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Article ; Online: A 20-year period of orthotopic liver transplantation activity in a single center: a time series analysis performed using the R Statistical Software.

Santori, G / Andorno, E / Morelli, N / Casaccia, M / Bottino, G / Di Domenico, S / Valente, U

2009 Volume 41, Issue 4, Page(s) 1286–1289

Abstract: ... in 2001 (n = 51), 2005 (n = 50), and 2004 (n = 49). A time series analysis performed using R Statistical ...

Abstract	In many Western countries a "minimum volume rule" policy has been adopted as a quality measure for complex surgical procedures. In Italy, the National Transplant Centre set the minimum number of orthotopic liver transplantation (OLT) procedures/y at 25/center. OLT procedures performed in a single center for a reasonably large period may be treated as a time series to evaluate trend, seasonal cycles, and nonsystematic fluctuations. Between January 1, 1987 and December 31, 2006, we performed 563 cadaveric donor OLTs to adult recipients. During 2007, there were another 28 procedures. The greatest numbers of OLTs/y were performed in 2001 (n = 51), 2005 (n = 50), and 2004 (n = 49). A time series analysis performed using R Statistical Software (Foundation for Statistical Computing, Vienna, Austria), a free software environment for statistical computing and graphics, showed an incremental trend after exponential smoothing as well as after seasonal decomposition. The predicted OLT/mo for 2007 calculated with the Holt-Winters exponential smoothing applied to the previous period 1987-2006 helped to identify the months where there was a major difference between predicted and performed procedures. The time series approach may be helpful to establish a minimum volume/y at a single-center level.
MeSH term(s)	Humans ; Liver Transplantation ; Seasons ; Software
Language	English
Publishing date	2009-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	82046-5
ISSN	1873-2623 ; 0041-1345
ISSN (online)	1873-2623
ISSN	0041-1345
DOI	10.1016/j.transproceed.2009.03.081
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Zs.A 835: Show issues

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Article: Editorial: Xenotransplantation for the therapy of diabetes: A new look.

Yamada, Kazuhiko / Bottino, Rita

Frontiers in endocrinology

2023 Volume 14, Page(s) 1190442

MeSH term(s)	Humans ; Transplantation, Heterologous ; Diabetes Mellitus, Type 1 ; Islets of Langerhans Transplantation
Language	English
Publishing date	2023-03-31
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2023.1190442
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Article ; Online: A brief review of the current status of pig islet xenotransplantation.

Cooper, David K C / Mou, Lisha / Bottino, Rita

Frontiers in immunology

2024 Volume 15, Page(s) 1366530

Abstract: An estimated 1.5 million Americans suffer from Type I diabetes mellitus, and its incidence is increasing worldwide. Islet allotransplantation offers a treatment, but the availability of deceased human donor pancreases is limited. The transplantation of ... ...

Abstract	An estimated 1.5 million Americans suffer from Type I diabetes mellitus, and its incidence is increasing worldwide. Islet allotransplantation offers a treatment, but the availability of deceased human donor pancreases is limited. The transplantation of islets from gene-edited pigs, if successful, would resolve this problem. Pigs are now available in which the expression of the three known xenoantigens against which humans have natural (preformed) antibodies has been deleted, and in which several human 'protective' genes have been introduced. The transplantation of neonatal pig islets has some advantages over that of adult pig islets. Transplantation into the portal vein of the recipient results in loss of many islets from the instant blood-mediated inflammatory reaction (IBMIR) and so the search for an alternative site continues. The adaptive immune response can be largely suppressed by an immunosuppressive regimen based on blockade of the CD40/CD154 T cell co-stimulation pathway, whereas conventional therapy (e.g., based on tacrolimus) is less successful. We suggest that, despite the need for effective immunosuppressive therapy, the transplantation of 'free' islets will prove more successful than that of encapsulated islets. There are data to suggest that, in the absence of rejection, the function of pig islets, though less efficient than human islets, will be sufficient to maintain normoglycemia in diabetic recipients. Pig islets transplanted into immunosuppressed nonhuman primates have maintained normoglycemia for periods extending more than two years, illustrating the potential of this novel form of therapy.
MeSH term(s)	Animals ; Infant, Newborn ; Humans ; Swine ; Transplantation, Heterologous/methods ; Islets of Langerhans Transplantation ; Diabetes Mellitus, Type 1/therapy ; Pancreas ; Immunosuppression Therapy/methods
Language	English
Publishing date	2024-02-23
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2024.1366530
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Article ; Online: Monocyte and Macrophage in Neuroblastoma: Blocking Their Pro-Tumoral Functions and Strengthening Their Crosstalk with Natural Killer Cells.

