Steven Lobritto - Academia.edu (original) (raw)

Papers by Steven Lobritto

Journal of pediatric gastroenterology and nutrition, Oct 1, 1999

Liver Transplantation, Nov 27, 2023

JAMA Network Open

ImportanceLive vaccines (measles-mumps-rubella [MMR] and varicella-zoster virus [VZV]) have not b... more ImportanceLive 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.ObjectiveTo determine the safety and immunogenicity of live vaccines in pediatric liver and kidney transplant recipients.Design, Setting, and ParticipantsThis 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.ExposuresExposure was defined as receipt of a posttransplant l...

The Journal of Pediatrics

Journal of Pediatric Gastroenterology and Nutrition, 2007

Journal of Pediatric Gastroenterology and Nutrition, Feb 22, 2021

Supplemental Digital Content is available in the text ABSTRACT Objective: Increased mortality ris... more Supplemental Digital Content is available in the text ABSTRACT Objective: Increased mortality risk because of severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) infection in adults with native liver disease (LD) and liver transplant (LT) is associated with advanced age and comorbid conditions. We aim to report outcomes for children with LD and LT enrolled in the NASPGHAN/SPLIT SARS-CoV2 registry. Methods: In this multicenter observational cohort study, we collected data from 91 patients <21 years (LD 44, LT 47) with laboratory-confirmed SARS-CoV2 infection between April 21 and September 17, 2020. Results: Patients with LD were more likely to require admission (70% vs 43% LT, P = 0.007) and pediatric intensive care unit (PICU) management (32% vs 4% LT, P = 0.001). Seven LD patients required mechanical ventilation (MV) and 2 patients died; no patients in the LT cohort died or required MV. Four LD patients presented in pediatric acute liver failure (PALF), 2 with concurrent multisystem inflammatory syndrome in children (MIS-C); all recovered without LT. Two LD patients had MIS-C alone and 1 patient died. Bivariable logistic-regression analysis found that patients with nonalcoholic fatty LD (NAFLD) (odds ratio [OR] 5.6, P = 0.02) and LD (OR 6.1, P = 0.01, vs LT) had higher odds of severe disease (PICU, vasopressor support, MV, renal replacement therapy or death). Conclusions: Although not directly comparable, LT recipients had lower odds of severe SARS-CoV2 infection (vs LD), despite immunosuppression burden. NAFLD patients reported to the registry had higher odds of severe SARS-CoV2 disease. Future controlled studies are needed to evaluate effective treatments and further stratify LD and LT patients with SARS-CoV2 infection.

Transplantation, Jan 15, 2010

Infants (<12 months) who require liver transplantation (LTx) represent a particularly challeng... more Infants (<12 months) who require liver transplantation (LTx) represent a particularly challenging and understudied group of patients. This retrospective study aimed to describe a large single-center experience of infants who received isolated LTx, illustrate important differences in infants versus older children, and identify pretransplant factors which influence survival. More than 25 pre-LTx demographic, laboratory, and operative variables were analyzed using the Log-rank test and Cox proportional hazards model. Between 1984 and 2006, 216 LTx were performed in 186 infants with a mean follow-up time of 62 months. Median age at LTx was 9 months, the majority had cholestatic liver disease, were hospitalized pre-LTx, and received whole grafts. Leading indications for re-LTx (n=30) included vascular complications (43%) and graft nonfunction (40%), whereas leading causes of death were sepsis and multiorgan failure. One-, 5-, and 10-year graft and patient survivals were 75%/72%/68% an...

Pediatric Solid Organ Transplantation

... of the pediatric liver transplant recipient, with rapid transition out of the ICU and early d... more ... of the pediatric liver transplant recipient, with rapid transition out of the ICU and early discharge home ... Preoperative factors affecting post-transplant care ... In addition, cirrhotic patients may enter a liver transplant with profound synthetic dysfunction and hypersplenism putting them ...

