Publications by authors named "Antonio Rampoldi"

47 Publications

Performance of the model for end-stage liver disease score for mortality prediction and the potential role of etiology.

J Hepatol 2021 Jul 30. Epub 2021 Jul 30.

Gastroenterology Unit, ASL Latina, Department of Translational and Precision Medicine, "Sapienza" University of Rome, Italy.

Background & Aims: Although the discriminative ability of the model for end-stage liver disease (MELD) score is generally considered acceptable, its calibration is still unclear. In a validation study, we assessed the discriminative performance and calibration of 3 versions of the model: original MELD-TIPS, used to predict survival after transjugular intrahepatic portosystemic shunt (TIPS); classic MELD-Mayo; and MELD-UNOS, used by the United Network for Organ Sharing (UNOS). We also explored recalibrating and updating the model.

Methods: In total, 776 patients who underwent elective TIPS (TIPS cohort) and 445 unselected patients (non-TIPS cohort) were included. Three, 6 and 12-month mortality predictions were calculated by the 3 MELD versions: discrimination was assessed by c-statistics and calibration by comparing deciles of predicted and observed risks. Cox and Fine and Grey models were used for recalibration and prognostic analyses.

Results: In the TIPS/non-TIPS cohorts, the etiology of liver disease was viral in 402/188, alcoholic in 185/130, and non-alcoholic steatohepatitis in 65/33; mean follow-up±SD was 25±9/19±21 months; and the number of deaths at 3-6-12 months was 57-102-142/31-47-99, respectively. C-statistics ranged from 0.66 to 0.72 in TIPS and 0.66 to 0.76 in non-TIPS cohorts across prediction times and scores. A post hoc analysis revealed worse c-statistics in non-viral cirrhosis with more pronounced and significant worsening in the non-TIPS cohort. Calibration was acceptable with MELD-TIPS but largely unsatisfactory with MELD-Mayo and -UNOS whose performance improved much after recalibration. A prognostic analysis showed that age, albumin, and TIPS indication might be used to update the MELD.

Conclusions: In this validation study, the performance of the MELD score was largely unsatisfactory, particularly in non-viral cirrhosis. MELD recalibration and candidate variables for an update to the MELD score are proposed.

Lay Summary: While the discriminative performance of the model for end-stage liver disease (MELD) score is credited to be fair to good, its calibration, the correspondence of observed to predicted mortality, is still unsettled. We found that application of 3 different versions of the MELD in 2 independent cirrhosis cohorts yielded largely imprecise mortality predictions particularly in non-viral cirrhosis. Thus, we propose a recalibration and suggest candidate variables for an update to the model.
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http://dx.doi.org/10.1016/j.jhep.2021.07.018DOI Listing
July 2021

Laparoscopic surgery versus radiofrequency ablation for the treatment of single hepatocellular carcinoma ≤3 cm in the elderly: a propensity score matching analysis.

HPB (Oxford) 2021 Jun 8. Epub 2021 Jun 8.

Division of Hepato-Pancreato-Biliary Surgery, "F. Miulli" General Hospital, Acquaviva delle Fonti, Bari, Italy. Electronic address:

Background: Laparoscopic liver resection (LLR) and radiofrequency ablation (RFA) represented potential treatments for patients with a single hepatocellular carcinoma (HCC) smaller than 3 cm. As the aging population soared, our study aimed to examine the advantage/drawback balance for these treatments, which should be reassessed in elderly patients.

Methods: A multicentric retrospective study compared 184 elderly patients (aged >70 years) (86 patients underwent LLR and 98 had RFA) with single ≤3 cm HCC, observed from January 2009 to January 2019.

Results: After propensity score matching (PSM), the estimated 1- and 3-year overall survival rates were 96.5 and 87.9% for the LLR group, and 94.6 and 68.1% for the RFA group (p = 0.001) respectively. The estimated 1- and 3-year disease-free survival rates were 92.5 and 67.4% for the LLR group, and 68.5 and 36.9% for the RFA group (p = 0.001). Patients with HCC of anterolateral segments were more often treated with laparoscopic resection (47 vs. 36, p = 0.04). The median operative time in the resection group was 205 min and 25 min in the RFA group (p = 0.01). Length of hospital stay was 5 days in the resection group and 3 days in the RFA group (p = 0.03).

Conclusion: Despite a longer length of hospital stay and operative time, LLR guarantees a comparable postoperative course and a better overall and disease-free survival in elderly patients with single HCC (≤3 cm), located in anterolateral segments.
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http://dx.doi.org/10.1016/j.hpb.2021.05.008DOI Listing
June 2021

Radiofrequency ablation surgical resection in elderly patients with hepatocellular carcinoma in Milan criteria.

World J Gastroenterol 2021 May;27(18):2205-2218

Unit of Hepato-Pancreatic-Biliary Surgery, "F. Miulli" General Regional Hospital, Acquaviva delle Fonti 70021, Italy.

Background: Surgical resection and radiofrequency ablation (RFA) represent two possible strategy in treatment of hepatocellular carcinoma (HCC) in Milan criteria.

Aim: To evaluate short- and long-term outcome in elderly patients (> 70 years) with HCC in Milan criteria, which underwent liver resection (LR) or RFA.

Methods: The study included 594 patients with HCC in Milan criteria (429 in LR group and 165 in RFA group) managed in 10 European centers. Statistical analysis was performed using the Kaplan-Meier method before and after propensity score matching (PSM) and Cox regression.

Results: After PSM, we compared 136 patients in the LR group with 136 patients in the RFA group. Overall survival at 1, 3, and 5 years was 91%, 80%, and 76% in the LR group and 97%, 67%, and 41% in the RFA group respectively ( = 0.001). Disease-free survival at 1, 3, and 5 years was 84%, 60% and 44% for the LR group, and 63%, 36%, and 25% for the RFA group ( = 0.001).Postoperative Clavien-Dindo III-IV complications were lower in the RFA group (1% 11%, = 0.001) in association with a shorter length of stay (2 d 7 d, = 0.001).In multivariate analysis, Model for End-stage Liver Disease (MELD) score (> 10) [odds ratio (OR) = 1.89], increased value of international normalized ratio (> 1.3) (OR = 1.60), treatment with radiofrequency (OR = 1.46) ,and multiple nodules (OR = 1.19) were independent predictors of a poor overall survival while a high MELD score (> 10) (OR = 1.51) and radiofrequency (OR = 1.37) were independent factors associated with a higher recurrence rate.

