Detection of viral RNA and DNA and immune response following administration of live attenuated measles and varicella vaccines in children with chronic liver disease.

Infections preventable by live virus vaccines are surging in the setting of decreased herd immunity. Many children with chronic liver diseases (CLDs) are unimmunized and at increased risk for infection due to guidelines recommending against live vaccines within 4 weeks pretransplant. This prospective study of 21 children with CLD and 13 healthy controls defined the timing of measles virus and varicella-zoster virus (VZV) RNA- and DNA-emia following vaccination and compared immune responses to measles and varicella vaccines in both groups. Measles virus RNA and VZV DNA real-time PCR were measured weekly following vaccination; measles virus RNA was undetectable in all by 14 days postvaccination, but VZV DNA, which can be managed with antivirals, was detected in 1 child in the CLD group at 21 days and 1 control at 28 days postvaccination. Humoral or cell-mediated vaccine response was 100% to measles virus and 94% to VZV in the CLD group postvaccination, whereas it was 100% to both vaccines in controls. Our pilot study suggests that both live vaccines can be safely and effectively administered up to 14 days prior to transplantation in children with CLD. We anticipate this will improve vaccination rates and thus decrease rates of vaccine-preventable infections in vulnerable children with CLD.

Gadolinium retention effect on macrophages - a potential cause of MRI contrast agent Dotarem toxicity.

Gadolinium is a component of the MRI contrast agent Dotarem. Although Dotarem is the least toxic among MRI contrasts used, gadolinium present in Dotarem accumulates for many years in various organs and tissues exerting toxic effects. We showed previously that gadolinium remains in macrophages for at least 7 days after exposure to Dotarem. However, very little is known about the effect of gadolinium retention on the immune cells such as macrophages. We studied the effect of 1-day and 7-day retention of gadolinium on various functions and molecular pathways of macrophages. Gadolinium retention for 7 days decreased macrophage adhesion and motility and dysregulated the expression of adhesion and fibrotic pathway-related proteins such as Notch1 and its ligand Jagged1, adhesion/migration-related proteins PAK1 and Shp1, immune response-related transcription factors Smad3 and TCF19, and chemokines CXCL10 and CXCL13, and dysregulated the mRNA expression of fibrosis-related genes involved in extracellular matrix (ECM) synthesis, such as Col6a1, Fibronectin, MMP9, and MMP12. It also completely (below a level of detection) shut down the transcription of anti-inflammatory M2 macrophage polarization marker the Arg-1. Such changes, if they occur in MRI patients, can be potentially detrimental to the patient's immune system and immune response-related processes.

Immunosuppression-Free Life after Pediatric Liver Transplant: A Case-Control Study from the Society of Pediatric Liver Transplant (SPLIT) Registry.

OBJECTIVE: To compare long-term outcomes of pediatric liver transplant (LT) recipients off immunosuppression (IS) with matched controls on IS using data from the Society of Pediatric Liver Transplant (SPLIT) registry. STUDY DESIGN: This was a retrospective case-control study. SPLIT participants <18 years of age, ≥4 years after isolated LT, and off IS for ≥1 year (cases) were age- and sex-matched 1:2 to patients with the same primary diagnosis and post-LT follow-up duration (controls). Primary outcomes included retransplantation, allograft rejection, IS comorbidities, and prevalence of SPLIT-derived composite ideal outcome (c-IO) achieved at the end of the follow-up period. Differences were compared using multiple linear regression for continuous outcomes and logistic regression for dichotomous data. RESULTS: The study cohort was composed of 33 cases (42.4% male, 60.6% biliary atresia, median age at LT of 0.7 [P25, P75, 0.5, 1.6] years, median IS withdrawal time of 9 [P25, P75, 6, 12] years after LT) and 66 age- and sex-matched controls. No cases required retransplantation. Cases and controls had similar growth parameters, laboratory values, calculated glomerular filtration rates, rates of post-transplant lymphoproliferative disease, graft rejection, and attainment of c-IO. CONCLUSIONS: No differences in allograft rejection rates, IS complications, or c-IO prevalence were seen between SPLIT patients off IS and age- and sex-matched controls remaining on IS. Discontinuation of IS most commonly occurred in the context of rigorously designed IS withdrawal trials. The available sample size was small, affecting generalizability to the broader pediatric LT population.

