Long-term teduglutide associated with improved response in pediatric short bowel syndrome-associated intestinal failure.

OBJECTIVES: Patients with short bowel syndrome-associated intestinal failure (SBS-IF) require long-term parenteral nutrition and/or intravenous fluids (PN/IV) to maintain fluid or nutritional balance. We report the long-term safety, efficacy, and predictors of response in pediatric patients with SBS-IF receiving teduglutide over 96 weeks. METHODS: This was a pooled, post hoc analysis of two open-label, long-term extension (LTE) studies (NCT02949362 and NCT02954458) in children with SBS-IF. Endpoints included treatment-emergent adverse events (TEAEs) and clinical response (≥20% reduction in PN/IV volume from baseline). A multivariable linear regression identified predictors of teduglutide response; the dependent variable was mean change in PN/IV volume at each visit over 96 weeks. RESULTS: Overall, 85 patients were analyzed; 78 patients received teduglutide in the parent and/or LTE studies (any teduglutide [TED] group), while seven patients did not receive teduglutide in either the parent or LTE studies. Most TEAEs were moderate or severe in intensity in both groups. By week 96, 82.1% of patients from the any TED group achieved a clinical response, with a mean fluid decrease of 30.1 mL/kg/day and an energy decrease of 21.6 kcal/kg/day. Colon-in-continuity, non-White race, older age at baseline, longer duration of teduglutide exposure, and increasing length of remaining small intestine were significantly associated with a reduction in mean PN/IV volume requirements. CONCLUSIONS: In pediatric patients with SBS-IF, teduglutide treatment resulted in long-term reductions in PN/IV requirements. The degree of PN/IV volume reduction depended on the duration of teduglutide exposure, underlying bowel anatomy, and demographics.

The pediatric solid organ transplant experience with COVID-19: An initial multi-center, multi-organ case series.

The clinical course of COVID-19 in pediatric solid organ transplant recipients remains ambiguous. Though preliminary experiences with adult transplant recipients have been published, literature centered on the pediatric population is limited. We herein report a multi-center, multi-organ cohort analysis of COVID-19-positive transplant recipients ≤ 18 years at time of transplant. Data were collected via institutions' respective electronic medical record systems. Local review boards approved this cross-institutional study. Among 5 transplant centers, 26 patients (62% male) were reviewed with a median age of 8 years. Six were heart recipients, 8 kidney, 10 liver, and 2 lung. Presenting symptoms included cough (n = 12 (46%)), fever (n = 9 (35%)), dry/sore throat (n = 3 (12%)), rhinorrhea (n = 3 (12%)), anosmia (n = 2 (8%)), chest pain (n = 2 (8%)), diarrhea (n = 2 (8%)), dyspnea (n = 1 (4%)), and headache (n = 1 (4%)). Six patients (23%) were asymptomatic. No patient required supplemental oxygen, intubation, or ECMO. Eight patients (31%) were hospitalized at time of diagnosis, 3 of whom were already admitted for unrelated problems. Post-transplant immunosuppression was reduced for only 2 patients (8%). All symptomatic patients recovered within 7 days. Our multi-institutional experience suggests the prognoses of pediatric transplant recipients infected with COVID-19 may mirror those of immunocompetent children, with infrequent hospitalization and minimal treatment, if any, required.

Outcomes from a 12-Week, Open-Label, Multicenter Clinical Trial of Teduglutide in Pediatric Short Bowel Syndrome.

