Nephrogenic fibrosing dermopathy after liver transplantation successfully treated with plasmapheresis

Nephrogenic fibrosing dermopathy (NFD) is a recently described cutaneous fibrosing disorder associated with renal dysfunction. It appears similar to scleromyxedema but with some notable exceptions, including the lack of involvement of the face and absence of plasma cells on histology, systemic involvement, and paraproteinemia. Patients can present with thickened or edematous skin with indurated papules and plaques involving the extremities and the trunk. We report the first three cases of NFD after liver transplantation successfully treated with plasmapheresis. Two patients underwent liver transplantation for hepatitis C virus-induced cirrhosis and one for hepatitis B virus-induced cirrhosis. All the patients had encephalopathy, refractory ascites, and malnutrition prior to transplantation. Like those patients with NFD, all three of our patients had renal dysfunction and required hemodialysis before and after transplantation. Two were not dependent on dialysis at the time of diagnosis, however. These patients had excellent liver allograft function, but the other patient had allograft failure secondary to recurrent hepatitis C. Immunosuppression therapy consisted of basiliximab, mycophenolate mofetil, calcineurin inhibitor, and prednisone. The patients developed "woody" skin induration of the distal extremities, erythematous papules, and contractures at 1, 2, and 120 months after transplantation. Skin biopsies resembled NFD. No paraproteinemia was evident. One to three 5-day courses of plasmapheresis resulted in moderate to marked clinical improvement. The improvement of the kidney function in two of our patients did not appear to correlate with that of the skin disorder, because the kidney function was improving at the time the diagnosis of NFD was made. In conclusion, we report the first three cases of NFD after liver transplantation. Plasmapheresis was moderately successful in resolving the skin-indurated papules, severe skin induration, and associated joint contractures. Preliminary studies (unpublished data) show that decreasing plasma levels of transforming growth factor-beta1 after plasmapheresis appear to correlate with the amelioration of this clinical condition.     

Aggressive Tumors of the Concha: Treatment with Postauricular Island Pedicle Flap

Background: The concha is a partially hidden anatomical area characterized by difficult access and reconstruction. Objective: We describe the use of the postauricular (revolving door) island pedicle flap in the treatment of aggressive tumors of the concha. Methods: We present two patients with aggressive cutaneous tumors localized in auricular concha. One of the patients presented with a large ulcerated basal cell carcinoma. The second patient had received a heart transplant, was receiving immunosuppressive therapy, and was affected by a squamous cell carcinoma. Results: Both defects were closed using a posterior auricular island flap that was advanced through cartilage with excellent cosmetic results. Conclusion: The postauricular island pedicle flap is well suited for conchal reconstruction because of its proximity to the defect. The flap was transferred from posterior to anterior toward the concha, followed by primary closure of the retroauricular donor site. Antécédents: La conque est une partie anatomique partiellement cachée, caractérisée par la difficulté d'y accéder et de la reconstruire. Objectif: Nous décrivons l'utilité d'un lambeau en Îlot rétro-auriculaire àpédicule dans le traitement des tumeurs agressives de la conque. Méthodes: Nous présentons le cas de deux patients souffrant de tumeurs cutanées agressives localisées dans la conque. L'un des patients présente un gros carcinome basocellulaire ulcéré. Le second patient a re¸u une transplantation cardiaque, suivait une thérapie immunosuppressive et présentait un carcinome spinocellulaire. Résultats: Les deux problèmes ont été résolus au moyen d'une chirurgie plastique en avan¸ant un lambeau en Îlot rétro-auriculaire grâce au cartilage, avec d'excellents résultats esthétiques. Conclusion: Le lambeau en Îlot rétro-auriculaire àpédicule convient parfaitement àla réparation de la conque, vu sa proximité. Le lambeau a été transféré de la partie postérieure àla partie antérieure, près de la conque, et le site rétro-auriculaire a été par la suite refermé.     