Innate immune cell dysfunction and systemic inflammation in children with chronic liver diseases undergoing transplantation.

Advanced liver diseases (ALD) can affect immune function and compromise host defense against infections. In this study, we examined the phenotypic and functional alterations in circulating monocyte and dendritic cells (DCs) in children with ALD undergoing liver transplantation (LT). Children were stratified into 2 clusters, C1 (mild) and C2 (severe), on the basis of laboratory parameters of ALD and compared with healthy pediatric controls. Children in C2 had a significant reduction in frequencies of nonclassical monocytes and myeloid DCs. Children in C2 displayed monocyte and DC dysfunction, characterized by lower human leucocyte antigen DR expression and reduced interleukin 12 production, and had an increased incidence of infections before and after LT. Children in C2 demonstrated immune dysregulation with elevations of pro- and anti-inflammatory cytokines in plasma. Alterations of innate immune cells correlated with multiple laboratory parameters of ALD, including plasma bile acids. In vitro, monocytes cultured with specific bile acids demonstrated a dose-dependent reduction in interleukin 12 production, similar to alterations in children with ALD. In conclusion, a cohort of children with ALD undergoing LT exhibited innate immune dysfunction, which may be related to the chronic elevation of serum bile acids. Identifying at-risk patients may permit personalized management pre- and post-transplant, thereby reducing the incidence of infection-related complications.

Impact of psychosocial factors on medication level variability index and outcomes in pediatric liver transplant recipients.

BACKGROUND: Caregivers play an important role in maintaining a functioning graft after pediatric liver transplantation. Therefore, the psychosocial factors of both patients and caregivers can have a critical impact on transplant outcomes. Appropriate assessment and recognition of these factors pre-transplantation may allow transplant teams to better define the needs of pediatric organ recipients and develop specific countermeasures, which may then contribute toward improving transplant outcomes. METHODS: We studied 136 pediatric LT recipients followed at Texas Children's Hospital. Licensed social workers conducted comprehensive pre-transplant assessments on each patient, consisting of 22 psychosocial variables that were thought to impact adherence, which were reviewed during our study period. Non-adherence was determined using the MLVI for up to 4 years after transplantation. Biopsy-confirmed rejection episodes were assessed in the first 3 years after liver transplantation. RESULTS: Factors significantly associated with non-adherence (defined as MLVI >2) included parental age and parental education level at assessment, type of insurance, and household income. The number of ACR episodes trended higher in patients with non-adherence, and these patients had a higher number of moderate to severe rejection episodes but this trend was not statistically significant. CONCLUSIONS: Psychosocial characteristics such as parental age, education level, insurance, and household income may contribute significantly to suboptimal adherence to medications after transplantation. Identification of these psychosocial factors and early intervention is essential to the success and equitable care of our pediatric LT recipients.

Multisystem inflammatory syndrome in children associated with SARS-CoV-2 in a solid organ transplant recipient.

We present the case of a 3-year-old female liver transplant recipient with a history of Caroli disease who presented with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction (RT-PCR) test and was ultimately diagnosed with multisystem inflammatory syndrome in children (MIS-C) complicated by portal vein thrombosis. To the best of our knowledge, this is the first case report of MIS-C in a pediatric solid organ transplant (SOT) recipient. Based on our patient, MIS-C could be a potential complication of Coronavirus disease 2019 (COVID-19) in SOT recipients and may have a negative outcome on transplant graft function.

Improved clinical outcome following liver transplant in patients with ethylmalonic encephalopathy.