OBJECTIVE: To determine safety and pharmacodynamics/efficacy of teduglutide in children with intestinal failure associated with short bowel syndrome (SBS-IF). STUDY DESIGN: This 12-week, open-label study enrolled patients aged 1-17 years with SBS-IF who required parenteral nutrition (PN) and showed minimal or no advance in enteral nutrition (EN) feeds. Patients enrolled sequentially into 3 teduglutide cohorts (0.0125 mg/kg/d [n = 8], 0.025 mg/kg/d [n = 14], 0.05 mg/kg/d [n = 15]) or received standard of care (SOC, n = 5). Descriptive summary statistics were used. RESULTS: All patients experienced ≥1 treatment-emergent adverse event; most were mild or moderate. No serious teduglutide-related treatment-emergent adverse events occurred. Between baseline and week 12, prescribed PN volume and calories (kcal/kg/d) changed by a median of -41% and -45%, respectively, with 0.025 mg/kg/d teduglutide and by -25% and -52% with 0.05 mg/kg/d teduglutide. In contrast, PN volume and calories changed by 0% and -6%, respectively, with 0.0125 mg/kg/d teduglutide and by 0% and -1% with SOC. Per patient diary data, EN volume increased by a median of 22%, 32%, and 40% in the 0.0125, 0.025, and 0.05 mg/kg/d cohorts, respectively, and by 11% with SOC. Four patients achieved independence from PN, 3 in the 0.05 mg/kg/d cohort and 1 in the 0.025 mg/kg/d cohort. Study limitations included its short-term, open-label design, and small sample size. CONCLUSIONS: Teduglutide was well tolerated in pediatric patients with SBS-IF. Teduglutide 0.025 or 0.05 mg/kg/d was associated with trends toward reductions in PN requirements and advancements in EN feeding in children with SBS-IF. TRIAL REGISTRATION: ClinicalTrials.gov:NCT01952080; EudraCT: 2013-004588-30.

Predictors of Enteral Autonomy in Children with Intestinal Failure: A Multicenter Cohort Study.

OBJECTIVES: In a large cohort of children with intestinal failure (IF), we sought to determine the cumulative incidence of achieving enteral autonomy and identify patient and institutional characteristics associated with enteral autonomy. STUDY DESIGN: A multicenter, retrospective cohort analysis from the Pediatric Intestinal Failure Consortium was performed. IF was defined as severe congenital or acquired gastrointestinal diseases during infancy with dependence on parenteral nutrition (PN) >60 days. Enteral autonomy was defined as PN discontinuation >3 months. RESULTS: A total of 272 infants were followed for a median (IQR) of 33.5 (16.2-51.5) months. Enteral autonomy was achieved in 118 (43%); 36 (13%) remained PN dependent and 118 (43%) patients died or underwent transplantation. Multivariable analysis identified necrotizing enterocolitis (NEC; OR 2.42, 95% CI 1.33-4.47), care at an IF site without an associated intestinal transplantation program (OR 2.73, 95% CI 1.56-4.78), and an intact ileocecal valve (OR 2.80, 95% CI 1.63-4.83) as independent risk factors for enteral autonomy. A second model (n = 144) that included only patients with intraoperatively measured residual small bowel length found NEC (OR 3.44, 95% CI 1.36-8.71), care at a nonintestinal transplantation center (OR 6.56, 95% CI 2.53-16.98), and residual small bowel length (OR 1.04 cm, 95% CI 1.02-1.06 cm) to be independently associated with enteral autonomy. CONCLUSIONS: A substantial proportion of infants with IF can achieve enteral autonomy. Underlying NEC, preserved ileocecal valve, and longer bowel length are associated with achieving enteral autonomy. It is likely that variations in institutional practices and referral patterns also affect outcomes in children with IF.

High rates of resolution of cholestasis in parenteral nutrition-associated liver disease with fish oil-based lipid emulsion monotherapy.

OBJECTIVE: To determine factors leading to resolution of cholestasis in patients with parenteral nutrition-associated liver disease treated with fish oil-based lipid emulsion (FOLE). STUDY DESIGN: Prospective observational study of 57 infants <6 months of age with parenteral nutrition-associated liver disease who received parenteral FOLE as monotherapy. RESULTS: Median gestational age of subjects at birth was 28 weeks (range 22.7-39.5). Median conjugated bilirubin level at initiation of therapy with FOLE was 7.5 mg/dL (range 2.1-25). Resolution of hyperbilirubinemia (conjugated bilirubin <2.0 mg/dL) and survival to hospital discharge occurred in 47 (82.5%) infants. Median number of days to resolution of cholestasis was 35 (range 7-129). Ten infants (17.5%) died. Non-survivors showed a trend towards being more premature than survivors at birth (25.9 vs 29.1 weeks, P = .056). Infants with higher conjugated bilirubin at initiation of therapy (>10.0 compared with <5.0 mg/dL) had longer times to resolution (98 vs 56 days, P < .005). Time to resolution correlated inversely with gestational age at birth (r(2) = 0.14, P = .02) and directly with time to receive 100% calories enterally (r(2) = 0.12, P = .03). CONCLUSIONS: Younger gestational age infants demonstrated higher degree of cholestasis, longer time to resolution of cholestasis, and increased mortality. Higher levels of cholestasis were associated with longer time to resolution. FOLE monotherapy led to resolution of cholestasis in all surviving infants.