Coagulation abnormalities in patients with single-ventricle physiology precede the Fontan procedure

OBJECTIVE: Thromboembolic events in patients who have undergone the Fontan operation have been reported to be as high as 20% to 33%. A hypercoagulable state with deficiencies in proteins C and S has been implicated. Using age-matched control subjects, we evaluated whether an altered coagulation state is present earlier in the course of staged single-ventricle repair. METHODS: After informed consent had been obtained, coagulation factors were assayed in 36 infants (mean age, 7.7 +/- 3.6 months) with single-ventricle cardiac defects immediately before undergoing the bidirectional Glenn procedure; 34 infants (mean age, 8.4 +/- 2.6 months) without cardiac disease were assayed as control subjects. Concentration of factors II, V, VII, VIII, IX, and X; antithrombin III; plasminogen; proteins C and S; fibrinogen; serum albumin; and liver enzymes were measured. Normal reference intervals on the basis of the control subjects were determined by using 95% confidence limits. Patient demographic and hemodynamic variables were evaluated as possible predictors of coagulation abnormalities. RESULTS: Concentrations of protein C; factors II, V, VII, IX, and X; plasminogen; fibrinogen; and antithrombin III were significantly lower in the pre-Glenn infants compared with the age-matched control subjects (all P <.001, Student t test). On the basis of multiple logistic regression, no specific hemodynamic variables were predictive of a procoagulant or anticoagulant deficiency. Ventricular dysfunction did predict the presence of multiple coagulation abnormalities (P <.001). CONCLUSION: Procoagulant and anticoagulant factor abnormalities occur early in the course of single-ventricle repair and precede the cavopulmonary connection.     

Arterial switch operation with a single coronary artery

OBJECTIVE: Our purpose was to evaluate the impact of coronary pattern on survival and reintervention in patients who underwent the arterial switch operation with a single coronary artery. METHODS: We conducted a retrospective analysis of 53 patients with a single coronary artery who underwent the arterial switch operation between 1983 and 2000 at Children's Hospital Boston. Recent follow-up information was obtained for 40 of the 46 long-term survivors (mean follow-up 7.3 +/- 4.5 years). RESULTS: Thirty-five patients had a single right coronary artery, with the left coronary artery posterior to the pulmonary artery in 27. Eighteen patients had a single left coronary artery (16 with the right coronary artery anterior to the aorta). Six of 7 total patients who died had a single right coronary artery; all died before 1992. There were 5 early deaths, all with a single right coronary artery, with 4 deaths due to coronary malperfusion. Survivals for all patients were 91% at 6 months and 87% at 1, 5, and 10 years after the arterial switch operation. Survival figures were lower for patients having a single right ostium with the left main coronary artery posterior to the pulmonary artery compared with all other subtypes (P =.02, log-rank test). Seven patients had reintervention, 4 because of right ventricular outflow tract obstruction, 1 for heart transplantation, 1 for mitral valve repair and 1 for pacemaker implantation. Freedom from reintervention for all patients was 96% at 6 months, 92% at 1 year, 86% at 5 years, and 82% at 10 years after the arterial switch operation, with lower rates for patients having a single left ostium with the right coronary artery anterior to the aorta (P =.0003, log-rank test). CONCLUSIONS: In the current era, the arterial switch operation with a single coronary artery can be performed safely irrespective of the coronary anatomy. Risk of reintervention is higher in patients having a single left ostium with the right coronary artery anterior to the aorta.     

Impact of anti-hepatitis Bc-positive grafts on the outcome of liver transplantation for HBV-related cirrhosis