Ethylmalonic encephalopathy (EE) is a rapidly progressive autosomal recessive mitochondrial disease caused by biallelic pathogenic variants in the ETHE1 gene that encodes the mitochondrial sulfur dioxygenase. It is characterized by neurodevelopmental delay and regression, pyramidal and extrapyramidal signs, recurrent petechiae, chronic diarrhea, and orthostatic acrocyanosis. Laboratory findings include elevated serum levels of lactate and C4-C5 acylcarnitines, and elevated urinary excretion of ethylmalonic acid and C4-C6 acylglycines, notably isobutyrylglycine and 2-methylbutyrylglycine. These findings are attributed to deficiency of the mitochondrial sulfur dioxygenase resulting in toxic accumulation of hydrogen sulfide metabolites in vascular endothelium and mucosal cells of the large intestine. Medical management has thus far been directed toward decreasing the accumulation of hydrogen sulfide metabolites using a combination of metronidazole and N-acetylcysteine. More recently, orthotopic liver transplant (OLT) has been reported as a new therapeutic option for EE. Here, we report two additional cases of EE who achieved psychomotor developmental improvement after 7- and 22-months following OLT. The second case serves as the longest developmental outcome follow-up reported, thus far, following OLT for EE. This report provides additional evidence to validate OLT as a promising therapeutic approach for what was considered to be a fatal disease.

Biliary Atresia as a Disease Starting In Utero: Implications for Treatment, Diagnosis, and Pathogenesis.

Biliary atresia (BA) is the most common reason for pediatric liver transplant. BA's varied presentation, natural history, and treatment with the Kasai portoenterostomy have been well described; however, when BA starts relative to birth has not been clearly defined. In this review, we discuss laboratory, imaging, and clinical data which suggest that most if not all forms of BA may start before birth. This early onset has implications in terms of delivering treatments earlier and identifying possible factors underlying BA's etiology.

Longitudinal assessment of T cell inhibitory receptors in liver transplant recipients and their association with posttransplant infections.

Current immunosuppression regimens in organ transplantation primarily inhibit T cells. However, T cells are also critical in protective immunity, especially in immune-compromised patients. In this study, we examined the association of T cell dysfunction, as marked by expression of T cell exhaustion molecules, and posttransplant infections in a cohort of liver transplant patients. We focused on Programmed Death 1 (PD-1) and T cell Ig- and mucin-domain molecule 3 (Tim-3), which are potent co-inhibitory receptors, and their persistent expression often leads to T cell dysfunction and compromised protective immunity. We found that patients with the highest expression of PD-1 +Tim-3+ T cells in the memory compartment before transplantation had increased incidence of infections after liver transplantation, especially within the first 90 days. Longitudinal analysis in the first year showed a strong association between variability of PD-1 and Tim-3 expression by T cells and infectious episodes in transplant patients. Furthermore, T cells that expressed PD-1 and Tim-3 had a significantly reduced capacity in producing interferon (IFN)-γ in vitro, and this reduced IFN-γ production could be partially reversed by blocking PD-1 and Tim-3. Interestingly, the percentage of Foxp3+ regulatory T cells in liver transplant patients was stable in the study period. We concluded that the functional status of T cells before and after liver transplantation, as shown by PD-1 and Tim-3 expression, may be valuable in prognosis and management of posttransplant infections.

ABO-incompatible deceased donor pediatric liver transplantation: Novel titer-based management protocol and outcomes.

ABO-ILT have re-emerged as an alternate option for select patients awaiting transplant. However, treatment protocols for children undergoing deceased donor ABO-ILT are not standardized. We implemented a novel IS protocol for children undergoing deceased donor ABO-ILT based on pretransplant IH titers. Children with high pretransplant IH titers (≥1:32) underwent an enhanced IS protocol including plasmapheresis, rituximab, IVIG, and mycophenolate, while children with IH titers ≤1:16 received steroids and tacrolimus. We retrospectively assessed our outcomes of ABO-ILT with ABO-compatible recipients of similar age and diagnosis over a 2-year period. Ten children with median age of 8.9 months underwent ABO-ILT, 4 of 10 patients underwent enhanced IS due to high IH titers. Rates of complications (rejection, infections, biliary, and vascular) at both 1 year and up to 3 years post-transplant were comparable between the groups. Patients with ABO-ILT had good graft function with 100% survival at a median follow-up of 3.3 years. In conclusion, IS tailored to pretransplant IH titers in pediatric deceased donor ABO-ILT is feasible and can achieve outcomes similar to ABO-CLT at 1 and 3 years post-transplantation.