Conclusion: Despite a longer length of stay and a higher rate of severe postoperative complications, surgery provided better results in long-term oncological outcomes as compared to ablation in elderly patients (> 70 years) with HCC in Milan criteria.
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http://dx.doi.org/10.3748/wjg.v27.i18.2205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117730PMC
May 2021

Surgical Resection vs. Percutaneous Ablation for Single Hepatocellular Carcinoma: Exploring the Impact of Li-RADS Classification on Oncological Outcomes.

Cancers (Basel) 2021 Apr 1;13(7). Epub 2021 Apr 1.

Department of General Surgery and Transplantation, Niguarda Ca' Granda Hospital, 20162 Milan, Italy.

: Single hepatocellular carcinoma (HCC) benefits from surgical resection (SR) or US-guided percutaneous ablation (PA), although the best approach is still debated. We evaluated the impact of Li-RADS classification on the oncological outcomes of SR vs. PA as single HCC first-line treatment. : We retrospectively and blindly classified treatment-naïve single HCC that underwent SR or PA between 2010 and 2016 according to Li-RADS protocol. Overall survival (OS), recurrence free survival (RFS) and local recurrence after SR and PA were compared for each Li-RADS subclass before and after propensity-score matching (PS-M). : Considering the general population, SR showed better 5-year OS (68.3% vs. 52.2%; = 0.049) and RFS (42.5% vs. 29.8%; = 0.002), with lower incidence of local recurrence (8.2% vs. 44.4%; < 0.001), despite a significantly higher frequency of clinically-relevant complications (12.8% vs. 1.9%; = 0.002) and a higher Comprehensive Complication Index (12.1 vs. 2.2; < 0.001). Focusing on different Li-RADS subclasses, we highlighted better 5-year OS (67.1% vs. 46.2%; = 0.035), RFS (45.0% vs. 27.0% RFS; < 0.001) and lower incidence of local recurrence (9.7% vs. 48.6%; < 0.001) after SR for Li-RADS-5 HCCs, while these outcomes did not differ for Li-RADS-3/4 subclasses; such results were confirmed after PS-M. : Our analysis suggests a potential prognostic role of Li-RADS classification, supporting SR over PA especially for Li-RADS-5 single HCC.
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http://dx.doi.org/10.3390/cancers13071671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038048PMC
April 2021

Functional and molecular effects of TNF-α on human iPSC-derived cardiomyocytes.

Stem Cell Res 2021 04 1;52:102218. Epub 2021 Feb 1.

Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA 30322, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30322, USA. Electronic address:

Proinflammatory molecule tumor necrosis factor alpha (TNF-α) is predominantly elevated in cytokine storm as well as worsening cardiac function. Here we model the molecular and functional effects of TNF-α in cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSC). We found that treatment of hiPSC-CMs with TNF-α increased reactive oxygen species (ROS) and caspase 3/7 activity and caused cell death and apoptosis. TNF-α treatment also resulted in dysregulation of cardiomyocyte function with respect to the increased abnormal calcium handling, calcium wave propagation between cells and excitation-contraction coupling. We also uncovered significant changes in gene expression and protein localization caused by TNF-α treatment. Notably, TNF-α treatment altered the expression of ion channels, dysregulated cadherins, and affected the localization of gap-junction protein connexin-43. In addition, TNF-α treatment up-regulated IL-32 (a human specific cytokine, not present in rodents and an inducer of TNF-α) and IL-34 and down-regulated glutamate receptors and cardiomyocyte contractile proteins. These findings provide insights into the molecular and functional consequences from the exposure of human cardiomyocytes to TNF-α. Our study provides a model to incorporate inflammatory factors into hiPSC-CM-based studies to evaluate mechanistic aspects of heart disease.
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http://dx.doi.org/10.1016/j.scr.2021.102218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080119PMC
April 2021

Endovascular approach for arteriovenous limb malformations: a single center experience.

Int Angiol 2021 Apr 26;40(2):165-169. Epub 2021 Jan 26.

Unit of Interventional Radiology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.

Background: To assess imaging findings, describe endovascular technical aspects and analyzed procedural outcomes in a population of patients underwent limb arteriovenous malformation (LAVMs).

Methods: From January 2015 to December 2018, all consecutive patients underwent an endovascular procedure for ICD-9-CM codex for arteriovenous malformation problems were retrospective reviewed. Among these, patients with LAVMs were selected. Demographic, preoperative imaging, interventional and postprocedural data were collected for each patient and procedure. The International Society of Vascular Anomalies, the Cho-Do angiographic classification and the Schobinger clinical stage were used to describe disease type, aspect and clinical severity. Angiographic and clinical outcomes were also described.

Results: During the study period, 76 intervention for AVMs were performed in 52 patients. Among these, 26 LAVMs were selected and analyzed in 21 patients (number of LAVMs per patient: 1.2±0.5), 14 affecting upper limbs, 17 lower limbs. Pain, discomfort and swelling were main symptoms reported (95%, 90% and 62%, respectively). Ultrasound scan, computed angiography tomography and magnetic resonance angiography were used - alone or in combination - as preoperative imaging in 67%, 62% and 48% of patients, respectively. Cho-Do class ≥3 was described in 70% of treated LAVMs and a Schobinger stage ≥2 in more than 90%. Ipsilateral femoral access with a 5F introducer was preferred. Selective embolization with glue was the most preferred technique (57%), in combination or not with microsphere embolization (19%) and/or direct nidus sclerotherapy (14%). Optimal and suboptimal results were achieved in 86% of cases. Further interventions were performed in 52% of cases, with more than two interventions in 29% of cases.

Conclusions: Quality of life, clinical picture and anatomical structure are items of paramount importance during preoperative LAVMs endovascular treatment planning. Treatment must be focused on LAVMs type, minimizing invasiveness and number of interventions, although secondary intervention rate remains quite high.
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http://dx.doi.org/10.23736/S0392-9590.21.04598-3DOI Listing
April 2021

Cryopreservation and CO-independent culture of 3D cardiac progenitors for spaceflight experiments.

Biomaterials 2021 02 11;269:120673. Epub 2021 Jan 11.

