Papers by Giuseppe Orlando
Acta gastro-enterologica Belgica
The authors present the results of a single centre study of 587 liver transplants performed in 52... more The authors present the results of a single centre study of 587 liver transplants performed in 522 adults during the period 1984-2002. Results have improved significantly over time due to better pre-, peri- and post-transplant care. One, five, ten and fifteen year actuarial survivals for the whole patient group are 81.2; 69.8; 58.9 and 51.2%. The high incidence of de novo tumors (12.3%), of cardiovascular diseases (7.5%) and of end-stage renal function (3.6%) should be further incentives to tailor the immunosuppression to the individual patient and to direct the attention of the transplant physician to the long-term quality of life of the liver recipient.
Transplantation proceedings, 1999
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation, 2014
We report the sixth case of osseous metaplasia that has occurred in the last 5 years, after a dec... more We report the sixth case of osseous metaplasia that has occurred in the last 5 years, after a deceased-donor renal transplant was performed on a young man. While its clinical significance is unclear and probably irrelevant, osseous metaplasia is one of the most relevant principles of regenerative medicine, where every bodily district contains progenitor cells that can generate cells specific to the germ layer from which they come. After the Case Report, we review the literature and speculate on the underlying pathophysiology of osseous metaplasia. Available data seem to support the hypothesis that osteogenic precursor cells, inducing factors, and a suitable environment are key for osseous metaplasia.

World journal of diabetes, Jan 15, 2014
To investigate the Wake Forest experience with pancreas transplantation in the new millennium wit... more To investigate the Wake Forest experience with pancreas transplantation in the new millennium with attention to surgical techniques and immunosuppression. A monocentric, retrospective review of outcomes in simultaneous kidney-pancreas transplant (SKPT) and solitary pancreas transplant (SPT) recipients was performed. All patients underwent pancreas transplantation as intent-to-treat with portal venous and enteric exocrine drainage and received depleting antibody induction; maintenance therapy included tapered steroids or early steroid elimination with mycophenolate and tacrolimus. Recipient selection was based on clinical judgment whether or not the patient exhibited measureable levels of C-peptide. Over an 11.25 year period, 202 pancreas transplants were performed in 192 patients including 162 SKPTs and 40 SPTs. A total of 186 (92%) were primary and 16 (8%) pancreas retransplants; portal-enteric drainage was performed in 179 cases. A total of 39 pancreas transplants were performed i...

Expert Opinion on Biological Therapy, 2014
The study purpose was to analyze midterm outcomes in a prospective trial of alemtuzumab (Alem) ve... more The study purpose was to analyze midterm outcomes in a prospective trial of alemtuzumab (Alem) versus rabbit anti-thymocyte globulin (rATG) induction in simultaneous pancreas-kidney transplantation (SPKT). From February 2005 to October 2008, 46 SPKTs (45 portal-enteric drainage) were prospectively randomized as part of a larger kidney transplant study to receive either single-dose Alem (30 mg intraoperatively) or multiple-dose rATG antibody induction (starting intraoperatively, minimum three doses administered) with tacrolimus/mycophenolate ± steroids. Of 222 kidney transplant patients enrolled in the study, 46 received SPKTs; 28 (61%) received Alem and 18 (39%) rATG induction. Follow-up ranged from 67 to 111 months (mean 80 months). There were no significant differences between the two groups in 5 years actual patient (86% Alem vs 89% rATG), kidney (82% Alem vs 61% rATG, p = 0.17) or pancreas (68% Alem vs 56% rATG) graft survival rates. Five years death-censored kidney (92% Alem vs 69% rATG, p = 0.09) and pancreas (76% Alem vs 56% rATG, p = 0.198) graft survival rates were slightly higher in patients receiving Alem. Acute rejection (21% Alem vs 44% rATG, p = 0.12) and major infection (39% Alem vs 67% rATG, p = 0.13) rates were slightly lower in the Alem group; cytomegalovirus infections were significantly lower (0 Alem vs 17% rATG, p = 0.05). The incidence of late acute rejection was low in both groups. There were no differences in early pancreas thrombosis (3.6% Alem vs 11% rATG), postoperative bleeding (11% Alem vs 0 rATG), other surgical complications, readmissions or freedom from steroids between groups. In patients with functioning grafts, 5 years mean serum creatinine (1.4 Alem vs 1.6 mg/dl rATG), calculated abbreviated modification of diet in renal disease glomerular filtration rate (55 Alem vs 52 ml/min/1.73 m(2) rATG), hemoglobin A1c (both 5.4%) and C-peptide (2.6 Alem vs 2.3 ng/ml rATG) levels were similar. Single-dose Alem and multiple-dose rATG induction provide similar midterm patient survival and graft functional outcomes with no major differences in morbidity or resource utilization.

