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Ignazio R Marino

Publications and source records attributed to Ignazio R Marino.

At least 19 recordsLinked to original sources
PubMed2007

From the laboratory bench to the patient's bedside: an update on clinical trials with mesenchymal stem cells.

Mesenchymal Stem Cells (MSCs) are non-hematopoietic multi-potent stem-like cells that are capable of differentiating into both mesenchymal and non-mesenchymal lineages. In fact, in addition to bone, cartilage, fat, and myoblasts, it has been demonstrated that MSCs are capable of differentiating into neurons and astrocytes in vitro and in vivo. MSCs are of interest because they are isolated from a small aspirate of bone marrow and can be easily expanded in vitro. As such, these cells are currently being tested for their potential use in cell and gene therapy for a number of human diseases. Nevertheless, there are still some open questions about origin, multipotentiality, and anatomical localization of MSCs. In this review, we discuss clinical trials based on the use of MSCs in cardiovascular diseases, such as treatment of acute myocardial infarction, endstage ischemic heart disease, or prevention of vascular restenosis through stem cell-mediated injury repair. We analyze data from clinical trials for treatment of osteogenesis imperfecta (OI), which is a genetic disease characterized by production of defective type I collagen. We describe progress for neurological disease treatment with MSC transplants. We discuss data on amyotrophic lateral sclerosis (ALS) and on lysosomal storage diseases (Hurler syndrome and metachromatic leukodystrophy). A section of review is dedicated to ongoing clinical trials, involving MSCs in treatment of steroid refractory Graft Versus Host Disease (GVHD); periodontitis, which is a chronic disease affecting periodontium and causing destruction of attachment apparatus, heart failure, and bone fractures. Finally, we will provide information about biotech companies developing MSC therapy.

Bone Marrow Cells↗
PubMed2007

The role of basiliximab induction therapy in organ transplantation.

Basiliximab is a chimeric monoclonal antibody that selectively binds to the alpha-subunit (CD25) of IL-2 receptors on the surface of activated T lymphocytes, and is a highly effective prophylaxis agent against rejection in organ transplant recipients. Its pharmacokinetic profile is characterized by a biphasic and slow clearance with long terminal half-life and a volume of distribution within the central compartment and outside the circulatory system. Basiliximab induction demonstrated an excellent safety profile, with no increase in the incidence of malignancy, infections or death. It has also been used effectively in high-risk recipients, steroid-sparing and steroid-minimization protocols, and in post-transplant patients with renal dysfunction who would benefit from delayed introduction of calcineurin inhibitors. Basiliximab induction therapy given at days 0 and 4 after transplantation appears to be safe and cost-effective for immunoprophylaxis in solid organ transplant recipients, specifically in kidney and liver transplantation, when given in conjunction with dual or triple immunosuppressive therapy.

Animals↗
PubMed2006

Fulminant hepatic failure bridged to liver transplantation with a molecular adsorbent recirculating system: a single-center experience.

We herein describe the clinical course of a consecutive series of fulminant hepatic failure patients treated with a molecular adsorbent recirculating system (MARS), a cell-free albumin dialysis technique. From November 2000 to September 2002, seven adult patients ages 22-61 (median, 41), one male (14.2%) and six females (85.7%), affected by fulminant hepatic failure underwent seven courses (one to five sessions each, 6 hr in duration) of extracorporeal support using the MARS technique. Pre- and posttreatment blood glucose, liver function tests, ammonia, arterial lactate, electrolytes, hemodynamic parameters, arterial blood gases, liver histology, Glasgow Coma Scale, and coagulation studies were reviewed. No adverse side effects such as generalized bleeding on noncardiogenic pulmonary edema, often seen during MARS treatment, occurred in the patients included in this study. Six patients (85.7%) are currently alive and well, and one (14.2%) died. Four patients (57%) were successfully bridged (two patients in 1 day and two other patients in 4 days) to liver transplantation, while two (5%) recovered fully without transplantation. All the measured variables stabilized after commencement of the MARS. No differences were noted between the pre- and the post-MARS histology. We conclude that the MARS is a safe, temporary life support mechanism for patients awaiting liver transplantation or recovering from fulminant hepatic failure.

Adult↗
PubMed2005

Bacteremia using the molecular adsorbent recirculating system in patients bridged to liver transplantation.