Division of Pediatric Cardiology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA. Electronic address:

Space experimentation of cardiomyocyte differentiation from human induced pluripotent stem cells offers an exciting opportunity to explore the potential of these cells for disease modeling, drug discovery and regenerative medicine. Previous studies on the International Space Station were done with 2D non-cryopreserved cultures of cardiomyocytes being loaded and cultivated in spaceflight culture modules with CO. Here we report the development of methods of cryopreservation and CO-independent culture of 3D cardiac progenitors. The cryopreservation allows preparation and pretesting of the cells before spaceflight, makes it easier to transport the cell culture, reduces the impact of strong gravitational force exerted on the cells during the launch of spaceflight, and accommodates a more flexible working schedule for the astronauts. The use of CO-independent medium with supplements supports cell growth and differentiation without a CO incubator. With these methods, we conducted a spaceflight experiment through the SpaceX-20 mission to evaluate the effect of microgravity on the survival and differentiation of 3D cardiac progenitors. Our cryopreserved cardiac progenitor spheres were successfully cultivated in a spaceflight culture module without CO for 3 weeks aboard the International Space Station. Beating cardiomyocytes were generated and returned to the earth for further study.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882209PMC
February 2021

Melphalan induces cardiotoxicity through oxidative stress in cardiomyocytes derived from human induced pluripotent stem cells.

Stem Cell Res Ther 2020 11 5;11(1):470. Epub 2020 Nov 5.

Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, 2015 Uppergate Drive, Atlanta, GA, 30322, USA.

Background: Treatment-induced cardiotoxicity is a leading noncancer-related cause of acute and late onset morbidity and mortality in cancer patients on antineoplastic drugs such as melphalan-increasing clinical case reports have documented that it could induce cardiotoxicity including severe arrhythmias and heart failure. As the mechanism by which melphalan impairs cardiac cells remains poorly understood, here, we aimed to use cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) to investigate the cellular and molecular mechanisms of melphalan-induced cardiotoxicity.

Methods: hiPSC-CMs were generated and treated with clinically relevant doses of melphalan. To characterize melphalan-induced cardiotoxicity, cell viability and apoptosis were quantified at various treatment durations. Ca transient and contractility analyses were used to examine the alterations of hiPSC-CM function. Proteomic analysis, reactive oxygen species detection, and RNA-Sequencing were conducted to investigate underlying mechanisms.

Results: Melphalan treatment of hiPSC-CMs induced oxidative stress, caused Ca handling defects and dysfunctional contractility, altered global transcriptomic and proteomic profiles, and resulted in apoptosis and cell death. The antioxidant N-acetyl-L-cysteine attenuated these genomic, cellular, and functional alterations. In addition, several other signaling pathways including the p53 and transforming growth factor-β signaling pathways were also implicated in melphalan-induced cardiotoxicity according to the proteomic and transcriptomic analyses.

Conclusions: Melphalan induces cardiotoxicity through the oxidative stress pathway. This study provides a unique resource of the global transcriptomic and proteomic datasets for melphalan-induced cardiotoxicity and can potentially open up new clinical mechanism-based targets to prevent and treat melphalan-induced cardiotoxicity.
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http://dx.doi.org/10.1186/s13287-020-01984-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643439PMC
November 2020

Proteomic Profiling Reveals Roles of Stress Response, Ca Transient Dysregulation, and Novel Signaling Pathways in Alcohol-Induced Cardiotoxicity.

Alcohol Clin Exp Res 2020 11 16;44(11):2187-2199. Epub 2020 Oct 16.

From the, Department of Pediatrics, (RL, PF, LCA, AR, DL, CX), Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia.

Background: Alcohol use in pregnancy increases the risk of abnormal cardiac development, and excessive alcohol consumption in adults can induce cardiomyopathy, contractile dysfunction, and arrhythmias. Understanding molecular mechanisms underlying alcohol-induced cardiac toxicity could provide guidance in the development of therapeutic strategies.

Methods: We have performed proteomic and bioinformatic analysis to examine protein alterations globally and quantitatively in cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CMs) treated with ethanol (EtOH). Proteins in both cell lysates and extracellular culture media were systematically quantitated.

Results: Treatment with EtOH caused severe detrimental effects on hiPSC-CMs as indicated by significant cell death and deranged Ca handling. Treatment of hiPSC-CMs with EtOH significantly affected proteins responsible for stress response (e.g., GPX1 and HSPs), ion channel-related proteins (e.g. ATP1A2), myofibril structure proteins (e.g., MYL2/3), and those involved in focal adhesion and extracellular matrix (e.g., ILK and PXN). Proteins involved in the TNF receptor-associated factor 2 signaling (e.g., CPNE1 and TNIK) were also affected by EtOH treatment.

Conclusions: The observed changes in protein expression highlight the involvement of oxidative stress and dysregulation of Ca handling and contraction while also implicating potential novel targets in alcohol-induced cardiotoxicity. These findings facilitate further exploration of potential mechanisms, discovery of novel biomarkers, and development of targeted therapeutics against EtOH-induced cardiotoxicity.
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http://dx.doi.org/10.1111/acer.14471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680409PMC
November 2020

Orthopedic injuries in patients with multiple injuries: Results of the 11th trauma update international consensus conference Milan, December 11, 2017.

J Trauma Acute Care Surg 2020 02;88(2):e53-e76

From the General Surgery-Trauma Team (S.C., S.S., F.B., F.R., F.S.), Niguarda Hospital, Milan, Italy; Department of Orthopedics (R.O.), R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, Maryland; Department of Traumatology and Orthopedic Surgery Cologne-Merheim Medical Center (M.M.), Institute for Research in Operative Medicine, University Witten-herdecke, Koln, Germany; Trauma Surgery (S.H., T.M.S.), R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, Maryland; Orthopedic Surgery (F.B., U.M., D.C., F.S.), Niguarda Hospital, Milan, Italy; Major Trauma Centre (N.K.), LeedsTeaching Hospitals NHS Trust, Leeds, United Kingdom; General and Emergency Surgery (F.C., L.A.), Bufalini Hospital Cesena, Cesena; Orthopedic Surgery (A.M.), Traumatologic Center, University of Turin, Turin; Interventional Radiology (A.R.), Infectious Disease (M.P.), Niguarda Hospital; Orthopedic Surgery, Humanitas Clinical Institute (M.B.), Milan; Orthopedic Surgery (B.M.), Policlinic Hospital of Bari, University of Bari, Bari, Italy; Trauma and Reconstructive Surgery (J.R.), University Medical Center, Hamburg-Eppendorf, Germany; Plastic and Reconstructive Surgery (Z.A.), State University of Trieste, Trieste, Plastic Surgery (M.d.B.), S. Gerardo Hospital, Monza; Neuro Intensive Care (A.C.), Niguarda Hospital, Milan; Intensive Care (M.M., G.G.), Maggiore Hospital, Bologna; Intensive Care (E.D.B.), Rummo Hospital, Benevento; Orthopedic Surgery (S.C.), Tempo Pausania Hospital, Olbia; General Surgery (P.D.), IRCCS Policlinico S.Matteo, University of Pavia, Pavia; Emergency Medicine, Emergency Department (A.F.), Morgagni-Pierantoni Hospital, Italy; General Surgery (I.S.), Valle Olona Hospital, Busto Arsizio; and General Surgery and Trauma Team, Department of Trauma Network (O.C.), State University of Milan, Niguarda Hospital, Milan, Italy.