Journal of the American College of Surgeons, 2014
In the past, type 2 (C-peptide positive) diabetes mellitus (DM) was a contraindication for simult... more In the past, type 2 (C-peptide positive) diabetes mellitus (DM) was a contraindication for simultaneous pancreas-kidney transplantation (SPKT). We retrospectively analyzed outcomes in SPKT recipients according to pretransplantation C-peptide levels ≥2.0 ng/mL or < 2.0 ng/mL. From November 2001 to March 2013, we performed 162 SPKTs including 30 (18.5%) in patients with C-peptide levels ≥2.0 ng/mL pretransplantation (C-peptide positive group, range 2.1 to 12.4 ng/mL) and 132 in patients with absent or low C-peptide levels (<2.0 ng/mL, C-peptide "negative"). C-peptide positive patients were older at SPKT, had a later age of onset and shorter duration of pretransplantation DM, and more were African-American (all p < 0.05) compared with C-peptide negative patients. With a mean follow-up of 5.6 years, patient (80% vs 82.6%), kidney graft (63.3% vs 68.9%), and pancreas graft survivals (50% vs 62.1%, all p = NS) rates were comparable in C-peptide positive and negative patients, respectively. At latest follow-up, there were no differences in acute rejection episodes, surgical complications, major infections, readmissions, hemoglobin A1c levels, serum creatinine, and estimated glomerular filtration rate levels between the 2 groups. C-peptide levels were higher (mean 5.0 vs 2.6 ng/mL, p < 0.05) and post-transplant weight gain (≥5 kg) was more common (57% vs 33%, p = 0.004) in the C-peptide positive group. Survival outcomes in C-peptide positive (n = 14) vs C-peptide negative (n = 22) African-American patients were similar, as were outcomes in C-peptide positive patients with a body mass index < or ≥ 28 kg/m(2). Patients with higher pretransplantion C-peptide levels appear to have a type 2 DM phenotype compared to insulinopenic patients undergoing SPKT. However, survival and functional outcomes were similar, suggesting that pretransplantation C-peptide levels should not be…

TECHNOLOGY, 2014
ABSTRACT Decellularization of whole organs, such as the kidney hold great promise in addressing d... more ABSTRACT Decellularization of whole organs, such as the kidney hold great promise in addressing donor shortage for transplantation. However, successful implantation of engineered whole kidney constructs has been challenged by the inability to maintain endothelial cell coverage of the vasculature matrix, resulting in excessive blood clots, loss of vascular patency, and cell death within the construct. In this study, we describe an endothelial cell seeding approach that permits effective coating of the vascular matrix of the decellularized porcine kidney scaffold using a combination of static and ramping perfusion cell seeding. Furthermore, conjugation of CD31 antibodies to the vascular matrix improved endothelial cell retention on the vasculatures, which enhanced vascular patency of the implanted scaffold. These results demonstrate that our endothelial cell seeding method combined with antibody conjugation improves endothelial cell attachment and retention leading to vascular patency of tissue-engineered whole kidney in vivo.

