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Biomedical subjects

F Filipponi

Publications and source records attributed to F Filipponi.

At least 37 records · Page 2Linked to original sources

Management of massive and persistent ascites and/or hydrothorax after liver transplantation.

PURPOSE: To describe the results of the treatment of eight liver transplantation (LT) patients subsequently developing large volumes of long-lasting ascites. PATIENTS AND METHODS: Between August 1996 and February 2003, 405 LTs were performed in 375 patients, eight (1.97%) of whom (six men and two women of mean age of 55.4 +/- 5.2 years) subsequently developed massive (> 500 mL/d) and persistent ascites and/or hydrothorax. All patients were HCV positive. The mean age of the liver donors was 66.8 +/- 21.9 years. All LTs were performed by replacement of the recipient retrohepatic vena cava. RESULTS: The eight patients displayed sinusoidal portal hypertension related to biopsy-proven recurrence of HCV infection. Mean wedged hepatic venous pressure was 14.9 +/- 5.1 mm Hg and mean portal vein/right atrial pressure gradient (PAPG) was 17.3 +/- 4.8 mm Hg. In two patients, the ascites appeared the day after LT; in the remaining six, ascites and/or hydrothorax appeared after 342.3 +/- 167.7 days. Seven patients with a mean PAPG of 18.4 +/- 3.9 mm Hg and a mean plasma/ascites albumin concentration gradient of 2.8 +/- 0.3 g/L were treated by means of a trans-jugular intrahepatic portosystemic shunt TIPS, and one (with a PAPG of 9 mm Hg and a plasma/ascites albumin concentration gradient of 1.38 g/L) by means of spleen arterial embolisation. After a mean follow-up of 558 +/- 147.2 days, the ascites and/or hydrothorax have resolved in five patients (62.5%), one (12.5%) has stable ascites not requiring paracentesis, and two (25%) have died of multiorgan failure. CONCLUSIONS: These data suggest the efficacy of the aggressive treatment of massive and persistent ascites and/or hydrothorax.

Ascites↗

Molecular analysis of V(H)I+ B lymphocytes in hepatitis C patients.

BACKGROUND AND AIMS: Hepatitis C virus infection is often associated with lymphoproliferative disorders such as essential mixed cryoglobulinemia and B-cell non-Hodgkin lymphoma, which show preferential expression of VHI family products. By analyzing immunoglobulin heavy chain usage, we addressed the question of whether or not clonal B-cell expansion occurrs in patients free of essential mixed cryoglobulinemia or non-Hodgkin lymphoma. PATIENTS AND METHODS: Four hepatitis C virus-positive patients, all undergoing liver transplantation, were studied. Peripheral blood, intra-hepatic, and lymph node lymphocytes were used as a source of B cells. A patient with hepatocellular carcinoma and fresh blood from four healthy donors were used as negative controls. VHI family sequences were cloned and analyzed by reverse transcription-polymerase chain reaction. RESULTS: Immunoglobulin heavy chain sequences from clonally expanded B lymphocytes were identified in three out of four hepatitis C virus-infected patients. The clonally expanded B lymphocyte populations showed a broad spectra of immunoglobulin heavy chain gene usage. CONCLUSIONS: HCV infection can induce B-cell expansion with larger clonal variation. The restricted V gene usage in hepatitis C virus-associated non-Hodgkin lymphoma suggests that there may be selection mechanisms to develop non-Hodgkin lymphoma from non-malignant, clonally expanded B-cell populations in hepatitis C virus-infected patients.

B-Lymphocytes↗

Increasing serum levels of IgM anti-HCV are diagnostic of recurrent hepatitis C in liver transplant patients with ALT flares.

