mastectomy, luminal B HER2-neg, triple negative subtypes, and ETP as independent risk factors for E-DR. These variables were combined to generate a risk assessment score, able to stratify patients in three-risk categories. The E-DR rates were 0, 4.7, and 13.5% in the low-, intermediate-, and high-risk categories (hazard ratio = 8.7;  < 0.05, low vs. high risk).  Our data validate the ETP parameter with a fully automated standardized system and confirm its significant contribution in identifying high-risk early breast cancer at risk for E-DR during chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0040-1722609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875677PMC
January 2021

Heparin-Induced Thrombocytopenia: A Review of New Concepts in Pathogenesis, Diagnosis, and Management.

J Clin Med 2021 Feb 10;10(4). Epub 2021 Feb 10.

Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), CH-1011 Lausanne, Switzerland.

Knowledge on heparin-induced thrombocytopenia keeps increasing. Recent progress on diagnosis and management as well as several discoveries concerning its pathogenesis have been made. However, many aspects of heparin-induced thrombocytopenia remain partly unknown, and exact application of these new insights still need to be addressed. This article reviews the main new concepts in pathogenesis, diagnosis, and management of heparin-induced thrombocytopenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10040683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916628PMC
February 2021

The New Hyperspectral Satellite PRISMA: Imagery for Forest Types Discrimination.

Sensors (Basel) 2021 Feb 8;21(4). Epub 2021 Feb 8.

Dipartimento di Scienze e Tecnologie Agrarie, Alimentari, Ambientali e Forestali, Università degli Studi di Firenze, 50145 Firenze, Italy.

Different forest types based on different tree species composition may have similar spectral signatures if observed with traditional multispectral satellite sensors. Hyperspectral imagery, with a more continuous representation of their spectral behavior may instead be used for their classification. The new hyperspectral Precursore IperSpettrale della Missione Applicativa (PRISMA) sensor, developed by the Italian Space Agency, is able to capture images in a continuum of 240 spectral bands ranging between 400 and 2500 nm, with a spectral resolution smaller than 12 nm. The new sensor can be employed for a large number of remote sensing applications, including forest types discrimination. In this study, we compared the capabilities of the new PRISMA sensor against the well-known Sentinel-2 Multi-Spectral Instrument (MSI) in recognition of different forest types through a pairwise separability analysis carried out in two study areas in Italy, using two different nomenclature systems and four separability metrics. The PRISMA hyperspectral sensor, compared to Sentinel-2 MSI, allowed for a better discrimination in all forest types, increasing the performance when the complexity of the nomenclature system also increased. PRISMA achieved an average improvement of 40% for the discrimination between two forest categories (coniferous vs. broadleaves) and of 102% in the discrimination between five forest types based on main tree species groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/s21041182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915604PMC
February 2021

Urogenital myiasis caused by Lucilia sericata (Diptera: Calliphoridae) in a domestic rabbit in Italy.

Vet Ital 2020 08 31;56(3):213-215. Epub 2020 Aug 31.

Department of Biology, Ecology and Earth Sciences, University of Calabria,Via P. Bucci, 87036 Arcavacata di Rende, Cosenza, Italy.

The report describes a case of urogenital myiasis in a domestic rabbit Oryctolagus cuniculus L. (Lagomorpha: Leporidae) caused by Lucilia sericata (Meigen; Diptera: Calliphoridae) in region Emilia-Romagna (Northern Italy). The case, occurring in June 2018, is the first one involving L. sericata as an agent of myiasis in a domestic rabbit in Italy. Species identification was based on morphological investigations of males through identification keys. The rabbit developed the urogenital myiasis as a consequence of chronic enteritis causing an accumulation of faeces in the perianal and perineal region.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12834/VetIt.2061.10978.2DOI Listing
August 2020

Viscoelastic control of spatiotemporal order in bacterial active matter.

Nature 2021 02 3;590(7844):80-84. Epub 2021 Feb 3.

Department of Physics and Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, P. R. China.

