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Biomedical subjects

Timothy C Lee

Publications and source records attributed to Timothy C Lee.

At least 19 recordsLinked to original sources

Risk stratification of adult patients undergoing orthotopic liver transplantation for fulminant hepatic failure.

BACKGROUND: Orthotopic liver transplantation (OLT) is an effective treatment for fulminant hepatic failure (FHF), but postOLT mortality is higher for patients with FHF than for patients with other indications for OLT. In the current study, a large cohort of patients who underwent OLT for FHF was evaluated to develop and validate a system useful for estimating postOLT patient survival. METHODS: The 1,457 patients who underwent OLT for FHF in the United States between 1988 and 2003 were enrolled through the UNOS database. This group was divided into a modeling group (n=972) and a crossvalidation group (n=486). With a multivariate regression analysis, the modeling group was used to identify clinical parameters that had a significant association with postOLT survival. This regression analysis was used to create a scoring system that was subsequently assessed in the crossvalidation group. RESULTS: Four risk factors were identified with the multivariate analysis: 1) body mass index > or = 30 kg/m2; 2) serum creatinine > 2.0 mg/dL; 3) recipient age > 50 years old; and 4) history of life support. By assigning points based on the number of risk factors present, the scoring system was able to differentiate between low-risk patients (5-year survival, 81%) and high-risk patients (5-year survival, 42%). The relative risk of postOLT mortality increased by approximately 150% for each additional point. CONCLUSION: The scoring system risk-stratified the crossvalidation group and accurately predicted postOLT survival. A scoring system utilizing clinical and demographic information readily available prior to OLT may help predict the probability of survival after OLT for FHF.

Adult↗

The pediatric end-stage liver disease (PELD) model as a predictor of survival benefit and posttransplant survival in pediatric liver transplant recipients.

The pediatric end-stage liver disease (PELD) model accurately estimates 90-day waitlist mortality for pediatric liver transplant candidates, but it has been unclear if PELD can identify patients who will derive survival benefit from undergoing liver transplantation (LT), if it correlates with posttransplant survival, or if it can identify patients for whom LT would be futile. Pediatric patients who underwent LT between 2001 and 2004 were enrolled through the United Network for Organ Sharing Organ Procurement and Transplant Network database. Survival benefit was measured in terms of life-years gained during the first year after LT. Complete data were available for 1,247 patients: 53% were listed as Status 1 at the time of orthotopic liver transplantation (OLT), while the remaining 47% had PELD scores. Only in patients with a PELD of 17+ or those designated as United Network for Organ Sharing Status 1 derived a survival benefit within 1 year of LT; patients with a PELD score of < or = 16 did not. In addition, a statistically significant association was seen between 1-year post-OLT survival and PELD at LT (P = 0.03). No "threshold" PELD score, beyond which risk of post-LT mortality increased dramatically, was apparent. In conclusion, pediatric patients with a PELD score of 17+ derive survival benefit early after LT, and increasing PELD scores are associated with increasing transplant benefit after liver transplantation. PELD does correlate with posttransplant survival but should not be used as a marker for futility.

Algorithms↗

The natural history of hepatitis C virus in pediatric liver transplant recipients.

Although rare in the pediatric population, the natural history of hepatitis C virus (HCV) recurrence in pediatric patients undergoing orthotopic liver transplantation (OLT) for end-stage liver disease secondary to HCV has not been well described. We performed an analysis of all 67 pediatric patients (< 17 years old) who have undergone OLT for HCV in the United States between 1/1988 and 6/2005. The 67 pediatric patients received a total of 83 OLTs for HCV. Following initial OLTs performed for HCV, the patient and allograft survival rates were 71.6% and 55.0%, respectively, at 5 years. Following retransplantation these rates decreased to 55.0% and 33.8%, respectively, following retransplantation. Recipients were listed for retransplantation after 31.3% of all OLTs, and overall recipients were retransplanted after 19.3% of OLTs. The overwhelming majority of retransplants were performed for HCV recurrence. A mean of 1.2 OLTs were performed per patient for HCV. The median time between OLTs for HCV was 290 days. In conclusion, the risk of HCV recurrence in pediatric OLT recipients is high and is associated with a high rate of retransplantation. Still, OLT represents the only treatment option that may achieve long-term survival in pediatric patients with end-stage liver disease secondary to HCV that is recalcitrant to medical management.

