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Article ; Online: Kidney transplants from elderly donors: what we have learned 20 years after the Crystal City consensus criteria meeting.

Mella, Alberto / Calvetti, Ruggero / Barreca, Antonella / Congiu, Giovanni / Biancone, Luigi

2024

Abstract: Based on the current projection of the general population and the combined increase in end-stage kidney disease with age, the number of elderly donors and recipients is increasing, raising crucial questions about how to minimize the discard rate of ... ...

Abstract	Based on the current projection of the general population and the combined increase in end-stage kidney disease with age, the number of elderly donors and recipients is increasing, raising crucial questions about how to minimize the discard rate of organs from elderly donors and improve graft and patient outcomes. In 2002, extended criteria donors were the focus of a meeting in Crystal City (VA, USA), with a goal of maximizing the use of organs from deceased donors. Since then, extended criteria donors have progressively contributed to a large number of transplanted grafts worldwide, posing specific issues for allocation systems, recipient management, and therapeutic approaches. This review analyzes what we have learned in the last 20 years about extended criteria donor utilization, the promising innovations in immunosuppressive management, and the molecular pathways involved in the aging process, which constitute potential targets for novel therapies.
Language	English
Publishing date	2024-03-06
Publishing country	Italy
Document type	Journal Article ; Review
ZDB-ID	1093991-x
ISSN	1724-6059 ; 1120-3625 ; 1121-8428
ISSN (online)	1724-6059
ISSN	1120-3625 ; 1121-8428
DOI	10.1007/s40620-024-01888-w
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Article ; Online: [Onconephrology in Renal Transplant Patient: A Challenge for the Transplant Nephrologist].

Sanna, Enrico / Manzione, Ana Maria / Mingozzi, Silvia / Biancone, Luigi

Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia

2023 Volume 40, Issue Suppl 81

Abstract: Onconephrology, an emerging field in modern medicine, is gaining importance due to its intricate challenges derived from the mixing field of tumorous and renal diseases. The growing incidence of tumors in transplant patients requires preventive ... ...

Abstract	Onconephrology, an emerging field in modern medicine, is gaining importance due to its intricate challenges derived from the mixing field of tumorous and renal diseases. The growing incidence of tumors in transplant patients requires preventive strategies and accurate monitoring. Pre-transplant screening is crucial, focusing on subjects with oncological history. Post-transplant follow-up must be personalized, tailoring screenings for patients with cancer history. Immunosuppressive therapy, although essential to prevent organ rejection, represents a delicate balance between controlling the immune response and cancer risk management. Immune checkpoint inhibitors emerge as a fascinating potential for cancer therapy, but their use in transplant patients requires caution and further research to carefully evaluate their safety and effectiveness, balancing potential benefits with actual risk of rejection. In summary, onconephrology is a growing field that requires an interdisciplinary approach and constant research, aimed at successfully addressing the complex challenges associated with oncological diseases in renal and transplant patients.
MeSH term(s)	Humans ; Kidney Transplantation ; Nephrologists ; Kidney ; Immunosuppression Therapy ; Neoplasms ; Graft Rejection/prevention & control ; Immunosuppressive Agents/adverse effects
Chemical Substances	Immunosuppressive Agents
Language	Italian
Publishing date	2023-10-03
Publishing country	Italy
Document type	English Abstract ; Journal Article ; Review
ZDB-ID	1237110-5
ISSN	1724-5990 ; 0393-5590
ISSN (online)	1724-5990
ISSN	0393-5590
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Article: Role of L-selectin in the vascular homing of peripheral blood-derived endothelial progenitor cells.

Biancone, Luigi / Cantaluppi, Vincenzo / Duò, Debora / Deregibus, Maria Chiara / Torre, Carlo / Camussi, Giovanni

Journal of immunology (Baltimore, Md. : 1950)

2004 Volume 173, Issue 8, Page(s) 5268–5274

Abstract: ... the mechanisms responsible for their homing are largely unknown. We observed the expression of L-selectin ... the copresence of L-selectin and endothelial lineage markers was confirmed. We therefore demonstrated ... that the expression of L-selectin by EPCs was functional because it mediates interaction with a murine ...

