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G Selvaggi

Publications and source records attributed to G Selvaggi.

87 records · Page 5Linked to original sources
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Etiology and management of alimentary tract ulcers in pediatric intestinal transplantation patients.

Patients who undergo intestinal transplantation encounter several complications in the posttransplant period, one of them being ulcer formation in the alimentary tract. During postoperative endoscopic monitoring of 112 pediatric intestinal transplantation patients at our institution, we identified chronic ulcer formation in 11 patients. There were no common or defining demographic or clinical variables that were found in the patients with ulcers. The ulcers could be located within the allograft or in native tissue. Biopsies were obtained from the ulcer edge and the intervening mucosa as well as an evaluation of possible infectious agents. The most common changes in the ulcers were compatible with Epstein-Barr virus-associated posttransplant lymphoproliferative disorder (PTLD; seven cases), acute rejection (six cases), and less commonly, infectious causes (one case). These changes could occur concomitantly and retrospective analysis after therapy showed that the ulcers could have multiple etiologies. Directed biopsies of ulcer edges often displayed morphological changes compatible with acute rejection of the graft, although some biopsies of the intervening mucosa did not show similar changes. Some patients treated based on the changes within the intervening mucosa responded well and led to resolution of the ulcers. Our findings demonstrate that PTLD and acute rejection are the most common causes of chronic ulcer formation and that biopsy samples should be collected simultaneously from both the ulcer edge and intervening mucosa since pathological changes can vary depending on the underlying cause(s). Infectious agents were rarely present but could be seen superimposed with the underlying cause.

Biopsy↗
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Growth after intestinal transplant in children.

Intestinal transplantation has been more frequent in children with intestinal failure. However, the growth after intestinal transplantation has not been well documented. The demographics, transplant information, postoperative complications, heights, and weights were obtained retrospectively from medical records on 23 children who underwent intestinal transplantation. Z-scores were calculated from the STAT Growth-BP, based on Centers for Disease Control and Prevention growth chart (2000). Transplantations were performed between 1999 and 2004. Patient median age was 1.1 years (range 0.5 to 6.9 years). Twelve were boys and 11 girls. Seventeen children received multivisceral transplantations, one modified multivisceral transplantation, and five isolated intestinal transplantations. Baseline immunosuppression consisted of tacrolimus and corticosteroids. Daclizumab was used as induction agent in 18 patients; alemtuzumab, in five patients. Median pretransplant Z-scores were median -1.67 (n = 23) in weight, and median -3.36 (n = 21) in height. Pretransplant growth was significantly retarded. We analyzed significantly retarded patients with Z-score <-2.0. The change of weight Z-score from pretransplant was: 1.25 at 6 months (n = 11), 1.46 at 12 months (n = 10), and 2.21 at 24 months (n = 7). The change of height Z-score: 1.9 at 6 months (n = 16), 1.42 at 12 months (n = 13), and 1.51 at 24 months (n = 10). Z-score significantly improved (P < .002, ANOVA). Among the analyzed factors sex, age at transplant, length of stay, and rejection within 6 months, were not associated with catch-up growth. Children with retarded growth showed significant catch-up after successful intestinal transplantation.

Body Height↗
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Renal function after pediatric intestinal transplant.

Data were analyzed from 44 patients who survived more than 2 years after intestinal transplantation performed between 1994 and 2002. Median age was 1.7 years. Tacrolimus level was defined as average tacrolimus level over 6 months. Kidney function was evaluated using a 6-month average serum creatinine. Glomerular filtration rate (GFR) was calculated with the Schwartz formula. The procedures were: isolated intestinal transplantation (n = 11), liver and intestinal transplantation (n = 9), multivisceral transplantation (n = 22), and modified multivisceral transplantation (n = 2). Forty-four patients were followed for a mean of 3.6 years on tacrolimus. Tacrolimus levels ranged between 3.5 and 19.9 ng/mL (median 14.6 ng/mL) at 0 to 6 months and 6.0 to 18.9 ng/mL (median 13.2 ng/mL) at 0 to 12 months. Pretransplant kidney function as mean GFR was 138 +/- 42 mL/min/1.73 m(2) (n = 44), posttransplant kidney function at 18 to 24 month as mean GFR was 102+/-35 mL/min/1.73 m(2) (n = 44), a value that was 81% of the pretransplant GFR (P < .0001). In an analysis of tacrolimus level versus renal function, a value greater than 13.5 ng/mL during the first 12 months was a significant predictor for impaired renal function at 2 years after transplantation (defined as average GFR less than 90 mL/min/1.73 m(2) at 18 to 24 months; P = .001). Only age among age, sex, diagnosis, transplant type, and rejection episodes showed a correlation with renal function. Renal function dropped significantly at 2 years after pediatric intestinal transplantation to 81% of the pretransplantation value. Tacrolimus level for the first 12 months seemed to predict subsequent development of renal impairment at 2 years.

