Presentation of Severe Acute Respiratory Syndrome-Coronavirus 2 Infection as Cholestatic Jaundice in Two Healthy Adolescents

© 2020 Elsevier Inc. Liver abnormalities in severe acute respiratory syndrome-coronavirus 2 infection, including hepatitis and cholestasis, have been observed in adults and are associated with worse outcomes. We describe 2 adolescents with cholestasis and hepatitis with mild presentation of severe acute respiratory syndrome-coronavirus 2 lacking typical symptoms. Our intention is to raise index of suspicion for testing and protective equipment use

Safety and Immunogenicity of Live Viral Vaccines in a Multicenter Cohort of Pediatric Transplant Recipients

IMPORTANCE: Live vaccines (measles-mumps-rubella [MMR] and varicella-zoster virus [VZV]) have not been recommended after solid organ transplant due to concern for inciting vaccine strain infection in an immunocompromised host. However, the rates of measles, mumps, and varicella are rising nationally and internationally, leaving susceptible immunocompromised children at risk for life-threating conditions. OBJECTIVE: To determine the safety and immunogenicity of live vaccines in pediatric liver and kidney transplant recipients. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included select pediatric liver and kidney transplant recipients who had not completed their primary MMR and VZV vaccine series and/or who displayed nonprotective serum antibody levels at enrollment between January 1, 2002, and February 28, 2023. Eligibility for live vaccine was determined by individual US pediatric solid organ transplant center protocols. EXPOSURES: Exposure was defined as receipt of a posttransplant live vaccine. Transplant recipients received 1 to 3 doses of MMR vaccine and/or 1 to 3 doses of VZV vaccine. MAIN OUTCOME AND MEASURE: Safety data were collected following each vaccination, and antibody levels were obtained at 0 to 3 months and 1 year following vaccination. Comparisons were performed using Mann-Whitney U test, and factors associated with development of postvaccination protective antibodies were explored using univariate analysis. RESULTS: The cohort included 281 children (270 [96%] liver, 9 [3%] kidney, 2 [1%] liver-kidney recipients) from 18 centers. The median time from transplant to enrollment was 6.3 years (IQR, 3.4-11.1 years). The median age at first posttransplant vaccine was 8.9 years (IQR, 4.7-13.8 years). A total of 202 of 275 (73%) children were receiving low-level monotherapy immunosuppression at the time of vaccination. The majority of children developed protective antibodies following vaccination (107 of 149 [72%] varicella, 130 of 152 [86%] measles, 100 of 120 [83%] mumps, and 124 of 125 [99%] rubella). One year post vaccination, the majority of children who initially mounted protective antibodies maintained this protection (34 of 44 [77%] varicella, 45 of 49 [92%] measles, 35 of 42 [83%] mumps, 51 of 54 [94%] rubella). Five children developed clinical varicella, all of which resolved within 1 week. There were no cases of measles or rubella and no episodes of graft rejection within 1 month of vaccination. There was no association between antibody response and immunosuppression level at the time of vaccination. CONCLUSIONS AND RELEVANCE: The findings suggest that live vaccinations may be safe and immunogenic after solid organ transplant in select pediatric recipients and can offer protection against circulating measles, mumps, and varicella

International Liver Transplantation Society Global Census:First Look at Pediatric Liver Transplantation Activity Around the World

Background. Over 16 000 children under the age of 15 died worldwide in 2017 because of liver disease. Pediatric liver transplantation (PLT) is currently the standard of care for these patients. The aim of this study is to describe global PLT activity and identify variations between regions. Methods. A survey was conducted from May 2018 to August 2019 to determine the current state of PLT. Transplant centers were categorized into quintile categories according to the year they performed their first PLT. Countries were classified according to gross national income per capita. Results. One hundred eight programs from 38 countries were included (68% response rate). 10 619 PLTs were performed within the last 5 y. High-income countries performed 4992 (46.4%) PLT, followed by upper-middle- (4704 [44·3%]) and lower-middle (993 [9·4%])-income countries. The most frequently used type of grafts worldwide are living donor grafts. A higher proportion of lower-middle-income countries (68·7%) performed ≥25 living donor liver transplants over the last 5 y compared to high-income countries (36%; P = 0.019). A greater proportion of programs from high-income countries have performed ≥25 whole liver transplants (52.4% versus 6.2%; P = 0.001) and ≥25 split/reduced liver transplants (53.2% versus 6.2%; P &lt; 0.001) compared to lower-middle-income countries. Conclusions. This study represents, to our knowledge, the most geographically comprehensive report on PLT activity and a first step toward global collaboration and data sharing for the greater good of children with liver disease; it is imperative that these centers share the lead in PLT.</p

International Liver Transplantation Society Global Census:First Look at Pediatric Liver Transplantation Activity Around the World