OBJECTIVE: To retrospectively analyze the incidence and implications of bacteremia in patients supported by a molecular adsorbent recirculating system bridged to liver transplantation. MATERIAL AND METHODS: From September 2000 to April 2003, 30 patients (17 males and 13 females, aged 15-70 years; median age, 52 years) presenting with acute-on-chronic liver failure were treated with a molecular adsorbent recirculating system. RESULTS: Nine patients (30%) developed bacteremia (positive blood culture) during treatment, 100% of them died during the same hospital admission. The most common isolates were Pseudomonas aeruginosa (44.4%) and Escherichia coli (33.3%). Sputum (44.4%) and ascites (33.3%) represented the most common sources of infection followed by urine and purely bloodborne infections (11.1% each). The isolate in the sputum was Pseudomonas aeruginosa 100% of the time, whereas Escherichia coli was found in 66.6% of the ascites cultures. The hemodynamic profile of patients who developed positive blood cultures showed significantly lower systemic vascular resistance indexes compared with those of nonbacteremic patients before and after treatment. There was a statistically significant difference (P = 0.0002) in survival between the bacteremic (who all died) and the nonbacteriemic patients treated. CONCLUSIONS: Bacteremia was found to be a negative prognostic factor for patients supported with a molecular adsorbent recirculating system and therefore, a contraindication to starting and/or continuing treatment. Infection should be carefully ruled out prior to initiating treatment using a molecular adsorbent recirculating system. Moreover, prophylaxis with broad-spectrum antibiotics that provide double coverage against Gram-negative bacteria should be mandatory.

Adolescent↗
PubMed2004

Preliminary report on surgical technique in hepatic parenchymal transection for liver tumors in the elderly: a lesson learned from living-related liver transplantation.

BACKGROUND AND OBJECTIVES: Availability of hi-tech surgical devices has elaborated the technique of parenchymal transection during hepatectomy from classic crushing clamp technique 1,2 to a combination of an ultrasonic dissection with special type of cautery 3,4. We have developed a new technique to resect hepatic parenchyma using an ultrasonic surgical aspirator in association with a monopolar floating ball. This combination has been utilized in 42 liver resections. METHODS: A retrospective analysis of perioperative mortality, length of hospitalization, and blood transfusion during surgery in two patient groups who underwent liver resection was carried out. We divided the patient population into Group A (42 patients), who underwent the new technique, and Group B (107 patients), who experienced the crushing clamp technique. A second analysis was performed, where we divided the same patient population group in Group 1 with age less than 65, and Group 2 including patients older than 65 years. RESULTS: We found that the new technique reduced length of stay, procedure length, and use of perioperative blood. We determined that the two age groups performed similarly in comparison to LOS, length of procedure, blood use, and complications. CONCLUSION: This enforces the fact that the elderly can receive such surgical treatment without hesitation.

Aged↗
PubMed2004

Efficacy and safety of basiliximab with a tacrolimus-based regimen in liver transplant recipients.

BACKGROUND: Induction with monoclonal antibodies for prevention of acute cellular rejection (ACR) may avoid many of the adverse events associated with polyclonal antibodies. Basiliximab, a chimeric monoclonal antibody directed against the alpha-chain of the interleukin 2 receptor (CD25), has been extensively evaluated as an induction therapy for kidney transplant recipients, more frequently in combination with a cyclosporine-based regimen. In this study, we assessed the efficacy and safety of basiliximab in combination with a tacrolimus-based regimen after liver transplantation. METHODS: Fifty consecutive liver transplants (47 cadaveric donors; 3 living donors) were analyzed. All patients received two 20-mg doses of basiliximab (days 0 and 4 after transplantation) followed by tacrolimus (0.15 mg/kg/day; 10-15 ng/mL target trough levels) and a tapered dose regimen of steroids. Follow-up ranged from 404 to 1,364 days after transplantation (mean 799.89 days, SD+/-257.37; median 796 days). RESULTS: A total of 88% of patients remained rejection-free during follow-up with an actuarial rejection-free probability of 75% within 3 months. The actuarial patient survival rate at 3 years was 88%, and the graft survival rate was 75%. Twelve (24%) patients experienced one episode of sepsis, requiring temporary reduction of immunosuppressive therapy. There were no immediate side effects associated with basiliximab and no evidence of cytomegalovirus infection or posttransplant lymphoproliferative disorder. CONCLUSIONS: Basiliximab in combination with a tacrolimus-based immunosuppressive regimen is effective in reducing episodes of ACR and increasing ACR-free survival after liver transplantation. In addition, basiliximab does not increase the incidence of adverse effects or infections.