Adolescent↗
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Temporary elevation of serum transaminases after pediatric intestinal transplantation: incidence and clinical correlation in multivisceral transplant vs isolated intestinal transplant.

Data were gathered from the records of 51 children of median age 1.5 years who survived more than 6 months after intestinal transplantation. Abnormal liver function tests (LFTs) were defined as serum aspartate aminotransferase (AST) greater than 100 IU/L or total bilirubin greater than 2.0 g/dL lasting more than 3 days. Temporary elevation was defined when LFTs returned to normal without graft loss or death. LFT elevation at the time of transplantation was not included as a temporary LFT elevation. Median follow-up was 36 months. In multivisceral transplant recipients, all patients (n = 34) showed abnormal LFTs at transplantation that normalized within a median period of 2 days. Temporary LFT elevations were seen in 20 of 34 (59%) in multivisceral transplantation and 5 of 17 (29%) in isolated intestinal transplantation. Median length of elevation was 14 days in multivisceral transplantation and 12 days in isolated intestinal transplantation. Peak AST was 353 +/- 190 IU/dL in multivisceral transplantation and 839 +/- 605 IU/dL in isolated intestinal transplantation (P = .0059). Events associated with temporary LFT elevations in multivisceral transplantation were total parental nutrition (TPN) (n = 8), dehydration (n = 2), viral infection (n = 2), others (n = 3), and nonspecific (n = 5). Events in isolated intestinal transplantation were posttransplant lymphoproliferative disorder (n = 2), TPN (n = 1), and nonspecific (n = 2). Temporary LFT elevations were commonly seen among pediatric intestinal recipients, which correlated with events other than rejection. Approximately half of the temporary LFT elevations were associated with no significant clinical events. They resolved spontaneously. Interestingly, the peak AST value was higher in isolated intestinal transplantation compared to multivisceral transplantation.

Adolescent↗
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Analysis of risk factors for the development of posttransplant lymphoprolipherative disorder among 119 children who received primary intestinal transplants at a single center.

UNLABELLED: Posttransplant lymphoproliferative disorder (PTLD) is a well-known complication after pediatric transplantation. We analyzed all potential risk factors to assess patient and graft outcomes of 119 children who received intestinal transplantations. MATERIALS AND METHODS: Between August 1994 and March 2005, 119 patients underwent cadaveric intestinal transplantation. Their median age at transplant was 1.4 years (range: 0.6-17), median weight was 9.5 kg (range: 4.7-67), and 57% were boys. The median follow-up among 49 ongoing survivors was 41 months (range: 4-121). All PTLD cases were biopsy proven. In the past 5 years, treatment included antiviral therapy, immunosuppression withdrawal, and use of rituximab. RESULTS: The incidence of PTLD was 11.8% (14/119). No patient experienced graft failure secondary to PTLD, while two patients died from PTLD (14.2%). The PTLD group was divided into an early onset group (<4 months, 6 of 14; 42.8%) and a late onset group (>2 years, 8 of 14; 57.2%). No patient experienced PTLD between 4 months and 2 years after transplantation. The use of OKT3 was the only significant risk factor for the development of PTLD. No factor was specifically associated with the early versus late development of PTLD. CONCLUSIONS: The only factor associated with a significantly higher risk of PTLD was the use of OKT3 to treat a rejection episode. Finally, since the the introduction of anti-CD20 antibodies as part of the treatment protocol for PTLD, the risk of death due to PTLD appears to have become manageably low.