Herbal and dietary supplement induced liver injury leading to hepatitis-associated severe aplastic anemia: A case report.

Herbal and dietary supplements (HDS) are a common etiology of drug induced liver injury and, specifically, Herbalife® supplements have been implicated. Hepatitis associated aplastic anemia (HAAA) is a rare and potentially fatal complication after acute hepatitis characterized by pancytopenia. While there have been rare cases of HDS leading to HAAA, no cases of Herbalife® induced liver injury leading to HAAA have been reported from this specific HDS. We report a unique case of severe aplastic anemia developing after sub-fulminant liver failure associated with chronic HDS use. This case illustrates the importance of warning the public about HDS as their use continues to increase. It is not only important to recognize HDS as etiology, but also for healthcare providers to carefully monitor these patients after resolution of liver injury for the development of HAAA.

Protein biomarkers GDF15 and FGF21 to differentiate mitochondrial hepatopathies from other pediatric liver diseases.

BACKGROUND: Mitochondrial hepatopathies (MHs) are primary mitochondrial genetic disorders that can present as childhood liver disease. No recognized biomarkers discriminate MH from other childhood liver diseases. The protein biomarkers growth differentiation factor 15 (GDF15) and fibroblast growth factor 21 (FGF21) differentiate mitochondrial myopathies from other myopathies. We evaluated these biomarkers to determine if they discriminate MH from other liver diseases in children. METHODS: Serum biomarkers were measured in 36 children with MH (17 had a genetic diagnosis); 38 each with biliary atresia, α1-antitrypsin deficiency, and Alagille syndrome; 20 with NASH; and 186 controls. RESULTS: GDF15 levels compared to controls were mildly elevated in patients with α1-antitrypsin deficiency, Alagille syndrome, and biliary atresia-young subgroup, but markedly elevated in MH (p<0.001). FGF21 levels were mildly elevated in NASH and markedly elevated in MH (p<0.001). Both biomarkers were higher in patients with MH with a known genetic cause but were similar in acute and chronic presentations. Both markers had a strong performance to identify MH with a molecular diagnosis with the AUC for GDF15 0.93±0.04 and for FGF21 0.90±0.06. Simultaneous elevation of both markers >98th percentile of controls identified genetically confirmed MH with a sensitivity of 88% and specificity of 96%. In MH, independent predictors of survival without requiring liver transplantation were international normalized ratio and either GDF15 or FGF21 levels, with levels <2000 ng/L predicting survival without liver transplantation (p<0.01). CONCLUSIONS: GDF15 and FGF21 are significantly higher in children with MH compared to other childhood liver diseases and controls and, when combined, were predictive of MH and had prognostic implications.

Interprovider variation of celiac disease testing in childhood chronic abdominal pain.

BACKGROUND: To determine within one tertiary care center: 1) the variation between providers in testing for celiac disease in children with chronic abdominal pain; 2) the characteristics of those children who were more likely to be tested, and 3) the prevalence of celiac disease in those evaluated. METHODS: Retrospective review of children with a primary complaint of chronic abdominal pain referred to a tertiary care children's hospital for pediatric gastroenterology evaluation over a 2-year period was conducted. Children with at least two visits and without an identified organic etiology for the pain were included. RESULTS: 160 children were evaluated by 16 pediatric gastroenterologists and one nurse practitioner. Celiac serologic testing was completed in 63 (39.4%) children. There was no significant variance in the frequency of celiac serologic testing between providers. Child age, gender, body mass index, and baseline gastrointestinal symptoms did not predict whether celiac serologic testing occurred, though Caucasians (P < 0.01) were more likely to be tested. Eighty-two (51.3%) children underwent either serologic testing and/or esophagogastroduodenoscopy. Four (4.9%, 95% CI: 1.6-11.3%) of the 82 tested were diagnosed with celiac disease. CONCLUSIONS: Though interprovider variation for celiac disease testing in children with chronic abdominal pain did not occur, a large number of these children were not evaluated for celiac disease. Children's race/ethnicity but not their associated gastrointestinal symptoms predicted whether celiac testing was undertaken. In those tested, celiac disease was identified in a higher percentage than that expected in the general population.