Background: In blunt trauma, orthopedic injuries are often associated with cerebral and torso injuries. The optimal timing for definitive care is a concern. The aim of the study was to develop evidence-based guidelines for damage-control orthopedic (DCO) and early total care (ETC) of pelvic and long-bone fractures, closed or open, and mangled extremities in adult trauma patients with and without associated injuries.

Methods: The literature since 2000 to 2016 was systematically screened according to Preferred Reporting Items for Systematic Reviews and meta-analyses protocol. One hundred twenty-four articles were reviewed by a panel of experts to assign grade of recommendation and level of evidence using the Grading of recommendations Assessment, Development, and Evaluation system, and an International Consensus Conference, endorsed by several scientific societies was held.

Results: The choice between DCO and ETC depends on the patient's physiology, as well as associated injuries. In hemodynamically unstable pelvic fracture patient, extraperitoneal pelvic packing, angioembolization, external fixation, C-clamp, and resuscitative endovascular balloon occlusion of the aorta are not mutually exclusive. Definitive reconstruction should be deferred until recovery of physiological stability. In long bone fractures, DCO is performed by external fixation, while ETC should be preferred in fully resuscitated patients because of better outcomes. In open fractures early debridement within 24 hours should be recommended and early closure of most grade I, II, IIIa performed. In mangled extremities, limb salvage should be considered for non-life-threatening injuries, mostly of upper limb.

Conclusion: Orthopedic priorities may be: to save a life: control hemorrhage by stabilizing the pelvis and femur fractures; to save a limb: treat soft tissue and vascular injuries associated with fractures, stabilize fractures, recognize, and prevent compartmental syndrome; to save functionality: treat dislocations, articular fractures, distal fractures. While DCO is the best initial treatment to reduce surgical load, ETC should be applied in stable or stabilized patients to accelerate the recovery of normal functions.

Level Of Evidence: Systematic review of predominantly level II studies, level II.
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http://dx.doi.org/10.1097/TA.0000000000002407DOI Listing
February 2020

Endovascular Treatment of Acute Posttransplant Portal Vein Thrombosis Due to Portal Steal From Mesocaval And Coronary Portosystemic Shunts.

Exp Clin Transplant 2020 10 7;18(5):653-656. Epub 2020 Feb 7.

>From the Department of General Surgery and Transplantation, Niguarda Ca' Granda Hospital, Milan, Italy.

The management of portosystemic shunts in liver transplant recipients relies on appropriate perioperative study. There are several strategies for shunt handling, ranging from preoperative interventional procedures to intraoperative surgical interruption or embolization. Appropriate management often results in a successful outcome, although wrong decisions could lead to serious consequences. Here, we report a liver transplant recipient with grade 2 portal vein thrombosis associated with 2 large portosystemic shunts (coronary and mesocaval), which were managed intraoperatively via thrombectomy without shunt ligation. Acute portal vein thrombosis developed early after transplant due to portal steal syndrome. The patient underwent a successful endovascular shunt embolization, with prompt restoration of hepatopetal portal flow and resolution of the portal steal. Use of interventional radiology in perioperative management of transplant patients has recently gained wider importance; our case reported here is particularly suggestive of the good outcomes of a multidisciplinary approach to a threatening complication such as postoperative acute portal vein thrombosis.
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http://dx.doi.org/10.6002/ect.2019.0273DOI Listing
October 2020

Treatment of hepatocellular carcinoma beyond the Milan criteria. A weighted comparative study of surgical resection versus chemoembolization.

HPB (Oxford) 2020 09 10;22(9):1349-1358. Epub 2020 Jan 10.

School of Medicine and Surgery, University of Milano - Bicocca, Italy; Department of General Surgery and Transplantation - ASST - Grande Ospedale Metropolitano Niguarda, Milan, Italy; International Center for Digestive Health, University of Milan-Bicocca, Milan, Italy.

Background: Optimal treatment of hepatocellular carcinoma (HCC) beyond the Milan criteria (MC) is debated. The aim of the study was to assess overall-survival (OS) and disease-free-survival (DFS) for HCC beyond MC when treated by trans-arterial-chemoembolization (TACE) or surgical resection (SR).

Method: between 2005 and 2015, all patients with a first diagnosis of HCC beyond MC(1 nodule>5 cm, or 3 nodules>3 cm without macrovascular invasion) were evaluated. Analyses were carried out through Kaplan-Meier, Cox models and the inverse probability weighting (IPW) method to reduce allocation bias. Sub-analyses have been performed for multinodular and single large tumors compared with a MC-IN cohort.

Results: 226 consecutive patients were evaluated: 118 in SR group and 108 in TACE group. After IPW, the two pseudo-populations were comparable for tumor burden and liver function. In the SR group, 1-5 years OS rates were 72.3% and 35% respectively and 92.7% and 39.3% for TACE (p = 0.500). The median DFS was 8 months (95%CI:8-9) for TACE, and 11 months (95%CI:9-12) for SR (p < 0.001). TACE was an independent predictor for recurrence (HR 1.5; 95%CI: 1.1-2.1; p = 0.015). Solitary tumors > 5 cm and multinodular disease had comparable OS and DFS as Milan-IN group (p > 0.05).

Conclusion: Surgery allowed a better control than TACE in patient bearing HCC beyond MC. This translated into a significant benefit in terms of DFS but not OS.
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http://dx.doi.org/10.1016/j.hpb.2019.12.011DOI Listing
September 2020

Hemoperitoneum in cirrhotic patients in the absence of abdominal trauma.

Expert Rev Gastroenterol Hepatol 2019 Sep 17;13(9):867-876. Epub 2019 Jun 17.

Department of Surgery, Division of Acute Care Surgery, New York University School of Medicine , New York , NY , USA.

