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Article ; Online: Trends and Obstacles to Implement Dynamic Perfusion Concepts for Clinical Liver Transplantation

Alessandro Parente / Mauricio Flores Carvalho / Rebecca Panconesi / Yuri L. Boteon / Riccardo De Carlis / Philipp Dutkowski / Paolo Muiesan / Daniele Dondossola / Andrea Schlegel

Journal of Clinical Medicine, Vol 12, Iss 3765, p

Results from a Global Web-Based Survey

2023 Volume 3765

Abstract: Background: Organ perfusion technology is increasingly used in many countries, with a focus, however, on the Western world. This study investigates the current international trends and obstacles to the broader routine implementation of dynamic perfusion ... ...

Abstract	Background: Organ perfusion technology is increasingly used in many countries, with a focus, however, on the Western world. This study investigates the current international trends and obstacles to the broader routine implementation of dynamic perfusion concepts in liver transplantation. Methods: A web-based anonymous survey was launched in 2021. Experts of all involved specializations from 70 centers in 34 countries were contacted, based on the published literature and experience in the field of abdominal organ perfusion. Results: Overall, 143 participants from 23 countries completed the survey. Most respondents were male (67.8%) and transplant surgeons (64.3%) working at university hospitals (67.9%). The majority had experience with organ perfusion (82%), applying mainly hypothermic machine perfusion (HMP; 38%) and other concepts. While most (94.4%) expect a higher utilization of marginal organs with machine perfusion, the majority considers HMP the best technique to reduce liver discard-rates. While most respondents (90%) believed machine perfusion should be fully commissioned, the lack of funding (34%) and knowledge (16%) as well as limited staff (19%) were the three main obstacles to a routine clinical implementation. Conclusion: Although dynamic preservation concepts are increasingly used in clinical practice, significant challenges remain. Specific financial pathways, uniform regulations, and tight collaborations among involved experts are needed to achieve wider global clinical use.
Keywords	liver transplantation ; organ perfusion ; dynamic organ preservation ; survey ; Medicine ; R
Subject code	610
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Effluent Molecular Analysis Guides Liver Graft Allocation to Clinical Hypothermic Oxygenated Machine Perfusion

Caterina Lonati / Andrea Schlegel / Michele Battistin / Riccardo Merighi / Margherita Carbonaro / Paola Dongiovanni / Patrizia Leonardi / Alberto Zanella / Daniele Dondossola

Biomedicines, Vol 9, Iss 1444, p

2021 Volume 1444

Abstract: Hypothermic-oxygenated-machine-perfusion (HOPE) allows assessment/reconditioning of livers procured from high-risk donors before transplantation. Graft referral to HOPE mostly depends on surgeons’ subjective judgment, as objective criteria are still ... ...

Abstract	Hypothermic-oxygenated-machine-perfusion (HOPE) allows assessment/reconditioning of livers procured from high-risk donors before transplantation. Graft referral to HOPE mostly depends on surgeons’ subjective judgment, as objective criteria are still insufficient. We investigated whether analysis of effluent fluids collected upon organ flush during static-cold-storage can improve selection criteria for HOPE utilization. Effluents were analyzed to determine cytolysis enzymes, metabolites, inflammation-related mediators, and damage-associated-molecular-patterns. Molecular profiles were assessed by unsupervised cluster analysis. Differences between “machine perfusion (MP)-yes” vs. “MP-no”; “brain-death (DBD) vs. donation-after-circulatory-death (DCD)”; “early-allograft-dysfunction (EAD)-yes” vs. “EAD-no” groups, as well as correlation between effluent variables and transplantation outcome, were investigated. Livers assigned to HOPE ( n = 18) showed a different molecular profile relative to grafts transplanted without this procedure ( n = 21, p = 0.021). Increases in the inflammatory mediators PTX3 ( p = 0.048), CXCL8/IL-8 ( p = 0.017), TNF-α ( p = 0.038), and ANGPTL4 ( p = 0.010) were observed, whereas the anti-inflammatory cytokine IL-10 was reduced ( p = 0.007). Peculiar inflammation, cell death, and coagulation signatures were observed in fluids collected from DCD livers compared to those from DBD grafts. AST ( p = 0.034), ALT ( p = 0.047), and LDH ( p = 0.047) were higher in the “EAD-yes” compared to the “EAD-no” group. Cytolysis markers and hyaluronan correlated with recipient creatinine, AST, and ICU stay. The study demonstrates that effluent molecular analysis can provide directions about the use of HOPE.
Keywords	hypothermic-oxygenated-machine-perfusion (HOPE) ; liver transplantation (LT) ; brain death donors (DBD) ; extended criteria donors (ECD) ; donation after circulatory death donors (DCD) ; effluent fluids ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2021-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Percutaneous Transhepatic Electrohydraulic Lithotripsy for the Treatment of Difficult Bile Stones