Congenital hepatic cyst with antenatal diagnosis: a case report and literature review.

Congenital hepatic cysts are rare lesions of infancy. While operative management and outcomes have been extensively studied in adult patients with hepatic cysts, data in pediatric patients are limited. We discuss our experience in an infant and review relevant literature regarding operative technique and surgical outcomes.

Natural history of pediatric intestinal failure: initial report from the Pediatric Intestinal Failure Consortium.

OBJECTIVE: To characterize the natural history of intestinal failure (IF) among 14 pediatric centers during the intestinal transplantation era. STUDY DESIGN: The Pediatric Intestinal Failure Consortium performed a retrospective analysis of clinical and outcome data for a multicenter cohort of infants with IF. Entry criteria included infants <12 months receiving parenteral nutrition (PN) for >60 continuous days. Enteral autonomy was defined as discontinuation of PN for >3 consecutive months. Values are presented as median (25th, 75th percentiles) or as number (%). RESULTS: 272 infants with a gestational age of 34 weeks (30, 36) and birth weight of 2.1 kg (1.2, 2.7) were followed for 25.7 months (11.2, 40.9). Residual small bowel length in 144 patients was 41 cm (25.0, 65.5). Diagnoses were necrotizing enterocolitis (71, 26%), gastroschisis (44, 16%), atresia (27, 10%), volvulus (24, 9%), combinations of these diagnoses (46, 17%), aganglionosis (11, 4%), and other single or multiple diagnoses (48, 18%). Prescribed medications included oral antibiotics (207, 76%), H2 blockers (187, 69%), and proton pump inhibitors (156, 57%). Enteral feeding approaches varied among centers; 19% of the cohort received human milk. The cohort experienced 8.9 new catheter-related blood stream infections per 1000 catheter days. The cumulative incidences for enteral autonomy, death, and intestinal transplantation were 47%, 27%, and 26%, respectively. Enteral autonomy continued into the fifth year after study entry. CONCLUSIONS: Children with IF endure significant mortality and morbidity. Enteral autonomy may require years to achieve. Improved medical, nutritional, and surgical management may reduce time on PN, mortality, and need for transplantation.

Medical update and potential advances in the treatment of pediatric intestinal failure.

Short bowel syndrome (SBS) and intestinal failure are chronic malabsorption disorders with considerable nutritional and growth consequences in children. Intestinal failure occurs when the functional gastrointestinal mass is reduced even if there is normal anatomical gastrointestinal length. A number of management strategies are often utilized to achieve successful intestinal rehabilitation and maintain adequate nutrition to avoid intestinal transplant. These strategies include minimizing the effect of parenteral associated liver disease, limiting catheter complications, and treating bacterial overgrowth in the remaining small intestine. In addition, there continues to be significant research interest in enhancing intestinal adaptation with targeted therapies. The purpose of this review is to discuss current perspectives and to highlight recent medical advances in novel investigational therapies.

Residents-as-teachers: implementing a toolkit in morning report to redefine resident roles.

BACKGROUND: Morning report was initially created to meet service needs. PURPOSE: The objective was to improve morning report through a toolkit combining principles of learning theory with resident teaching. METHODS: The toolkit consists of three parts: a guideline describing expectations, a worksheet outlining teaching plans, and a feedback form facilitating post-presentation feedback. In 2009-2010, internal medicine residents met with a chief resident before their presentations to refine teaching plans. The chief resident then supported the presenter in achieving their objectives and provided post-presentation feedback. Residents were surveyed before and 6 months after the intervention. Mean scores were compared using an unpaired t test. RESULTS: Residents' ratings improved in the following domains: understanding expectations (3.10 vs. 4.02, p = .0003), presentation organization (3.50 vs. 4.25, p = .005), and creating and accomplishing learning objectives (3.31 vs. 4.00, p = .002). Residents commented positively on the improved presentations. CONCLUSIONS: This toolkit, based on educational principles, improved morning report presentations.