: Hemoperitoneum can be a life-threating condition in cirrhotic patients who have a limited compensatory reserve during hemorrhagic shock. We aim to review the literature on the different etiologies associated with non-traumatic hemoperitoneum (NTH), summarizing the most relevant conditions associated with spontaneous and iatrogenic peritoneal and retroperitoneal bleeding that may occur in cirrhotic patients and to illustrate the most relevant diagnostic strategies and optimal management. : This review encompasses the current literature in hemoperitoneum in cirrhotic patients in the absence of abdominal trauma. Established diagnostic procedures, therapeutic interventions and potential novel targets are reported and discussed. : To ensure the optimal management regardless of the underlying etiology of NTH, the first goal for the clinician is to obtain immediate hemodynamic stabilization with supportive measures and to control the source of bleeding. The latter can be achieved with angiographic embolization, which is usually the first choice, or with open surgery. Other therapeutic options according to specific etiologies include transjugular intrahepatic portosystemic shunt (TIPS), balloon-occluded retrograde transvenous obliteration (BRTO), balloon-occluded anterograde transvenous obliteration (BATO) or intra operative radio frequency (RF).
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http://dx.doi.org/10.1080/17474124.2019.1631159DOI Listing
September 2019

Endoscopic entero-enteral bypass: an effective new approach to the treatment of postsurgical complications of hepaticojejunostomy.

Endoscopy 2019 12 4;51(12):1146-1150. Epub 2019 Jun 4.

Digestive and Interventional Endoscopy Unit, Niguarda-Ca' Granda Hospital, Milan, Italy.

Background: Management of biliary adverse events (BAEs) after biliodigestive anastomosis is challenging. We propose a new endoscopic approach to improve BAEs in this clinical setting.

Methods: Patients who had BAEs after a hepaticojejunostomy with Roux-en-Y loop or a Whipple procedure underwent creation of an entero-enteral endoscopic bypass (EEEB) between the duodenal/gastric wall and the biliary jejunal loop under endoscopic ultrasound (EUS) and fluoroscopic guidance using specifically designed fully covered self-expandable metal stents.

Results: 32 consecutive patients underwent EEEB, which was successful in all but one patient. One procedural and five long-term mild adverse events occurred. Endoscopic retrograde cholangiography (ERC) through the EEEB successfully treated all types of BAEs in these patients. Disease recurred in two patients who were successfully re-treated through the EEEB.

Conclusions: Our retrospective study showed that in patients with BAEs after biliodigestive anastomosis, EEEB is safe, feasible, and allows a successful long-term treatment of different BAEs in a tertiary referral center with high-level experience in both endoscopic retrograde cholangiopancreatography and EUS.
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http://dx.doi.org/10.1055/a-0914-2855DOI Listing
December 2019

Targeting HIF-1α in combination with PPARα activation and postnatal factors promotes the metabolic maturation of human induced pluripotent stem cell-derived cardiomyocytes.

J Mol Cell Cardiol 2019 07 11;132:120-135. Epub 2019 May 11.

Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA. Electronic address:

Immature phenotypes of cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) limit the utility of these cells in clinical application and basic research. During cardiac development, postnatal cardiomyocytes experience high oxygen tension along with a concomitant downregulation of hypoxia-inducible factor 1α (HIF-1α), leading to increased fatty acid oxidation (FAO). We hypothesized that targeting HIF-1α alone or in combination with other metabolic regulators could promote the metabolic maturation of hiPSC-CMs. We examined the effect of HIF-1α inhibition on the maturation of hiPSC-CMs and investigated a multipronged approach to promote hiPSC-CM maturation by combining HIF-1α inhibition with molecules that target key pathways involved in the energy metabolism. Cardiac spheres of highly-enriched hiPSC-CMs were treated with a HIF-1α inhibitor alone or in combination with an agonist of peroxisome proliferator activated receptor α (PPARα) and three postnatal factors (triiodothyronine hormone T3, insulin-like growth factor-1 and dexamethasone). HIF-1α inhibition significantly increased FAO and basal and maximal respiration of hiPSC-CMs. Combining HIF-1α inhibition with PPARα activation and the postnatal factors further increased FAO and improved mitochondrial maturation in hiPSC-CMs. Compared with mock-treated cultures, the cultures treated with the five factors had increased mitochondrial content and contained more cells with mitochondrial distribution throughout the cells, which are features of more mature cardiomyocytes. Consistent with these observations, a number of transcriptional regulators of mitochondrial metabolic processes were upregulated in hiPSC-CMs treated with the five factors. Furthermore, these cells had significantly increased Ca transient kinetics and contraction and relaxation velocities, which are functional features for more mature cardiomyocytes. Therefore, targeting HIF-1α in combination with other metabolic regulators significantly improves the metabolic maturation of hiPSC-CMs.
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http://dx.doi.org/10.1016/j.yjmcc.2019.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683286PMC
July 2019

Cardiac Toxicity From Ethanol Exposure in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Toxicol Sci 2019 05;169(1):280-292

Division of Pediatric Cardiology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia.

Alcohol use prior to and during pregnancy remains a significant societal problem and can lead to developmental fetal abnormalities including compromised myocardia function and increased risk for heart disease later in life. Alcohol-induced cardiac toxicity has traditionally been studied in animal-based models. These models have limitations due to physiological differences from human cardiomyocytes (CMs) and are also not suitable for high-throughput screening. We hypothesized that human-induced pluripotent stem cell-derived CMs (hiPSC-CMs) could serve as a useful tool to study alcohol-induced cardiac defects and/or toxicity. In this study, hiPSC-CMs were treated with ethanol at doses corresponding to the clinically relevant levels of alcohol intoxication. hiPSC-CMs exposed to ethanol showed a dose-dependent increase in cellular damage and decrease in cell viability, corresponding to increased production of reactive oxygen species. Furthermore, ethanol exposure also generated dose-dependent increased irregular Ca2+ transients and contractility in hiPSC-CMs. RNA-seq analysis showed significant alteration in genes belonging to the potassium voltage-gated channel family or solute carrier family, partially explaining the irregular Ca2+ transients and contractility in ethanol-treated hiPSC-CMs. RNA-seq also showed significant upregulation in the expression of genes associated with collagen and extracellular matrix modeling, and downregulation of genes involved in cardiovascular system development and actin filament-based process. These results suggest that hiPSC-CMs can be a novel and physiologically relevant system for the study of alcohol-induced cardiac toxicity.
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http://dx.doi.org/10.1093/toxsci/kfz038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484889PMC
May 2019

[Spontaneous rectus sheath hematoma as a complication of anticoagulant and antiplatelet therapy: a case report.]