Adolescent↗
PubMed2004

Transplant quality in Italy: analysis of the 1995-2000 period.

Evaluation of outcomes is a major step in quality assessment of any health process. In the transplant field, the evaluation of outcome is extremely important for both patients' growing demand for health and for the joint commitment the transplant process requires. In this study, the outcome of 12,647 transplants, carried out between 1995 and 2000 were analysed. Graft survival at 5 years was 79% for kidney, 67% for liver, 72% for heart and 38% for lung. Patient survival was 92% for kidney, 76% for liver, 72% for heart and 38% for lung. In comparison to other international case records [Collaborative Transplant Study (CTS) and The United Network for Organ Sharing (UNOS)], results are similar or even better for all transplant programmes. As a whole, survival after solid organ transplant in Italy ranks among the best for both donations and transplantation. The quality of transplants carried out is above European standards. Nevertheless, the growing health needs of patients require improvement in both the procurement process and in the use of available organs.

Age Distribution↗
PubMed2004

Thromboelastography used to assess coagulation during treatment with molecular adsorbent recirculating system.

Coagulopathy is a life-threatening complication of liver cirrhosis. We describe the effect of molecular adsorbent recirculating system (MARS), a cell-free dialysis technique, on the blood coagulation of cirrhotic patients. From February 2002 to July 2002, nine patients--five males (55.5%) and four females (44.4%), age 47-70 yr (median 56)--underwent 12 courses (4-7 sessions each) of MARS. Patients were treated for the following indications: six (66.6%) acute-on-chronic hepatic failure, three (33.3%) intractable pruritus. Platelet count, prothrombin time (PT), international standardized ratio and thromboelastography were measured before and after each MARS session. Coagulation factors II, V, VII, VIII, IX, X, XI, XII, XIII, von Willebrand, lupus anticoagulant, protein C, protein S, antithrombin III, plasminogen, alpha 2 antiplasmin, D-dimer, fibrin monomers, complement, and C(1) inactivator were measured before and at the end of each MARS treatment. We found a statistically significant difference (p < 0.05) in the platelet count, PT, all the thromboelastograph variables (reaction and constant time, alpha angle, and maximal amplitude), factor VIII, von Willebrand, and D-dimer, when measured before and after MARS. Previous reports have shown amelioration of blood coagulation following MARS treatments. However, we document that MARS induces coagulopathy through a platelet-mediated mechanism, whereby platelet may be mechanically destroyed during the passage of blood through the filters and lines. An alternative postulated mechanism is an immune-mediated platelet disruption - coagulopathy.

Aged↗
PubMed2003

Posttransplant lymphoproliferative disorders presenting at sites of previous surgical intervention.

Early diagnosis of posttransplant lymphoproliferative disorder (PTLD) requires a high level of clinical suspicion. PTLD occurs mainly in the lymphoid tissue, allograft organ, bowel, and central nervous system. The diagnosis may not be considered initially when disease is localized to other sites. Retrospective review of the PTLD series at the University of Pittsburgh Medical Center showed that 4 of 418 patients (1%) presented with signs and symptoms localized to sites of previous surgical intervention (choledochojejunostomy site, ileosigmoid anastomotic site, site of saphenous vein stripping, and intrabiliary site of percutaneous transhepatic catheter). All patients showed symptomatic, Epstein-Barr virus-positive B-cell PTLD of varying histology. Three of four patients ultimately died with tumor, and the fourth died of unrelated causes. PTLD should be included in the differential diagnosis when clinical signs and symptoms localize to anastomotic sites, surgical incision sites, or sites of longstanding catheter placement in immunosuppressed organ transplant recipients.

Aged↗
PubMed2003

Noncardiogenic pulmonary edema induced by a molecular adsorbent recirculating system: case report.