Adolescent↗

The effect of whole organ pancreas transplantation and PIT on diabetic complications.

Diabetes mellitus is a leading cause of morbidity and mortality in the Western world. Currently, the only forms of beta-cell replacement are whole organ pancreas transplantation and pancreatic islet transplantation. Whole organ transplantation has demonstrated benefits in prevention and reversal of diabetic complications with sustainable long-term outcomes. Pancreatic islet transplantation continues to be a field that needs further study to ascertain the true benefit of islet transplantation for diabetic complications. This can only be achieved with improvement in long-term islet allograft survival.

Diabetes Complications↗

Resolution of medically resistant hypothyroidism after liver transplantation for hepatic hemangioendothelioma.

Hepatic hemangioendothelioma (HHE) is a rare vascular tumor in neonates and may cause high-output cardiac failure and coagulopathy, and rarely has been associated with hypothyroidism. Hepatic hemangioendothelioma treatment options consist of corticosteroids, alpha-interferon, surgical resection, and liver transplantation. Herein, we report the case of a 6-week-old female neonate that presented with an HHE that involved all segments of the liver, resulting in respiratory failure and severe hypothyroidism that was recalcitrant to exogenous L-thyroxine therapy. After failure of medical and supportive therapy for the HHE, the patient underwent a cadaveric orthotopic liver transplantation that resulted in successful treatment of the severe hypothyroidism, respiratory failure, and cardiac symptoms. The patient is currently 1-year posttransplantation and disease free with normal thyroid function.

Female↗

Hepatitis C viral recurrence in a pediatric patient following liver transplantation.

Hepatitis C virus (HCV) infections are known to have a more benign course in children than in adults. Although the natural history of HCV recurrence after liver transplantation has been well studied in adult patients, much less is known about HCV recurrence after liver transplantation in pediatric patients. Herein, we report a case of a pediatric patient with HCV presumably acquired through vertical transmission. She underwent liver transplantation at 14 yr of age. The first three yr after liver transplantation were uneventful. However, in the past 12 months she has been hospitalized twice after developing ascites, hematemesis and esophagogastroduodenoscopy (EGD)-documented esophageal varices. Post-transplant biopsy has demonstrated chronic inflammation complicated with active hepatitis C and stage 2-3 scarring. This case report demonstrates the need for further epidemiologic studies to study the natural history of the rate of HCV recurrence after liver transplantation in the pediatric population.

Adolescent↗

Combined lung and liver transplantation: the United States experience.

BACKGROUND: Combined transplantation of the lungs and liver is indicated for patients who would not be expected to survive transplantation of either organ alone. No single center has accumulated a significant experience, and as a result the expectations for this operation in the current era are unknown. METHODS: Patients that have undergone combined lung-liver transplantation in the United States were enrolled through the United Network for Organ Sharing Organ Procurement and Transplantation Network database. In addition, the English-language literature was searched for additional cases of combined lung-liver transplantation. RESULTS: Eleven patients have undergone combined lung and liver transplantation in the United States at different centers. The 1- and 5-year patient survival rates are of 79% and 63%, respectively, and no patient has required retransplantation. These patient survival rates are equivalent to similar a combined lung-liver case series from the United Kingdom (P=0.37, log-rank test) and isolated orthotopic liver transplantation in the United States (P=0.59, log-rank test), and are comparable to patient survival rates following isolated lung transplantation in the United States. CONCLUSIONS: Patient survival of combined lung-liver transplantation is comparable to that of isolated liver and isolated bilateral lung transplantation. This option should be considered for patients with end-stage lung disease and liver disease when transplantation of a single organ transplantation is precluded by severe disease in the other organ system.

Adolescent↗

Health-related quality of life after pancreatic islet transplantation: a longitudinal study.

