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R Fiocchi

Publications and source records attributed to R Fiocchi.

At least 19 recordsLinked to original sources

Anti-CD20 antibody (rituximab) administration in patients with late occurring lymphomas after solid organ transplant.

BACKGROUND AND OBJECTIVES: Aggressive diffuse large cell non-Hodgkin's lymphoma (DLCL) occurring late after a solid organ transplant fails to regress after discontinuation of immunosuppression. Moreover, chemotherapy treatment is associated with a high mortality rate due to severe toxicity. Since the majority of post-transplant lymphoproliferative disorders derive from B-lineage lymphocytes, the administration of anti-B monoclonal antibodies represents a rational therapeutic option. DESIGN AND METHODS: Five patients who developed CD20-positive DLCL more than two years after heart or liver transplantation were treated with a weekly chemotherapy program (2 patients), radiotherapy (2 patients) and surgery (1 patient) followed by a minimum of 4 intravenous doses of rituximab (375 mg/m(2)). RESULTS: A favorable clinical outcome was observed in three patients in whom surgery or radiotherapy had produced significant tumor debulking. Only a partial clinical effect was documented in the two patients with advanced clinical stage disease. INTERPRETATION AND CONCLUSIONS: Rituximab can be safely administered to patients with aggressive CD20-positive DLCL occurring late after a solid organ transplant. However, a positive clinical outcome may be expected only in patients in whom surgery or radiotherapy has achieved significant regression of tumor burden.

Adult↗

Prevalence and outcome of invasive fungal infections in 1,963 thoracic organ transplant recipients: a multicenter retrospective study. Italian Study Group of Fungal Infections in Thoracic Organ Transplant Recipients.

BACKGROUND: Fungal infections (FI) after solid organ transplantation (Tx) remain a major cause of morbidity and mortality. Aspergillus and Candida account for more than 80% of FI. METHODS: One thousand nine hundred and sixty-three patients undergoing thoracic organ Tx [1,852 heart and 111 lung (35 heart-lung Tx, 30 double-lung Tx, 46 single-lung Tx)] in 12 Italian Centers between November 1985 and January 1997 were included in the study. RESULTS: Fifty-one patients (41 heart Tx - 2.2%; 9 heart-lung Tx - 25.7%; 1 single-lung Tx - 2.2%) developed 53 invasive FI at a median of 58 days (range 6-2479) after Tx. Aspergillosis was the most frequent FI in our series accounting for 64.1% (34/53) of all FI [A fumigatus, n=29 (85.3%); A nidulans, n=2 (5.9%); A niger, n=2 (5.9%); A terreus, n=1 (2.9%)]; 30 (88.2%) patients developed invasive lung aspergillosis, 2 (5.9%) a tracheobronchitis, 1 (2.9%) a skin infection, and 1 (2.9%) a sternal wound infection. Twelve patients (22.6%) developed candidiasis [C albicans, n=8 (66.6%); C krusei, n=1 (8.3%); C glabrata, n=1 (8.3%); C parapsilosis, n=1 (8.3%); C sake, n=1 (8.3%)]. There were seven episodes (58.3%) of candidemia, two (16.7%) esophagitis, two (16.7%) gastritis, and one (8.3%) tracheobronchitis. Mortality was 29.4% for patients developing aspergillosis and 33.3% for those experiencing candidiasis. Furthermore, four patients developed the following: one C neoformans meningitis, one Sporothrix cyanescens pneumonia, one Rhizopus spp. tracheobronchitis, and one Trichosporon beigelii disseminated infection. Three additional patients were diagnosed affected by deep mould infection by histology alone. CONCLUSIONS: Deep-seated FI were relatively rare in our series, although their mortality rate is still very high.

Adult↗

Epstein-Barr virus-negative lymphoproliferate disorders in long-term survivors after heart, kidney, and liver transplant.