Adolescent↗
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Intestinal transplantation with alemtuzumab (Campath-1H) induction for adult patients.

BACKGROUND: Alemtuzumab (Campath-1H [C1H]) is a humanized monoclonal antibody directed against the CD 52 antigen that is present on the surface of T cells, B cells, natural killer cells and monocytes. We studied its application in intestinal transplantation. METHODS: This is a retrospective review of adult patients who underwent intestinal transplantation between December 1994 and May 2005. Group 1: non-C1H group (n = 39); group 2: C1H group (n = 37). C1H was administered as an induction immunosuppression in four doses (0.3 mg/kg), or in two doses (30 mg/kg). Tacrolimus levels were maintained at low level (5-10 ng/dL). No maintenance steroids were given. RESULTS: One-year survival of group 1 and group 2 patients were 57% and 70%, respectively. This difference is not statistically significant. Of 37 patients in group 2, 21 are alive. The incidence of rejection was lower in group 2 (P < .005). Average current tacrolimus level is 6.97 +/- 3.98 ng/dL. Seventeen patients (81%) are steroid free, and 15 (71%) are maintained solely on tacrolimus. There was no graft versus host disease in group 2. CONCLUSIONS: Our preliminary data suggest that C1H can provide effective immunosuppression for intestinal transplantation. Incidence of rejection was less with this regimen using low maintenance tacrolimus and minimal steroids.

Adult↗
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Association of emergence of HLA antibody and acute rejection in intestinal transplant recipients: a possible evidence of acute humoral sensitization.

Development of HLA antibody has been associated with chronic allograft failure in kidney recipients. We tested HLA antibody in posttransplant sera of intestinal recipients: 126 sera from 28 pediatric recipients were tested for HLA antibody by flow PRA (f-PRA). Median age was 1.1 years (0.44-17). Graft types included isolated intestine (n = 6), liver and intestine (n = 3), modified multivisceral (n = 3), and multivisceral grafts (n = 16). Greater than 10% of either class I (CI) or class II (CII) f-PRA was considered positive, and >30% strongly positive. Five of 28 patients had positive f-PRA in multiple samples; the remaining 23 had either no positive or only one positive sample. Three patients had strongly positive f-PRA. Patients with multiple positive samples were recipients of two modified multivisceral and three multivisceral grafts. Only one of these patients had a positive PRA pretransplant. Cytotoxic cross-match at transplant was negative for all. The three with strongly positive f-PRA showed significant episodes of rejection around the time of positive samples. One of them who persistently had f-PRA value >80% (from day 13-113) died of refractory rejection. The other two had f-PRA of 76% and 53% during the early postoperative course with associated episodes of rejection. F-PRA value decreased with rejection therapy. Only one of the 23 patients (4%) with negative f-PRA had an episode of rejection around the time of sample collection. Development of HLA antibody after intestinal transplantation seems to have significant association with acute rejection episodes.

Adolescent↗
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Inclusion of spleen in pediatric multivisceral transplantation.

Inclusion of the donor spleen may be beneficial for small children who receive multivisceral transplantation (MVT) because asplenia is associated with increased risk of bacterial sepsis. Beginning in 2003, the spleen was transplanted together with multivisceral transplantation in 17 children under daclizumab induction (spleen group). The results were compared to 23 children who received multivisceral transplantation without the spleen (control group) with the same immunosuppression regimen. Median age of 17 patients who received a spleen was 0.80 years (range 0.54-1.66). Platelet counts at 30 and 60 days posttransplant were significantly lower in the spleen group (average values: day 30: 399,000 vs 636,000, P = .015; day 60: 413,000 vs 622,000, P = .0056). WBC counts at 30 and 60 days posttransplant were also decreased in the spleen group but the difference was not statistically significant. Median rejection-free survival was 205 days in the spleen group and 101 days in the control group (P = NS). Median length of hospital stay was 39 days in the spleen group and 61 days in the control group. With a median follow-up of 398 days (spleen group) and 1232 days (control group), 3 of 17 (17%) in the spleen group developed graft versus host disease (GVHD), whereas 1 of 23 (4.5%) in control group did (P = NS). In one patient in each group, GVHD was fatal. No patient developed posttransplant lymphoproliferative disorder (PTLD) in the spleen group, whereas 4 of 23 (17%) in the control group developed PTLD. One-year patient survival was 84% in the spleen group and 86% in the control group. Recipients of the spleen as part of a multivisceral graft had significantly lower platelet counts. Rejection-free survival may be prolonged, but the risk of GVHD may be increased.