Recurrent hepatitis and acute rejection share common features which make difficult for diagnosis in liver transplant hepatitis C virus (HCV) positive patients. We studied the usefulness of quantitative monitoring of HCV RNA and immunoglobulin (Ig)M anti-HCV in the differential diagnosis between recurrent hepatitis and acute rejection in 98 consecutive anti-HCV positive liver transplant patients. Aminotransferase levels, serum HCV RNA and IgM anti-HCV were measured at the time of transplantation and monthly thereafter. A liver biopsy (LB) was obtained when serum aminotransferase levels increased to twice or more than normal. During a mean follow-up of 16 months 86 aminotransferase flares were observed. Histology was compatible with recurrent hepatitis C in 44 cases and with acute rejection in 28, doubtful in 14. The fluctuations of HCV RNA serum levels were not significantly different in the three groups. Serum IgM anti-HCV levels increased (from negative to positive or with value variations > or = 0.18) in 36 of 44 cases with recurrent hepatitis C at the time of alanine aminotransferase (ALT) flare. IgM anti-HCV remained unchanged in all rejection cases (P < 0.001), but increased in 10 of 11 histologically doubtful cases that were diagnosed as hepatitis at the second LB. Increasing serum levels of IgM anti-HCV at the time of ALT flares are significantly associated with recurrent hepatitis C in liver transplant patients. The quantitative monitoring of IgM anti-HCV appears to be an additional diagnostic tool for distinguishing recurrent hepatitis C from acute graft rejection with a 100% specificity; 100% positive predictive value and 88.9% diagnostic accuracy.

Adult↗

A 59-year-old liver-transplanted woman with fever, dyspnea and pulmonary infiltrates.

A 59-year-old woman was admitted to hospital 10 months after receiving a liver transplant (LT) for hepatitis C virus (HCV) cirrhosis because of fever, dyspnea and basal patchy peripheral infiltrates. Microscopic examinations and blood, sputum and BAL cultures were negative. Empirical anti-infective therapy was ineffective. Thoracoscopic lung biopsy was performed, and histology showed a pattern suggesting bronchiolitis obliterans organizing pneumonia (BOOP). Prednisone led to rapid clinical and radiologic improvement. BOOP has been anecdotally reported in LT cases, and this case was unrelated to any infectious agent. BOOP should be taken into account in the differential diagnosis of pneumonia in LT.

Anti-Infective Agents↗

Regional filter heparinization for continuous veno-venous hemofiltration in liver transplant recipients.

AIM: To study safety, clinical and operative feasibility of continuous veno-venous hemofiltration (CVVH) with anticoagulation only of the filter in patients at risk for bleeding. METHODS: This prospective, comparative, non randomised study was completed at an intensive care unit of a teaching NHS hospital. Sixteen liver transplant (LT) recipients with acute renal failure needing CVVH were treated with a regional anticoagulation protocol (heparin and protamine were administered respectively pre- and post-filter) and compared to 11 critically ill subjects who received a standard low-heparin treatment. Activated coagulation time (ACT) monitoring was used to adjust anticoagulation and heparin neutralization. RESULTS: Mean circuit life was 35.8+/-13.6 hours (95% CI 28.5-43.1) in patients receiving regional anticoagulation and 34.4+/-14 hours in controls (95% CI 25.5-43.3; p=0.7). Fourty-eight circuits (47.5% of the total) in the heparin-protamine group had a life-span longer than 30 hours and other 22 (21.7%) were changed intentionally after 24 hours of use in absence of clots. None of the patients in both the studied groups had bleeding or hemodynamic complications and their azotemic control was always satisfactory. CONCLUSION: In LT recipients, regional anticoagulation can achieve a circuits life-span comparable to that from systemic anticoagulation with satisfactory safety and simplicity of use.

Acute Kidney Injury↗

Surgical complications after liver transplantation.