World Journal of Nephrology, 2014
In 2012, about 16487 people received kidney transplants in the United States, whereas 95022 candi... more In 2012, about 16487 people received kidney transplants in the United States, whereas 95022 candidates were on the waiting list by the end of the year. Despite advances in renal transplant immunology, approximately 40% of recipients will die or lose graft within 10 years. The limitations of current therapies for renal failure have led researchers to explore the development of modalities that could improve, restore, or replace the renal function. The aim of this paper is to describe a reasonable approach for kidney regeneration and review the current literature regarding cell sources and mechanisms to develop a bioengineering kidney. Due to kidneys peculiar anatomy, extracellular matrix based scaffolds are rational starting point for their regeneration. The perfusion of detergents through the kidney vasculature is an efficient method for delivering decellularizing agents to cells and for removing of cellular material from the tissue. Many efforts have focused on the search of a reliable cell source to provide enrichment for achieving stable renal cell systems. For an efficient bioengineered kidney, these cells must be attached to the organ and then maturated into the bioractors, which simulates the human body environment. A functional bioengineered kidney is still a big challenge for scientists. In the last ten years we have got many improvements on the field of solid organ regeneration; however, we are still far away from the main target. Currently, regenerative centers worldwide have been striving to find feasible strategies to develop bioengineered kidneys. Cell-scaffold technology gives hope to end-stage renal disease patients who struggle with morbidity and mortality due to extended periods on dialysis or immunosupression. The potential of bioengineered organ is to provide a reliable source of organs, which can be refunctionalized and transplanted.
... 3952 Page 4. Define the following discrete-time sliding surfaces: sω(k) = (ωe(k) − ω∗ e (k))... more ... 3952 Page 4. Define the following discrete-time sliding surfaces: sω(k) = (ωe(k) − ω∗ e (k)) + λω(ωe(k − 1) − ω∗ e (k − 1)) = 0 (24) siq(k)=(iq(k) − i∗ q(k)) + λq(iq(k − 1) − i∗ q(k − 1)) = 0 (25) sid = id(k) + λdid(k − 1) = 0 (26) where ...
This paper presents a neural networks based discrete time variable structure control and a robust... more This paper presents a neural networks based discrete time variable structure control and a robust speed estimator designed for a Permanent Magnet Synchronous Motor (PMSM). Radial basis function neural networks are used to learn about uncertainties affecting the system. A cascade control scheme is proposed which provides accurate speed tracking performance. In this control scheme the speed estimator is a robust digital differentiator that provides the first derivative of the encoder position measurement. The analysis of the control stability is given and the ultimate boundedness of the speed tracking error is proved. The controller performance has been evaluated by simulation using the model of a commercial PMSM drive. Simulations show that the proposed solution produces good speed trajectory tracking performance.
In this paper a robust sensorless cascade control scheme for a Permanent Magnet Synchronous Motor... more In this paper a robust sensorless cascade control scheme for a Permanent Magnet Synchronous Motor (PMSM) drive is proposed. A Discrete Time Variable Structure Control (DTVSC) is considered and the rotor position and speed are obtained through an Adaptive Extended Kalman Filter (AEKF). The proposed solution is experimentally tested on a commercial PMSM drive equipped with a control system based on a floating point Digital Signal Processor (DSP).

The use of synthetic and naturally-derived scaffolds for bioengineering of solid organs has been ... more The use of synthetic and naturally-derived scaffolds for bioengineering of solid organs has been limited due to a lack of an integrated vascular network. Here, we describe fabrication of a bioscaffold system with intact vascular tree. Animal-donor organs and tissues, ranging in size up-to thirty centimeters, were perfused with decellularization solution to selectively remove the cellular component of the tissue and leave an intact extracellular matrix and vascular network. The vascular tree demonstrated sequential fluid flow through a central inlet vessel that branched into an extensive capillary bed and coalesced back into a single outlet vessel. In one example, the liver, we used central inlet vessels to perfuse human and animal liver cells through the bioscaffold to create a functional liver tissue construct in vitro. These results demonstrate a novel yet simple and scalable method to obtain whole organ vascularized bioscaffolds with potential for liver, kidney, pancreas, intestine and other organs' bioengineering. These bioscaffolds can further provide a tool to study cells in their natural three-dimensional environment, which is superior for drug discovery platform compared with cells cultured in two-dimensional petri dishes.
In this paper a Power Factor Control (PFC) of an AC-DC boost converter operating in light load co... more In this paper a Power Factor Control (PFC) of an AC-DC boost converter operating in light load condition has been presented. A Passivity-Based current control able to operate in either Continuous Conduction Mode (CCM) and in Discontinuous Conduction Mode (DCM) has been presented. Cascaded control with outer PI voltage loop and intermediary input voltage feedforward has been implemented in order to increase Power Factor (PF). The proposed solution has been numerically tested using a powerful software simulation platform.

