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Article ; Online: Recent insights into extracorporeal photopheresis for graft-versus-host disease.

Del Fante, Claudia / Perotti, Cesare

2024 Volume 20, Issue 4, Page(s) 339–348

Abstract: Introduction: Extracorporeal Photopheresis (ECP) may be considered the unique large-scale cell therapy currently available. It is currently employed mainly as second-line treatment, especially in steroid-resistant or steroid-dependent Graft versus Host ... ...

Abstract	Introduction: Extracorporeal Photopheresis (ECP) may be considered the unique large-scale cell therapy currently available. It is currently employed mainly as second-line treatment, especially in steroid-resistant or steroid-dependent Graft versus Host Disease (GvHD) with good results and very few limitations. Areas covered: Many points need to be clarified regarding the ECP mechanism of action, that conditions the lack of uniqueness among the different centers, essentially cycle frequency, treatment duration, and the number of cells to be treated to obtain a response, according to the organs involved. Moreover, reliable biomarkers for prediction of response are lacking, as well as the best pharmacological combination. We will focus on the recent advances concerning ECP for GvHD treatment. We performed a systematic literature research in Pubmed and Embase as of September 2023. Expert opinion: The recent studies on ECP mechanism of action along with the promising biomarkers of response, and the synergistic benefit of ECP in association with the new drugs render this therapy an important weapon for GvHD resistant to conventional treatment and can be proposed as a valid first-line therapy option with promising results. We believe that it should be used early in all categories of patients, considering its high safety profile.
MeSH term(s)	Humans ; Photopheresis/methods ; Hematopoietic Stem Cell Transplantation ; Graft vs Host Disease/drug therapy ; Steroids/therapeutic use ; Biomarkers
Chemical Substances	Steroids ; Biomarkers
Language	English
Publishing date	2024-02-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2274260-8
ISSN	1744-8409 ; 1744-666X
ISSN (online)	1744-8409
ISSN	1744-666X
DOI	10.1080/1744666X.2023.2295405
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Article ; Online: Convalescent plasma for COVID-19. TSUNAMI is not the final word.

Franchini, Massimo / Focosi, Daniele / Casadevall, Arturo / Joyner, Michael J / Perotti, Cesare

European journal of internal medicine

2022 Volume 97, Page(s) 116–118

MeSH term(s)	COVID-19/therapy ; Humans ; Immunization, Passive ; Plasma
Language	English
Publishing date	2022-01-07
Publishing country	Netherlands
Document type	Letter ; Comment
ZDB-ID	1038679-8
ISSN	1879-0828 ; 0953-6205
ISSN (online)	1879-0828
ISSN	0953-6205
DOI	10.1016/j.ejim.2022.01.016
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Article: Continuous Change in Membrane and Membrane-Skeleton Organization During Development From Proerythroblast to Senescent Red Blood Cell.

Minetti, Giampaolo / Achilli, Cesare / Perotti, Cesare / Ciana, Annarita

Frontiers in physiology

2018 Volume 9, Page(s) 286

Abstract: Within the context of erythropoiesis and the possibility of producing artificial red blood cells (RBCs) ...

Abstract	Within the context of erythropoiesis and the possibility of producing artificial red blood cells (RBCs)
Language	English
Publishing date	2018-03-26
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2018.00286
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Article ; Online: An Open-Source Algorithm for 3D ROck Slope Kinematic Analysis (ROKA)

Niccolò Menegoni / Daniele Giordan / Cesare Perotti

Applied Sciences, Vol 11, Iss 4, p

2021 Volume 1698

Abstract: The Markland test is one of the most diffused and adopted methods of kinematic analysis for the identification of critical intersections of rock discontinuities that could generate rock failures. Traditionally, the kinematic analysis is based on the use ... ...