AIM: The number of liver transplantations in Italy has steadily increased over the last 10 years as a result of the use of donors aged more than 60 years. The use of organs with a reduced functional reserve has been compensated for by improvements in immunosuppressive therapy, surgical techniques and the management of postoperative complications. This article describes the incidence and treatment of the main surgical complications after liver transplantation. METHODS: Between January 1996 and June 2003, 398 patients received 430 transplants at our Centre. Thirty-seven early relaparotomies were performed (8.6%), including 12 retransplantation (2.8%). The 1-, 3- and 5-year actuarial survival of the patients was 79.8%, 72.2% and 67.5%, and that of the grafts was 75.9%, 68% and 63.4%. Perioperative mortality was 10.5% (with no intraoperative deaths). RESULTS: The overall incidence of biliary complications was 31.6%, 9.1% of which were due to the removal of the Kehr tube. There were 42 (9.8%) anastomotic stenoses, 5 (1.2%) extra-anastomotic stenoses, 1 (0.2%) anastomotic leak, 5 (1.2%) extra-anastomotic leaks, and 19 (4.4%) ischemic-type biliary lesions. The overall incidence of vascular complications was 6.9%: 7 (1.6%) cases of hepatic artery thrombosis, 17 (4.0%) arterial stenoses, 1 (0.2%) arterial pseudoaneurysm, 4 (0.9%) cases of portal thromboses and 1 (0.2%) case of caval laminar thrombosis. Eight patients (1.9%) developed massive and persistent post-transplant ascites and/or hydrothorax. CONCLUSION: The use of donors aged more than 60 years makes it possible to maintain high standards of patient and graft survival that is not only due to the optimisation of immunosuppressive protocols, but also to improvements in surgical techniques, intensive care and the management of surgical complications.

Adolescent↗

Molecular monitoring of Candida albicans infections in liver transplant recipients.

This report describes the use of the 27A probe for the molecular monitoring of Candida albicans infections in liver transplant recipients. Nosocomial candidiasis is the major fungal infection in liver transplant recipients, with Candida albicans being the species most frequently isolated. The molecular epidemiology of Candida albicans infections has been widely investigated, but scant attention has been focused on monitoring the identity of infecting strains in individual patients over the entire course of their hospitalization. In the study presented here, a total of 179 Candida albicans isolates were collected from 10 liver transplant recipients during multiple surveillance cultures performed before and after liver transplantation and from three healthcare workers at the Transplant Unit of Ospedale di Cisanello, Pisa (Italy). Computer-aided analysis of the 27A-probed DNA fingerprints, used to compare the genetic relatedness of all the Candida albicans isolates, showed that most of the patients colonized with Candida albicans before transplantation harbored a unique Candida albicans genotype. This genotype persisted over the entire course of hospitalization and caused multiorgan failure in two patients, both of whom died from endogenously borne Candida albicans infections. Nosocomial acquisition of Candida albicans strains could be monitored in a timely manner in the other patients; for some of them, subsequent strain replacement was registered at different body sites during the post-transplant period. Neither cross-infection between patients nor transmission from healthcare workers to patients occurred in this hospital setting. These results indicate that the molecular monitoring of Candida albicans strains isolated from liver transplant recipients during their hospitalization may provide timely information about the identity of individual Candida albicans strains causing infections.

Adult↗

Detection of biliary complications after orthotopic liver transplantation with MR cholangiography.

To assess the diagnostic value of magnetic resonance cholangiography (MRC) when evaluating biliary complications in the follow-up of liver transplant patients. One hundred and thirteen patients prospectively underwent MR imaging and MR cholangiography at 1.5-T unit after orthotopic liver transplantation (OLT). After the acquisition of axial T1- and T2-weighted sequences, MRC involved a coronal, non breath-hold, respiratory-triggered, fat-suppressed, two-dimensional, thin-slab, heavily T2-weighted fast spin-echo sequence, and coronal breath-hold, thick-slab, single-shot T2-weighted sequences. The images and maximum intensity projections were evaluated by two readers in order to determine biliary anatomy and the presence of complications, whose final diagnosis was based on endoscopic retrograde cholangiography (ERC) in 50 patients, percutaneous trans-hepatic cholangiography (PTC) in five, and by integrating clinical follow-up with ultrasound and MR findings in 58 cases. MRC had a sensitivity of 93%, a specificity of 92%, a positive predictive value of 86%, a negative predictive value of 96%, and a global diagnostic accuracy of 93% in detecting all types of biliary complications in OLT patients. MRC is a reliable technique for detecting post-OLT biliary complications. We now restrict the use of ERC to patients for whom therapeutic procedures are advocated or whose MRC results are equivocal.