Active matter consists of units that generate mechanical work by consuming energy. Examples include living systems (such as assemblies of bacteria and biological tissues), biopolymers driven by molecular motors and suspensions of synthetic self-propelled particles. A central goal is to understand and control the self-organization of active assemblies in space and time. Most active systems exhibit either spatial order mediated by interactions that coordinate the spatial structure and the motion of active agents or the temporal synchronization of individual oscillatory dynamics. The simultaneous control of spatial and temporal organization is more challenging and generally requires complex interactions, such as reaction-diffusion hierarchies or genetically engineered cellular circuits. Here we report a simple technique to simultaneously control the spatial and temporal self-organization of bacterial active matter. We confine dense active suspensions of Escherichia coli cells and manipulate a single macroscopic parameter-namely, the viscoelasticity of the suspending fluid- through the addition of purified genomic DNA. This reveals self-driven spatial and temporal organization in the form of a millimetre-scale rotating vortex with periodically oscillating global chirality of tunable frequency, reminiscent of a torsional pendulum. By combining experiments with an active-matter model, we explain this behaviour in terms of the interplay between active forcing and viscoelastic stress relaxation. Our findings provide insight into the influence of bacterial motile behaviour in complex fluids, which may be of interest in health- and ecology-related research, and demonstrate experimentally that rheological properties can be harnessed to control active-matter flows. We envisage that our millimetre-scale, tunable, self-oscillating bacterial vortex may be coupled to actuation systems to act a 'clock generator' capable of providing timing signals for rhythmic locomotion of soft robots and for programmed microfluidic pumping, for example, by triggering the action of a shift register in soft-robotic logic devices.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-020-03168-6DOI Listing
February 2021

Investigational Studies on a Hit Compound Cyclopropane-Carboxylic Acid Derivative Targeting -Acetylserine Sulfhydrylase as a Colistin Adjuvant.

ACS Infect Dis 2021 02 29;7(2):281-292. Epub 2021 Jan 29.

P4T Group, Department of Food and Drugs, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy.

Antibacterial adjuvants are of great significance, since they allow the therapeutic dose of conventional antibiotics to be lowered and reduce the insurgence of antibiotic resistance. Herein, we report that an acetylserine sulfhydrylase (OASS) inhibitor can be used as a colistin adjuvant to treat infections caused by Gram-positive and Gram-negative pathogens. A compound that binds OASS with a nM dissociation constant was tested as an adjuvant of colistin against six critical pathogens responsible for infections spreading worldwide, , serovar Typhimurium, , , methicillin-resistant , and . The compound showed promising synergistic or additive activities against all of them. Knockout experiments confirmed the intracellular target engagement supporting the proposed mechanism of action. Moreover, compound toxicity was evaluated by means of its hemolytic activity against sheep defibrinated blood cells, showing a good safety profile. The 3D structure of the compound in complex with OASS was determined at 1.2 Å resolution by macromolecular crystallography, providing for the first time structural insights about the nature of the interaction between the enzyme and this class of competitive inhibitors. Our results provide a robust proof of principle supporting OASS as a potential nonessential antibacterial target to develop a new class of adjuvants and the structural basis for further structure-activity relationship studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsinfecdis.0c00378DOI Listing
February 2021

Child brides: the age estimation problem in young girls.

J Forensic Odontostomatol 2020 Dec 30;3(38):2-7. Epub 2020 Dec 30.

Department of Biomedical Sciences and Public Health, Polytechnic University of Marche, Ancona, Italy.

The aim of this work is to study a sample of girls from 15 different countries using Third Molar Maturity Index (I3M ), to assess the probability that a girl has reached the legal age of 18 years. The studied sample consisted of 3228 Orthopantomograms of healthy female subjects from 15 different countries. The cut-off value of I3M = 0.08 was tested to discriminate adults (≥18 years) and minors (<18 years). X-ray images were processed by computer-aided drafting program ImageJ. The information on sensitivity and specificity of I3M coming from the 15 countries was pooled together using a bivariate Bayesian modeling approach. Specificity of the I3M test did not change when the country was considered, and its value remains greater than 85% for each studied country. This method is useful to estimate the age of the girls involved in suspected early marriage because of the high probability of correctly identifying a minor with similar results observed among tested populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
December 2020

Dermoscopy Proficiency Expectations for US Dermatology Resident Physicians: Results of a Modified Delphi Survey of Pigmented Lesion Experts.

JAMA Dermatol 2021 Feb;157(2):189-197

The Ronald O. Perelman Department of Dermatology, NYU Grossman School of Medicine, New York, New York.

Importance: Dermoscopy education in US dermatology residency programs varies widely, and there is currently no existing expert consensus identifying what is most important for resident physicians to know.

Objectives: To identify consensus-based learning constructs representing an appropriate foundational proficiency in dermoscopic image interpretation for dermatology resident physicians, including dermoscopic diagnoses, associated features, and representative teaching images. Defining these foundational proficiency learning constructs will facilitate further skill development in dermoscopic image interpretation to help residents achieve clinical proficiency.

Design, Setting, And Participants: A 2-phase modified Delphi surveying technique was used to identify resident learning constructs in 3 sequential sets of surveys-diagnoses, features, and images. Expert panelists were recruited through an email distributed to the 32 members of the Pigmented Lesion Subcommittee of the Melanoma Prevention Working Group. Twenty-six (81%) opted to participate. Surveys were distributed using RedCAP software.