Characteristics of infections and their risk factors in children with biliary atresia.

BACKGROUND: Children with biliary atresia (BA) may experience various infections (e.g., cholangitis, bacteremia, and viral respiratory infections (VRI)) throughout their disease course. This study aimed to identify and describe these infections and their risk factors for development in children with BA. METHODS: This retrospective observational study identified infections in children with BA using predefined criteria, including VRI, bacteremia with and without central line (CL), bacterial peritonitis, positive stool pathogens, urinary tract infections, and cholangitis. Infections were identified until liver transplant, death or last follow-up with native liver. Infection-free survival was estimated by Kaplan-Meier analysis. Logistic regression was used to estimate odds of infection per clinical characteristics. Cluster analysis was performed to identify patterns of infection development. RESULTS: 48 of 65 (73.8%) children had ≥1 infection during their disease course (mean length of follow up: 40.2 months). Cholangitis (n = 30) and VRI (n = 21) were most common. Nearly half (45%) of all infections developed within 3-months of Kasai hepatoportoenterostomy. Kasai performed ≥45 days of life was associated with 3.5-fold increased risk of any infection (95% CI 1.2-11.4). Risk of VRI was inversely related to platelet count at 1-month post-Kasai (OR 0.5, 0.19-0.99). Cluster analysis of infectious patterns identified three unique cohorts of patients based on their infection history: no/few infections (n = 18), mostly cholangitis (n = 20) or mixed infections (n = 27). CONCLUSION: Variability of infection risk exists amongst children with BA. Age at Kasai and platelet count are risk factors for future infections, suggesting that patients with more severe disease are at greater risk. Cirrhosis associated immune deficiency may exist in chronic pediatric liver disease and should be the subject of future investigations in order to optimize outcomes.

Pediatric Acute Liver Failure Secondary to Autoimmune Hepatitis in an Infant With Thrombocytopenia-Absent Radius (TAR) Syndrome: A Case Report.

Thrombocytopenia absent radius (TAR) syndrome is a rare genetic disorder that has been associated with food protein-induced allergic proctocolitis and transient leukemoid reactions, among other manifestations. There has been no prior reports of its association with autoimmune disease, more specifically, autoimmune hepatitis (AIH) or the development of pediatric acute liver failure (PALF). We present a case of an 8-month-old infant with TAR syndrome who presented with PALF, secondary to AIH with elevated liver-kidney microsomal antibody (>1:2560). She received a liver transplant and had a very complicated postoperative course including severe T-cell-mediated rejection, infection, biliary stricture, persistently elevated liver-kidney microsomal antibodies, and antibody-mediated rejection. Ultimately, these complications led to graft failure, severe sepsis, and death. This case highlights a new association of TAR syndrome with AIH and PALF and a potentially aggressive nature of AIH both pre- and post-transplant.

Elevated bile acids are associated with left ventricular structural changes in biliary atresia.

BACKGROUND: In children with biliary atresia (BA), pathologic structural changes within the heart, which define cirrhotic cardiomyopathy, are associated with adverse perioperative outcomes. Despite their clinical relevance, little is known about the pathogenesis and triggers of pathologic remodeling. Bile acid excess causes cardiomyopathy in experimental cirrhosis, but its role in BA is poorly understood. METHODS: Echocardiographic parameters of left ventricular (LV) geometry [LV mass (LVM), LVM indexed to height, left atrial volume indexed to BSA (LAVI), and LV internal diameter (LVID)] were correlated with circulating serum bile acid concentrations in 40 children (52% female) with BA listed for transplantation. A receiver-operating characteristic curve was generated to determine optimal threshold values of bile acids to detect pathologic changes in LV geometry using Youden index. Paraffin-embedded human heart tissue was separately analyzed by immunohistochemistry for the presence of bile acid-sensing Takeda G-protein-coupled membrane receptor type 5. RESULTS: In the cohort, 52% (21/40) of children had abnormal LV geometry; the optimal bile acid concentration to detect this abnormality with 70% sensitivity and 64% specificity was 152 µmol/L (C-statistics=0.68). Children with bile acid concentrations >152 µmol/L had ∼8-fold increased odds of detecting abnormalities in LVM, LVM index, left atrial volume index, and LV internal diameter. Serum bile acids positively correlated with LVM, LVM index, and LV internal diameter. Separately, Takeda G-protein-coupled membrane receptor type 5 protein was detected in myocardial vasculature and cardiomyocytes on immunohistochemistry. CONCLUSION: This association highlights the unique role of bile acids as one of the targetable potential triggers for myocardial structural changes in BA.