Adult↗

Animal models of fulminant hepatic failure: need to test liver support devices.

Fulminant hepatic failure is one of the most dramatic entities in clinical medicine, but experimental studies of its pathogenesis, evolution and treatment have, so far been limited by the lack of satisfactory animal models for testing new supportive treatment options. The variable aetiology, complex pathogenetic mechanisms and inconstant clinical evolution of human fulminant hepatic failure make it particularly difficult to establish an "ideal fulminant hepatic failure animal model" suitable for all studies: it is no longer mandatory to develop one single model serving all possible scientific needs, but the use of a specific model for a specific issue is more advisable. The currently available animal models of fulminant hepatic failure are the hepatotoxic, surgical and combined hepatotoxic and surgical models. From a general point of view, surgical models may be particularly appropriate for studying the consequences of hepatic necrosis on cerebral oedema. The anhepatic model is very useful for validating new supportive measures to bridge the period between the onset of fulminant hepatic failure and the time at which a suitable organ becomes available and, despite the many difficulties involved in their development, hepatotoxic models may still be useful for mimicking an acetaminophen overdose. The efficacy and reproducibility of a liver support system can be demonstrated by means of preclinical experimental models that mimic the specific application required in humans as closely as possible.

Acetaminophen↗

Very early tracheal extubation without predetermined criteria in a liver transplant recipient population.

This study of all patients undergoing orthotopic liver transplantation (OLT) at our center between January 1997 and December 1999 evaluated the feasibility and safety of very early tracheal extubation without previous selection. Anesthetic management was the same in all cases, and tracheal extubation was performed on the basis of standardized criteria routinely adopted in operating rooms throughout the world, i.e., no residual curarization or anesthetic action, ability to swallow efficiently, and stable hemodynamics. One hundred sixty-nine patients underwent 181 OLTs during the study period. Tracheal extubation was performed within 3 hours of surgery in 115 cases, 8 hours in 19 cases, and 8 to 24 hours in 10 cases. In 36 cases, artificial ventilation was required for more than 24 hours or weaning was not possible. One patient died of primary graft nonfunction within 24 hours and was excluded from the analysis. The feasibility of early extubation was influenced by the amount of intraoperative transfused blood; efficacy of kidney, cardiac, and pulmonary function; and presence of encephalopathy (P <.001). No correlation was found with age or pre-OLT severity of hepatic disease, and the postoperative period was not compromised by early weaning. Very early extubation was feasible and safe in a large number of unselected transplant recipients, thus suggesting that the definition of early tracheal extubation should be changed from 8 to 3 hours after surgery.

Adult↗

Inhibited differentiation of Langerhans cells in the rat epidermis upon systemic treatment with cyclosporin A.

The immunosuppressant drug cyclosporin A (CsA) is known to cause reduction in number, DNA synthesis and function of Langerhans cells (LC). Since also the differentiation of LC is known to be hampered in conditions of acquired immunodeficiency not due to drugs, we investigated whether this occurs with CsA. Rats were injected subcutaneously with CsA (5, 10 and 50 mgxkg(-1) x d(-1)) for three weeks; the skin was analyzed by Ia immunohistochemistry and by electron microscopy. Epidermal immunolabeled cells were 15+/-3.5 (mean +/- SEM) per 100 basal keratinocytes in untreated controls and 8.75+/-1.3, 4.75+/-1.0 and 1.7+/-1.2 upon increasing doses of CsA (p<0.01). By electron microscopy, monocytoid cells with deep invaginations of the plasma membrane and roundish LC poor in Birbeck granules appeared in the epidermis upon treatment. The results suggest that CsA inhibits the differentiation of LC precursors in the epidermis and that this can in part explain the selective increase in the risk of skin viral disease and cancer in chronically treated patients.