BACKGROUND: The present scarcity of organ donors requires consideration of grafts from sources not previously used. Several studies have addressed the use of grafts from donors who have antibodies to the hepatitis B core antigen (anti-HBc+). The aim of this study was to evaluate the impact of the use of anti-HBc+ grafts in patients transplanted for hepatitis B virus (HBV)-related cirrhosis. METHODS: Recipients of first hepatic transplants from donors with antibodies to HBV were identified retrospectively. All patients who had serology suggestive of active HBV and were negative for hepatitis C and D were included in the analysis. The Kaplan-Meier method was used to assess the actuarial recurrence-free survival on patients with graft survival longer than 1.5 months. The stepwise Cox regression model was used to identify independent predictors of HBV recurrence. RESULTS: One thousand seven hundred seventeen first liver transplants were performed at the Thomas E. Starzl Transplantation Institute from September 1, 1990, to December 31, 1999. HBV was the cause of cirrhosis in 112 patients (6.5%). Thirty-three patients had coexistent viral infection (23 HCV and 10 HDV). Fourteen donors (17.2%) were positive for HBV markers, with nine anti-HBc+ and with five both anti-HBc+ and anti-HB surface-positive; of these, 13 anti-HBc+ organ recipients had long-term survival. Nine (69.2%) of these cases were reinfected versus 20 (35.7%) in the group that received grafts from HBV- donors (P<0.05, Fisher's exact test). The mean time to reinfection was shorter in the anti-HBc+ group (2.9 yr vs. 6.4 yr, P<0.005). There were no statistical differences in graft or patient survival between the two groups. HBV prophylaxis with combined lamivudine and hepatitis B immunoglobulin (HBIG) significantly reduced the reinfection rate (P<0.03). Hepatitis Be (Hbe) antigen-positive recipients trended to faster reinfection (not significant). Cox regression analysis revealed that both anti-HBc graft donor status (RR, 2.796; P=0.020) and combination of lamivudine/HBIG (RR, 0.249; P=0.021) are independently associated with reinfection. CONCLUSIONS: The use of anti-HBc+ liver grafts does not affect graft or patient survival. However, patients who receive these organs are 2.5 times more likely to develop HBV recurrence. Lamivudine and HBIG combination decreases HBV recurrence 4-fold.     

Superior long-term results of renal transplantation in children under 5 years of age

Despite improving overall results of pediatric renal transplantation children under 5 years of age remain a high-risk group with poorer outcomes often because of a higher rate of surgical complications. This retrospective report details a 12-year experience at a single center and examines the outcome in this high-risk group of patients. We reviewed the medical records of 21 children under 5 years of age who received renal transplantation at Loma Linda University Medical Center between July 1988 and August 2000. The patients were evaluated regularly by the same pediatric nephrologist throughout the study period at our outpatient clinic. Mean recipient age was 3 +/- 1.2 (range 2-5) years; weight at transplantation was 13.3 +/- 5.4 kg. Ten (48%) patients received living related donor (LRD) kidneys and 11 (52%) received cadaver (CAD) kidneys. Mean donor ages for CAD and LRD were 14.4 +/- 10 years and 26.6 +/- 4.9 years, respectively. The mean cold ischemia time (CAD only) was 23.3 +/- 10.6 hours. Renal dysplasia (n = 8) and obstructive uropathy (n = 5) were the most common primary diagnoses. Maintenance immunosuppression consisted of Azathioprine or mycophenolate mofetil (MMF), cyclosporine or tacrolimus and prednisone. Mean follow-up was 80.1 +/- 51.4 months. Twelve (57%) grafts have a follow-up >5 years. Patient survival was 100 per cent. Overall graft survival at one, 3, 5, and 10 years were 95, 95, 88, and 88 per cent respectively. Graft survival for LRD recipients was 100 per cent. No graft was lost as a result of a technical problem or vascular thrombosis. One graft each was lost because of delayed graft function complicated by severe cytomegalovirus infection and chronic rejection. At one year the mean serum creatinine was 0.6 +/- 0.2 mg/dL with a mean calculated glomerular filtration rate of 93 +/- 32 mL/min. All 17 children who are now of school age are attending school. We conclude that excellent rehabilitation and superior long-term patient and graft survival can be achieved with renal transplantation in children of this age group with the use of good surgical techniques and close follow-up.     

Modeling of the sedative and airway obstruction effects of propofol in patients with Parkinson disease undergoing stereotactic surgery

BACKGROUND: Functional stereotactic surgery requires careful titration of sedation since patients with Parkinson disease need to be rapidly awakened for testing. This study reports a population pharmacodynamic model of propofol sedation and airway obstruction in the Parkinson disease population. METHODS: Twenty-one patients with advanced Parkinson disease undergoing functional stereotactic surgery were included in the study and received propofol target-controlled infusion to achieve an initial steady state concentration of 1 microg/ml. Sedation was measured using the Ramsay Sedation Scale. Airway obstruction was measured using a four-category score. Blood samples were drawn for propofol measurement. Individual pharmacokinetic profiles were constructed nonparametrically using linear interpolation. Time course of sedation and respiratory effects were described with population pharmacodynamic models using NONMEM. The probability (P) of a given level of sedation or airway obstruction was related to the estimated effect-site concentration of propofol (Ce) using a logistic regression model. RESULTS: The concentrations predicted by the target-controlled infusion system generally exceeded the measured concentrations. The estimates of C(50) for Ramsay scores 3, 4, and 5 were 0.1, 1.02, and 2.28 microg/ml, respectively. For airway obstruction scores 2 and 3, the estimates of C(50) were 0.32 and 2.98 microg/ml, respectively. Estimates of k(e0) were 0.24 and 0.5 1/min for the sedation and respiratory effects, respectively. CONCLUSIONS: The pharmacokinetic behavior of propofol in patients with Parkinson disease differs with respect to the population from which the model used by the target-controlled infusion device was developed. Based on the results from the final models, a typical steady state plasma propofol concentration of 0.35 microg/ml eliciting a sedation score of 3 with only minimal, if any, airway obstruction has been defined as the therapeutic target.     