Liver Transplantation, 2005

Serum concentrations of the actin scavenger Gc-globulin are reduced in acute liver failure (ALF).... more Serum concentrations of the actin scavenger Gc-globulin are reduced in acute liver failure (ALF). Prospectively, we tested Gc-globulin's value to predict outcome following ALF using sera from 182 patients with ALF from the U.S. ALF Study Group. Admission serum levels of Gc-globulin (normal range: 350-500 mg/L) were studied by an immunonephelometric method. The median (range) serum Gcglobulin level on admission for the entire group was 91 (5-307) mg/L. Gc-globulin levels were significantly higher in spontaneous survivors than in patients who died or underwent transplantation (113 [5-301] mg/L vs. 73 [5-307] mg/L, P < 0.001). Those surviving non-acetaminophen (paracetamol)-induced ALF without transplantation had higher Gc-globulin levels than nonsurvivors (102 [5-301] mg/L vs. 61 [5-232] mg/L, P ‫؍‬ 0.002), whereas there was no significant difference in levels between the groups in patients with acetaminophen-induced ALF. A cutoff level of 80 mg/L in the non-acetaminophen group yielded positive and negative predictive values of 85% and 43%, respectively. The corresponding Abbreviation: ALF, acute liver failure.

Drug Metabolism and Disposition, Nov 1, 2018

Uridine diphosphate glucuronosyltransferases (UGTs) are key enzymes responsible for the body's ab... more Uridine diphosphate glucuronosyltransferases (UGTs) are key enzymes responsible for the body's ability to process a variety of endogenous and exogenous compounds. Significant gains in understanding UGT function have come from the analysis of variants seen in patients. We cared for a Sudanese child who showed clinical features of type 1 Crigler-Najjar syndrome (CN-1), namely severe unconjugated hyperbilirubinemia leading to liver transplantation. CN-1 is an autosomal recessive disorder caused by damaging mutations in the gene for UGT1A1, the hepatic enzyme responsible for bilirubin conjugation in humans. Clinical genetic testing was unable to identify a known pathogenic UGT1A1 mutation in this child. Instead, a novel homozygous variant resulting in an in-frame deletion, p.Val275del, was noted. Sanger sequencing demonstrated that this variant segregated with the disease phenotype in this family. We further performed functional testing using recombinantly expressed UGT1A1 with and without the patient variant, demonstrating that p.Val275del results in a complete lack of glucuronidation activity, a hallmark of CN-1. Sequence analysis of this region shows a high degree of conservation across all known catalytically active human UGTs, further suggesting that it plays a key role in the enzymatic function of UGTs. Finally, we note that the patient's ethnicity likely played a role in his variant being previously undescribed and advocate for greater diversity and inclusion in genomic medicine.

Journal of Gastrointestinal Surgery, Apr 6, 2021

To determine the patient characteristics and surgical procedure factors related to increased rate... more To determine the patient characteristics and surgical procedure factors related to increased rates of 30-day unplanned readmission and major perioperative complications after spinal fusion surgery, as well as the association between unplanned readmission and major complications. Summary of Background Data: Reducing unplanned readmissions can reduce the cost of healthcare. Payers are implementing penalties for 30-day readmissions following discharge. There is limited data regarding the current rates and risk factors for unplanned readmission and major complications related to spinal fusion surgery. Methods: Spine fusion patients were identified using the 2012 and 2013 American College of Surgeons National Surgical Quality Improvement Program Participant User File. Rates of readmissions within 30 days following spine fusion surgery were calculated using the person-years method. Cox proportional hazards models were used to assess the independent associations of spine surgical procedure types, diagnoses, patient profiles and major perioperative complications with unplanned related readmissions. Independent risk factors for major complications were assessed by multivariable logistic regression. Results: Of 18,602 identified patients, there was a 5.2% overall major perioperative complication rate. There was a rate of 4.4% per 30 person-days for unplanned readmissions related to index surgery. Independent risk factors for both readmissions and major perioperative complications included combined anterior and posterior surgery, diagnosis of solitary tumor, older age, and higher American Society of Anesthesiologists Copyright © 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. class. Patients with deep/organ surgical site infection carried higher risk of having unplanned readmission, followed by pulmonary embolism, acute renal failure and stroke/CVA with neurological deficit. Conclusions: This study provides benchmark rates of 30-day readmission based on diagnosis and procedure codes from a high-quality database for adult spinal fusion patients and showed increased rates of 30-day unplanned readmission and major perioperative complications for patients with specific risk factors. Targeted preoperative planning on modifiable risk factors with proportional reimbursement may promote higher quality healthcare.