Safety Findings in Pediatric Patients During Long-Term Treatment With Teduglutide for Short-Bowel Syndrome-Associated Intestinal Failure: Pooled Analysis of 4 Clinical Studies.

BACKGROUND: This analysis assessed combined safety data from 4 clinical studies of teduglutide in pediatric patients with short-bowel syndrome-associated intestinal failure (SBS-IF). METHODS: Safety data from teduglutide-treated patients in 4 clinical trials were pooled. The completed 12-week and 24-week phase 3 core studies (NCT01952080/EudraCT 2013-004588-30 and NCT02682381/EudraCT 2015-002252-27) enrolled children aged 1-17 years with SBS-IF. Patients could elect to enroll in ongoing open-label extensions (NCT02949362/EudraCT 2016-000863-17 and NCT02954458/EudraCT 2016-000849-30). Interim data from ongoing studies were included. RESULTS: Safety data are reported for 89 pediatric patients treated with teduglutide for a median (range) of 51.7 (5.0-94.7) weeks. Adverse events (AEs) were reported in all patients; the most common were vomiting (51.7%), pyrexia (43.8%), upper respiratory tract infection (41.6%), and cough (33.7%). Thirty-five patients (39.3%) had AEs considered related to teduglutide treatment; abdominal pain and vomiting were most frequent (5.6% each). Three serious AEs in 3 patients (3.4%) were considered related to teduglutide treatment: ileus, d-lactic acidosis, and gastrointestinal obstruction due to hard stools. All 3 events resolved. One cecal polyp was detected, which was not biopsied or found on repeat colonoscopy. No cases of neoplasia occurred. CONCLUSION: Based on integrated data from 4 clinical studies, including long-term follow-up for ≤161 weeks, teduglutide had a safety profile consistent with the individual core pediatric studies and as expected for pediatric patients with SBS-IF who never received teduglutide. The most frequent AEs reflected treatment with teduglutide, complications of the underlying disease, and typical childhood illnesses.

Safety and Efficacy of Teduglutide in Pediatric Patients With Intestinal Failure due to Short Bowel Syndrome: A 24-Week, Phase III Study.

BACKGROUND: This study evaluated the safety and efficacy of teduglutide in pediatric patients with short bowel syndrome-associated intestinal failure (SBS-IF). METHODS: A 24-week, phase III trial with 2 randomized, double-blind teduglutide dose groups and a nonblinded standard of care (SOC) arm was used; patients received 0.025 mg/kg or 0.05 mg/kg teduglutide once daily. Safety end points included treatment-emergent adverse events (TEAEs) and growth parameters. The primary efficacy/pharmacodynamic end point was the number of patients who achieved a ≥20% reduction in parenteral support (PS) from baseline at week 24. RESULTS: All 59 enrolled patients completed the study (0.025 mg/kg, n = 24; 0.05 mg/kg, n = 26; SOC, n = 9). Baseline demographics and disease characteristics were comparable among groups. TEAEs were reported by 98% and 100% of patients in the teduglutide and SOC groups, respectively. The most common TEAEs in the teduglutide-treated groups were pyrexia and vomiting. The primary end point was achieved by 13 (54.2%), 18 (69.2%), and 1 (11.1%) patients who received 0.025 mg/kg teduglutide, 0.05 mg/kg teduglutide, and SOC, respectively (P < 0.05 vs SOC). Both 0.025-mg/kg and 0.05-mg/kg teduglutide groups showed clinically significant reductions in PS volume (P < 0.05 vs SOC), PS calories, days per week and hours per day of PS infusions, and increases in enteral nutrition and plasma citrulline at week 24 compared with baseline. Two (8.3%, 0.025 mg/kg teduglutide) and 3 patients (11.5%, 0.05 mg/kg teduglutide) achieved enteral autonomy. CONCLUSION: The safety profile of teduglutide was similar to that reported previously in children and adults. Treatment with teduglutide was associated with significant reductions in PS for pediatric patients with SBS-IF over 24 weeks.

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.