Anna Maria Ierardi / Giovanni Maria Rodà / Letizia Di Meglio / Giuseppe Pellegrino / Paolo Cantù / Daniele Dondossola / Giorgio Rossi / Gianpaolo Carrafiello

Journal of Clinical Medicine, Vol 10, Iss 1372, p

2021 Volume 1372

Abstract: Objectives: To evaluate the efficacy and safety of percutaneous transhepatic lithotripsy (PTL) using an electro-hydraulic (EH) system for difficult bile stones. Methods: We retrospectively evaluated two patients with recurrent cholangitis, jaundice and ... ...

Abstract	Objectives: To evaluate the efficacy and safety of percutaneous transhepatic lithotripsy (PTL) using an electro-hydraulic (EH) system for difficult bile stones. Methods: We retrospectively evaluated two patients with recurrent cholangitis, jaundice and fever for the presence of difficult bile stones, inaccessible by an endoscopic approach, treated with PTL. Both procedures were conducted using the same protocol, with two different accesses. The treatments were performed using a 10 Fr flexible choledoscopy SpyGlass DS TM for visualization and an EH system for lithotripsy. Results: Technical success, clinical success and complications were evaluated. The two procedures were successfully concluded in both patients without any residual stones in the biliary tree. For both patients, a short follow-up period of six months was available, during which they remained asymptomatic. Neither major nor minor complications were registered. Conclusion: PTL was determined to be an effective and safe technique. This procedure allows a direct visualization of the stone, reducing fluoroscopy time and permitting a less invasive and less traumatic method for the percutaneous management of difficult bile stones. Advances in knowledge: The direct visualization, the high quality of the digital view, the adequate length of the device and the less traumatic approach of EH systems represent advantages compared with other available technologies.
Keywords	percutaneous lithotripsy ; electrohydraulic lithotripsy ; biliary stone ; percutaneous choledoscopy ; cholangiography ; Medicine ; R
Subject code	600
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Quantitative Metabolomics of Tissue, Perfusate, and Bile from Rat Livers Subjected to Normothermic Machine Perfusion

Caterina Lonati / Daniele Dondossola / Laimdota Zizmare / Michele Battistin / Leonie Wüst / Luigi Vivona / Margherita Carbonaro / Alberto Zanella / Stefano Gatti / Andrea Schlegel / Christoph Trautwein

Biomedicines, Vol 10, Iss 538, p

2022 Volume 538

Abstract: Machine perfusion (MP) allows the maintenance of liver cells in a metabolically active state ex vivo and can potentially revert metabolic perturbations caused by donor warm ischemia, procurement, and static cold storage (SCS). The present preclinical ... ...