BACKGROUND: Solid organ transplant patients undergoing long-term immunosuppression have high risk of developing lymphomas. The pathogenesis of the late-occurring posttransplantation lymphoproliferative disorders (PTLD) have not yet been extensively investigated. METHODS: We studied 15 patients who developed PTLD after a median of 79 months (range 22-156 months) after organ transplant. Clonality, presence of Epstein-Barr virus (EBV) genome, and genetic lesions were evaluated by Southern blot analysis or polymerase chain reaction. RESULTS: All monomorphic PTLD and two of three polymorphic PTLD showed a monoclonal pattern. Overall, 44% of samples demonstrated the presence of the EBV genome. Within monomorphic PTLD, the EBV-positive lymphomas were even lower (31%). A c-myc gene rearrangement was found in two cases (13%), whereas none of the 15 samples so far investigated showed bcl-1, bcl-2, or bcl-6 rearrangement. The modulation of immunosuppression was ineffective in all patients with monomorphic PTLD independent of the presence of the EBV genome. The clinical outcome after chemotherapy was poor because of infectious complications and resistant disease. With a median follow-up of 4 months, the median survival time of these patients was 7 months. CONCLUSIONS: Late occurring lymphomas could be considered an entity distinct from PTLD, occurring within 1 year of transplant, because they show a histological and clinical presentation similar to lymphomas of immunocompetent subjects, are frequently negative for the EBV genome, are invariably clonal, and may rearrange the c-myc oncogene. New therapeutic strategies are required to reduce the mortality rate, and new modalities of long-lasting immunosuppression are called for.

Adolescent↗

Continuous retrograde warm blood reperfusion reduces cardiac troponin I release after heart transplantation: a prospective randomized study.

During heart surgery, cardiac troponin I (cTn-I) measurement provides a tool to evaluate different cardioprotective techniques. To investigate myocardial protection during heart transplantation (HTx), cTn-I and creatine kinase (CK)-MB release was measured in 42 patients randomized to receving either continuous retrograde warm blood reperfusion or no reperfusion after cold cardioplegia. A significant linear correlation was found between donor heart ischemic time and peaks and the area under the curve of cTn-I and CK-MB release. In patients with an ischemic time longer than 90 min, cTn-I release was significantly lower in those receiving continuous retrograde warm cardioplegia than in controls. No significant difference was observed for CK-MB, tCK, and myoglobin. Our data suggest that the measurement of postoperative cTn-I release may provide a method to evaluate ischemic cardiac damage after HTx. When the ischemic time is longer than 90 min, warm retrograde blood cardioplegia provides better myocardial protection than no reperfusion.

Biomarkers↗

High levels of Epstein-Barr virus DNA in blood of solid-organ transplant recipients and their value in predicting posttransplant lymphoproliferative disorders.

Epstein-Barr virus (EBV) DNA was quantitated in peripheral blood mononuclear cells (PBMC) from 25 healthy subjects, 105 asymptomatic solid-organ transplant (SOT) recipients, and 15 SOT recipients with symptomatic EBV infections by using a newly developed quantitative-PCR technique. Patients with symptomatic EBV infections had significantly higher (P < 0.001) median EBV DNA levels than asymptomatic SOT recipients and immunocompetent individuals. In SOT recipients, the positive predictive value of EBV DNA levels of >1, 000 genome equivalents (GE)/0.5 microg of total PBMC DNA was 64.7% for symptomatic EBV infection, while the negative predictive value was 96.1%. In 19 of 32 (59.3%) asymptomatic SOT recipients, EBV DNA levels were consistently below 1,000 GE for as long as 18 months, while 10 of 32 (31.2%) patients had 1,000 to 5,000 EBV GE at least once during follow-up. In a minority of patients (3 of 32; 9.3%), >/=5,000 GE could be detected at least once during follow-up. Reduction of immunosuppressive treatment decreased EBV DNA levels by >/=1 log(10) unit in patients with symptomatic EBV infections. Quantification of EBV DNA is valuable for the diagnosis and monitoring of symptomatic EBV infections in SOT recipients.

Adolescent↗

Primary effusion lymphoma after heart transplantation: a new entity associated with human herpesvirus-8.

Deep immunosuppression and Epstein-Barr virus (EBV) infection promote the emergence of lymphoproliferative disorders in patients undergoing solid organ transplantation. In the last few years a new herpesvirus, named human herpesvirus-8 (HHV-8), has been identified in Kaposi's sarcoma and primary effusion lymphoma (PEL) developing in AIDS patients. Subsequently, the same viral DNA sequences have been identified in almost all cases of Kaposi's sarcoma emerged outside HIV infection, thus suggesting their possible pathogenetic role in this tumor. Similarly, the association between HHV-8 and PEL also emerged in cases without HIV infection, even though the total number of these patients is still limited. Here, we focus on the emergence of this unusual lymphoma in patients undergoing solid organ transplant and underline once again its association with the HHV-8. Moreover, despite the characteristic local growth of this peculiar type of lymphoma, we demonstrate at the molecular level, an early neoplastic spread to the bone marrow suggesting the need to investigate in more detail the origin of the disease, as well as the molecular mechanisms controlling its systemic dissemination.