Noncardiogenic pulmonary edema is a well-recognized manifestation of acute lung injury which has been related, among others, to blood or blood-product transfusion, intravenous contrast injection, air embolism, and drug ingestion. We describe two cases of noncardiogenic pulmonary edema after use of a molecular adsorbent recirculating system, a cell-free dialysis technique. Patients in this series presented at our institution to be evaluated for liver transplantation. Subsequently, they developed an indication for the molecular adsorbent recirculating system. Two patients of 30 (6.6%) treated with the molecular adsorbent recirculating system for acute-on-chronic liver failure and intractable pruritus had normal chest X-rays before treatment and developed severe pulmonary edema, in the absence of cardiogenic causes, following use of the molecular adsorbent recirculating system. For each patient we reviewed the history of blood or blood-product transfusion, echocardiograms if available, daily chest X-rays, and when available pre- and postmolecular adsorbent recirculating systemic blood pressure, central venous pressure, pulmonary arterial pressures, cardiac output, cardiac index, systemic vascular resistance index, and arterial blood gas. Our data suggest that the molecular adsorbent recirculating system may cause noncardiogenic pulmonary edema, possibly by an immune-mediated mechanism.

Aged↗
PubMed2003

Effect of molecular adsorbent recirculating system in hepatitis C virus-related intractable pruritus.

Intractable pruritus is more common in cholestatic liver diseases and may be the presenting symptom and/or major complaint of hepatitis C and/or hepatitic C virus-related cirrhosis. From September 2000 to May 2002, three patients affected by intractable pruritus secondary to hepatitis C cirrhosis that failed medical treatment were treated with a molecular adsorbent recirculating system (MARS). MARS is an artificial liver support system that aims to clear the blood of metabolic waste products normally metabolized by the liver. Each patient underwent seven MARS sessions. Liver function tests, the 36-Item Short Form quality-of-life test, visual analog scale for itching, and bile acid measurement in the serum, albumin circuit and ultrafiltrate were performed before and after each MARS session. Moreover, at hospital admission, each patient underwent a psychological workup and abdominal imaging study. Subjective improvement in pruritus and quality of life, along with a decrease in serum bile acid concentration, was observed in every patient; no patient underwent retreatment and/or liver transplantation up to a 9-month follow-up. One patient died 201 days after MARS treatment. Although we observed a decreased level of serum bile acids, one cannot conclude that this was the mechanism of action for the reduction in pruritus intensity in patients in our series. Different toxins and/or a placebo effect might have had a role in this setting.

Aged↗
PubMed2003

Conversion from tacrolimus to cyclosporine--a based immunosuppression following liver transplantation.

We examined the frequency, reasons and outcome after conversion from Tacrolimus to Cyclosporine A. From August 1989 to December 1992, 1000 consecutive liver transplantation patients were studied, which included 834 adults (age>18 yr.) and 166 children with mean follow-up of 77 months (range 56 to 96). A prospectively populated electronic database was queried to identify patients that underwent conversion, the clinical indication and outcomes. Thirty-seven out of 834 adult recipients (4.43%), mean age of 48.4+/-12.9 years, 19 male (51.35%) and 18 females (48.64%) required conversion from Tacrolimus to Cyclosporine A baseline immunosuppressive therapy. No pediatric patient required conversion. The mean time interval from liver transplantation to Cyclosporine A conversion was 443.45+/-441.44 days (range 22 to 1641). The clinical indications for conversion included: 20 neurological (54%), 6 gastrointestinal (16%), 5 hematological (14%), and 6 other (16%) scenarios. Seven of the 37 patients (18.9%) died. The causes of death were multi-organ failure (2), sepsis (2), pancreatitis (1), hepatic failure due to relapse of ethanol abuse (1), and unknown cause (1). Nine out of 37 patients (24.32%) had to be reconverted to Tacrolimus (mean 282.22+/-499.79 days; range 15 to 1583 day with a median of 135) after institution of Cyclosporine A; none showed recurrence of the original symptoms. The reasons for these re-conversions were acute cellular rejection (44%, n=4), chronic rejection (11%, n=1), increased hepatic enzymes (33%, n=3) and progressively worsening neurological symptoms (11%, n=1). The frequency of conversion from Tacrolimus to Cyclosporine A was 4.43%. Conversion is safe and efficacious if done in a controlled setting. Additionally, re-conversion to Tacrolimus for lack of efficacy of Cyclosporine A did not appear to be associated with a recurrence of the condition that caused the initial switch.

Adult↗