Abstract	Machine perfusion (MP) allows the maintenance of liver cells in a metabolically active state ex vivo and can potentially revert metabolic perturbations caused by donor warm ischemia, procurement, and static cold storage (SCS). The present preclinical research investigated the metabolic outcome of the MP procedure by analyzing rat liver tissue, bile, and perfusate samples by means of high-field (600 MHz) nuclear magnetic resonance (NMR) spectroscopy. An established rat model of normothermic MP (NMP) was used. Experiments were carried out with the addition of an oxygen carrier (OxC) to the perfusion fluid (OxC-NMP, n = 5) or without (h-NMP, n = 5). Bile and perfusate samples were collected throughout the procedure, while biopsies were only taken at the end of NMP. Two additional groups were: (1) Native, in which tissue or bile specimens were collected from rats in resting conditions; and (2) SCS, in which biopsies were taken from cold-stored livers. Generally, NMP groups showed a distinctive metabolomic signature in all the analyzed biological matrices. In particular, many of the differentially expressed metabolites were involved in mitochondrial biochemical pathways. Succinate, acetate, 3-hydroxybutyrate, creatine, and O-phosphocholine were deeply modulated in ex vivo perfused livers compared to both the Native and SCS groups. These novel results demonstrate a broad modulation of mitochondrial metabolism during NMP that exceeds energy production and redox balance maintenance.
Keywords	nuclear magnetic resonance (NMR) spectroscopy ; liver machine perfusion (MP) ; ischemia/reperfusion (IR) ; mitochondrial metabolism ; tricarboxylic acid (TCA) cycle ; preclinical research ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Simvastatin Prevents Liver Microthrombosis and Sepsis Induced Coagulopathy in a Rat Model of Endotoxemia

Vincenzo La Mura / Nicoletta Gagliano / Francesca Arnaboldi / Patrizia Sartori / Patrizia Procacci / Luca Denti / Eleonora Liguori / Niccolò Bitto / Giuseppe Ristagno / Roberto Latini / Daniele Dondossola / Francesco Salerno / Armando Tripodi / Massimo Colombo / Flora Peyvandi

Cells, Vol 11, Iss 1148, p

2022 Volume 1148

Abstract: Background: Endotoxemia causes endothelial dysfunction and microthrombosis, which are pathogenic mechanisms of coagulopathy and organ failure during sepsis. Simvastatin has potential anti-thrombotic effects on liver endothelial cells. We investigated the ...

Abstract	Background: Endotoxemia causes endothelial dysfunction and microthrombosis, which are pathogenic mechanisms of coagulopathy and organ failure during sepsis. Simvastatin has potential anti-thrombotic effects on liver endothelial cells. We investigated the hemostatic changes induced by lipopolysaccharide (LPS) and explored the protective effects of simvastatin against liver vascular microthrombosis. Methods and results: We compared male Wistar rats exposed to LPS (5 mg/kg one i.p. dose) or saline in two experimental protocols—placebo (vehicle) and simvastatin (25 mg/kg die, orally, for 3 days before LPS). Morphological studies were performed by light- and electron-microscopy analyses to show intravascular fibrin deposition, vascular endothelial structure and liver damage. Peripheral- and organ-hemostatic profiles were analyzed using whole blood viscoelastometry by ROTEM, liver biopsy and western-blot/immunohistochemistry of thrombomodulin (TM), as well as immunohistochemistry of the von Willebrand factor (VWF). LPS-induced fibrin deposition and liver vascular microthrombosis were combined with a loss of sinusoidal endothelial TM expression and VWF-release. These changes were associated with parenchymal eosinophilia and necrosis. ROTEM analyses displayed hypo-coagulability in the peripheral blood that correlated with the degree of intrahepatic fibrin deposition ( p < 0.05). Simvastatin prevented LPS-induced fibrin deposition by preserving TM expression in sinusoidal cells and completely reverted the peripheral hypo-coagulability caused by endotoxemia. These changes were associated with a significant reduction of liver cell necrosis without any effect on eosinophilia. Conclusions: Simvastatin preserves the antithrombotic properties of sinusoidal endothelial cells disrupted by LPS, deserving pharmacological properties to contrast sepsis-associated coagulopathy and hepatic failure elicited by endotoxemia
Keywords	sepsis ; sinusoidal endothelial cells ; thrombomodulin ; coagulation ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Congenital Hepatic Fibrosis as a Cause of Recurrent Cholangitis