Vitale, Chiara / Bottino, Cristina / Castriconi, Roberta

Cells

2023 Volume 12, Issue 6

Abstract: Over the past decade, immunotherapy has represented an enormous step forward in the fight against cancer. Immunotherapeutic approaches have increasingly become a fundamental part of the combined therapies currently adopted in the treatment of patients ... ...

Abstract	Over the past decade, immunotherapy has represented an enormous step forward in the fight against cancer. Immunotherapeutic approaches have increasingly become a fundamental part of the combined therapies currently adopted in the treatment of patients with high-risk (HR) neuroblastoma (NB). An increasing number of studies focus on the understanding of the immune landscape in NB and, since this tumor expresses low or null levels of MHC class I, on the development of new strategies aimed at enhancing innate immunity, especially Natural Killer (NK) cells and macrophages. There is growing evidence that, within the NB tumor microenvironment (TME), tumor-associated macrophages (TAMs), which mainly present an M2-like phenotype, have a crucial role in mediating NB development and immune evasion, and they have been correlated to poor clinical outcomes. Importantly, TAM can also impair the antibody-dependent cellular cytotoxicity (ADCC) mediated by NK cells upon the administration of anti-GD2 monoclonal antibodies (mAbs), the current standard immunotherapy for HR-NB patients. This review deals with the main mechanisms regulating the crosstalk among NB cells and TAMs or other cellular components of the TME, which support tumor development and induce drug resistance. Furthermore, we will address the most recent strategies aimed at limiting the number of pro-tumoral macrophages within the TME, reprogramming the TAMs functional state, thus enhancing NK cell functions. We also prospectively discuss new or unexplored aspects of human macrophage heterogeneity.
MeSH term(s)	Humans ; Monocytes ; Neuroblastoma/pathology ; Killer Cells, Natural ; Antineoplastic Agents/pharmacology ; Macrophages/pathology ; Tumor Microenvironment
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2023-03-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12060885
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Article: B7-H3 in Pediatric Tumors: Far beyond Neuroblastoma.

Bottino, Cristina / Vitale, Chiara / Dondero, Alessandra / Castriconi, Roberta

Cancers

2023 Volume 15, Issue 13

Abstract: B7-H3 is a 4Ig transmembrane protein that emerged as a tumor-associated antigen in neuroblastoma. It belongs to the B7 family, shows an immunoregulatory role toward NK and T cells, and, therefore, has been included in the growing family of immune ... ...

Abstract	B7-H3 is a 4Ig transmembrane protein that emerged as a tumor-associated antigen in neuroblastoma. It belongs to the B7 family, shows an immunoregulatory role toward NK and T cells, and, therefore, has been included in the growing family of immune checkpoints. Besides neuroblastoma, B7-H3 is expressed by many pediatric cancers including tumors of the central nervous system, sarcomas, and acute myeloid leukemia. In children, particularly those affected by solid tumors, the therapeutic protocols are aggressive and cause important life-threatening side effects. Moreover, despite the improved survival observed in the last decade, a relevant number of patients show therapy resistance and fatal relapses. Immunotherapy represents a new frontier in the cure of cancer patients and the targeting of tumor antigens or immune checkpoints blockade showed exciting results in adults. In this encouraging scenario, researchers and clinicians are exploring the possibility to use immunotherapeutics targeting B7-H3; these include mAbs and chimeric antigen receptor T-cells (CAR-T). These tools are rapidly evolving to improve the efficacy and decrease the unwanted side effects; drug-conjugated mAbs, bi-tri-specific mAbs or CAR-T, and, very recently, NK cell engagers (NKCE), tetra-specific molecules engaging a tumor-associated antigen and NK cells, have been generated. Preclinical data are promising, and clinical trials are ongoing. Hopefully, the B7-H3 targeting will provide important benefits to cancer patients.
Language	English
Publishing date	2023-06-21
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15133279
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Article ; Online: Biofabrication Strategies for Oral Soft Tissue Regeneration.

Rahimnejad, Maedeh / Makkar, Hardik / Dal-Fabbro, Renan / Malda, Jos / Sriram, Gopu / Bottino, Marco C

Advanced healthcare materials

2024 , Page(s) e2304537

Abstract: Gingival recession, a prevalent condition affecting the gum tissues, is characterized by the exposure of tooth root surfaces due to the displacement of the gingival margin. This review explores conventional treatments, highlighting their limitations and ... ...