Abstract	The Markland test is one of the most diffused and adopted methods of kinematic analysis for the identification of critical intersections of rock discontinuities that could generate rock failures. Traditionally, the kinematic analysis is based on the use of a stereographic approach that is able to identify the critical combination between the orientations of discontinuities and the rock wall. The recent improvements in the use of Digital Outcrop Models (DOMs) created the conditions for the development of a new automatized approach. We present ROck Slope Kinematic Analysis (ROKA) which is an open-source algorithm aimed at performing the Kinematic Analysis using the discontinuity measures collected onto a 3D DOM. The presented algorithm is able to make a local identification of the possible critical combination between the identified discontinuities and the orientation of the slope. Using this approach, the algorithm is able to identify on the slope the presence of critical combinations according to the traditional kinematic analysis of planar failure, flexural toppling, wedge failure, and direct toppling modes of failures and then visualize them on DOMs. In this way, the traditional approach is more effective and can be adopted for a more detailed analysis of large and complex areas.
Keywords	rock kinematic analysis ; Unamanned Aerial Vehicle (UAV) ; Digital Outcrop Model (DOM) ; Markland tests ; Technology ; T ; Engineering (General). Civil engineering (General) ; TA1-2040 ; Biology (General) ; QH301-705.5 ; Physics ; QC1-999 ; Chemistry ; QD1-999
Subject code	629
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article: Patient Blood Management after Hematopoietic Stem Cell Transplantation in a Pediatric Setting: Starting Low and Going Lower.

Del Fante, Claudia / Mortellaro, Cristina / Recupero, Santina / Giorgiani, Giovanna / Agostini, Annalisa / Panigari, Arianna / Perotti, Cesare / Zecca, Marco

Diagnostics (Basel, Switzerland)

2023 Volume 13, Issue 13

Abstract: Despite the substantial transfusion requirements, there are few studies on the optimal transfusion strategy in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). Our study aimed to retrospectively analyze red blood cell (RBC) ... ...

Abstract	Despite the substantial transfusion requirements, there are few studies on the optimal transfusion strategy in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). Our study aimed to retrospectively analyze red blood cell (RBC) and platelet (PLT) transfusion practices during the first 100 days after HSCT at the pediatric hematology/oncology unit of our hospital between 2016 and 2019, due to a more restrictive approach adopted after 2016. We also evaluated the impact on patient outcomes. A total of 146 consecutive HSCT patients were analyzed. In patients without hemorrhagic complications, the Hb threshold for RBC transfusions decreased significantly from 2016 to 2017 (from 7.8 g/dL to 7.3 g/dL;
Language	English
Publishing date	2023-07-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics13132257
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Article ; Online: Bioprinting Soft 3D Models of Hematopoiesis using Natural Silk Fibroin-Based Bioink Efficiently Supports Platelet Differentiation.

Di Buduo, Christian Andrea / Lunghi, Marco / Kuzmenko, Volodymyr / Laurent, Pierre-Alexandre / Della Rosa, Giulia / Del Fante, Claudia / Dalle Nogare, Damian Edward / Jug, Florian / Perotti, Cesare / Eto, Koji / Pecci, Alessandro / Redwan, Itedale Namro / Balduini, Alessandra

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

2024 , Page(s) e2308276

Abstract: Hematopoietic stem and progenitor cells (HSPCs) continuously generate platelets throughout one's life. Inherited Platelet Disorders affect ≈ 3 million individuals worldwide and are characterized by defects in platelet formation or function. A critical ... ...

Abstract	Hematopoietic stem and progenitor cells (HSPCs) continuously generate platelets throughout one's life. Inherited Platelet Disorders affect ≈ 3 million individuals worldwide and are characterized by defects in platelet formation or function. A critical challenge in the identification of these diseases lies in the absence of models that facilitate the study of hematopoiesis ex vivo. Here, a silk fibroin-based bioink is developed and designed for 3D bioprinting. This bioink replicates a soft and biomimetic environment, enabling the controlled differentiation of HSPCs into platelets. The formulation consisting of silk fibroin, gelatin, and alginate is fine-tuned to obtain a viscoelastic, shear-thinning, thixotropic bioink with the remarkable ability to rapidly recover after bioprinting and provide structural integrity and mechanical stability over long-term culture. Optical transparency allowed for high-resolution imaging of platelet generation, while the incorporation of enzymatic sensors allowed quantitative analysis of glycolytic metabolism during differentiation that is represented through measurable color changes. Bioprinting patient samples revealed a decrease in metabolic activity and platelet production in Inherited Platelet Disorders. These discoveries are instrumental in establishing reference ranges for classification and automating the assessment of treatment responses. This model has far-reaching implications for application in the research of blood-related diseases, prioritizing drug development strategies, and tailoring personalized therapies.
Language	English
Publishing date	2024-03-21
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2808093-2
ISSN	2198-3844 ; 2198-3844
ISSN (online)	2198-3844
ISSN	2198-3844
DOI	10.1002/advs.202308276
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Article: Blood Transfusion for Major Trauma in Emergency Department.