Isolated orthotopic liver transplantation for parenteral nutrition-associated liver injury.

BACKGROUND: Mild liver dysfunction is common after prolonged use of parenteral nutrition (PN), but end-stage liver failure occurs only rarely. Few treatment options other than combined liver-intestine transplantation exist for patients with liver failure associated with PN use, however. Herein, we report the results of a cohort of patients undergoing isolated orthotopic liver transplantation (OLT) for PN-associated liver injury. METHODS: A retrospective cohort study of 80 patients (73 pediatric patients and 7 adults) who have undergone isolated OLT for PN-associated liver injury as the primary indication for transplantation was performed. RESULTS: At the time of OLT, the mean total serum bilirubin was 19.5 mg/dL and the mean serum albumin level was 2.9 mg/dL. Severe hepatic encephalopathy was seen in 5%, spontaneous bacterial peritonitis was seen in 6.3%, and respiratory failure requiring mechanical ventilation was seen in 14% of patients at the time of OLT. Overall 1- and 5-year survival rates were 72% and 52%, respectively, with infection being the most common cause of death after OLT. Retransplantation was required in 25% of patients, and the 5-year posttransplant patient survival rate only reached 35% in these cases. CONCLUSIONS: Patients with end-stage liver disease associated with PN administration often have very severe liver disease, multiple comorbidities, and poor prognosis by the time they are listed for OLT. Nonetheless, isolated OLT is associated with good long-term survival and should be considered for selected patients with combined intestine-liver failure.

The Fecal Microbiome in Pediatric Patients With Short Bowel Syndrome.

BACKGROUND: Changes in the intestinal microbiome of patients with short bowel syndrome (SBS) are thought to significantly affect clinical outcome. These changes may not only delay enteral diet advancement but may also predispose patients to bacterial translocation, bacteremia, and liver disease. Patients with SBS are thought to be more susceptible to changes in gut microbial communities due to intestinal dysmotility and/or lack of anatomic safeguards such as the ileocecal valve. MATERIALS AND METHODS: We analyzed the bacterial composition of 21 fecal specimens from 9 children with SBS and 8 healthy children ages 4 months to 8 years by 16S ribosomal RNA gene sequencing. The sequences were quality filtered and analyzed using QIIME, the Ribosomal Database Project Classifier, and the randomForest supervised learning algorithm. RESULTS: The fecal microbiome of patients with SBS is different from that of healthy controls. Stool from patients with SBS had a significantly greater abundance of the bacterial classes Gammaproteobacteria and Bacilli. Stool from patients with SBS who experienced increased stool frequency tended to have increased abundance of Lactobacillus (P = .057) and decreased abundance of Ruminococcus. CONCLUSION: This study shows that the fecal microbiome of patients with SBS is significantly different from that of healthy controls when analyzed by 16S metagenomics. Differences in the composition and function of gut microbiomes in children with SBS may affect bowel physiology, and these findings may provide new opportunities for intestinal rehabilitation and clinical management.

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.

Intravenous Cidofovir therapy for disseminated adenovirus in a pediatric liver transplant recipient.

BACKGROUND: No definitive antiviral therapy exists for adenovirus (ADV) in immunosuppressed hosts. Cidofovir (CDV), a broad spectrum anti-DNA viral agent, has previously been shown to be of therapeutic benefit in life-threatening adenoviral disease in bone marrow stem-cell recipients. METHODS: A 71/2-month-old girl with a history of biliary atresia developed fevers, hematochezia, tachypnea, and laboratory evidence of hepatitis and pancreatitis 12 days after liver transplantation. A stool culture, oropharyngeal culture, blood viral culture, and blood polymerase chain reaction (PCR) confirmed ADV. Cidofovir 1 mg/kg intravenously three times per week was initiated. The patient received intravenous hydration and probenecid with the infusions to reduce the nephrotoxicity of CDV. Immunosuppression was reduced to achieve tacrolimus trough levels of approximately 8 ng/mL and prednisone at 0.1 mg/kg per day. Complete blood cell count, urinalysis, and viral studies were obtained weekly. RESULTS: Detection of ADV DNA by PCR made a transition from positive to negative during CDV therapy. Blood viral cultures became negative after two CDV doses. Alanine aminotransferase normalized by 5 weeks of therapy. CDV was discontinued after 7 weeks secondary to transient acidosis and proteinuria. The patient never developed azotemia, neutropenia, or ocular abnormalities. CONCLUSIONS: CDV was associated with improved clinical status, viral clearance, and minimal transient side effects in a pediatric liver transplant recipient with disseminated adenoviral disease. The current report documents clearance of disseminated ADV infection in a liver transplant recipient receiving CDV infusions.