Aged↗

[Heterotropic heart transplantation in young patients with elevated pulmonary vascular resistance].

UNLABELLED: Right heart failure due to elevated PVR is one of the major causes of mortality and morbidity after orthotopic heart transplantation. In 5 patients (median age 14 years) with dilated or restrictive cardiomyopathy and important elevation of the PVR, a heterotopic heart transplantation was performed using the technique reported by Yacoub (the donor pulmonary artery was implanted on the recipient right atrium). All the patients presented with at least two of the following parameters: PVR/m2 > 6 U, transpulmonary gradient > 15 mmHg, mean pulmonary pressure > 50 mmHg. One patient with restrictive cardiomyopathy died three months after transplantation of severe failure of the native right ventricle. The other four patients, with a mean follow-up of 29 months, are in good clinical and hemodynamic condition and later post-operative catheterizations showed a progressive reduction of the pulmonary pressure. CONCLUSIONS: Our experience suggests that this type of heterotopic heart transplantation can be performed successfully in patients with secondary pulmonary hypertension. Particular attention should be paid to patients with restrictive cardiomyopathy and important right ventricle dysfunction, in which a complete heterotopic heart transplantation could be a better solution.

Adolescent↗

The risk of coronary artery disease after heart transplantation is increased in patients receiving low-dose cyclosporine, regardless of blood cyclosporine levels.

BACKGROUND: Coronary artery disease (CAD) of allografted hearts is the main cause of late mortality after cardiac transplant, but its etiology is still undetermined. HYPOTHESIS: This study was undertaken to evaluate the relevance of several risk factors, including cyclosporine (CsA) dose and blood CsA levels, to the incidence of CAD. METHODS: In 163 heart transplants performed between November 1985 and August 1994 at our Institution, CAD was diagnosed by coronary angiography or at postmortem examination. Patients in whom postmortem examination or coronary angiography was not performed, as well as those < 15 years of age and those who died within 1 month of surgery, were excluded from the study. The following risk factors were analyzed: recipient age, gender, pretransplant diagnosis, donor age, number of human leukocyte antigen (HLA)-AB mismatches, cytomegalovirus serology, mear serum cholesterol and triglyceride levels, the number of treated acute rejections, mean weighted CsA dose (CsA dosew and weighted blood CsA levels (blood CsA levelw). RESULTS: Coronary artery disease was diagnosed in 32 patients (19.6%). A low mean CsA dosew was the only significant predictor for CAD at multivariate analysis (p < 0.01): there was no correlation with blood CsA levelw. In the patients receiving a CsA dosew > 4 mg/kg/day, the 8.9 year probability of their remaining CAD free was 69% [confidence interval (CI) 50-87%] in comparison with 31% (CI 0-65%) in patients receiving a CsA dosew < 4 mg/kg/day. CONCLUSION: In our experience, a low CsA maintenance dose is the main risk factor for CAD, irrespective of blood CsA levels.

Adolescent↗

Troponin I as a specific marker for heart damage after heart transplantation in a patient with becker type muscular dystrophy.

In a patient with Becker type muscular dystrophy, the development of cardiomyopathy may require heart transplantation, and during both the perioperative period and later it is useful to determine whether myocardial cell damage is occurring; however, the measurement of serum levels of creatine kinase (CK), MB isoenzyme, is not useful because that isoenzyme is released by the dystrophic skeletal muscle, as well as damaged myocardium. Because cardiac troponin I (cTn I) seems to be quite specific for myocardial cells, we reasoned that measurement of serum levels of this protein could distinguish between myocardial damage and skeletal muscle disease in this patient during and after transplantation. During the immediate postoperative period, the time course of the release of total CK (tCK), CK MB mass, myoglobin, and cTn I were different, yielding a peak within 4 hours for CK MB, 24 hours for myoglobin and 36 hours for tCK and cTn I. During the first postoperative year, the patient displayed a release of tCK, CK MB, and myoglobin; cTn I was constantly lower than the reference value for cardiac myocyte necrosis, suggesting the presence of a continuous muscular damage without any myocardial involvement and an accurate specificity of cTn I to differentiate between myocardial and muscular cell damage in patients with neuromuscular disorders.

Adolescent↗

Medical treatment of end-stage heart failure.

