The Epidemiology of Biliary Atresia: Exploring the Role of Developmental Factors on Birth Prevalence.

OBJECTIVE: To identify key epidemiologic factors relevant to fetal development that are associated with biliary atresia. STUDY DESIGN: This population-based registry study examined infants born in Texas between 1999 and 2014. Epidemiologic data relevant to fetal development were compared between cases of biliary atresia identified in the Texas Birth Defects Registry (n = 305) vs all live births (n = 4 689 920), and Poisson regression was used to calculate prevalence ratios (PRs) and 95% CIs. RESULTS: The prevalence of biliary atresia over the study period was 0.65 per 10 000 live births. Biliary atresia was positively associated with female sex (adjusted PR, 1.68; 95% CI, 1.33-2.12), delivery before 32-37 weeks of gestation (adjusted PR, 1.64; 95% CI, 1.18-2.29), delivery before 32 weeks of gestation (adjusted PR, 3.85; 95% CI, 2.38-6.22), and non-Hispanic Black vs non-Hispanic White maternal race/ethnicity (adjusted PR, 1.54, 95% CI, 1.06-2.24), while biliary atresia was inversely associated with season of conception in the fall relative to spring (adjusted PR, 0.62; 95% CI, 0.45-0.86). In addition, biliary atresia was associated with maternal diabetes (adjusted PR, 2.34; 95% CI, 1.57-3.48), with a stronger association with pregestational diabetes compared with gestational diabetes. In subgroup analyses, these associations were present in isolated biliary atresia cases that do not have any additional birth defects. CONCLUSIONS: Biliary atresia is associated with multiple factors related to fetal development, including pregestational maternal diabetes, female sex, and preterm birth. These associations also were observed in isolated cases of biliary atresia without other malformations or laterality defects. Our results are consistent with early life events influencing the pathogenesis of biliary atresia, and support further studies investigating in utero events to better understand etiology and time of onset.

Characteristics of catheter-related bloodstream infections in children with intestinal failure: implications for clinical management.

Catheter-related bloodstream infection is a major cause of mortality and morbidity in the intestinal-failure population. This study reports characteristics of CRBSI with implications for clinical management in parenteral nutrition-dependent children with intestinal failure. The researchers report the rate of central catheter infections, and the causative organisms, as well as identify risk factors in our intestinal-failure patients that would be amenable to preventive measures.The study is a retrospective review of the medical records of 101 patients with intestinal failure (IF), seen in the Intestinal Rehabilitation Clinic at Children's Medical Center of Dallas from May 2005 to March 2007. Catheter-related bloodstream infections (CRBSIs) were categorized as nosocomial or community-acquired. Data collected for each episode include microorganisms isolated from blood and potential risk factors. Z test was done to compare the infection rates.There were 92 episodes of CRBSIs in 45 parenteral nutrition (PN)-dependent patients with central venous catheters (CVC) in place for a total of 13,978 days. Eighty-three percent (n = 76) of CRBSIs developed in the community at a rate of 7.0 per 1,000 days. Seventeen percent (n = 16) nosocomial CRBSIs were observed at a rate of 5.5 per 1,000 catheter days. CRBSI rate was not statistically different between the two groups (7.0 vs. 5.5, p = .378).CRBSI in the intestinal-failure population is due to a wide variety of organisms with numerous risk factors. Education of CVC management with the practice of consistent guidelines may reduce CRBSI incidence, thus reducing the morbidity and mortality in the intestinal-failure patients.

Transplantation of the abdominal wall.