Fish oil-based lipid emulsions in the treatment of parenteral nutrition-associated liver disease: an ongoing positive experience.

We previously reported the beneficial effect of fish oil-based lipid emulsions (FOLEs) as monotherapy in the treatment of parenteral nutrition-associated liver disease (PNALD). In this report, we share our ongoing experience at Texas Children's Hospital, Houston, Texas in the use of FOLE in treatment of PNALD as presented at the 2013 Experimental Biology meeting. We describe the findings of a single center, prospective, observational study of infants <6 mo of age with PNALD who received parenteral FOLE as monotherapy. A total of 97 infants received FOLE under the compassionate-use protocol for the treatment of PNALD. Eighty-three (86%) survived with resolution of cholestasis and 14 (14%) died. The median conjugated bilirubin (CB) concentration at the initiation of FOLE therapy was 4.8 mg/dL (range 2.1-26). The median time to resolution of cholestasis was 40 d (range 3-158). Compared with infants with mild cholestasis (CB of 2.1-5 mg/dL at the initiation of FOLE), nonsurvivors were significantly more premature and took longer to resolve their cholestasis. Gestational age at birth correlated inversely with CB at the beginning of FOLE and peak CB. Infants with an initial CB >10 mg/dL had a higher mortality rate than infants with an initial CB <5 mg/dL (35% vs. 6%; P < 0.05). Our experience with the use of FOLE in PNALD continues to be encouraging. Prematurity continues to be a major determinant in mortality and severity of cholestasis. This calls for further controlled studies designed to optimize dose and timing of intervention in the use of FOLE in neonates.

Green tea extract: a potential cause of acute liver failure.

The use of herbal products has increased significantly in recent years. Because these products are not subject to regulation by the Food and Drug Administration and are often used without supervision by a healthcare provider, the indication for and consumption of these supplements is quite variable. Moreover, their use is generally regarded as safe and natural by the lay-public. Unfortunately, there has been an increase in the number of reported adverse events occurring with the use of herbal products. We present a case of acute impending liver failure in an adolescent male using a weight-loss product containing green tea extract. Our case adds to the growing concern surrounding the ingestion of green tea extract and serves to heighten healthcare provider awareness of a potential green tea extract hepatotoxicity. Despite the generally touted benefits of green tea as a whole, clinical concern regarding its use is emerging and has been linked to its concentration in multiple herbal supplements. Interestingly, the suspected harmful compounds are those previously proposed to be advantageous for weight-loss, cancer remedy, and anti-inflammatory purposes. Yet, we emphasize the need to be aware of not just green tea extract, but the importance of monitoring patient use of all dietary supplements and herbal products.

Absent smooth muscle actin immunoreactivity of the small bowel muscularis propria circular layer in association with chromosome 15q11 deletion in megacystis-microcolon-intestinal hypoperistalsis syndrome.

Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS; OMIM%249210) is a rare and severe form of congenital intestinal and urinary dysfunction and malformation. Histologic studies suggest that the predominant intestinal manifestation is smooth muscle myopathy. Molecular observations have linked the disease to the neuronal nicotinic acetylcholine receptor (ηAChR), namely the absence of a functional α3 subunit of the ηAChR in patients with MMIHS. We describe a case of MMIHS in association with a de novo deletion of the proximal long arm of chromosome 15 (15q11.2). Histologic evaluation revealed an appropriate light microscopic appearance of both the circular and longitudinal layers of the small bowel muscularis propria. Immunohistochemical staining for smooth muscle actin, however, was selectively absent in the circular layer, demonstrating isolated absence in a unique and previously undescribed pattern. These observations raise the possibility that the proximal long arm of chromosome 15 (15q11) may be of clinical significance in MMIHS.