Main Outcomes And Measures: Consensus on diagnoses, associated dermoscopic features, and representative teaching images reflective of a foundational proficiency in dermoscopic image interpretation for US dermatology resident physicians.

Results: Twenty-six pigmented lesion and dermoscopy specialists completed 8 rounds of surveys, with 100% (26/26) response rate in all rounds. A final list of 32 diagnoses and 116 associated dermoscopic features was generated. Three hundred seventy-eight representative teaching images reached consensus with panelists.

Conclusions And Relevance: Consensus achieved in this modified Delphi process identified common dermoscopic diagnoses, associated features, and representative teaching images reflective of a foundational proficiency in dermoscopic image interpretation for dermatology residency training. This list of validated objectives provides a consensus-based foundation of key learning points in dermoscopy to help resident physicians achieve clinical proficiency in dermoscopic image interpretation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamadermatol.2020.5213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788510PMC
February 2021

Heparin induced thrombocytopenia: position paper from the Italian Society on Thrombosis and Haemostasis (SISET).

Blood Transfus 2021 01 28;19(1):14-23. Epub 2020 Dec 28.

IRCCS "Ca' Granda Maggiore" Hospital Foundation, "Angelo Bianchi Bonomi" Haemophilia and Thrombosis Center and "Fondazione Luigi Villa", Milan, Italy.

Heparin induced thrombocytopenia (HIT) is a rare immune mediated adverse drug reaction occurring after exposure to heparin. It is a serious and potentially fatal condition, which may be associated with the development of arterial or venous thrombotic events. Although known for many years, HIT is still often misdiagnosed. Pre- test clinical probability, screening for anti-PF4/heparin antibodies and documentation of their platelet activating capacity are the cornerstones of diagnosis. However, both clinical algorithms and test modalities have limited predictive values and limited diffusion so that the diagnosis and management is challenging in the clinical practice. For this reason, there is an unmet need for novel rational non-anticoagulant therapies based on the pathogenesis of HIT.The present paper reports the position of the Italian Society on Haemostasis and Thrombosis (SISET) in order to increase awareness of HIT among clinicians and other health care professionals and to provide information on the most appropriate management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2450/2020.0248-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850929PMC
January 2021

DReLAB - Deep REinforcement Learning Adversarial Botnet: A benchmark dataset for adversarial attacks against botnet Intrusion Detection Systems.

Data Brief 2021 Feb 8;34:106631. Epub 2020 Dec 8.

Department of Engineering "Enzo Ferrari", University of Modena and Reggio Emilia, Italy.

We present the first dataset that aims to serve as a benchmark to validate the resilience of botnet detectors against adversarial attacks. This dataset includes realistic adversarial samples that are generated by leveraging two widely used Deep Reinforcement Learning (DRL) techniques. These adversarial samples are proved to evade state of the art detectors based on Machine- and Deep-Learning algorithms. The initial corpus of malicious samples consists of network flows belonging to different botnet families presented in three public datasets containing real enterprise network traffic. We use these datasets to devise detectors capable of achieving state-of-the-art performance. We then train two DRL agents, based on and , to generate realistic adversarial samples: the goal is achieving misclassifications by performing small modifications to the initial malicious samples. These alterations involve the features that can be more realistically altered by an expert attacker, and do not compromise the underlying malicious logic of the original samples. Our dataset represents an important contribution to the cybersecurity research community as it is the first including thousands of automatically generated adversarial samples that are able to thwart state of the art classifiers with a high evasion rate. The adversarial samples are grouped by malware variant and provided in a CSV file format. Researchers can validate their defensive proposals by testing their detectors against the adversarial samples of the proposed dataset. Moreover, the analysis of these samples can pave the way to a deeper comprehension of adversarial attacks and to some sort of explainability of machine learning defensive algorithms. They can also support the definition of novel effective defensive techniques.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dib.2020.106631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749366PMC
February 2021

Cutaneous myiasis in cats and dogs: Cases, predisposing conditions and risk factors.

Vet Med Sci 2021 03 18;7(2):378-384. Epub 2020 Dec 18.

Department of Biology, Ecology and Earth Science, University of Calabria, Arcavacata di Rende, Cosenza, Italy.