Animals↗

Personality change as defensive responses of patients evaluated for liver transplant.

Patients affected by endstage liver disease and awaiting liver transplant suffer very stressful conditions. The aim of this study was to evaluate the person ality and behavioral responses of a group of liver transplant candidates, 95 men (M age 50 yr.) and of a group of 18 normal men (M age 49 yr.). The 16 Personality Factor Questionnaire of Cattell, and the PSY Inventory for Behavioral Assessment were administered to assess personality and behavior. On the 16PF Questionnaire, patients had significantly different mean scores from normal subjects on Scale B- (low mental capacity), G (conformity), N (shrewdness), and Q1- (conservatism). They also showed a somewhat lower but not a statistically significant mean on Scale E (submissiveness). In addition, on the four second-order factors of the 16PF (Anxiety, Control, Pathemia, and Extraversion) patients had a significantly higher mean on Control. With respect to PSY Inventors factors, patients showed impairment in energy, sleep, sexual disturbances, and obsessive behaviors. It appears these patients with endstage liver disease, who were evaluated for liver transplant, showed psychological regressive functioning, i.e., high control and dependency on medical staff, submissiveness, which are interpretable as defensive responses to upcoming transplant.

Adult↗

[Blood coagulation monitoring during liver transplantation: Sonoclot analysis and laboratory tests].

BACKGROUND: Aim of this paper is to validate blood coagulation data obtained using the Sonoclot thromboelastographic analyser (Sienco Inc., Morrison, USA) by means of standard laboratory tests during orthotopic liver transplantation (OLT). METHODS DESIGN: comparative study between laboratory data and Sonoclot analysis on simultaneously collected blood samples. SETTING: National Health System Liver Transplantation Center. PATIENTS: fifty-one patients, both males and females, affected by terminal hepatic disease submitted to OLT were enrolled in the study. DATA COLLECTION: simultaneous blood samples were collected during the pre-anhepatic, anhepatic and post-reperfusion phases of OLT; coagulation status was assessed by means of either standard Laboratory tests (INR, aPTT, Fibrinogen, PLT, D-Dimer) and Sonoclot analyser data (SonACT, Rate, Time to Peak, Downward Deflection); a statistical analysis was performed (Pearson s chi(2) test). RESULTS: A statistically significative correlation between the analysed data was found. The Sonoclot analyser was useful in identifying platelets dysfunction and was more sensitive to detect fibrinolysis. CONCLUSIONS: The Sonoclot thromboelastographic analyser is a reliable device for monitoring coagulation during OLT.

Adult↗

[Prevention of mycotic infections in liver transplant recipients: comparison of two chemoprophylactic protocols].

BACKGROUND: The aim of the study was to compare and evaluate the efficacy of two chemoprophylactic protocols against mycotic infections in a liver transplant recipients population. DESIGN: single-blind, randomized. SETTING: Liver transplant Center of a National Health System teaching hospital. METHODS: Eighty-eight consecutive patients submitted to liver transplantation were enrolled in the study. Immediately before surgery they were randomized to receive sequential treatment with intravenous liposomal amphotericine B + oral itraconazole or intravenous fluconazole + oral itraconazole. Intravenous drugs were administered in the first postoperative week, and oral treatments for the following three weeks. In addition to analyzing the frequency and incidence of colonization, local and disseminated infection of mycotic origin, the causes of death and the possible risk factors for mycotic disease have been examined. RESULTS: Eighty-five patients completed the study. No significative difference was evident in the two groups as regards to single organ and systemic fungal infection rate. Two out of a total of 5 deaths were related to mycotic disease. Pre-transplant fungal colonization, more severe liver disease indicating the transplant procedure and the rejection of the graft were all risk factors for the development of mycotic infection. CONCLUSIONS: The two protocols used in the study showed and equal efficacy in preventing fungal infections in liver transplant recipients.

Adult↗