Emanuele Palomba / Marco Maggioni / Giulia Viero / Davide Mangioni / Rosa Lombardi / Barbara Antonelli / Daniele Dondossola / Massimo Iavarone / Anna Ludovica Fracanzani / Alessandra Bandera / Andrea Gori / Andrea Lombardi

Livers, Vol 1, Iss 12, Pp 132-

A Case Report and Review of the Literature

2021 Volume 137

Abstract: Rare liver diseases caused by ductal plate malformation, such as congenital hepatic fibrosis (CHF), Caroli syndrome, and polycystic liver disease, can have clinical manifestations such as recurrent cholangitis—frequently involving multidrug-resistant ... ...

Abstract	Rare liver diseases caused by ductal plate malformation, such as congenital hepatic fibrosis (CHF), Caroli syndrome, and polycystic liver disease, can have clinical manifestations such as recurrent cholangitis—frequently involving multidrug-resistant microorganisms—leading to difficulties in selecting the optimal antimicrobial treatment. Without prompt recognition, these infections severely hamper the patient’s quality of life and can develop into life-threatening complications. We report here the case of a 50-year-old woman with a history of recurring cholangitis with occasional systemic involvement leading to bloodstream infection, who ultimately received a diagnosis of CHF and was put on chronic suppressive antibiotic therapy while on the waiting list for a liver transplant. We also reviewed the literature collecting cases of recurrent infections occurring in patients with ductal plate malformation.
Keywords	congenital hepatic fibrosis ; cholangitis ; liver transplantation ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Human Red Blood Cells as Oxygen Carriers to Improve Ex-Situ Liver Perfusion in a Rat Model

Daniele Dondossola / Alessandro Santini / Caterina Lonati / Alberto Zanella / Riccardo Merighi / Luigi Vivona / Michele Battistin / Alessandro Galli / Osvaldo Biancolilli / Marco Maggioni / Stefania Villa / Stefano Gatti

Journal of Clinical Medicine, Vol 8, Iss 11, p

2019 Volume 1918

Abstract: Ex-situ machine perfusion (MP) has been increasingly used to enhance liver quality in different settings. Small animal models can help to implement this procedure. As most normothermic MP (NMP) models employ sub-physiological levels of oxygen delivery ( ... ...

Abstract	Ex-situ machine perfusion (MP) has been increasingly used to enhance liver quality in different settings. Small animal models can help to implement this procedure. As most normothermic MP (NMP) models employ sub-physiological levels of oxygen delivery (DO 2 ), the aim of this study was to investigate the effectiveness and safety of different DO 2 , using human red blood cells (RBCs) as oxygen carriers on metabolic recovery in a rat model of NMP. Four experimental groups (n = 5 each) consisted of (1) native (untreated/control), (2) liver static cold storage (SCS) 30 min without NMP, (3) SCS followed by 120 min of NMP with Dulbecco-Modified-Eagle-Medium as perfusate (DMEM), and (4) similar to group 3, but perfusion fluid was added with human RBCs (hematocrit 15%) (BLOOD). Compared to DMEM, the BLOOD group showed increased liver DO 2 ( p = 0.008) and oxygen consumption ( <math display="inline"> <semantics> <mrow> <mover> <mrow> <mi>V</mi> <mi>O</mi> </mrow> <mo>˙</mo> </mover> </mrow> </semantics> </math> 2 ) ( p < 0.001); lactate clearance ( p < 0.001), potassium ( p < 0.001), and glucose ( p = 0.029) uptake were enhanced. ATP levels were likewise higher in BLOOD relative to DMEM ( p = 0.031). <math display="inline"> <semantics> <mrow> <mover> <mrow> <mi>V</mi> <mi>O</mi> </mrow> <mo>˙</mo> </mover> </mrow> </semantics> </math> 2 and DO 2 were highly correlated ( p < 0.001). Consistently, the main metabolic parameters were directly correlated with DO 2 and <math display="inline"> <semantics> <mrow> <mover> <mrow> <mi>V</mi> <mi>O</mi> </mrow> <mo>˙</mo> </mover> </mrow> </semantics> </math> 2 . No human RBC related damage was detected. In conclusion, an optimized DO 2 significantly reduces hypoxic damage-related effects ...
Keywords	normothermic machine perfusion ; rat ; human red blood cells ; oxygen consumption ; oxygen delivery ; Medicine ; R
Subject code	610
Language	English
Publishing date	2019-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A Review of Clinical Practice Guidelines and Treatment Recommendations for Cancer Care in the COVID-19 Pandemic