Two cases of cutaneous myiasis diagnosed in 2018 in Emilia-Romagna region (northern Italy) were reported. The first one, described in a domestic cat Felis silvestris catus L. (Carnivora: Felidae) and caused by Calliphora vicina Robineau-Desvoidy (Diptera: Calliphoridae), was the first one of this type ever reported in Italy in cats. The second one was described in a domestic dog Canis lupus familiaris L. (Carnivora: Canidae) and caused by Lucilia sericata (Meigen) (Diptera: Calliphoridae) and was unusual because it occurred in absence of lesions. An extensive literature search on cutaneous myiasis in these two domestic animal species was performed in order to draw attention to predisposing conditions and risk factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/vms3.370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025654PMC
March 2021

Estimated direct costs of non-small cell lung cancer by stage at diagnosis and disease management phase: A whole-disease model.

Thorac Cancer 2021 01 21;12(1):13-20. Epub 2020 Nov 21.

Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padova, Italy.

Background: Non-small cell lung cancer (NSCLC) is the first cause of cancer-related death among men and the second among women worldwide. It also poses an economic threat to the sustainability of healthcare services. This study estimated the direct costs of care for patients with NSCLC by stage at diagnosis, and management phase of pathway recommended in local and international guidelines.

Methods: Based on the most up-to-date guidelines, we developed a very detailed "whole-disease" model listing the probabilities of all potentially necessary diagnostic and therapeutic actions involved in the management of each stage of NSCLC. We assigned a cost to each procedure, and obtained an estimate of the total and average per-patient costs of each stage of the disease and phase of its management.

Results: The mean expected cost of a patient with NSCLC is 21,328 € (95% C.I. -20 897-22 322). This cost is 16 291 € in stage I, 19530 € in stage II, 21938 € in stage III, 22175 € in stage IV, and 28 711 € for a Pancoast tumor. In the early stages of the disease, the main cost is incurred by surgery, whereas in the more advanced stages radiotherapy, medical therapy, treatment for progressions, and supportive care become variously more important.

Conclusions: An estimation of the direct costs of care for NSCLC is fundamental in order to predict the burden of new oncological therapies and treatments on healthcare services, and thus orient the decisions of policy-makers regarding the allocation of resources.

Key Points: SIGNIFICANT FINDINGS OF THE STUDY: The high costs of surgery make the early stages of the disease no less expensive than the advanced stages.

What This Study Adds: An estimation of the direct costs of care is fundamental in order to orient the decisions of policy-makers regarding the allocation of resources.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1759-7714.13616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779199PMC
January 2021

Association between the dermoscopic morphology of peripheral globules and melanocytic lesion diagnosis.

J Eur Acad Dermatol Venereol 2021 Apr 23;35(4):892-899. Epub 2020 Dec 23.

Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Background: The presence of peripheral globules is associated with enlarging melanocytic lesions; however, there are numerous patterns of peripheral globules distribution and it remains unknown whether specific patterns can help differentiate enlarging naevi from melanoma.

Objective: To investigate whether morphological differences exist between the peripheral globules seen in different subsets of naevi and in melanoma.

Methods: A cross-sectional study of clinical notes that mentioned peripheral globules, in addition to all melanoma images with peripheral globules on the International Skin Imaging Collaboration archive. Dermoscopic images were reviewed and annotated. Associations between diagnosis and categorical features were measured with odds ratios. Non-parametric tests were used for continuous factors.

Results: 184 lesions with peripheral globules from our clinic were included in the analysis; only 6 of these proved to be melanoma. 109 melanomas with peripheral globules from the International Skin Imaging Collaboration archive were added to the analysis. Melanomas were more common on the extremities and among older individuals. Melanomas were more likely to display atypical, tiered and/or focal peripheral globules. Only 5% of melanomas lacked dermoscopic melanoma-specific structures compared to 48% of naevi.

Conclusions: Melanocytic lesions with atypical or asymmetrically distributed peripheral globules, especially when located on the extremities, should raise suspicion for malignancy. Melanocytic lesions with typical and symmetrically distributed peripheral globules, and with no other concerning dermoscopic features, are unlikely to be malignant.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jdv.17035DOI Listing
April 2021

Fine Structure of Maxillary Palps in Adults of Hermetia illucens (Diptera: Stratiomyidae).

J Med Entomol 2021 03;58(2):658-665

Department of Biology, Ecology and Earth Science, University of Calabria, Cosenza, Italy.