Transplantation, Jul 1, 2019

Journal of Pediatric Gastroenterology and Nutrition, Oct 21, 2021

ABSTRACTChildren are seldom affected by severe forms of severe acute respiratory syndrome coronav... more ABSTRACTChildren are seldom affected by severe forms of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV2) infection; however, the impact of comorbidities in the clinical presentation and outcome of SARS-CoV2 in children is poorly characterized including that of chronic liver disease (CLD) and those taking immunosuppressive medications for autoimmune liver disease or following liver transplantation (LT). Although not the main target organ, a spectrum of liver involvement has been described in children infected with SARS-CoV2 and those presenting with Multisystem Inflammatory Syndrome in Children (MIS-C). The Hepatology Committee of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the Society of Pediatric Liver Transplantation (SPLIT) present an evidence-based position paper on liver involvement in children with SARS-CoV2 infection and its impact on those with CLD as well as LT recipients. All children may exhibit acute liver injury from SARS-CoV2 infection, and those with CLD and may experience hepatic decompensation. Preventative and therapeutic measures are discussed.

Transplantation, Jul 1, 2014

By preserving part of the native liver, auxiliary partial orthotopic liver transplantation (APOLT... more By preserving part of the native liver, auxiliary partial orthotopic liver transplantation (APOLT) provides the advantage of potential immunosuppression (ISP) withdrawal if the native liver recovers but has had limited acceptance, especially in the United States, due to technical complications and low rates of native liver regeneration. No previous study has evaluated APOLT specifically for preadolescent children with fulminant hepatic failure (FHF). This population might benefit especially based on greater capacity for liver regeneration. Data from 13 preadolescent children who underwent APOLT were compared to 13 matched controls who underwent orthotopic liver transplantation (OLT) for FHF from 1996 to 2013. There were no significant differences in patient demographics or survival between the 2 groups. However, all surviving OLT recipients (10/13) remain on ISP, while all but 1 surviving APOLT recipient (12/13) showed native liver regeneration, and the first 10 recipients (76.9%) are currently off ISP with 2 additional patients currently weaning. In our experience, APOLT produced excellent survival and high rates of native liver regeneration in preadolescent children with FHF. This represents the largest series to date to report such outcomes. Liberating these children from lifelong ISP without the downside of increased surgical morbidity makes APOLT an attractive alternative. In conclusion, we therefore propose that, with the availability of technical expertise and with the technical modifications above, APOLT for FHF should be strongly considered for preteenage children with FHF.

Gastroenterology, Apr 1, 2015

Introduction: Orthotopic liver transplantation (OLT) is a life-saving procedure for children with... more Introduction: Orthotopic liver transplantation (OLT) is a life-saving procedure for children with end-stage liver disease. Advances in surgical techniques have made OLT in children younger than one year of age increasingly feasible. Previous studies have suggested that infants may experience high operative complications, difficult post-operative courses, and poor graft and patient survival. Many transplant centers have required infants to reach a specific weight or age prior to OLT to minimize morbidity and mortality. As a result, many children have died or experienced significant decompensation while awaiting the required weight or age, thereby making them worse candidates for the procedure. Aim: To review our single center experience with OLT in children younger than one year of age at the time of transplantation. Methods: We retrospectively reviewed the charts of patients 365 days of age and younger that underwent OLT at Morgan Stanley Children's Hospital of New-York Presbyterian from 1998 to 2014. We specifically reviewed data related to intraoperative course, length of hospitalization, duration of stay in intensive care unit (ICU), duration of mechanical ventilation, post-transplant complications within 90 days and 90-day and 1year patient and graft survival. Results: Data for 65 of 116 eligible patients were included in this interim analysis (median age:240 days, range:21-365 days; median weight:5.9 kg, range:2.0-8.5 kg). The most common indications for OLT were biliary atresia (n= 51, 78.5%) and cryptogenic cirrhosis (n=5, 7.7%). Forty-three patients (66.2%) received deceased donor grafts, of which 55.8% were whole organs. Mean duration of transplant surgery was 7.2 hours. Intra-operatively, 53 patients (89.8%) required blood transfusions (mean:72 mL/kg), 32 patients (55.2%) required fresh frozen plasma (mean:48 mL/kg) and 6 patients (11.8%) required platelet transfusions (mean:13 mL/kg). Median post-transplant hospitalization was 17 days, ICU stay was 8 days, and mechanical ventilation duration was 2 days. Posttransplant complications included bile leak (26.2%), acute rejection (18.5%), hepatic artery thrombosis (13.8%), portal vein thrombosis (13.8%), wound dehiscence (13.8%), abdominal compartment syndrome (9.2%), and bleeding (9.2%). The reoperation rate was 49.2%. Four patients required re-transplantation, 2 of whom died. Patient survival was 93.8% at both 90 days and 1 year. Graft survival was 90.8% at 90 days and 89.2% at 1 year. Conclusion: Infants can have excellent outcomes after OLT with acceptable operative complications and high survival rates in a center of excellence. The use of partial or whole grafts can yield patient and graft survivals approaching that of children greater than 1 year of age. OLT should not be delayed in infants merely because of low weight or young age, reducing pretransplant morbidity and mortality.