BACKGROUND: Closure of the abdomen in patients undergoing intestinal transplantation can be extremely difficult, if not impossible. We describe our initial experience with abdominal wall allotransplantation to facilitate abdominal closure. METHODS: We undertook nine cadaveric abdominal wall composite allograft transplants in eight patients. The graft's blood supply was based on the inferior epigastric vessels left in continuity with the donor femoral and iliac vessels. Skin biopsies were undertaken randomly and when rejection was suspected. Vessel patency was monitored by doppler ultrasound. FINDINGS: Six patients have survived, five of whom have intact, viable abdominal wall grafts. Two patients have had a clinically mild episode of acute rejection of the skin of the abdominal wall that resolved with corticosteroid therapy. No clinically apparent graft-versus-host disease has been noted. INTERPRETATION: Transplantation of an abdominal wall composite allograft can facilitate reconstruction and closure of the abdominal compartment in intestinal transplant recipients with complex abdominal wall defects.

Successful treatment of posttransplant lymphoproliferative disease with prolonged rituximab treatment in intestinal transplant recipients.

BACKGROUND: Posttransplant Epstein-Barr virus-associated B-cell lymphoproliferative disease (PTLD) has a higher incidence after intestinal transplantation than after transplantation of other solid organs and is associated with a high mortality. A new anti-CD20 monoclonal antibody, rituximab, has shown efficiency in the treatment of B-cell lymphoma, including PTLD, but its use has not yet been reported in intestinal transplant recipients. METHODS: We retrospectively reviewed five patients who were diagnosed with PTLD from March 1999 to August 2001, after intestinal transplantation. These patients were primarily managed with rituximab, associated with reduction or interruption of immunosuppression and antiviral therapy with ganciclovir and cytomegalovirus immune globulin. Rituximab was administered at weekly doses of 375 mg/m until full remission was ascertained, and the interval between doses was then increased. No patient received chemotherapy. RESULTS: One patient had nonmalignant lymphoproliferation, and four had malignant PTLD, as assessed by histopathology and monoclonality of the tumor. Two pediatric patients had severe generalized disease. All patients had received OKT3 as treatment of rejection before developing PTLD. All tumors showed proliferation of CD20 cells and were positive for Epstein-Barr virus by in situ hybridization. All patients responded to rituximab therapy and have achieved full remission with a follow-up of 3 to 30 (median, 8) months. CONCLUSION: Prolonged rituximab treatment, in association with reduction of immunosuppression and antiviral therapy, is highly efficient as part of the first-line treatment of CD20 B-cell PTLD after intestinal transplantation.

Portal versus systemic drainage of small bowel allografts: comparative assessment of survival, function, rejection, and bacterial translocation.

BACKGROUND: Portal venous drainage of small bowel grafts is theoretically more physiologic than systemic drainage, but is technically more demanding. Comparisons in animal models have not demonstrated a clear advantage of one technique over the other, but clinical data are lacking. STUDY DESIGN: Clinical records of 36 patients who underwent 37 small bowel transplantation procedures from January 1995 to August 2001 were reviewed. Portal drainage was performed in 19 patients (PD group). Systemic drainage was performed in 18 patients (SD group). Median followup was 531 days. RESULTS: PD and SD patients had similar ICU stays (median 7 versus 9 days) and endotracheal intubation durations (median 3 versus 5 days). All current survivors, with the exception of one patient in each group, are independent from parenteral nutrition. Liver function tests were similar in both groups. There was a twofold increase in tacrolimus dosage in the PD group to achieve similar trough levels indicating a "first-pass" hepatic clearance effect. Cumulative incidence of acute rejection episodes and OKT3-requiring rejection episodes were similar in both groups. To the contrary, a lower incidence of gram-negative rods of Enterococcus sp. in blood or bronchoalveolar lavage suggested that the clearance of translocated intestinal bacteria was more efficient in the PD group. Graft and patient survival rates were similar in both groups. CONCLUSIONS: Systemic venous drainage of small bowel transplants is a dependable technique, associated with similar results as portal venous drainage, in terms of overall mortality, morbidity, rejection, function, and patient and graft survival. But attention should be paid to an impaired clearance of intestinal bacterial translocation after systemic drainage.

Current status of small bowel transplantation in children: update 2003.

This article reviews the current indications for intestinal transplantation and advances in immunosuppression and postoperative care, which help to improve the outcome results of intestinal transplantation. Major current controversies and future trends are discussed briefly.