A relevant species in waste management but also in forensic, medical, and veterinary sciences is the black soldier fly, Hermetia illucens (Linnaeus; Diptera: Stratiomyidae). An ultrastructural study by scanning electron microscopy (SEM) was conducted for the first time on maxillary palps of both sexes, describing in detail the morphology and distribution of sensilla and microtrichia. The maxillary palps, composed of two segments, show sexual dimorphism in length and shape. In both sexes, the first segment is covered only by microtrichia, but the second one is divided into two parts: the proximal one, covered only by microtrichia, and the distal one containing both microtrichia and sensory structures. These structures include two types of sensory pits and one of chaetic sensilla. Due to sexual dimorphism in palp size, females have a higher number of sensory pits. The sexual dimorphism of palps and the presence and role of sensilla in H. illucens was discussed in comparison to other species of the family Stratiomyidae and of other Diptera. This study may represent a base for further investigations on mouthpart structures of this species, involved in key physiological activities, such as feeding, mating and oviposition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jme/tjaa251DOI Listing
March 2021

The Determinants of Out-of-Pocket Expenditure in IBD Italian Patients. Results from the AMICI Survey.

Int J Environ Res Public Health 2020 11 4;17(21). Epub 2020 Nov 4.

National Center for HTA, Istituto Superiore di Sanità, 00161 Rome, Italy.

Decision makers are used to consider Out-of-Pocket Expenditure (OOPE) within a health technology assessment framework in order to account for an indicator relying on the level of fairness and on the quality of care of a health system. In this paper, we provide estimates on the determinants of OOPE in Italy by using data coming from an observational cross-sectional study that enrolled a sample of 2526 patients suffering from inflammatory bowel diseases. We explore the association between OOPE and: (1) geographical location; (2) income effects; (3) performances in delivering healthcare. A regression model was used. Individuals' age were in the range of 18-88 (mean 44 ± 14.55). Forty-six percent were females, 54% were married and 19% held a bachelor degree. Ninety-six percent of respondents declared an OOPE >0 whose mean value was €960 ± €950. Individuals belonging to low-income and low-performance regions were more likely to declare an OOPE >0 (99%). Regression findings suggest that increases in OOPE could be considered as a response from patients aiming to compensate for lacks and inefficiencies in the public healthcare offers. Policymakers should consider increases in OOPE in patients with Inflammatory Bowel Diseases (IBDs) as an indicator of poor quality of care and poor fairness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph17218156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663576PMC
November 2020

Multi-Criteria-Decision-Analysis (MCDA) for the Horizon Scanning of Health Innovations an Application to COVID 19 Emergency.

Int J Environ Res Public Health 2020 10 26;17(21). Epub 2020 Oct 26.

National Centre for HTA, Istituto Superiore di Sanità, 00161 Rome, Italy.

In this article, we aim to present a tool for the early assessment of medical technologies. This evaluation system was designed and implemented by the National Centre for HTA and the National Centre for Innovative Technologies of the Istituto Superiore di Sanita, Italy, in order to respond to an institutional commitment within the "Health Technologies Assessment Team" that was established to face the huge demand for the evaluation of Health Technologies during the pandemic event caused by COVID-19, with a smart and easy-to-use framework. Horizon scanning was conducted through a brief assessment carried out according to the multicriteria decision analysis methodology. Each HTA domain was attributed a score according to a pros/cons and opportunities/threats system, derived from evidence in the literature. Scores were weighted according to different perspectives. Scores were presented in a Cartesian graph showing the positioning according to the potential value and the perceived risk associated with the technology. Two case studies regarding the early assessment were reported, concerning two specific technologies: an individual protection device and a contact tracking system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph17217823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662805PMC
October 2020

The role of hyaluronic acid and amino acid against the aging of the human skin: A clinical and histological study.

J Cosmet Dermatol 2021 Jul 9;20(7):2296-2304. Epub 2020 Nov 9.

Aesthetic Medicine and Wellness, University of Palermo, Palermo, Italy.

Background: In esthetic medicine, different techniques have been used against the aging of the human skin especially in the facial area. Hyaluronic acid is used for improving the quantity of water and extracellular matrix molecule. The aim of this study is a clinical and histological evaluation of the effect of low-molecular-weight hyaluronic acid fragments mixed with amino acid (HAAM) on the rejuvenation the face skin treated with intradermal microinjections.

Methods: Twenty women with mean age 45 range from 35 to 64 were studied, thereof 8 in menopause and 12 of childbearing age. The patients were treated with the HAAM products by mesotherapy technique; before and after 3 months of the therapeutic procedure, each patient underwent small biopsies with a circular punch biopsy.

Results: The clinical results of the present study showed that the administration of the dermal filler containing fragments of hyaluronic acid between 20 and 38 monomers and amino acid via dermis injection technique produces an esthetic improvement in the faces of the treated patients, while the histological evaluation shows an increased fibroblast activity with the production of type III reticular collagen and increased number of vessels and epidermis thickness.