Congestive heart failure is a lethal condition that affects an increasing number of patients. In recent years a great amount of data have accumulated on the pathophysiology and medical and surgical therapy of this condition. In spite of the advances in its management and the great number of patients affected, common errors are still made by internists and cardiologists in the use of drugs and therapeutic strategies. Digitalis has only recently been shown to affect hemodynamics, exercise capacity, and clinical symptoms, but the effects on survival still have to be demonstrated. Loop diuretics, eventually combined with thiazides and antialdosterone drugs in patients with clinical signs and symptoms of fluid retention, are the mainstays of therapy of congestive heart failure. In order to make diuretic therapy efficacious, moderate salt and water intake restriction is mandatory. Angiotensin-converting enzyme (ACE) inhibitors are now considered unavoidable drugs in the management of heart failure, and an attempt to reach the doses that have been shown to be efficacious for survival in the large trials has to be made in every patient with this condition. Other vasodilators, such as hydralazine and nitrates, which show a less pronounced effect on survival but more effective hemodynamic actions than ACE inhibitors, may be used to control mitral insufficiency or to improve hemodynamics in very sick patients. Hemodynamic instability refractory to increasing doses of vasodilators and diuretics is a severe condition that requires hospital admission to administer drugs parenterally. These patients are usually treated with the combination of catecholamines and phosphodiesterase inhibitors associated with intravenous diuretics until clinical stability is again achieved and oral therapy is resumed and restructured. The use of aggressive pharmacological therapy and phosphodiesterase inhibitors has reduced the need for assisted circulatory support in these patients. Beta-blockers have shown promising results when administered to patients with heart failure, although a definitive demonstration of their effects on survival is still lacking. Other additional measures that need to be considered in patients with end-stage congestive heart failure are the use of antiarrhythmic drugs and anticoagulation.

Adrenergic beta-Antagonists↗

Balloon aortic valvuloplasty in the first year of life.

Between February 1988 and September 1993 balloon aortic valvuloplasty was attempted in 33 consecutive patients in the first year of life: 20 patients (61%) were younger than 1 month. Major associated anomalies such as mitral stenosis, coarctation, and hypoplastic left ventricle were found in 11 cases (33%). The balloon dilation of the aortic valve was accomplished through the right carotid cut-down approach in neonates and patients with body weight < 5 kg, through a percutaneous femoral approach in the others; the procedure was completed in all. The peak systolic gradient across the aortic valve measured at catheterization fell from 80 +/- 33 mmHg (range 25-165) before the dilation to 27 +/- 17 mmHg (range 0-65), afterwards (p < 0.0001). The left ventricular ejection fraction increased from 44% +/- 26% to 61% +/- 17%, 24-48 hours after the procedure (p < 0.0001). Aortic insufficiency developed in 17 cases, being moderate in 2, mild in 6, and trivial in 9. Seven patients (21%), all in the first month of life, died within 30 days from the valvuloplasty; major associated anomalies were present in six; the death was due to a procedure related complication in one. No mortality was observed among the patients undergoing valvuloplasty beyond the first month of life. On follow-up (6 months to 6 years) aortic restenosis occurred in 3 cases; 1 was treated by surgical valvotomy, 2 by repeat balloon valvatomy; in another 2 cases, a subvalvular aortic obstruction developed and was relieved by surgical resection. There was no late mortality. Thus, balloon valvuloplasty appears to be an effective palliation for critical aortic stenosis in infancy. Early mortality is mainly related to associated anomalies.

Aortic Valve Stenosis↗

Reduction of haemorrhagic complications during mechanically assisted circulation with the use of a multi-system anticoagulation protocol.

Two different anticoagulation protocols were used in 49 consecutive patients mechanically supported either for bridge to transplantation (11) or for recovery of myocardial function after cardiac surgery (35). In 46 patients a Biomedicus centrifugal pump was used and in 3 patients a Pierce-Donachy ventricles. Mechanical support was provided to the left ventricle in 14 patients, to the right ventricle in 6 and to both ventricles in 12 patients; an extra-corporeal membrane oxygenator (ECMO) support was used in 17 patients. Thirty-seven males and 12 females, aged 0.2 to 58 years, were supported for an average time of 6.3 days (range 1-43). Anticoagulation was either based on a continuous infusion of heparin in the first 27 patients (group A) or on a multi-system therapy ("La Pitié" protocol) in the other 22 patients (group B). Overall survival rate was 47%. Patients in group A had a 30% (8/27) survival rate, whereas in group B a 68% (15/22) survival rate was observed (p = 0.006). Transplantation and ventricular assist device (VAD) removal was successfully obtained in 59% (16/27) and 91% (20/22) of patients in group A and group B respectively (p = 0.05). Significant bleeding occurred in 21 patients (81%) in group A and in 2 (9%) of group B (p = 0.001). In these patients bleeding averaged 230 +/- 231 ml/kg in group A versus 55 +/- 18 ml/kg in group B (p = 0.001). Surgical revision was necessary for cardiac tamponade or persistent bleeding in 12 patients of group A (25 procedures: mean 0.9/patient) and in 3 patients of group B (one each patient: mean 0.1/patient) (p = 0.01). Infection, thrombo-embolism and brain hemorrhage were also less frequent in group A than in group B. Our data suggest that the "La Pitié" protocol provides a better control of bleeding than the conventional heparin infusion in patients receiving assist device. this reduction in thrombo-hemorrhagic complications might improve the results of mechanical circulatory support.