Abstract	Ex vivo expanded endothelial progenitor cells (EPCs) represent a new potential approach for the revascularization of ischemic sites. However, local accumulation of infused EPCs in these sites is poor, and the mechanisms responsible for their homing are largely unknown. We observed the expression of L-selectin, an adhesion receptor that regulates lymphocyte homing and leukocyte rolling and migration, on ex vivo expanded blood-derived human EPCs. When EPCs were subcloned in SV40-T large Ag-transfected isolates, the copresence of L-selectin and endothelial lineage markers was confirmed. We therefore demonstrated that the expression of L-selectin by EPCs was functional because it mediates interaction with a murine endothelial cell line (H.end) expressing L-selectin ligands by way of transfection with alpha(1,3/4)-fucosyltransferase. Indeed, adhesion of EPCs after incubation at 4 degrees C on a rotating platform was enhanced on alpha(1,3/4)-fucosyltransferase-transfected H.end cells compared with control vector-transfected cells, and treatment with anti-L-selectin Abs prevented this event. We then studied the role of L-selectin in EPC homing in vivo. H.end cells were implanted s.c. in SCID mice to form endothelioma tumors, and EPCs were subsequently i.v. injected. L-selectin+ EPCs localized into alpha(1,3/4)-fucosyltransferase-transfected endothelial tumors to a greater extent than in control tumors, and they were able to directly contribute to tumor vascularization by forming L-selectin+ EPC-containing vessels. In conclusion, our results showed that a mechanism typical of leukocyte adhesion is involved in the vascular homing of EPCs within sites of selectin ligand expression. This observation may provide knowledge about the substrate to design strategies to improve EPC localization in damaged tissues.
MeSH term(s)	Animals ; Blood Cells/physiology ; Cell Adhesion ; Cell Line ; Cell Movement ; Endothelial Cells/physiology ; Humans ; L-Selectin/physiology ; Mice ; Mice, SCID ; Stem Cells/physiology
Chemical Substances	L-Selectin (126880-86-2)
Language	English
Publishing date	2004-11-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.173.8.5268
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Article ; Online: Metformin, chronic nephropathy and lactic acidosis: a multi-faceted issue for the nephrologist.

Mariano, Filippo / Biancone, Luigi

Journal of nephrology

2020 Volume 34, Issue 4, Page(s) 1127–1135

Abstract: Metformin is currently considered a first-line therapy in type 2 diabetic patients. After issuing warnings for decades about the risks of lactic acidosis in patients with chronic nephropathy, metformin is now being re-evaluated. The most recent evidence ... ...

Abstract	Metformin is currently considered a first-line therapy in type 2 diabetic patients. After issuing warnings for decades about the risks of lactic acidosis in patients with chronic nephropathy, metformin is now being re-evaluated. The most recent evidence from the literature has demonstrated both a low, acceptable risk of lactic acidosis and a series of favorable effects, which go beyond its hypoglycemic activity. Patients treated with metformin show a significant mortality reduction and lower progression towards end-stage renal disease in comparison with those treated with other hypoglycemic drugs. Concerning lactic acidosis, in the last few years it has been shown how lactic acidosis almost always developed when patients kept taking the drug in the face of a concomitant disease or situation such as sepsis, fever, diarrhea, vomiting, which reduced metformin renal clearance. Actually, clearance of metformin is mainly renal, both by glomerular filtration and tubular secretion (apparent clearance 933-1317 ml/min, half-life < 3 h). As regards treatment, in cases of lactic acidosis complicated by acute kidney injury, continuous renal replacement therapy (CRRT) plays a crucial role. Besides the elimination of metformin, CRRT improves survival by correcting acidosis, electrolyte alterations, and maintaining fluid balance. Lactic acidosis almost always develops because of preventable drug accumulation. Therefore, prevention is a key factor. Patients should be aware that discontinuation for a limited time does not affect their health, even when it may be inappropriate, but it may avoid a serious, potentially fatal adverse event.
MeSH term(s)	Acidosis, Lactic/chemically induced ; Acidosis, Lactic/therapy ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Humans ; Hypoglycemic Agents/adverse effects ; Kidney Failure, Chronic ; Metformin/adverse effects ; Nephrologists
Chemical Substances	Hypoglycemic Agents ; Metformin (9100L32L2N)
Language	English
Publishing date	2020-12-29
Publishing country	Italy
Document type	Journal Article ; Review
ZDB-ID	1093991-x
ISSN	1724-6059 ; 1120-3625 ; 1121-8428
ISSN (online)	1724-6059
ISSN	1120-3625 ; 1121-8428
DOI	10.1007/s40620-020-00941-8
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Article: Safety and Metabolic Tolerance of Citrate Anticoagulation in Critically Ill Polytrauma Patients with Acute Kidney Injury Requiring an Early Continuous Kidney Replacement Therapy.