Antibodies, Monoclonal↗
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Expanded use of multivisceral transplantation for small children with concurrent liver and intestinal failure.

Fifty-five children with liver and intestinal failure have been transplanted at our center under daclizumab induction therapy since 1998. Of those, 19 received five multiviceral transplantation (MVT), 12 liver-intestine-pancreas transplants, and 2 noncomposite liver and intestine transplants (NCLIT) before 2001 (group 1). During this period, MVT was only used in children with gastric dysmotility. After 2001, we expanded the use of MVT. Therefore, 36 children in this period (group 2) received MVT except for two who received NCLIT. Median age was 1.08 in group 1 and 1.06 in group 2. Median recipient weight was 8.2 kg in group 1 and 7.5 kg in group 2. Six-month, 1-, and 2-year patient survivals were 54%, 37%, and 32% in group 1 and 94%, 91%, and 71% in group 2 (P = .00037). A statistically significant difference was observed in freedom from rejection between the two groups with group 2 being favorable (P = .0019). A statistically significant difference was observed in freedom from rejection between the two groups with group 2 being favorable (P = .0019) Four died of rejection in group 1 (21%); none died of rejection in group 2. There have been two esophago-gastrostomy strictures (one in each group) and a serious reflux of this anastomosis (group 2). Strictures were treated with balloon dilatation, and the reflux was surgically corrected. In 24 recent cases, gastro-gastric anastomosis was used in MVT with no complications to date. No pancreatic rejection was seen. Small children tolerated MVT with improved survival rates and reduced rates of rejection. Use of MVT may be considered as an alternative to liver-intestine-pancreas transplant.

Antibodies, Monoclonal↗
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Analysis of rejection episodes in over 100 pediatric intestinal transplant recipients.

Rejection after intestinal transplant is a significant source of morbidity and mortality. We analyzed number of rejections, severity, and duration of episodes in pediatric recipients of intestinal transplants. One hundred eighteen intestinal transplants were performed: intestine (n = 27), liver-intestine (n = 27), modified multivisceral (n = 7), and multivisceral (n = 57). A total of 186 rejections were classified: mild (n = 89), moderate (n = 70), severe (n = 27). Duration of episodes doubled for each increasing step in severity. Treatment of mild rejection was with steroids, moderate rejection was treated with OKT3, severe rejection required OKT3 and organ removal. Most rejections occurred during the first month posttransplant, with the incidence of all rejections declining after 6 months posttransplant. Intestine and liver-intestine recipients had significantly higher probability of developing severe rejections, as compared to MVT. In summary, recipients of MVT seemed to be protected from rejection as compared to intestine or liver-intestine recipients.

Adolescent↗
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Renal dysfunction following adult intestinal transplant under tacrolimus-based immunosuppression.