Recenti Prog Med 2019 Feb;110(2):89-92

UOC Cardiologia Riabilitativa CTO, ASST Gaetano Pini/CTO, Milano.

Spontaneous rectus sheath hematoma (RSH) is an uncommon and often clinically misdiagnosed cause of abdominal pain, characterized by a presence of blood within rectus muscle sheath, with palpable mass. Hemorrhage may originate from the epigastric artery and branches or directly from rectus sheath rupture. The most frequent cause of hematoma is anticoagulant therapy. Diagnosis is based on ultrasonography and computed tomography. Conservative treatment and, in case of active bleeding, intravascular embolization is the treatment of choice, while surgery is indicated in case of failure of endovascular procedure or in patients with intra-abdominal rupture causing hemodynamic instability and abdominal compartment syndrome. Here we present a case of RSH that developed after hip replacement surgery in a patient on anticoagulant therapy and dual antiplatelet therapy.
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http://dx.doi.org/10.1701/3112.31004DOI Listing
February 2019

[Spontaneous rectus sheath hematoma as a complication of anticoagulant and antiplatelet therapy: a case report.]

Recenti Prog Med 2019 Feb;110(2):89-92

UOC Cardiologia Riabilitativa CTO, ASST Gaetano Pini/CTO, Milano.

Spontaneous rectus sheath hematoma (RSH) is an uncommon and often clinically misdiagnosed cause of abdominal pain, characterized by a presence of blood within rectus muscle sheath, with palpable mass. Hemorrhage may originate from the epigastric artery and branches or directly from rectus sheath rupture. The most frequent cause of hematoma is anticoagulant therapy. Diagnosis is based on ultrasonography and computed tomography. Conservative treatment and, in case of active bleeding, intravascular embolization is the treatment of choice, while surgery is indicated in case of failure of endovascular procedure or in patients with intra-abdominal rupture causing hemodynamic instability and abdominal compartment syndrome. Here we present a case of RSH that developed after hip replacement surgery in a patient on anticoagulant therapy and dual antiplatelet therapy.
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http://dx.doi.org/10.1701/3112.31004DOI Listing
February 2019

Long-term Effect of Islet Transplantation on Glycemic Variability.

Cell Transplant 2018 05 5;27(5):840-846. Epub 2018 Jun 5.

6 Division of Nephrology, Dialysis and Renal Transplantation Niguarda Hospital, Milan, Italy.

Islet transplantation has been reported to restore normoglycemia and the overall metabolic control in type 1 diabetes mellitus (DM). In the most experienced centers, islet transplantation clinical outcome is similar to that of the whole pancreas transplantation. Long-term islet transplantation function remains a very interesting matter worth discussing. A progressive islet function decrease was reported, probably due to islet exhaustion. In 5 islet-transplanted patients with at least 3-yr follow-up and still insulin independent, their glycemic control was characterized by a blinded retrospective continuous glucose monitoring system (CGMS). Islet transplantation restored glycemic control and glucose variability. Data were compared with patients in the waiting list. All the parameters of glycemic variability tested had improved significantly in patients who had islet transplantation compared with those patients who were on the waiting list. In conclusion, islet transplantation is able to maintain a proper glucose control and normalize glycemic variability in selected patients. A blinded retrospective CGMS is a useful method to characterize glucose homeostasis deeply in vivo in islet-transplanted patients.
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http://dx.doi.org/10.1177/0963689718763751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047271PMC
May 2018

Multiple Idiopathic Aneurysms in a 6-Year-Old Boy.

Ann Vasc Surg 2018 Oct 22;52:314.e7-314.e11. Epub 2018 May 22.

Vascular Surgery Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.

We report the rare case of a young boy affected by idiopathic multiple aneurysms at different arterial locations who was treated at our institution with different surgical and endovascular techniques.
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http://dx.doi.org/10.1016/j.avsg.2018.03.034DOI Listing
October 2018

The Evaluation of Aortic Diameter Changes During Long-Term Follow-Up After Endovascular Treatment of Acute Blunt Traumatic Thoracic Aortic Injuries.

Vasc Endovascular Surg 2018 Jul 25;52(5):335-343. Epub 2018 Mar 25.

1 Department of Radiology, University of Insubria, Circolo Hospital, Varese, Italy.

Purpose: To evaluate the variations in aortic diameters and long-term results in patients who underwent thoracic endovascular aortic repair (TEVAR) for acute blunt traumatic thoracic aortic injuries (BTTAIs).

Materials And Methods: We retrospectively evaluated 23 patients with a mean age of 39 years (range: 17-74 years) who underwent TEVAR for BTTAI between October 2000 and November 2014. All of the patients underwent computed tomography angiography (CTA) before hospital discharge as a baseline imaging for the subsequent follow-up examinations. The technical success, overall survival, and complications were evaluated. Furthermore, the aortic diameters outside of the stent-graft (1 cm proximal and 1 cm distal to the stent-graft) and the aortic diameters within the stent-graft (2 cm distal to the proximal end and 2 cm proximal to the distal end) were assessed. The diameters at baseline on CTA were compared with those of the latest available follow-up examination.

Results: Technical success was 100% with a mean follow-up of 65.4 months (range: 12-171 months). No death was registered, and 2 (8.7%) of 23 endograft-related complications (1 stent-graft distal infolding and 1 endoleak 2 and 4 months after the procedure, respectively) were observed. An increase in aortic diameter either proximal or distal to the stent-graft (mean value 0.7 and 0.5 mm, respectively) or within the stent-graft (mean value of 0.5 mm for both proximal and distal diameters) was registered (mean follow-up at 65.4 months, range: 12-171 months).

Conclusion: Aortic dilatation following TEVAR for BTTAI is minimal during long-term follow-up. Endovascular treatment represents a durable and safe option in acute BTTAIs.
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http://dx.doi.org/10.1177/1538574418765385DOI Listing
July 2018

Under-dilated TIPS Associate With Efficacy and Reduced Encephalopathy in a Prospective, Non-randomized Study of Patients With Cirrhosis.

Clin Gastroenterol Hepatol 2018 07 3;16(7):1153-1162.e7. Epub 2018 Mar 3.

HPB Surgery and Liver Transplantation Unit, Modena Hospital, University of Modena and Reggio Emilia, Modena, Italy.