Conclusions: The clinical and histological assessment showed that subcutaneous HAAM infiltration has a significant impact on the dermis and clinical aspects of the face.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jocd.13811DOI Listing
July 2021

Tissue Plasminogen Activator Levels and Risk of Breast Cancer in a Case-Cohort Study on Italian Women: Results from the Moli-sani Study.

Thromb Haemost 2021 Apr 18;121(4):449-456. Epub 2020 Oct 18.

Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Isernia, Italy.

Background:  Elevated levels of key enzymes of the fibrinolytic system, such as tissue plasminogen activator (tPA), are reported as predictors of poor outcome in cancer patients. Limited information is available about their potential predictive value for breast cancer (BC) risk in the general population.

Aim:  We examined the association of tPA levels with BC risk in a case-cohort study including women from the prospective Moli-sani cohort.

Methods:  A sample of 710 women (mean age: 54.6 ± 12.1 years) was selected as a subcohort and compared with 84 BC cases, in a median follow-up of 4.2 years. Incident cases of BC were validated through medical records. tPA plasma levels were measured using an enzyme-linked immunosorbent assay kit. Hazard ratio (HR) and 95% confidence interval (CI), adjusted for relevant covariates, were estimated by a Cox regression model using the Prentice method.

Results:  Compared with the lowest quartile (<4.9 ng/mL), women in the highest quartile of tPA (>11.2 ng/mL) had increased risk of BC (HR: 2.20, 95% CI: 1.13-4.28) after adjusted for age, smoking, education, menopause, and residence. Further adjustment for biochemical markers did not modify this association. The risk of BC increased by 34% for each increase in 1 standard deviation of log-transformed tPA levels ( = 0.046). Elevated levels of tPA were associated mainly with estrogen-receptor-positive BC (2.08, 95% CI: 1.18-3.66).

Conclusion:  Higher levels of tPA, reported to predict cardiovascular risk, are a potential biomarker for BC risk, supporting the hypothesis of a "common soil" linking the pathogenic mechanisms of hormone-dependent tumors and cardiovascular disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0040-1718531DOI Listing
April 2021

Multiclass Artificial Intelligence in Dermatology: Progress but Still Room for Improvement.

J Invest Dermatol 2021 May 10;141(5):1325-1328. Epub 2020 Oct 10.

Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jid.2020.06.040DOI Listing
May 2021

Performance of a deep neural network in teledermatology: a single-centre prospective diagnostic study.

J Eur Acad Dermatol Venereol 2021 Feb 22;35(2):546-553. Epub 2020 Nov 22.

Department of Dermatology, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.

Background: The use of artificial intelligence (AI) algorithms for the diagnosis of skin diseases has shown promise in experimental settings but has not been yet tested in real-life conditions.

Objective: To assess the diagnostic performance and potential clinical utility of a 174-multiclass AI algorithm in a real-life telemedicine setting.

Methods: Prospective, diagnostic accuracy study including consecutive patients who submitted images for teledermatology evaluation. The treating dermatologist chose a single image to upload to a web application during teleconsultation. A follow-up reader study including nine healthcare providers (3 dermatologists, 3 dermatology residents and 3 general practitioners) was performed.

Results: A total of 340 cases from 281 patients met study inclusion criteria. The mean (SD) age of patients was 33.7 (17.5) years; 63% (n = 177) were female. Exposure to the AI algorithm results was considered useful in 11.8% of visits (n = 40) and the teledermatologist correctly modified the real-time diagnosis in 0.6% (n = 2) of cases. The overall top-1 accuracy of the algorithm (41.2%) was lower than that of the dermatologists (60.1%), residents (57.8%) and general practitioners (49.3%) (all comparisons P < 0.05, in the reader study). When the analysis was limited to the diagnoses on which the algorithm had been explicitly trained, the balanced top-1 accuracy of the algorithm (47.6%) was comparable to the dermatologists (49.7%) and residents (47.7%) but superior to the general practitioners (39.7%; P = 0.049). Algorithm performance was associated with patient skin type and image quality.

Conclusions: A 174-disease class AI algorithm appears to be a promising tool in the triage and evaluation of lesions with patient-taken photographs via telemedicine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jdv.16979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274350PMC
February 2021

Biological activities of essential oil extracted from leaves of Atalantia sessiflora Guillauminin Vietnam.

J Infect Dev Ctries 2020 09 30;14(9):1054-1064. Epub 2020 Sep 30.

Faculty of Pharmacy, Hue University of Medicine and Pharmacy, Hue University, Hue city, Viet Nam.

Introduction: The present study aimed to determine the chemical compositions and bioactivities of the essential oil of Atalantia sessiflora Guillaumin (A. sessiflora), including antibacterial, antimycotic, antitrichomonas, anti-inflammatory and antiviral effects.