Saviano, Angela / Perotti, Cesare / Zanza, Christian / Longhitano, Yaroslava / Ojetti, Veronica / Franceschi, Francesco / Bellou, Abdelouahab / Piccioni, Andrea / Jannelli, Eugenio / Ceresa, Iride Francesca / Savioli, Gabriele

Diagnostics (Basel, Switzerland)

2024 Volume 14, Issue 7

Abstract: Severe bleeding is the leading cause of death in patients with major trauma admitted to the emergency department. It is estimated that about 50% of deaths happen within a few minutes of the traumatic event due to massive hemorrhage; 30% of deaths are ... ...

Abstract	Severe bleeding is the leading cause of death in patients with major trauma admitted to the emergency department. It is estimated that about 50% of deaths happen within a few minutes of the traumatic event due to massive hemorrhage; 30% of deaths are related to neurological dysfunction and typically happen within two days of trauma; and approximately 20% of patients died of multiorgan failure and sepsis within days to weeks of the traumatic event. Over the past ten years, there has been an increased understanding of the underlying mechanisms and pathophysiology associated with traumatic bleeding leading to improved management measures. Traumatic events cause significant tissue damage, with the potential for severe blood loss and the release of cytokines and hormones. They are responsible for systemic inflammation, activation of fibrinolysis pathways, and consumption of coagulation factors. As the final results of this (more complex in real life) cascade, patients can develop tissue hypoxia, acidosis, hypothermia, and severe coagulopathy, resulting in a rapid deterioration of general conditions with a high risk of mortality. Prompt and appropriate management of massive bleeding and coagulopathy in patients with trauma remains a significant challenge for emergency physicians in their daily clinical practice. Our review aims to explore literature studies providing evidence on the treatment of hemorrhage with blood support in patients with trauma admitted to the Emergency Department with a high risk of death. Advances in blood transfusion protocols, along with improvements in other resuscitation strategies, have become one of the most important issues to face and a key topic of recent clinical research in this field.
Language	English
Publishing date	2024-03-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics14070708
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Article: Validation of a new automated irradiation system for off-line ECP.

Del Fante, Claudia / Klersy, Catherine / Barone, Eugenio / De Vitis, Simona / Troletti, Daniela / Mortellaro, Cristina / Musella, Valeria / Perotti, Cesare

Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis

2023 Volume 62, Issue 3, Page(s) 103724

Abstract: Extracorporeal photopheresis (ECP) is a cell therapy originally employed for cutaneous T cell lymphoma and later for GvHD, solid organ rejection and other immunological diseases demonstrating an excellent safety profile. Mononuclear cell (MNCs) apoptosis ...

Abstract	Extracorporeal photopheresis (ECP) is a cell therapy originally employed for cutaneous T cell lymphoma and later for GvHD, solid organ rejection and other immunological diseases demonstrating an excellent safety profile. Mononuclear cell (MNCs) apoptosis triggered by UV-A light irradiation in the presence of 8-methoxypsoralene has a key role in priming the cells, ultimately leading to immunomodulation. We report preliminary data about an evaluation of the new automated irradiator device LUMILIGHT (Pelham Crescent srl) for off-line ECP. Fifteen MNCs samples collected by apheresis from 15 adult patients undergoing ECP at our Center were cultured immediately after irradiation along with untreated samples and evaluated at 24, 48 and 72 h timepoints for T cell apoptosis and viability by flow cytometry with Annexin V and Propide Iodidum staining. Post irradiation Hematocrit (HCT), calculated by the device, was compared with that of the automated cell counter. Bacterial contamination was also tested. In irradiated samples after 24-48 and 72 h, the average total apoptosis was 47 %, 70 % and 82 %, respectively, showing a significant difference from untreated samples; residual viable lymphocytes at 72 h were, on average, 18 %. The greatest initiation of apoptosis occurred from 48 h of irradiation onwards. Average early apoptosis of irradiated samples decreased over time (26 %, 17 % and 10 % at 24, 48 and 72 h, respectively). HCT measured by LUMILIGHT was over-estimated, possibly due to the low pre irradiation red blood cell contamination. Bacterial tests resulted negative. Our study showed the LUMILIGHT device to be a valid instrument for MNCs irradiation with good handling and no major technical problems as well as no adverse events in the patients. Our data need to be confirmed in larger studies.
MeSH term(s)	Adult ; Humans ; Photopheresis/methods ; Blood Component Removal ; Lymphocytes ; Leukocytes ; Skin Neoplasms/therapy ; Graft vs Host Disease/therapy
Language	English
Publishing date	2023-05-10
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2046795-3
ISSN	1878-1683 ; 1473-0502
ISSN (online)	1878-1683
ISSN	1473-0502
DOI	10.1016/j.transci.2023.103724
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Article: Extracorporeal photopheresis for bronchiolitis obliterans syndrome after allogeneic stem cell transplant: An emerging therapeutic approach?