Coagulation factor abnormalities in patients with single-ventricle physiology immediately prior to the Fontan procedure

Background. Coagulation abnormalities have been reported following the Fontan operation and have been attributed to various aspects of Fontan-associated physiology. Using age-matched controls, this study evaluated coagulation abnormalities in children who had undergone a bidirectional Glenn procedure to test the hypothesis that coagulation abnormalities are present before the Fontan operation.

Methods. Coagulation factors were assayed in 38 children (mean age 34.4 ± 15 months) immediately before the Fontan operation; 37 healthy children (mean age 33 ± 17 months) were assayed as controls. Concentration of factors II, V, VII, VIII, IX, and X and of antithrombin III, plasminogen, proteins C and S, fibrinogen, serum albumin, and liver enzymes were measured. Normal reference intervals based on the control patients were determined using 95% confidence limits. Patient demographic data, hemodynamic variables, and elapsed time after the Glenn procedure were evaluated as possible predictors of coagulation abnormalities.

Results. Concentrations of protein C; factors II, V, VII, and X; plasminogen; and antithrombin III were significantly lower before the Fontan operation compared with age-matched controls (p < 0.01); no specific hemodynamic variables were predictive of a pro- or anticoagulant deficiency. There were significant positive correlations between patients who had abnormally low factor VII, protein S, and protein C levels and a longer interval between the bidirectional Glenn procedure and the Fontan operation (p < 0.001).

Conclusions. Coagulation abnormalities that could predispose patients to increased risk for clotting or bleeding are evident early in the course of staged single-ventricle repair.     

Improving results of the modified Fontan operation in patients with heterotaxy syndrome

BACKGROUND: Historically the Fontan operation in patients with single ventricle heterotaxy syndrome and atrial isomerism has been associated with high mortality. We studied whether recent modifications of the surgical technique have improved outcome. METHODS: A retrospective review of 135 patients with heterotaxy syndrome who underwent a Fontan operation between 1981 and 2000 was performed. RESULTS: There were 93 patients with right isomerism and 42 with left isomerism. Anomalies of venous return included 25 patients with extracardiac pulmonary venous connection (19%) and 37 patients with an interrupted inferior vena cava (27%). Thirty-six patients (27%) had at least moderate atrioventricular valve regurgitation. The type of Fontan procedure included 17 patients with an atriopulmonary Fontan connection, 67 with a lateral tunnel modification, 19 with an intraatrial tube graft, 25 with an extracardiac tubegraft, and 7 with an intra-extra atrial tube graft. A fenestration was placed in 93 patients (78%). Early mortality was 19% before 1991, 3% since 1991, and no patient has died early since 1993. Ten-year survivals were 70% for Fontan operations before 1990 and 93% for Fontan operations after 1990. Thirty-two patients (23%) had prolonged pleural effusions. Risk factors for death included anomalous pulmonary venous connection (p = 0.02) and higher preoperative pulmonary vascular resistance (p = 0.002). Sixty-two patients (47%) had some form of early postoperative arrhythmia. At 10 years, freedom from late bradyarrhythmia and late tachyarrhythmia were 78% and 70%, respectively. Preoperative arrhythmias, older age at operation, and anatomic features were each independent predictors of late arrhythmia. CONCLUSIONS: The Fontan operation can now be performed in patients with heterotaxy syndrome with excellent survival. However, morbidity in terms of postoperative arrhythmias and prolonged pleural effusions remains significant. Fontan staging, appropriate choice of Fontan modification, aggressive treatment of concomitant malformations, and use of a baffle fenestration contribute to improved outcome.