Methodology: The essential oil from leaves of A. sessiflora was extracted by hydrodistillation using a Clevenger apparatus. Chemical compositions of oil were identified by GC/MS. Antimicrobial and antitrichomonas activity were determined by the microdilution method; anti-inflammatory and antiviral were determined by the MTT method.

Results: The average yield of oil was 0.46 ± 0.01% (v/w, dry leaves). A number of 45 constituents were identified by GC/MS. The essential oil comprised four main components. The oil showed antimicrobial activities against Gram-positive strains as Staphylococcus; Gram-negative bacteria such as Klebsiella pneumoniae and Escherichia coli; and finally four Candida species. Enterococcus faecalis and Pseudomonas aeruginosa were least susceptible to the oil of A. sessiflora, as seen in their MIC and MLC values over 16% (v/v). Activity against Trichomonas vaginalis was also undertaken, showing IC50, IC90 and MLC values of 0.016, 0.03 and 0.06% (v/v) respectively, after 48 hours of incubation. The oil of A. sessiflora displayed activity against the nitric oxide generation with the IC50 of 95.94 ± 6.18 µg/mL. The oil was completely ineffective against tested viruses, ssRNA+, ssRNA-, dsRNA, and dsDNA viruses.

Conclusions: This is the first yet comprehensive scientific report about the chemical compositions and pharmacological properties of the essential oil of A. sessiflora. Further studies should be done to evaluate the safety and toxicity of A. sessiflora oil.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3855/jidc.12469DOI Listing
September 2020

Chemotaxonomic Evaluation by Volatolomics Analysis of Fifty-Two Genotypes of L.

Plants (Basel) 2020 Sep 29;9(10). Epub 2020 Sep 29.

Department of Agriculture, University of Sassari, Via De Nicola 9, I-07100 Sassari, Italy.

A population of 52 genotypes of Myrtle ( L.), selected in the framework of a domestication program and growing in the same collection field at Oristano (Central Western Sardinia, 39°54' N 8°35' E), was analyzed by GC/MS for leaf essential oil composition. The chemical composition of essential oils was quite variable with a number of compounds ranging from 31 to 78 depending on cultivar. One hundred and eighteen compounds were globally identified in the various genotypes. However, α-pinene, limonene, 1,8-cineole, α-terpineol, and linalool always resulted as main components with few differences among samples. Minor compounds have been the determining factors in differentiating or associating genotypes in the outputs of a principal component analysis (PCA), where the results of another analysis of fruit essential oils of the same genotypes were also jointly used. Genotypes were discriminated according to mother plant characterization or ecological variables, such as site altitude, soil nature, and presence or absence of calcareous soils in the substrate of the localities of origin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/plants9101288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650784PMC
September 2020

Efficacy of bendamustine and rituximab in unfit patients with previously untreated chronic lymphocytic leukemia. Indirect comparison with ibrutinib in a real-world setting. A GIMEMA-ERIC and US study.

Cancer Med 2020 11 24;9(22):8468-8479. Epub 2020 Sep 24.

Hematology, Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.

Limited information is available on the efficacy of front-line bendamustine and rituximab (BR) in chronic lymphocytic leukemia (CLL) with reduced renal function or coexisting conditions. We therefore analyzed a cohort of real-world patients and performed a matched adjusted indirect comparison with a cohort of patients treated with ibrutinib. One hundred and fifty-seven patients with creatinine clearance (CrCl) <70 mL/min and/or CIRS score >6 were treated with BR. The median age was 72 years; 69% of patients had ≥2 comorbidities and the median CrCl was 59.8 mL/min. 17.6% of patients carried TP53 disruption. The median progression-free survival (PFS) was 45 months; TP53 disruption was associated with a shorter PFS (P = 0.05). The overall survival (OS) at 12, 24, and 36 months was 96.2%, 90.1%, and 79.5%, respectively. TP53 disruption was associated with an increased risk of death (P = 0.01). Data on 162 patients ≥65 years treated with ibrutinib were analyzed and compared with 165 patients ≥65 years treated with BR. Factors predicting for a longer PFS at multivariable analysis in the total patient population treated with BR and ibrutinib were age (HR 1.06, 95% CI 1.02-1.10, P < 0.01) and treatment with ibrutinib (HR 0.55, 95% CI 0.33-0.93, P = 0.03). In a post hoc analysis of patients in advanced stage, a significant PFS advantage was observed in patient who had received ibrutinib (P = 0.03), who showed a trend for OS advantage (P = 0.08). We arrived at the following conclusions: (a) BR is a relatively effective first-line regimen in a real-world population of unfit patients without TP53 disruption, (b) ibrutinib provided longer disease control than BR in patients with advanced disease stage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.3470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666748PMC
November 2020

Incidence of New Primary Cutaneous Melanoma in Patients With Metastatic Melanoma Treated With Immune Checkpoint Inhibitors: A Single-Center Cohort Study.