Abstract	Gingival recession, a prevalent condition affecting the gum tissues, is characterized by the exposure of tooth root surfaces due to the displacement of the gingival margin. This review explores conventional treatments, highlighting their limitations and the quest for innovative alternatives. Importantly, it emphasizes the critical considerations in gingival tissue engineering leveraging on cells, biomaterials, and signaling factors. Successful tissue-engineered gingival constructs hinge on strategic choices such as cell sources, scaffold design, mechanical properties, and growth factor delivery. Unveiling advancements in recent biofabrication technologies like 3D bioprinting, electrospinning, and microfluidic organ-on-chip systems, this review elucidates their precise control over cell arrangement, biomaterials, and signaling cues. These technologies empower the recapitulation of microphysiological features, enabling the development of gingival constructs that closely emulate the anatomical, physiological, and functional characteristics of native gingival tissues. The review explores diverse engineering strategies aiming at the biofabrication of realistic tissue-engineered gingival grafts. Further, the parallels between the skin and gingival tissues are highlighted, exploring the potential transfer of biofabrication approaches from skin tissue regeneration to gingival tissue engineering. To conclude, the exploration of innovative biofabrication technologies for gingival tissues and inspiration drawn from skin tissue engineering look forward to a transformative era in regenerative dentistry with improved clinical outcomes.
Language	English
Publishing date	2024-03-26
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	2649576-4
ISSN	2192-2659 ; 2192-2640
ISSN (online)	2192-2659
ISSN	2192-2640
DOI	10.1002/adhm.202304537
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Zs.A 6966: Show issues

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Article ; Online: Molecular diagnosis of Cytomegalovirus infection: clinical performance of the Aptima transcription-mediated amplification assay toward conventional qPCR chemistry on whole blood samples.

Bottino, Paolo / Pastrone, Lisa / Zanotto, Elisa / Sidoti, Francesca / Cavallo, Rossana / Costa, Cristina

Journal of clinical microbiology

2024 Volume 62, Issue 3, Page(s) e0090623

Abstract: Human Cytomegalovirus (HCMV) infection is life-threatening for immunocompromised patients. Quantitative molecular assays on whole blood or plasma are the gold standard for the diagnosis of invasive HCMV infection and for monitoring antiviral treatment in ...

Abstract	Human Cytomegalovirus (HCMV) infection is life-threatening for immunocompromised patients. Quantitative molecular assays on whole blood or plasma are the gold standard for the diagnosis of invasive HCMV infection and for monitoring antiviral treatment in individuals at risk of HCMV disease. For these reasons, an accurate standardization toward the WHO 1st International Standard among different centers and diagnostic kits represents an effort for better clinical management of HCMV-positive patients. Herein, we evaluate, for the first time, the performance of a new transcription-mediated amplification (TMA) assay versus quantitative polymerase chain reaction (qPCR) chemistry, used as a routine method, on whole blood samples. A total of 755 clinical whole blood specimens were collected and tested simultaneously with TMA and qPCR assays. The data showed a qualitative agreement of 99.27% for positive quantified samples and 89.39% for those undetected between the two tested methods. Evaluation of viremia in positive samples highlighted a good correlation between TMA and qPCR chemistries in terms of International Units (ΔLog Importance: In this paper, we describe the clinical performance of a novel transcription-mediated amplification (TMA) assay for the detection and quantification of human Cytomegalovirus (HCMV) DNA from whole blood samples. This is a pivotal analysis in immunocompromised patients [transplanted, HIV-positive, and Hematopoietic Stem Cell (HSC) recipients], and molecular tests with high sensitivity and specificity are necessary to evaluate the HCMV viral load in these patients. To our knowledge, this is the first in-depth evaluation of TMA chemistry for HCMV diagnosis on whole blood samples. Moreover, also technical aspects of this assay make it suitable for clinical diagnostics.
MeSH term(s)	Humans ; Viremia ; Polymerase Chain Reaction/methods ; Cytomegalovirus Infections ; Cytomegalovirus/genetics ; Immunocompromised Host ; DNA, Viral/genetics
Chemical Substances	DNA, Viral
Language	English
Publishing date	2024-02-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	390499-4
ISSN	1098-660X ; 0095-1137
ISSN (online)	1098-660X
ISSN	0095-1137
DOI	10.1128/jcm.00906-23
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Zs.A 1188: Show issues

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Article: Direct Oral Anticoagulants for Stroke Prevention in Special Populations: Beyond the Clinical Trials.