Del Fante, Claudia / Perotti, Cesare

Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis

2017 Volume 56, Issue 1, Page(s) 17–19

Abstract: Bronchiolitis obliterans syndrome (BOS) is the main manifestation of pulmonary GVHD. It has often a dramatic and fast evolution and current treatment (change or increase in immunosuppression, macrolides and inhaled therapy) is poor with high mortality ... ...

Abstract	Bronchiolitis obliterans syndrome (BOS) is the main manifestation of pulmonary GVHD. It has often a dramatic and fast evolution and current treatment (change or increase in immunosuppression, macrolides and inhaled therapy) is poor with high mortality rates. In this scenario, extracorporeal photopheresis (ECP) bursts as a new immunomodulatory approach with a different philosophical purpose. In fact, available data show that ECP treatment is intended to delay the inflammatory process and consequently respiratory lung function decline, rather than reverse the damage itself. Preliminary results reported in literature show that ECP may effectively improve/slow lung function decline in cGVHD patients with BOS after standard treatment failure. Further studies are needed to confirm the efficacy of ECP, assess the optimal schedule and consider it for early treatment.
MeSH term(s)	Bronchiolitis Obliterans/physiopathology ; Graft vs Host Disease/therapy ; Humans ; Lung Transplantation/methods ; Photopheresis/methods ; Transplantation, Homologous/methods
Language	English
Publishing date	2017-02
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2046795-3
ISSN	1878-1683 ; 1473-0502
ISSN (online)	1878-1683
ISSN	1473-0502
DOI	10.1016/j.transci.2016.12.010
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Article: Membrane Rearrangements in the Maturation of Circulating Human Reticulocytes.

Minetti, Giampaolo / Bernecker, Claudia / Dorn, Isabel / Achilli, Cesare / Bernuzzi, Stefano / Perotti, Cesare / Ciana, Annarita

Frontiers in physiology

2020 Volume 11, Page(s) 215

Abstract: Red blood cells (RBCs) begin their circulatory life as reticulocytes (Retics) after their egress from the bone marrow where, as R1 Retics, they undergo significant rearrangements in their membrane and intracellular components, via autophagic, proteolytic, ...

Abstract	Red blood cells (RBCs) begin their circulatory life as reticulocytes (Retics) after their egress from the bone marrow where, as R1 Retics, they undergo significant rearrangements in their membrane and intracellular components, via autophagic, proteolytic, and vesicle-based mechanisms. Circulating, R2 Retics must complete this maturational process, which involves additional loss of significant amounts of membrane and selected membrane proteins. Little is known about the mechanism(s) at the basis of this terminal differentiation in the circulation, which culminates with the production of a stable biconcave discocyte. The membrane of R1 Retics undergoes a selective remodeling through the release of exosomes that are enriched in transferrin receptor and membrane raft proteins and lipids, but are devoid of Band 3, glycophorin A, and membrane skeletal proteins. We wondered whether a similar selective remodeling occurred also in the maturation of R2 Retics. Peripheral blood R2 Retics, isolated by an immunomagnetic method, were compared with mature circulating RBCs from the same donor and their membrane protein and lipid content was analyzed. Results show that both Band 3 and spectrin decrease from R2 Retics to RBCs on a "per cell" basis. Looking at membrane proteins that are considered as markers of membrane rafts, flotillin-2 appears to decrease in a disproportionate manner with respect to Band 3. Stomatin also decreases but in a more proportionate manner with respect to Band 3, hinting at a heterogeneous nature of membrane rafts. High resolution lipidomics analysis, on the contrary, revealed that those lipids that are typically representative of the membrane raft phase, sphingomyelin and cholesterol, are enriched in mature RBCs with respct to Retics, relative to total cell lipids, strongly arguing in favor of the selective retention of at least certain subclasses of membrane rafts in RBCs as they mature from Retics. Our hypothesis that rafts serve as additional anchoring sites for the lipid bilayer to the underlying membrane-skeleton is corroborated by the present results. It is becoming ever more clear that a proper lipid composition of the reticulocyte is necessary for the production of a normal mature RBC.
Language	English
Publishing date	2020-03-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2020.00215
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