Hepatology, Jul 1, 2021

BaCKgRoUND aND aIMS: Glecaprevir/pibrentasvir (GLE/PIB) has shown high efficacy and safety in chr... more BaCKgRoUND aND aIMS: Glecaprevir/pibrentasvir (GLE/PIB) has shown high efficacy and safety in chronic HCV-infected adults and adolescents; data in children were limited. DORA part 2 is a phase 2/3, nonrandomized, openlabel study evaluating the pharmacokinetics, efficacy, and safety of a pediatric formulation of GLE and PIB in children ages 3 to < 12 years. appRoaCH aND ReSUltS: Children with chronic HCV infection, genotype 1-6, with or without compensated cirrhosis, were divided into three cohorts by age-cohort 2 (9 to < 12 years), cohort 3 (6 to < 9 years), and cohort 4 (3 to < 6 years)-and given weight-based doses of GLE and PIB for 8, 12, or 16 weeks. Primary endpoints were sustained virologic response at posttreatment week 12 (SVR12) and steady-state exposure; secondary endpoints were rates of persistent viremia, relapse, and reinfection. Safety and laboratory abnormalities were assessed. Final pediatric dosages determined to be efficacious were 250 mg GLE + 100 mg PIB (in children weighing ≥ 30 to < 45 kg), 200 mg GLE + 80 mg PIB (≥ 20 to < 30 kg), and 150 mg GLE + 60 mg PIB (12 to < 20 kg). Of 80 participants enrolled and dosed, 96% (77/80) achieved SVR12. One participant, on the initial dose ratio, relapsed by posttreatment week 4; no participants had virologic failures on the final dose ratio of GLE 50 mg/PIB 20 mg. Two nonresponders prematurely discontinued the study. Most adverse events (AEs) were mild; no drug-related serious AEs occurred. Pharmacokinetic exposures were comparable to those of adults. CoNClUSIoNS: A pediatric formulation of GLE/PIB was highly efficacious and well tolerated in chronic HCV-infected children 3 to < 12 years old. (Hepatology 2021;74:19-27). G lobally, 71 million people are infected with HCV; of those, approximately 13.2 million are children between 1 and 15 years of age. (1,2) Vertical transmission is the primary route of viral acquisition in pediatrics. (2) While 20% of children infected this way may clear HCV infection spontaneously in the first few years of life, 80% will go on to develop long-term infection. HCV infection acquired during infancy or childhood can lead to chronic hepatitis and cirrhosis; HCC has also been reported in children.

Pediatric Transplantation, Jan 15, 2018

The liver's capacity to grow in response to metabolic need is well known. However, long-term grow... more The liver's capacity to grow in response to metabolic need is well known. However, long-term growth of liver allografts in pediatric recipients has not been characterized. A retrospective review of pediatric recipients at a single institution identified patients who had cross-sectional imaging at 1, 5, and 10-years post-transplant. Using volumetric calculations, liver allograft size was calculated and percent standard liver volumes (SLV) were compared across the different time points. 18 patients ranging from 0.3-17.7 years old were identified that had imaging at two or more time points. Measured liver volumes increased by 59% after 5 years and 170% after 10 years. The measured liver volumes compared to calculated %SLV for these patients were 123 ± 37%, 97 ± 19%, and 118 ± 27% at 1, 5, and 10 years after transplant, respectively. Our data