We analyzed data from the records of 24 adult patients who survived more than 2 years after intestinal transplantation performed between 1995 and 2002 under tacrolimus-based immunosuppression. Ages ranged from 19.3 to 59.2 years old (median 32.1 years). Tacrolimus cumulative level was defined as a sum of weekly average tacrolimus level over time. Kidney function was evaluated by the 6-month average serum creatinine level. Estimated creatinine clearance was calculated with the Cockcroft-Gault formula. Student's t test was used for analysis. Primary diseases were mesenteric thrombosis (n = 7), trauma (n = 4), Crohn's (n = 3), Gardner's (n = 5), and others (n = 7). Procedures were isolated intestinal transplant (n = 10), liver and intestine (n = 1), multivisceral transplant (n = 9), or modified multivisceral transplant (n = 4). Cumulative tacrolimus levels ranged between 1161 and 8623 ng*day/mL (median 4132 ng*day/mL) at 0 to 12 months. Pretransplant kidney function as mean creatinine clearance was 114 mL/min per 1.73 m(2) (n = 24). Creatinine clearance decreased to a mean of 49.6 mL/min per 1.73 m(2) (43.5% of pretransplant) at 2 years (P < .0001). The average creatinine clearance at 18 to 24 months in each patient with a cumulative tacrolimus level <4500 ng*day/mL was 63% +/- 25% of preoperative creatinine clearance. In patients with a cumulative tacrolimus level >4500 ng*day/mL, it was 34% +/- 17%. Cumulative tacrolimus level >4500 ng ng*day/mL was significantly associated with a decreased creatinine clearance at 2 years (P = .006). Renal function decreased significantly after intestinal transplantation in adults. Cumulative tacrolimus level in the first year affected renal function at 2 years.

Adult↗
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Induction of donor-specific transplantation tolerance to skin and cardiac allografts using mixed chimerism in (A + B-->A) in rats.

Mixed allogeneic chimerism (A + B-->A) was induced in rats by reconstitution of lethally irradiated LEW recipients with a mixture of T-cell depleted (TCD) syngeneic and TCD allogeneic ACI bone marrow. Thirty-seven percent of animals repopulated as stable mixed lymphopoietic chimeras, while the remainder had no detectable allogeneic chimerism. When evaluated for evidence of donor-specific transplantation tolerance, only those recipients with detectable allogeneic lymphoid chimerism exhibited acceptance of donor-specific skin and cardiac allografts. Despite transplantation over a major histocompatibility complex (MHC)- and minor-disparate barrier, animals accepted donor-specific ACI skin and primarily vascularized cardiac allografts permanently, while rejecting third party Brown Norway (BN) grafts. The tolerance induced was also donor-specific in vitro as evidenced by specific hyporeactivity to the allogeneic donor lymphoid elements, yet normal reactivity to MHC-disparate third party rat lymphoid cells. This model for mixed chimerism in the rat will be advantageous to investigate specific transplantation tolerance to primarily vascularized solid organ grafts that can be performed with relative ease in the rat, but not in the mouse, and may provide a method to study the potential existence of organ- or tissue-specific alloantigens in primarily vascularized solid organ allografts.

Animals↗
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[Effects of different dialysis membranes and techniques on the nutritional status, morbidity and mortality of hemodialysis patients].

To evaluate long-term effects of different hemodialysis (HD) membranes and techniques on nutritional status, morbidity, and mortality in HD patients, we prospectively studied 138 stable HD patients (59 females, 79 males, mean age 53 +/- 13 yrs) on maintenance HD from at least 1 yr with bicarbonate (BD) and cellulose acetate (AC). Patients were randomly assigned to one of four groups: comparable for age, sex, underlying nephropathy, time on dialysis, comorbidity, and followed-up for 5 yrs. Group A (n=38) BD/AC; group B (n=30) BD/low-flux polysulfone (PS); group C (n=30) BD/middle-flux PS or PA; group D (n=20) hemodiafiltration (HDF)/high-flux polysulfone (PS-HDF); group E (n=20) acetate free biofiltration (AFB) with PAN. Nutritional status was evaluated by anthropometric index, visceral protein compartment index, immunological index and bioelectrical impedance analysis. In all patients, we evaluated yearly plasma values of Beta2-microglobulin and of C-reactive protein (CRP) before and after dialysis. A significant and sustained improvement in nutritional status and a striking reduction in CRP and in pre- and post-dialysis beta2-microglobulin levels was observed in groups C, D and E. Morbidity (calculated from the number of clinical complications/patient/yr and from the number of hospital admissions/patient/yr) and mortality were significantly higher in groups A and B (mortality: group A=24%, group B=23%, group C=10%, group D=5%, and group E=5%; p<0.001). The results of our study indicate that the use of middle and high-flux biocompatible membranes is associated with a remarkable and sustained amelioration in nutritional status and with a significant improvement in the prognosis of HD patients, explained by the notable reduction in beta2-microglobulin and in the systemic inflammatory response.

Adolescent↗