Background. Over 16 000 children under the age of 15 died worldwide in 2017 because of liver disease. Pediatric liver transplantation (PLT) is currently the standard of care for these patients. The aim of this study is to describe global PLT activity and identify variations between regions. Methods. A survey was conducted from May 2018 to August 2019 to determine the current state of PLT. Transplant centers were categorized into quintile categories according to the year they performed their first PLT. Countries were classified according to gross national income per capita. Results. One hundred eight programs from 38 countries were included (68% response rate). 10 619 PLTs were performed within the last 5 y. High-income countries performed 4992 (46.4%) PLT, followed by upper-middle- (4704 [44·3%]) and lower-middle (993 [9·4%])-income countries. The most frequently used type of grafts worldwide are living donor grafts. A higher proportion of lower-middle-income countries (68·7%) performed ≥25 living donor liver transplants over the last 5 y compared to high-income countries (36%; P = 0.019). A greater proportion of programs from high-income countries have performed ≥25 whole liver transplants (52.4% versus 6.2%; P = 0.001) and ≥25 split/reduced liver transplants (53.2% versus 6.2%; P &lt; 0.001) compared to lower-middle-income countries. Conclusions. This study represents, to our knowledge, the most geographically comprehensive report on PLT activity and a first step toward global collaboration and data sharing for the greater good of children with liver disease; it is imperative that these centers share the lead in PLT.</p

The Creation the Federal Contract System in Russia

Ovchinsky V. A. The Creation the Federal Contract System in Russia [Электронный ресурс] / V. A. Ovchinsky// Дни аспирантуры РГГУ : Материалы научных конференций. Материалы Круглого стола. Научные статьи. Переводы / Минобрнауки России, Федер. гос. бюджетное образоват. учреждение высш. проф. образования "Рос. гос. гуманитарный ун-т" (РГГУ), Упр. аспирантурой и докторантурой . - М. : РГГУ, 2012. - Вып. 6, ч. 1 - С. 457-460

ANALYSIS OF LONG-TERM SAFETY IN MARALIXIBAT-TREATED PARTICIPANTS WITH PROGRESSIVE FAMILIAL INTRAHEPATIC CHOLESTASIS: DATA FROM MARCH-ON

Background: Maralixibat (MRX) is a novel, minimally absorbed, orally-administered inhibitor of the ileal bile acid transporter (IBAT) that interrupts the enterohepatic circulation of bile acids to reduce toxic bile acids and improve cholestatic pruritus. In MARCH, a 26-week, randomized, placebo-controlled, Phase 3 study (N=93) for patients with progressive familial intrahepatic cholestasis (PFIC), MRX was well tolerated with mild/self-limiting diarrhea and abdominal pain being the most commonly reported gastrointestinal adverse events (AEs) and were more common in the treatment group vs placebo (PBO). Bilirubin increase and fat soluble vitamin (FSV) deficiency events were more frequent in the PBO group, and ALT laboratory assessments were not different between groups. MARCH-ON is an ongoing, open-label, long-term extension study for participants who completed MARCH. In this interim safety analysis up to 106 weeks, we describe the evidence of safety with longer follow-up, and inclusion of the MARCH PBO participants into MARCH-ON, adding to the overall safety analysis. Methods: Treatment-emergent AEs (TEAEs) and laboratory data from MARCH-ON were analyzed longitudinally for all participants who opted to enroll (N=85) as of June 23, 2022. Safety was assessed for participants who received PBO in MARCH and initiated MRX in MARCH-ON (PBO-MRX group: n=38) and for participants who received MRX in MARCH and continued beyond 26 weeks of treatment into MARCH-ON (MRX-MRX group; n=47). Data are reported below for events of interest using pooled FDA Medical Query (FMQ) terms (gastrointestinal events, transaminases increased, bilirubin increased, and FSV deficiency). Results: In MARCH-ON, mean (SD) exposure in all MRX-treated participants was 340 (205) days [MRX-MRX: 386 (205) days; PBO-MRX: 284 (193) days]. There were 82 (96.5%) participants with a TEAE, with the most common affected system being gastrointestinal (n=63; 74.1%). Overall, 7 (8.2%) had a severe AE, none of which were considered related to MRX; 14 (16.5%) had a serious AE with 1 (1.2%) considered related to MRX (increased blood bilirubin). There was 1 (1.2%) death due to respiratory infection and not related to MRX. Three participants (3.5%) had 4 AEs (diarrhea; bilirubin and ALT increase; and cirrhosis) leading to discontinuation. The proportion of participants with AEs of interest from the PBO-MRX group in MARCH-ON were lower than those observed from the MRX-treated participants from MARCH for diarrhea (13 [34.2%] vs 27 [57.4%]), abdominal pain (8 [21.1%] vs 12 [25.5%]), hyperbilirubinemia (1 [2.6%] vs 7 [14.9%]), transaminases increased (5 [13.2%] vs 8 [17.0%]), and FSV deficiency (10 [26.3%] vs 13 [27.7%]). Participants who previously received MRX in MARCH and did not report an event were less likely to report an event in MARCH-ON. New initial onsets of the following terms were reported: diarrhea (n=3), increased bilirubin (n=3), transaminases increased (n=1), and FSV deficiency (n=4). Conclusions: In this safety analysis of long-term treatment with MRX out to 106 weeks from MARCH-ON, no new safety signals were observed. The frequency of events was slightly lower than previously reported and decreased over time in participants with extended follow-up. MRX was well-tolerated overall, as evidenced by a low rate of discontinuatio