Clinical spectrum and genetic causes of mitochondrial hepatopathy phenotype in children.

BACKGROUND: Alterations in both mitochondrial DNA (mtDNA) and nuclear DNA genes affect mitochondria function, causing a range of liver-based conditions termed mitochondrial hepatopathies (MH), which are subcategorized as mtDNA depletion, RNA translation, mtDNA deletion, and enzymatic disorders. We aim to enhance the understanding of pathogenesis and natural history of MH. METHODS: We analyzed data from patients with MH phenotypes to identify genetic causes, characterize the spectrum of clinical presentation, and determine outcomes. RESULTS: Three enrollment phenotypes, that is, acute liver failure (ALF, n = 37), chronic liver disease (Chronic, n = 40), and post-liver transplant (n = 9), were analyzed. Patients with ALF were younger [median 0.8 y (range, 0.0, 9.4) vs 3.4 y (0.2, 18.6), p < 0.001] with fewer neurodevelopmental delays (40.0% vs 81.3%, p < 0.001) versus Chronic. Comprehensive testing was performed more often in Chronic than ALF (90.0% vs 43.2%); however, etiology was identified more often in ALF (81.3% vs 61.1%) with mtDNA depletion being most common (ALF: 77% vs Chronic: 41%). Of the sequenced cohort (n = 60), 63% had an identified mitochondrial disorder. Cluster analysis identified a subset without an underlying genetic etiology, despite comprehensive testing. Liver transplant-free survival was 40% at 2 years (ALF vs Chronic, 16% vs 65%, p < 0.001). Eighteen (21%) underwent transplantation. With 33 patient-years of follow-up after the transplant, 3 deaths were reported. CONCLUSIONS: Differences between ALF and Chronic MH phenotypes included age at diagnosis, systemic involvement, transplant-free survival, and genetic etiology, underscoring the need for ultra-rapid sequencing in the appropriate clinical setting. Cluster analysis revealed a group meeting enrollment criteria but without an identified genetic or enzymatic diagnosis, highlighting the need to identify other etiologies.

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.

Diagnostic utility of wireless motility capsule in gastrointestinal dysmotility.

GOALS: To examine the diagnostic utility of wireless motility capsule (WMC) in patients with suspected gastrointestinal (GI) dysmotility. BACKGROUND: Subjects with suspected GI motility disorders undergo invasive and expensive diagnostic tests. In these patients, whether WMC provides clinically useful information is unknown. STUDY: Patients with symptoms of dysmotility and normal endoscopic/radiologic evaluations were assessed with WMC test and conventional motility tests (CMT). Diagnostic utility of WMC was assessed retrospectively by examining device agreement and new information compared with CMT. RESULTS: On the basis of predominant symptom(s), 86 patients were classified into 2 subgroups: lower GI (LGI=50) and upper GI (UGI=36). Clinical suspicion was confirmed in 52% and 66% of patients, respectively, and there was good device agreement between WMC and CMT in 76% and 81% in the LGI and UGI groups, respectively. There was new diagnostic information with the WMC test in 53% of the LGI (P=0.006) and 47% of the UGI group (P=0.001). WMC detected generalized motility disorder in 44 (51%) patients and influenced management in 30% of LGI and 50% of UGI subjects. CONCLUSIONS: WMC confirmed clinical suspicion, provided new diagnostic information, influenced clinical management, and detected many patients with generalized motility disorder. It had good device agreement with conventional tests.