JAMA Dermatol 2021 01;157(1):79-83

Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

Importance: The development of new primary cutaneous melanoma (CM) after starting immune checkpoint inhibitor (ICI) therapy is poorly characterized.

Objective: To determine the incidence of new CM in patients treated with ipilimumab, nivolumab, and/or pembrolizumab for metastatic melanoma.

Design, Setting, And Participants: Single-center, retrospective, observational cohort study using an institutional database to identify patients diagnosed with melanoma at a tertiary care cancer hospital in New York, New York.

Exposures: Ipilimumab, nivolumab, and/or pembrolizumab treatment for metastatic melanoma.

Main Outcomes And Measures: Primary outcomes were the incidence proportion, the incidence rate, and the 5-year cause-specific cumulative risk.

Results: A total of 2251 patients were included in the study; mean (SD) age at the time of ICI start was 62.8 (14.4) years. The majority were male (63.8%, n = 1437), White (92.7%, n = 2086), and non-Hispanic (92.1%, n = 2073). Forty-two of 2251 patients who received ipilimumab, nivolumab, and/or pembrolizumab were diagnosed with 48 new CMs at a median (range) of 397.5 (39-2409) days after ICI initiation. The median age of affected patients at the time of ICI first dose was 66.5 years. The majority were male (66.7%, n = 28), White (92.9%, n = 39), and non-Hispanic (100.0%, n = 42). There were no differences in age, sex, race, and ethnicity among patients who did and did not develop a new CM. Patients who developed a new CM were more likely to have a family history of melanoma (23.8% vs 16.3%, P = .02). Most new CMs (n = 30, 62.5%) were diagnosed after the last date of ICI administration. Twenty-seven (56.3%) new CMs were in situ and 21 (43.8%) were invasive. Of the invasive CMs with a reported Breslow thickness (n = 20), the median (range) thickness was 0.4 (0.1-8.4) mm. The overall incidence proportion of new CM was 1.9% (95% CI, 1.4%-2.5%) and the incidence rate was 1103 cases per 100 000 person-years (95% CI, 815-1492). The 5-year cumulative cause-specific risk of new CM was 4.9% (95% CI, 3.3%-7.4%).

Conclusions And Relevance: Patients treated with ICI therapy for metastatic melanoma remain at risk for the development of new CM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamadermatol.2020.3671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495326PMC
January 2021

Acute Radiation Colitis after Preoperative Short-Course Radiotherapy for Rectal Cancer: A Morphological, Immunohistochemical and Genetic Study.

Cancers (Basel) 2020 Sep 9;12(9). Epub 2020 Sep 9.

Pathology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy.

Preoperative radiotherapy is a widely accepted treatment procedure in rectal cancer. Radiation-induced changes in the tumor are well described, whereas less attention has been given to the non-neoplastic mucosa. Our aim is to provide a detailed analysis of the morphological features present in non-neoplastic mucosa that pathologists need to be familiar with, in order to avoid misdiagnosis, when evaluating rectal cancer specimens of patients preoperatively treated with radiotherapy, especially with short-course regimen. We compared 2 groups of 95 rectal cancer patients treated preoperatively with either short-course (45 patients) or long-course radiotherapy (50 patients). Depending on the type of protocol, different histopathological features, in terms of inflammation, glandular abnormalities and endocrine differentiation were seen in the non-neoplastic mucosa within the irradiated volume. Of note, features mimicking dysplasia, such as crypt distortion, nuclear and cytoplasmic atypia of glandular epithelium, were identified only in the short-course group. DNA mutation analysis, using a panel of 56 genes frequently mutated in cancer, and p53 immunostaining were performed on both tumor and radiation-damaged mucosa in a subset of short course cases. Somatic mutations were identified only in tumors, supporting the concept that tissues with radiation-induced "dysplastic-like" features are not genetically transformed. Pathologists should be aware of the characteristic morphological changes induced by radiation. The presence of features simulating dysplasia in the group treated with short-course radiotherapy may lead to serious diagnostic mistakes, if erroneously interpreted. Next generation sequencing (NGS) analysis further validated the morphological concept that radiation-induced abnormalities do not represent pre-neoplastic lesions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12092571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563849PMC
September 2020
-->