Background & Aims: Portosystemic encephalopathy (PSE) is a major complication of trans-jugular intrahepatic porto-systemic shunt (TIPS) placement. Most devices are self-expandable polytetrafluoroethylene-covered stent grafts (PTFE-SGs) that are dilated to their nominal diameter (8 or 10 mm). We investigated whether PTFE-SGs dilated to a smaller caliber (under-dilated TIPS) reduce PSE yet maintain clinical and hemodynamic efficacy. We also studied whether under-dilated TIPS self-expand to nominal diameter over time.

Methods: We performed a prospective, non-randomized study of 42 unselected patients with cirrhosis who received under-dilated TIPS (7 and 6 mm) and 53 patients who received PTFE-SGs of 8 mm or more (controls) at referral centers in Italy. After completion of this study, dilation to 6 mm became the standard and 47 patients were included in a validation study. All patients were followed for 6 months; Doppler ultrasonography was performed 2 weeks and 3 months after TIPS placement and every 6 months thereafter. Stability of PTFE-SG diameter was evaluated by computed tomography analysis of 226 patients with cirrhosis whose stent grafts increased to 6, 7, 8, 9, or 10 mm. The primary outcomes were incidence of at least 1 episode of PSE grade 2 or higher during follow up, incidence of recurrent variceal hemorrhage or ascites, incidence of shunt dysfunction requiring TIPS recanalization, and reduction in porto-caval pressure gradient.

Results: PSE developed in a significantly lower proportion of patients with under-dilated TIPS (27%) than controls (54%) during the first year after the procedure (P = .015), but the proportions of patients with recurrent variceal hemorrhage or ascites did not differ significantly between groups. No TIPS occlusions were observed. These results were confirmed in the validation cohort. In an analysis of self-expansion of stent grafts, during a mean follow-up period of 252 days after placement, none of the PTFE-SGs self-expanded to the nominal diameter in hemodynamically relevant sites (such as portal and hepatic vein vascular walls).

Conclusions: In prospective, non-randomized study of patients with cirrhosis, we found under-dilation of PTFE-SGs during TIPS placement to be feasible, associated with lower rates of PSE, and effective.
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http://dx.doi.org/10.1016/j.cgh.2018.01.029DOI Listing
July 2018

Nonoperative management of abdominal solid-organ injuries following blunt trauma in adults: Results from an International Consensus Conference.

J Trauma Acute Care Surg 2018 03;84(3):517-531

From the General Surgery-Trauma Team (S.C., O.C., M.M., S.S., F.B., F.R., F.S.), Grande Ospedale Metropolitano Niguarda, Milan, Italy; Emergency Surgery, Department of Surgery (A.L.), Meilahti Hospital, Helsinki, Finland; Shock Trauma Center (S.H., T.M.S., K.S.), R Adams Cowley, Baltimore, Maryland; Acute Care Surgery (W.B.), The Queen's Medical Center, Honolulu, Hawaii; Emergency Surgery (F.C.), Parma Hospital, Parma; General Surgery (L.A., F.C.), Papa Giovanni XXIII Hospital, Bergamo; Trauma Surgery (G.T., S.d.S.), Maggiore Hospital, Bologna; Intensive Care (E.D.B.), Rummo Hospital, Benevento; Neurosurgical Intensive Care (A.C.), Grande Ospedale Metropolitano Niguarda, Milan; Intensive Care (G.G.), Maggiore Hospital, Bologna, Italy; Emergency Medicine (M.C.), Desio and Vimercate Hospital, Desio; Emergency Surgery (S.R.), Umberto I Hospital, Roma; General Surgery (M.C., P.F.), Cardarelli Hospital, Napoli; Urology (A.G.), Grande Ospedale Metropolitano Niguarda; Digestive Endoscopy (M.M.), Grande Ospedale Metropolitano Niguarda, Milan; Department of Surgery (S.R.), Insubria University, Varese; Department of Surgery and Translational Medicine (D.P.), University of Florence, Ospedale Careggi, Firenze; Division of Interventional Radiology, Department of Radiology (A.R.), Grande Ospedale Metropolitano Niguarda, Milan; General Surgery (L.F.), San Gerardo Hospital, Monza; and Department of Surgery (S.M.), University of Bari, Bari, Italy.

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http://dx.doi.org/10.1097/TA.0000000000001774DOI Listing
March 2018

Leptin signaling and cancer chemoresistance: Perspectives.

World J Clin Oncol 2017 Apr;8(2):106-119

Pierre V Candelaria, Antonio Rampoldi, Adriana Harbuzariu, Ruben R Gonzalez-Perez, Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, United States.

Obesity is a major health problem and currently is endemic around the world. Obesity is a risk factor for several different types of cancer, significantly promoting cancer incidence, progression, poor prognosis and resistance to anti-cancer therapies. The study of this resistance is critical as development of chemoresistance is a serious drawback for the successful and effective drug-based treatments of cancer. There is increasing evidence that augmented adiposity can impact on chemotherapeutic treatment of cancer and the development of resistance to these treatments, particularly through one of its signature mediators, the adipokine leptin. Leptin is a pro-inflammatory, pro-angiogenic and pro-tumorigenic adipokine that has been implicated in many cancers promoting processes such as angiogenesis, metastasis, tumorigenesis and survival/resistance to apoptosis. Several possible mechanisms that could potentially be developed by cancer cells to elicit drug resistance have been suggested in the literature. Here, we summarize and discuss the current state of the literature on the role of obesity and leptin on chemoresistance, particularly as it relates to breast and pancreatic cancers. We focus on the role of leptin and its significance in possibly driving these proposed chemoresistance mechanisms, and examine its effects on cancer cell survival signals and expansion of the cancer stem cell sub-populations.
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http://dx.doi.org/10.5306/wjco.v8.i2.106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385432PMC
April 2017

Prostatic Artery Embolization as an Alternative to Indwelling Bladder Catheterization to Manage Benign Prostatic Hyperplasia in Poor Surgical Candidates.

Cardiovasc Intervent Radiol 2017 Apr 27;40(4):530-536. Epub 2017 Jan 27.

Department of Urology, Ospedale Niguarda Ca' Granda, Piazza Ospedale Maggiore, 3, 20100, Milan, Italy.

Purpose: To prospectively assess discontinuation of indwelling bladder catheterization (IBC) and relief of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) following prostate artery embolization (PAE) in poor surgical candidates.

Methods: Patients ineligible for surgical intervention were offered PAE after at least 1 month of IBC for management of urinary retention secondary to BPH; exclusion criteria for PAE included eligibility for surgery, active bladder cancer or known prostate cancer. Embolization technical and clinical success were defined as bilateral prostate embolization and removal of IBC, respectively. Patients were followed for at least 6 months and evaluated for International Prostate Symptom Score, quality of life, prostate size and uroflowmetric parameters.