Clinical Transplantation, 2014
We performed a retrospective single-center review of 884 deceased donor (DD) kidney transplants (... more We performed a retrospective single-center review of 884 deceased donor (DD) kidney transplants (KTs) in patients (pts) aged ≥40 yr. One hundred and four (11.8%) pts were ≥70 (mean 74), 286 (32.3%) were 60-69 (mean 64), and 494 (55.9%) were 40-59 (mean 51) yr of age; the proportion receiving expanded criteria donor (ECD) kidneys were 66%, 49%, and 30%, respectively (p < 0.001). Mean waiting time (15 months) was shorter for pts ≥70 yr compared to the other two groups combined (23 months, p = 0.002). With mean follow-up ranging from 54 to 70 months, actual pt (81% vs. 72%, p = 0.002) and graft (66% vs. 58.5%, p = 0.03) survival rates were higher in the younger compared to the two older groups, whereas death-censored graft survival was similar (76% vs. 73%, p = NS). The incidence of death with a functioning graft correlated with older recipient age group, increasing from 13% to 18% to 23% (p = 0.01). The incidence of delayed graft function was similar (31.8% overall), and renal function, morbidity, and resource utilization were similar among groups. By directing ECD kidneys to selected older pts, waiting times are reduced and censored survival outcomes are similar to middle-aged patients, suggesting that matching strategies for graft and patient lifespan are warranted.
4th International Conference on Power Engineering, Energy and Electrical Drives, 2013
In this paper a system for PMSM control with Power Factor Correction (PFC) has been designed. A r... more In this paper a system for PMSM control with Power Factor Correction (PFC) has been designed. A robust sensorless cascade speed control scheme for a Permanent Magnet Synchronous Motor (PMSM) drive has been proposed. A Discrete Time Sliding Mode Control (DTSMC) and a Sliding Mode Observer (SMO) have been considered. An averaged current control with input voltage feedforward has been implemented for an AC-DC boost converter to increase Power Factor (PF). The proposed solution has been experimentally tested on a commercial PMSM drive equipped with a control system based on a microcontroller (MCU) of the Texas Instrument family C2000 T M .

Surgery, 2015
Background. There is no consensus on the optimal perioperative antibiotic prophylaxis regimen for... more Background. There is no consensus on the optimal perioperative antibiotic prophylaxis regimen for renal transplant recipients. Some studies have reported that irrigation of the wound at the time of closure without systemic antibiotics may suffice to minimize the risk for surgical site infection (SSI), but many centers still use long-term, multidose regimens in which antibiotics are administered until removal of foreign bodies occur, such as the urethral catheter, drain and central line. Methods. We designed a prospective, randomized, multicenter, controlled trial to compare a single dose versus a multidose regimen of systemic antibiotic prophylaxis in adult, nondiabetic, non-morbidly obese patients undergoing renal transplantation. The primary endpoint was the incidence of SSI; the assessment of other infection in the first postoperative month was the secondary endpoint. Results. Two hundred five patients were enrolled and randomized to receive either a single (n = 103) or multidose antibiotic regimen (n = 102) for prophylaxis. The incidences of SSI and urinary tract infection were similar in both groups. Conclusion. As the dramatic increase in antibiotic resistance has mandated the implementation of global programs to optimize the use of antibiotic agents in humans, we believe that the single dose regimen is preferred, at least in nondiabetic, non-morbidly obese, adult renal transplant recipients. (Surgery 2014;

World Journal of Gastroenterology, 2012
A number of congenital and acquired disorders require esophageal tissue replacement. Various surg... more A number of congenital and acquired disorders require esophageal tissue replacement. Various surgical techniques, such as gastric and colonic interposition, are standards of treatment, but frequently complicated by stenosis and other problems. Regenerative medicine approaches facilitate the use of biological constructs to replace or regenerate normal tissue function. We review the literature of esophageal tissue engineering, discuss its implications, compare the methodologies that have been employed and suggest possible directions for the future. Medline, Embase, the Cochrane Library, National Research Register and ClinicalTrials.gov databases were searched with the following search terms: stem cell and esophagus, esophageal replacement, esophageal tissue engineering, esophageal substitution. Reference lists of papers identified were also examined and experts in this field contacted for further information. All full-text articles in English of all potentially relevant abstracts were reviewed. Tissue engineering has involved acellular scaffolds that were either transplanted with the aim of being repopulated by host cells or seeded prior to transplantation. When acellular scaffolds were used to replace patch and short tubular defects they allowed epithelial and partial muscular migration whereas when employed for long tubular defects the results were poor leading to an increased rate of stenosis and mortality. Stenting has been shown as an effective means to reduce stenotic changes and promote cell migration, whilst omental wrapping to induce vascularization of the construct has an uncertain benefit. Decellularized matrices have been recently suggested as the optimal choice for scaffolds, but smart polymers that will incorporate signalling to promote cell-scaffold interaction may provide a more reproducible and available solution. Results in animal models that have used seeded scaffolds strongly suggest that seeding of both muscle and epithelial cells on scaffolds prior to implantation is a prerequisite for complete esophageal replacement. Novel approaches need to be designed to allow for peristalsis and vascularization in the engineered esophagus. Although esophageal tissue engineering potentially offers a real alternative to conventional treatments for severe esophageal disease, important barriers remain that need to be addressed.
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Papers by Giuseppe Orlando