Mariano, Filippo / Mella, Alberto / Randone, Paolo / Agostini, Fulvio / Bergamo, Daniela / Berardino, Maurizio / Biancone, Luigi

Biomedicines

2023 Volume 11, Issue 9

Abstract: For severe polytrauma patients with an early AKI requiring renal replacement therapy, anticoagulation remains a great challenge. Due to a high bleeding risk, hemodynamic instability, and increased lactate levels, continuous modality (CKRT) and citrate ... ...

Abstract	For severe polytrauma patients with an early AKI requiring renal replacement therapy, anticoagulation remains a great challenge. Due to a high bleeding risk, hemodynamic instability, and increased lactate levels, continuous modality (CKRT) and citrate anticoagulation seem to be the most appropriate. However, their safety with regard to the potential risk of impaired citrate metabolism is not documented. A retrospective study of 60 severe polytrauma patients admitted to the emergency department between January 2000 and December 2021 was conducted; the patients requiring CKRT during the first 72 h were treated with citrate (n. 46, group Citrate) or with heparin (n. 14, group Heparin). Out of 60 patients, 31 survived (51.7%). According to logistic regression analysis, age and SOFA score were significant predictors of mortality. The incidence of rhabdomyolysis was more common in the survivors (77.4 vs. 51.7%), and Kaplan-Meyer analysis showed a better trend towards survival at 90 days for the group Citrate than the group Heparin (
Language	English
Publishing date	2023-09-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11092570
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Article ; Online: CytoSorb® in burn patients with septic shock and Acute Kidney Injury on Continuous Kidney Replacement Therapy is associated with improved clinical outcome and survival.

Mariano, Filippo / Greco', Domenico / Depetris, Nadia / Mella, Alberto / Sciarrillo, Alberto / Stella, Maurizio / Berardino, Maurizio / Risso, Daniela / Gambino, Roberto / Biancone, Luigi

Burns : journal of the International Society for Burn Injuries

2024

Abstract: Background: In burn patients, septic shock and acute kidney injury (AKI) with use of continuous renal replacement therapy (CRRT) severely increase morbidity and mortality. Sorbent therapies could be an adjunctive therapy to address the underlying ... ...

Abstract	Background: In burn patients, septic shock and acute kidney injury (AKI) with use of continuous renal replacement therapy (CRRT) severely increase morbidity and mortality. Sorbent therapies could be an adjunctive therapy to address the underlying metabolic changes in inflammatory and anti-inflammatory cytokines dysregulated production. Methods: A retrospectively observational study of 35 severe burn patients admitted to the Burn Center (Turin, Italy, from January 2017 to December 2022), who underwent CRRT for AKI-associated septic shock. Out of 35 patients, 11 were treated with CytoSorb® as adjunctive therapy to CRRT (Sorbent group) and 24 patients only with CRRT (Control group). Results: The application of CytoSorb® took place in a very dispersed way. Out of 11 patients, 7 started the CRRT together with the sorbent application. The patients of the sorbent group exhibited a significant reduction in norepinephrine use compared to that of the control group. A clinical improvement over the first 4 days of Cytosorb® was observed in both survivors and no survivors of the sorbent group, with significant norepinephrine decreased use on day 4 compared to day 1. In-hospital mortality was 45.4% and 70.8% in the sorbent and control group, respectively, and significantly better at Kaplan-Meier survival analysis at 270 days (p = 0.0445). In both groups, all survivor patients recovered renal function at discharge, whereas no survivors did not. Conclusions: Adjunctive treatment with CytoSorb® for burn patients with AKI-CRRT and septic shock poorly responsive to standard therapy led to a significant clinical improvement, and was associated with a lower mortality rate compared to CRRT alone.
Language	English
Publishing date	2024-03-01
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	197308-3
ISSN	1879-1409 ; 0305-4179
ISSN (online)	1879-1409
ISSN	0305-4179
DOI	10.1016/j.burns.2024.02.028
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Article ; Online: Comprehensive overview of novel chemical drugs for ulcerative colitis: focusing on phase 3 and beyond.

Neri, Benedetto / Mancone, Roberto / Fiorillo, Mariasofia / Schiavone, Sara Concetta / De Cristofaro, Elena / Migliozzi, Stefano / Biancone, Livia

Expert opinion on pharmacotherapy

2024 , Page(s) 1–15

Abstract: Introduction: Despite the growing number of highly efficacious biologics and chemical drugs for ulcerative colitis (UC), steroid-free disease control is still difficult to achieve in subgroups of patients due to refractoriness, adverse events, primary ... ...