BACKGROUND: Pancreatic islet transplantation (PIT) has proven effective in achieving insulin independence, but to date, the impact of PIT on health-related quality of life (HRQL) has not been studied. METHODS: Ten patients who have undergone PIT at our institution were administered three HRQL questionnaires: the Hypoglycemia Fear Survey, the 36-Item Short Form Health Survey (SF-36), and a fatigue questionnaire. HRQL was assessed before PIT, then 3, 6, and 12 months after PIT. Responses were compared by analysis of variance and paired Student's t tests. RESULTS: Hypoglycemia Fear Survey responses demonstrated that hypoglycemia-related anxiety and hypoglycemia-related behavior modification occurred less frequently after PIT (P=0.003 and 0.0001, respectively). The total scores of the hypoglycemia questionnaire were also significantly improved after PIT, from a median score of 156 points before transplantation to 55 points 3 months after PIT (P=0.004), 38 points 6 months after PIT (P=0.001), and 69 points 12 months after PIT (P=0.04). The median scores of all SF-36 components also improved after PIT. No significant changes were seen in the fatigue symptoms as assessed by the fatigue questionnaire. CONCLUSION: PIT recipients have less anxiety about the symptoms and consequences of hypoglycemia. PIT recipients also indicate that their behavior requires significantly less modification to prevent or treat hypoglycemia after PIT compared with before PIT. Further investigation is needed to determine whether PIT improves generic measures of HRQL.

Anxiety↗

Liver transplantation for severe hepatic graft-versus-host disease: an analysis of aggregate survival data.

Graft-versus-host disease (GVHD) often occurs after bone marrow transplantation (BMT). GVHD may lead to cirrhosis or complete destruction of the bile ducts, and few effective treatment options exist for such cases. Orthotopic liver transplantation (OLT) has been described as an option, but to date the patient survival, graft survival, and GVHD recurrence rates after OLT have been unknown. Cases of OLT for GVHD were accumulated from several sources: (1) cases of OLT performed at a single institution, (2) the English-language medical literature, and (3) the United Network for Organ Sharing (UNOS) liver transplant registry. Descriptive data were derived from pre- and post-OLT information; survival analysis was performed using the Kaplan-Meier method. One case of OLT for GVHD after BMT was found at our institution, and another 6 cases were previously reported in the literature. Extrahepatic GVHD recurred in 2 cases, but no recurrence of hepatic GVHD was reported. The UNOS registry contained an additional 73 patients who underwent OLT for hepatic GVHD. The 1- and 5-year actuarial patient survival rates were 72.4% and 62.9%, respectively. Although 4 patients required retransplantation, no deaths or retransplants were attributed to the recurrence of hepatic GVHD. OLT is an effective treatment for hepatic GVHD after BMT or non-liver organ transplant. Long-term disease-free survival is obtainable in these cases, and recurrence of hepatic GVHD has not been reported. These findings suggest that OLT should be considered as an effective treatment option for cases of hepatic GVHD recalcitrant to medical treatment.

Adolescent↗

Orthotopic liver transplantation for biliary atresia: the U.S. experience.

Biliary atresia is the most common indication for orthotopic liver transplantation (OLT) in the pediatric population. The outcomes of liver transplantation for biliary atresia, however, have not been formally examined on a national scale. The objective of this study was to identify pretransplant variables that predict patient survival after primary liver transplantation for biliary atresia. A cohort of 1,976 pediatric patients undergoing primary liver transplantation for biliary atresia between 1/1988 to 12/2003 was enrolled from the United Network for Organ Sharing database after excluding patients with a history of multiorgan transplant or previous liver transplant. Follow-up data up to 16 years post-OLT was available. The 5- and 10-year actuarial survival rates of patients that underwent liver transplantation for biliary atresia in the United States are 87.2% and 85.8%, respectively, and the 5- and 10-year graft actuarial survival rates are 76.2% and 72.7%, respectively. Early deaths (< or =90 days post-OLT) were more often caused by graft failure (P = 0.01), whereas late deaths (>90 days post-OLT) were more often due to malignancy (P < 0.01). An analysis of outcomes over time demonstrated a decrease in post-OLT survival and an increase in the number of OLTs done for biliary atresia at an increasing number of centers. A multivariate analysis revealed that cadaveric partial/reduced liver grafts, a history of life support at the time of OLT, and decreased age were independent predictors of increased post-OLT mortality. In conclusion, OLT is an effective treatment for biliary atresia. Certain pretransplant variables may help predict patient survival following liver transplantation for biliary atresia.

Age Distribution↗

Transaminitis after pancreatic islet transplantation.