Carbone, Andreina / Bottino, Roberta / D'Andrea, Antonello / Russo, Vincenzo

Biomedicines

2023 Volume 11, Issue 1

Abstract: Currently, direct oral anticoagulants (DOACs) are the first-line anticoagulant strategy in patients with non-valvular atrial fibrillation (NVAF). They are characterized by a more favorable pharmacological profile than warfarin, having demonstrated equal ... ...

Abstract	Currently, direct oral anticoagulants (DOACs) are the first-line anticoagulant strategy in patients with non-valvular atrial fibrillation (NVAF). They are characterized by a more favorable pharmacological profile than warfarin, having demonstrated equal efficacy in stroke prevention and greater safety in terms of intracranial bleeding. The study population in the randomized trials of DOACs was highly selected, so the results of these trials cannot be extended to specific populations such as obese, elderly, frail, and cancer patients, which, on the other hand, are sub-populations widely represented in clinical practice. Furthermore, due to the negative results of DOAC administration in patients with mechanical heart valves, the available evidence in subjects with biological heart valves is still few and often controversial. We sought to review the available literature on the efficacy and safety of DOACs in elderly, obese, underweight, frail, cancer patients, and in patients with bioprosthetic heart valves with NVAF to clarify the best anticoagulant strategy in these special and poorly studied subpopulations.
Language	English
Publishing date	2023-01-04
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11010131
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Article ; Online: Respuesta inmunitaria innata pulmonar en la infección por Sars-Cov-2

Emanuel Bottino / Andrés Alberto Ponce

Revista de la Facultad de Ciencias Médicas de Córdoba, Vol 79, Iss

2022 Volume 1

Abstract: Introducción: La infección emergente producida por el nuevo coronavirus SARS-CoV-2, se ha constituido en un verdadero desafío para la comunidad científica. Actualmente, es escaso el conocimiento acerca de la patogenia de COVID-19 y en el último tiempo, ... ...

Abstract	Introducción: La infección emergente producida por el nuevo coronavirus SARS-CoV-2, se ha constituido en un verdadero desafío para la comunidad científica. Actualmente, es escaso el conocimiento acerca de la patogenia de COVID-19 y en el último tiempo, se ha propuesto la participación de la respuesta inmunitaria propia del huésped, en la progresión de la enfermedad. La inmunidad innata pulmonar se constituye como la primera barrera ante diferentes noxas, que puedan provocar lesión tisular, con la consiguiente alteración de la función respiratoria. Sin embargo, una pérdida en la regulación de estos mecanismos inflamatorios puede provocar una disrupción en la homeostasis del tejido afectado. Objetivo: Evaluar el papel de la respuesta inmune innata pulmonar en la patogenia de COVID-19. Materiales y métodos: Se realizó una revisión sistemática de estudios publicados en buscadores científicos: PubMed, Google Scholar, Science Direct. Se utilizaron las siguientes palabras claves: “COVID-19”; “Acute Respiratory Distress Syndrome”; “SARS-CoV-2”; “Innate pulmonary immunity”; “innate immune response”. Resultados: Se encontró una alteración global de la respuesta inmune innata pulmonar en la infección por SARS-CoV-2, que tendría relevancia en la patogenia de COVID-19. Conclusión: La afectación global de la respuesta inmune innata y por consiguiente de la homeostasis tisular pulmonar, en la infección por SARS-CoV-2, requiere el diseño de nuevas estrategias terapéuticas destinadas a la modulación de los mecanismos pro inflamatorios alterados en COVID-19.
Keywords	coronavirus ; covid-19 ; inmunidad innata ; Medicine ; R ; Medicine (General) ; R5-920
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Universidad Nacional de Córdoba
Document type	Article ; Online
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Article ; Online: Xenotransplantation literature update, January/February 2019.

Bottino, Rita / Burlak, Christopher

Xenotransplantation

2019 Volume 26, Issue 2, Page(s) e12518

MeSH term(s)	Animals ; Heterografts/history ; History, 21st Century ; Humans ; Islets of Langerhans Transplantation/history ; Publications ; Transplantation, Heterologous/history
Language	English
Publishing date	2019-04-11
Publishing country	Denmark
Document type	Historical Article ; Journal Article ; Review
ZDB-ID	1236298-0
ISSN	1399-3089 ; 0908-665X
ISSN (online)	1399-3089
ISSN	0908-665X
DOI	10.1111/xen.12518
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