Abstract	Introduction: Despite the growing number of highly efficacious biologics and chemical drugs for ulcerative colitis (UC), steroid-free disease control is still difficult to achieve in subgroups of patients due to refractoriness, adverse events, primary or secondary failure. New treatments are therefore still required in order to optimize clinical management of patients with UC. Areas covered: The efficacy and safety of both currently available and newly developed small molecules have been summarized. The PubMed database and clinicaltrials.gov were considered in order to search for phase 2b and 3 trials on new chemical drugs for UC. The study drugs reviewed included Janus kinases (JAK) and sphingosine-1-phosphate receptor (S1Pr) inhibitors, α4 integrin antagonist, and micro-RNA-124 upregulators. Expert opinion: Rapidity of onset, low immunogenicity, and safety are the main characteristics of small molecules currently available or under evaluation for treatment patients with UC. Among the currently available chemical drugs, the selective JAK and the S1Pr inhibitors are characterized by a good safety profile combined with the ability to induce clinical remission in UC. A relatively low frequency of endoscopic improvement and healing currently appears associated with their use, being higher in UC patients treated with S1Pr inhibitor Etrasimod. Overall, additional new safe and effective drugs are still required in order to optimize disease control in a larger majority of UC patients.
Language	English
Publishing date	2024-04-09
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2001535-5
ISSN	1744-7666 ; 1465-6566
ISSN (online)	1744-7666
ISSN	1465-6566
DOI	10.1080/14656566.2024.2339926
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Article ; Online: Surgical management of colon cancer in ulcerative colitis patients with orthotopic liver transplant for primary sclerosing cholangitis. A systematic review.

Sica, G S / Sensi, B / Siragusa, L / Blasi, F / Crispino, B / Pirozzi, B / Angelico, R / Biancone, L / Khan, J

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology

2023 Volume 49, Issue 10, Page(s) 106922

Abstract: Introduction: Colon cancer in ulcerative colitis patients with liver transplant (UCCOLT) due to primary sclerosing cholangitis carries significant treatment challenges. Aim of this literature search is to review management strategies and provide a ... ...

Abstract	Introduction: Colon cancer in ulcerative colitis patients with liver transplant (UCCOLT) due to primary sclerosing cholangitis carries significant treatment challenges. Aim of this literature search is to review management strategies and provide a framework to facilitate the decisional process in this clinical setting. Methods: PRISMA-compliant systematic search was followed by critical expert commentary of the results and development of a surgical management algorithm. Endpoints included surgical management, operative strategies, functional and survival outcomes. Technical and strategics aspects with particular regard to the choice of reconstruction were evaluated to tentatively develop an integrated algorithm. Results: Ten studies reporting treatment of 20 UCCOLT patients were identified after screening. Nine patients underwent proctocolectomy and end-ileostomy (PC) and eleven had restorative ileal pouch-anal anastomosis (IPAA). Reported results for perioperative outcomes, oncological outcomes, and graft loss were comparable for both procedures. There were no reports of subtotal colectomies and ileo-rectal anastomosis (IRA). Conclusions: Literature in the field is scarce and decision-making is particularly complex. PC and IPAA have been reported with good results. Nevertheless, IRA may also be considered in UCCOLT patients in selected cases, reducing the risks of sepsis, OLT and pouch failure; furthermore, in young patients, it has the advantage of preserving fertility or sexual function. The proposed treatment algorithm may represent a valuable support in guiding surgical strategy.
MeSH term(s)	Humans ; Colitis, Ulcerative/complications ; Colitis, Ulcerative/surgery ; Liver Transplantation/adverse effects ; Cholangitis, Sclerosing/complications ; Cholangitis, Sclerosing/surgery ; Proctocolectomy, Restorative/methods ; Anastomosis, Surgical/methods ; Colonic Neoplasms/complications ; Colonic Neoplasms/surgery ; Treatment Outcome ; Postoperative Complications/etiology
Language	English
Publishing date	2023-05-13
Publishing country	England
Document type	Systematic Review ; Journal Article ; Review
ZDB-ID	632519-1
ISSN	1532-2157 ; 0748-7983
ISSN (online)	1532-2157
ISSN	0748-7983
DOI	10.1016/j.ejso.2023.04.021
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Article: Expression of L-selectin ligands by transformed endothelial cells enhances T cell-mediated rejection.