BACKGROUND: An asymptomatic, self-limited transaminitis uniformly follows pancreatic islet transplantation (PIT) performed through portal vein (PV) infusion. The underlying cause and significance of this transaminitis is unclear. STUDY DESIGN: Records of all patients with insulin-dependent diabetes mellitus who had undergone PIT at our institution were reviewed. All PITs were performed in conjunction with a remote pancreatic islet isolation center and done through percutaneous transhepatic PV infusion. Alanine aminotransferase (ALT) levels, serum glucose concentrations, insulin requirements, and color-flow Doppler ultrasonography examinations of the right upper quadrant were assessed before and after PIT. RESULTS: Eleven patients have undergone a total of 26 PITs. An elevated ALT level occurred in all 11 patients (100%) after the first PIT, with the median post-PIT peak ALT level reaching 187 IU/L. Transaminitis was less frequent and less marked after the second PIT. A negative correlation between viability of the pancreatic islets transplanted (r = -0.44, p = 0.03) and a positive correlation between the ratio of maximum to initial PV pressure (r = 0.41, p = 0.04) were seen with the subsequent ALT peak. Color-flow Doppler ultrasonography examinations showed no occurrences of PV thrombosis or intrahepatic hematoma. Finally, the degree of transaminitis did not correlate with post-PIT insulin requirements, indicating that post-PIT transaminitis cannot be used to measure allograft rejection or function. CONCLUSIONS: Transaminitis after PIT is common and self-limited. Post-PIT transaminitis does not signal acute rejection or serious procedure-related complications such as PV thrombosis or intrahepatic hematoma.

Adult↗

Conservative surgical treatment of a profoundly immunosuppressed pediatric patient with Boerhaave syndrome.

Boerhaave syndrome is a condition described as spontaneous rupture of the esophagus that often results in mediastinitis, sepsis, and death. The authors report a case of Boerhaave syndrome in a child with acute lymphoblastic leukemia. At the time of diagnosis (10 days after rupture), the patient had an absolute neutrophil count of 0 and was treated with T-tube drainage of the perforation. The T-tube was removed 2 months after the operation. The patient has required three endoscopic esophageal dilatations of a mild esophageal stricture. He remains in remission from his leukemia, has normal growth and development, and is on a regular diet.

Esophageal Diseases↗

Split-liver transplantation using the left lateral segment: a collaborative sharing experience between two distant centers.

Split-liver transplantation (SLT) increases the pool of organs for pediatric orthotopic liver transplantation (pOLT). With increased collaboration and organ sharing, transplant centers can fully maximize the use of all split donor allografts. Herein, we report the collaborative results between two distant centers involved in a sharing alliance. The current study consists of a retrospective review of 56 pediatric LLS transplants performed at two collaborating centers between 9/1997 and 10/2003. Fifty-three patients (41% Status 1) were transplanted using 56 left lateral segment (LLS) grafts. Sixteen percent of LLS grafts were shared between the two institutions. Overall patient survival at both 1 and 3 years was 90% and 90%, respectively. Overall graft survival at both 1 and 3 years was 82% and 82%, respectively. Shared patient and graft survival was 89% and 89%, respectively. There was an 11% biliary complication and 18% vascular complication rate. Five patients required retransplantation. In conclusion, SLT increases the number of available allografts for pOLT. While SLT is technically demanding, with a significant learning curve, patient and graft survival rates compare favorably with United Network Organ Sharing (UNOS) averages. Sharing of grafts between centers is a safe and effective way to maximize organ usage and should be actively pursued through collaborative networks.

Adolescent↗

Adult liver transplant candidate attitudes toward graft sharing are not obstacles to split liver transplantation.

Split liver transplantation (SLT) benefits society by increasing the total number of transplants that can be performed, but it is yet unknown if a decreased post-transplant survival (in comparison to whole liver transplantation) would make participation in SLT less appealing to adult liver transplant candidates. A 20-item questionnaire was administered to 50 adult candidates to assess attitudes toward SLT and organ sharing. The overall attitudes of 60% of participants were classified as utilitarian (maximizing benefit to greatest number of candidates), while 26% were classified as self-preserving (maximizing individual benefit) and 14% were undecided. Ninety percent of participants would be willing to share even if expected survival was less than that of whole liver transplantation, and 69% felt that pediatric candidates should have priority over adult candidates. In conclusion, attitudes toward graft sharing and the possibility of compromised survival benefit are not barriers to SLT for most adult liver transplant candidates.