Adolescent↗

A new frontier for cardiac therapy. Principles and practice of aerobic cardiac surgery.

As recently reported in the literature, aerobic cardiac surgery (normothermic total body perfusion + continuous normothermic blood cardioplegia) might achieve optimal heart protection by virtually eliminating myocardial ischemia during aortic cross-clamping. Two-hundred and fifty consecutive patients underwent cardiac surgery by this technique. Mean cross-clamp time was 72.6 +/- 30.7 minutes. Ten patients (4%) died, 20 (8%) needed major inotropic support and 8 (3.2%) required circulatory assistance. Two-hundred and twenty-three patients (89.2%) returned spontaneously to normal sinus rhythm and 8 (3.2%) had evidence of perioperative myocardial infarction. Nineteen patients (7.6%) had a cross-clamp time longer than 120 minutes and no significant difference in mortality was observed with those undergoing a shorter cross-clamping. When comparing 154 patients receiving retrograde continuous normothermic blood cardioplegia induction with 46 receiving antegrade induction, no difference was found in perioperative parameters, mortality and morbidity. By univariate analysis, impaired preoperative LV performance was identified as the only risk factor for operative mortality. In our experience aerobic cardiac surgery appears most suitable for emergency and redo operations, extensive coronary revascularization, complex mitral reconstruction, aortic valve replacement (particularly with unstented biological prostheses), cardiac transplants and whenever two or more valvular and/or coronary procedures are associated. Retrograde induction is as effective as antegrade and simplifies the technique, facilitating unmodified continuous normothermic blood cardioplegia in different anatomical and clinical situations.

Adolescent↗

Arthrolysis in the treatment of ankylosis and severe post traumatic stiffness of the elbow.

Between 1977 and 1989 the authors performed arthrolysis on 18 patients with ankylosis or severe post traumatic elbow stiffness. After an analysis of the cases, the operative technique is described and original parameters are proposed to evaluate the consequent results. The validity of arthrolysis as a possible alternative to arthroplasty or arthroprosthesis is confirmed by the 67% positive results.

Adolescent↗

Assisted circulation for myocardial recovery after repair of congenital heart disease.

Between January 1987 and May 1990, six children underwent ventricular assisted circulation for recovery of myocardial function after cardiac surgery. Their ages ranged from 9 months to 12 years. Three patients had tetralogy of Fallot and one had atrioventricular discordance with ventriculoarterial concordance, ventricular septal defect, and under-over ventricles. Double outlet left ventricle and a large ventricular septal defect with pulmonary hypertension was present in the remaining two. The duration of circulatory support averaged 126 +/- 57 h. An extracorporeal membrane oxygenator (ECMO) was used in four patients, biventricular assistance with centrifugal pumps in one, and left ventricular assistance followed by ECMO in the last patient. Circulatory support was begun in the operating room in two patients who could not be weaned from cardiopulmonary bypass. Both these patients are long-term survivors. Assisted circulation was implanted in four patients in the intensive care unit because of low cardiac output refractory to any pharmacological treatment. Only one of these patients could be weaned from circulatory support but he died 20 days later because of multiorgan failure due to persistent poor myocardial function. The causes of death in the remaining three patients were intracranial hemorrhage, untreatable bleeding, and failure of myocardial recovery, respectively. We believe that early postoperative use of circulatory support can be a major determinant for recovery of myocardial function in patients who have severe low cardiac output following repair of congenital cardiac lesions. Our initial experience with the use of biventricular assistance in small children is encouraging. Nevertheless, further observations are clearly necessary to establish the role of postoperative circulatory support in children with congenital cardiac lesions.

Cardiac Output, Low↗