Alberto Zaniboni / Michele Ghidini / Francesco Grossi / Alice Indini / Francesca Trevisan / Alessandro Iaculli / Lorenzo Dottorini / Giovanna Moleri / Alessandro Russo / Ivano Vavassori / Alessandra Brevi / Emanuele Rausa / Luigi Boni / Daniele Dondossola / Nicola Valeri / Antonio Ghidini / Gianluca Tomasello / Fausto Petrelli

Cancers, Vol 12, Iss 2452, p

2020 Volume 2452

Abstract: The COVID-19 pandemic has inevitably caused those involved in cancer care to change clinical practice in order to minimize the risk of infection while maintaining cancer treatment as a priority. General advice during the pandemic suggests that most ... ...

Abstract	The COVID-19 pandemic has inevitably caused those involved in cancer care to change clinical practice in order to minimize the risk of infection while maintaining cancer treatment as a priority. General advice during the pandemic suggests that most patients continue with ongoing therapies or planned surgeries, while follow-up visits may instead be delayed until the resolution of the outbreak. We conducted a literature search using PubMed to identify articles published in English language that reported on care recommendations for cancer patients during the COVID-19 pandemic from its inception up to 1st June 2020, using the terms “(cancer or tumor) AND (COVID 19)”. Articles were selected for relevance and split into five categories: (1) personal recommendations of single or multiple authors, (2) recommendations of single authoritative centers, (3) recommendations of panels of experts or of multiple regional comprehensive centers, (4) recommendations of multicenter cooperative groups, (5) official guidelines or recommendations of health authorities. Of the 97 included studies, 10 were personal recommendations of single or multiple independent authors, 16 were practice recommendations of single authoritative cancer centers, 35 were recommendations provided by panel of experts or of multiple regional comprehensive centers, 19 were cooperative group position papers, and finally, 17 were official guidelines statements. The COVID-19 pandemic is a global emergency, and has rapidly modified our clinical practice. Delaying unnecessary treatment, minimizing toxicity, and identifying care priorities for surgery, radiotherapy, and systemic therapies must be viewed as basic priorities in the COVID-19 era.
Keywords	cancer ; patients ; treatment ; COVID-19 ; pandemic ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282 ; covid19
Subject code	610
Language	English
Publishing date	2020-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Visceral artery aneurysms in liver transplant candidates and in patients after liver transplantation.

Umberto Maggi / Daniele Dondossola / Dario Consonni / Stefano Gatti / Rossella Arnoldi / Manuela Bossi / Giorgio Rossi

PLoS ONE, Vol 6, Iss 12, p e

2011 Volume 29544

Abstract: There are only few reviews concerning visceral aneurysms in cirrhotics, and a small number of papers on visceral aneurysms in liver transplant patients. The present paper investigates this condition in both groups of patients in a 10-year-retrospective ... ...

Abstract	There are only few reviews concerning visceral aneurysms in cirrhotics, and a small number of papers on visceral aneurysms in liver transplant patients. The present paper investigates this condition in both groups of patients in a 10-year-retrospective study.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2011-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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