Results: A total of 43 patients were enrolled; bilateral embolization was performed in 33 (76.7%), unilateral embolization was performed in 8 (18.6%), and two patients could not be embolized due to tortuous and atherosclerotic pelvic vasculature (4.7%). Among the patients who were embolized, mean prostate size decreased from 75.6 ± 33.2 to 63.0 ± 23.2 g (sign rank p = 0.0001, mean reduction of 19.6 ± 17.3%), and IBC removal was achieved in 33 patients (80.5%). Clavien II complications were reported in nine patients (21.9%) and included urinary tract infection (three patients, 7.3%) and recurrent acute urinary retention (six patients, 14.6%). Nine patients (22.0%) experienced post-embolization syndrome.

Conclusions: PAE is a safe and feasible for the relief of LUTS and IBC in highly comorbid patients without surgical treatment options.
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http://dx.doi.org/10.1007/s00270-017-1582-8DOI Listing
April 2017

Leptin-Notch signaling axis is involved in pancreatic cancer progression.

Oncotarget 2017 Jan;8(5):7740-7752

Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, 30310 USA.

Pancreatic cancer (PC) shows a high death rate. PC incidence and prognosis are affected by obesity, a pandemic characterized by high levels of leptin. Notch is upregulated by leptin in breast cancer. Thus, leptin and Notch crosstalk could influence PC progression. Here we investigated in PC cell lines (BxPC-3, MiaPaCa-2, Panc-1, AsPC-1), derived tumorspheres and xenografts whether a functional leptin-Notch axis affects PC progression and expansion of pancreatic cancer stem cells (PCSC). PC cells and tumorspheres were treated with leptin and inhibitors of Notch (gamma-secretase inhibitor, DAPT) and leptin (iron oxide nanoparticle-leptin peptide receptor antagonist 2, IONP-LPrA2). Leptin treatment increased cell cycle progression and proliferation, and the expression of Notch receptors, ligands and targeted molecules (Notch1-4, DLL4, JAG1, Survivin and Hey2), PCSC markers (CD24/CD44/ESA, ALDH, CD133, Oct-4), ABCB1 protein, as well as tumorsphere formation. Leptin-induced effects on PC and tumorspheres were decreased by IONP-LPrA2 and DAPT. PC cells secreted leptin and expressed the leptin receptor, OB-R, which indicates a leptin autocrine/paracrine signaling loop could also affect tumor progression. IONP-LPrA2 treatment delayed the onset of MiaPaCa-2 xenografts, and decreased tumor growth and the expression of proliferation and PCSC markers. Present data suggest that leptin-Notch axis is involved in PC. PC has no targeted therapy and is mainly treated with chemotherapy, whose efficiency could be decreased by leptin and Notch activities. Thus, the leptin-Notch axis could be a novel therapeutic target, particularly for obese PC patients.
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http://dx.doi.org/10.18632/oncotarget.13946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352357PMC
January 2017

Sustained Islet Allograft Function After Peritransplant Treatment Using Exenatide With and Without Everolimus.

Transplantation 2016 11;100(11):e117-e118

1 Diabetology Unit, Niguarda Hospital, Milan, Italy. 2 Tissue Therapy Unit, Niguarda Hospital, Milan, Italy. 3 Surgical Department, Niguarda Hospital, Milan, Italy. 4 Interventional Radiology Unit, Niguarda Hospital, Milan, Italy. 5 Anesthesiology Unit, Niguarda Hospital, Milan, Italy. 6 Division of Nephrology, Dialysis and Renal Transplantation, Niguarda Hospital, Milan, Italy.

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http://dx.doi.org/10.1097/TP.0000000000001441DOI Listing
November 2016

Direct Transaortic TEVAR: An Alternative Option for Selected Patients With Unsuitable Peripheral Access.

Ann Thorac Surg 2016 Aug;102(2):e117-9

Cardiac Surgery, Niguarda Hospital, Milano, Italy.

Thoracic endovascular aortic repair (TEVAR) is effectively executed in patients with arch or descending aortic diseases. Peripheral access sites are preferably used as standard gates for TEVAR. Feasibility of a peripheral approach might need an intraoperative evaluation and alternative routes should have been carefully assessed. In this article, we report 2 successful cases of direct transaortic TEVAR, where stent grafts were directly introduced into the native ascending aorta without external conduits. A satisfactory result and the absence of aortic-related complications were observed at 2 and 5 years' follow-up, respectively.
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http://dx.doi.org/10.1016/j.athoracsur.2016.01.010DOI Listing
August 2016

Effects of Renal Sympathetic Denervation on Arterial Stiffness and Blood Pressure Control in Resistant Hypertensive Patients: A Single Centre Prospective Study.

High Blood Press Cardiovasc Prev 2015 Dec 12;22(4):411-6. Epub 2015 Oct 12.

Cardiology IV, Cardiovascular "A' De Gasperis" Department, Niguarda Ca' Granda Hospital, Piazza Ospedale Maggiore 3, 20161, Milan, Italy.

Renal denervation (RD) is an intriguing treatment strategy for resistant hypertension. However, limited data are available about its long time efficacy as well as its effects on intermediate phenotypes like arterial stiffness and carotid IMT. 12 patients (9 males, mean 69 years) with resistant hypertension underwent bilateral RDN (Medtronic System) since April 2012 in Niguarda Ca' Granda Hospital (Milan). Patients were studied before intervention, and at 1, 3, 6 and 12 months after RD. Carotid intima media thickness (Esaote Mylab) and carotid-femoral pulse wave velocity (Complior, Alam medical) were assessed at each step. Compared to baseline, patients showed a marked reduction of office systolic blood pressure at each follow-up step (p < 0.05 versus baseline for all steps) as well as pulse wave velocity (p < 0.01 at 1 year versus baseline). Moreover, reduction in pulse wave velocity was higher than the expected value obtained only considering blood pressure drop. Conversely, no significant effect was observed on diastolic blood pressure as well as carotid intima-media thickness. In our study, renal denervation was a safe and effective procedure. The BP lowering effect was maintained during follow-up and a beneficial effect on arterial stiffness was observed, which implies that this effect can't passively originate from the BP fall but rather from an improvement of arterial mechanical properties, possibly related to a reduced sympathetic arterial drive.
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http://dx.doi.org/10.1007/s40292-015-0121-4DOI Listing
December 2015
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