Biancone, L / Stamenkovic, I / Cantaluppi, V / Boccellino, M / De Martino, A / Bussolino, F / Camussi, G

Journal of immunology (Baltimore, Md. : 1950)

1999 Volume 162, Issue 9, Page(s) 5263–5269

Abstract: Recent immunohistochemical studies have suggested that L-selectin ligands may be implicated ... Kaposi's sarcoma, were engineered to express L-selectin ligands by stable transfection with a cDNA encoding alpha(1 ... endhygro cells supported L-selectin-dependent adhesion and cytolytic T cell activity in vitro. Taken ...

Abstract	Recent immunohistochemical studies have suggested that L-selectin ligands may be implicated in the infiltration of tumors and rejected transplants by lymphocytes. In the present study, polyoma-middle T Ag-transformed endothelial cells (H.end), which typically form in vivo immunogenic vascular tumors resembling Kaposi's sarcoma, were engineered to express L-selectin ligands by stable transfection with a cDNA encoding alpha(1,3/4)-fucosyltransferase (H.endft). The ability of these cells to form tumors in the s.c. tissues of normal and immunocompromised mice was then compared with that of H.end cells transfected with the hygromycin-resistance vector only (H. endhygro). H.endhygro cells rapidly formed local and metastatic tumors in normal syngeneic mice, leading to death within 2-3 mo postinjection. By contrast, tumors derived from H.endft cells displayed a slower rate of growth, an absence of metastasis, and marked lymphocyte infiltration. Animals bearing these tumors survived for a significantly longer duration than animals injected with H.endhygro cells. Alternatively, H.endft and H.endhygro cells formed tumors with comparable aggressiveness in immunocompromised mice, resulting in animal death within 3 wk of injection. H.endft but not H.endhygro cells supported L-selectin-dependent adhesion and cytolytic T cell activity in vitro. Taken together, our observations indicate that the in situ expression of fucosyltransferase may significantly influence the cellular immune response in endothelioma tumors. These results may be relevant in understanding the development of vascular opportunistic tumors such as Kaposi's sarcoma.
MeSH term(s)	Animals ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/pathology ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/pathology ; Cell Division/immunology ; Cell Line, Transformed ; Cell Movement/immunology ; Endothelium, Vascular/enzymology ; Endothelium, Vascular/metabolism ; Endothelium, Vascular/physiology ; Fucosyltransferases/metabolism ; Graft Rejection/etiology ; Graft Rejection/immunology ; Hemangioendothelioma/enzymology ; Hemangioendothelioma/metabolism ; Hemangioendothelioma/pathology ; Humans ; Jurkat Cells ; L-Selectin/metabolism ; L-Selectin/physiology ; Ligands ; Mice ; Mice, Inbred DBA ; Mice, Nude ; Neoplasm Transplantation ; Oligosaccharides/biosynthesis ; Oligosaccharides/metabolism ; Survival Rate ; T-Lymphocytes/immunology ; Tumor Cells, Cultured
Chemical Substances	Ligands ; Oligosaccharides ; L-Selectin (126880-86-2) ; Fucosyltransferases (EC 2.4.1.-) ; galactoside 3-fucosyltransferase (EC 2.4.1.152)
Language	English
Publishing date	1999-05-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
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Article ; Online: C1q-binding donor-specific antibody assays help define risk and prognosis in antibody-mediated rejection.

Cozzi, Emanuele / Biancone, Luigi

Kidney international

2018 Volume 94, Issue 4, Page(s) 657–659

Abstract: Antibody-mediated rejection represents the first cause of graft loss in renal transplant recipients, and it is imperative to identify appropriate tools to enable risk stratification of such patients. Lately, the usefulness of measuring complement-binding ...

Abstract	Antibody-mediated rejection represents the first cause of graft loss in renal transplant recipients, and it is imperative to identify appropriate tools to enable risk stratification of such patients. Lately, the usefulness of measuring complement-binding anti-human leukocyte antigen (HLA) donor-specific antibodies (DSAs) in renal transplantation has been intensely debated. While the jury is still out, recent data suggest that monitoring complement-binding DSAs may help to recognize high-risk patients and possibly trigger more effective interventions in selected patients.
MeSH term(s)	Graft Rejection ; Graft Survival ; HLA Antigens ; Humans ; Kidney Transplantation ; Prognosis ; Tissue Donors
Chemical Substances	HLA Antigens
Language	English
Publishing date	2018-09-19
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1016/j.kint.2018.06.032
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