Adult↗

Quantitative EBV viral loads and immunosuppression alterations can decrease PTLD incidence in pediatric liver transplant recipients.

Epstein-Barr virus (EBV) is a common viral infection in pediatric liver transplant patients and can lead to development of post-transplant lymphoproliferative disorder (PTLD). Differing studies have used immunosuppression reduction, antiviral medications or i.v. CMV-immunogloublin for EBV prevention and treatment. The purpose of this study was to determine whether implementation of a protocol for frequent EBV monitoring and EBV viral load-driven immunosuppression reduction could decrease the incidence of PTLD in our patient population. All data were prospectively collected between 2001 and 2004 at a single institution. Seventy-three patients were entered into the study. Patients were divided into a historical control group (pre-2001, 30 patients) and a treatment group (post-2001, 43 patients). Approximately 1271 blood samples of 73 patients were collected between 2001 and 2004. Eleven out of 43 patients received immunosuppression tapering due to high EBV viral loads (>4000 copies/microg DNA). One patient developed allograft rejection after immunosuppression modulation. Prior to 2001, the incidence of PTLD at our institution was 16%. After instituting a protocol for EBV monitoring, the incidence of PTLD decreased to 2% (p-value<0.05). These findings illustrate that frequent EBV viral load monitoring and preemptive immunosuppression modulation have an integral role in preventing PTLD in the pediatric liver transplant population.

Adolescent↗

Procurement of the human pancreas for pancreatic islet transplantation.

BACKGROUND: The full potential of pancreatic islet transplantation (PIT) has not been realized because of the difficulties associated with islet isolation, particularly when associated with a remote islet isolation center. Herein, we describe the principles of pancreatic procurement for PIT, which have allowed us to achieve a successful pancreatic islet isolation rate 67% of the time when using a remote islet isolation center. METHODS: Between January 16, 2002 and June 30, 2003, 39 pancreata were procured and processed for PIT at a distant islet isolation center. All pancreata were procured by a single surgeon, and special attention was given to careful dissection of the pancreas, maintenance of arterial inflow and the pressure differential between arterial and venous systems during perfusion, rapid organ cooling, and rapid removal of the pancreas from the body. RESULTS: Twenty-six of 39 (67%) procured pancreata yielded more tha 5,000 islet equivalents (IEQ)/kg recipient weight and were transplanted. Median IEQs per isolation was 413,867, whereas median purity and viability were 65% and 100%, respectively. The median time for pancreatic excision was 34 minutes, whereas cold ischemia time was 6 hours and 40 minutes. DISCUSSION: The principles we have adopted for pancreatic procurement for PIT have resulted in a 67% islet isolation success rate despite the maintenance of more than 5,000 IEQ/kg and the use of a remote islet isolation center.

Adolescent↗

Use of a predictive equation for diagnosis of acute gangrenous cholecystitis.

BACKGROUND: Factors previously identified by multivariate logistic regression that were predictive for gangrenous cholecystitis (GC) were used to develop a predictive equation. Our objective was to evaluate the sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values of this equation for detecting GC in patients with acute cholecystitis (AC). METHODS: Medical records of patients who presented to a tertiary care hospital with AC were reviewed. Twenty-one patient and clinical variables were recorded. We prospectively tested the results of the following equation against pathologic diagnosis: P=e((0.7116+0.9944.DM+1.7157.WBC-1.0319.ALT.2.0518.ALP+2.7078.PCF))/(1+e([-0.7116+0.9944.DM+1.7157.WBC-1.0319.ALT-2.0518.ALP+2.7078.PCF])), where P = predicted value; DM = diabetes mellitus; WBC = white blood cell count; ALT = alanine aminotransferase; AST = aspartate aminotransferase; and PCF = pericholecystic fluid. RESULTS: Ninety-eight patients presented with AC and 18% had GC (18 of 98). Using a cutoff of P = 0.724, our equation had a specificity of 93%, sensitivity of 83%, PPV of 71%, and NPV of 96%, P <0.001 for the detection of GC. CONCLUSIONS: Our study demonstrates the equation may be useful in detecting the subset of AC patients who have GC.

Adult↗