Pediatric Solid Organ Research Articles

Presentation, management, and outcomes of norovirus in adult and pediatric solid organ and hematopoietic stem cell transplant recipients: A multicenter, retrospective study.

Norovirus (NoV) can cause chronic relapsing and remitting diarrhea in immunocompromised patients. Few multicenter studies have described the clinical course, outcomes, and complications of chronic NoV in transplant recipients. A multicenter retrospective study of adult and pediatric SOT and HSCT recipients diagnosed with NoV between November 1, 2017, and February 28, 2021. Data were obtained from electronic medical records (EMR) and entered into a central REDCap database. Descriptive statistics were calculated. A total of 280 NoV+ patients were identified across eight sites. The majority were adults (74.1%) and SOT recipients (91.4%). Initial diagnosis of NoV occurred a median of 36 months post-Tx (IQR [15.0, 90.0]). Most NoV cases had >3 diarrheal episodes daily (66.0%), nausea and vomiting (60.1%). Duration of diarrhea varied greatly (median = 10 days, mean = 85.9 days, range (1, 2100)). 71.3% were hospitalized. Adjustment of immunosuppression, including reduction and discontinuation of mToR inhibitor, CNI, and/or MMF, was the most common management intervention for NoV. Other therapies resulted only in temporary improvement. Four patients died within 30 days and three others died by 180 days postdiagnosis. Clinically significant renal dysfunction was observed in 12.5% by 30 days and 21.4% by 180 days post-NoV diagnosis. In HSCT and SOT patients, NoV frequently resulted in severe symptoms, prolonged diarrhea (30% persistent with diarrhea for >30 days), and clinically significant renal dysfunction (up to 21% of patients). Utilized therapies did not reliably result in the resolution of infection demonstrating the need for more effective treatment.

Viral meningoencephalitis in pediatric solid organ or hematopoietic cell transplant recipients: a diagnostic and therapeutic approach.

Neurologic complications, both infectious and non-infectious, are frequent among hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients. Up to 46% of HCT and 50% of SOT recipients experience a neurological complication, including cerebrovascular accidents, drug toxicities, as well as infections. Defects in innate, adaptive, and humoral immune function among transplant recipients predispose to opportunistic infections, including central nervous system (CNS) disease. CNS infections remain uncommon overall amongst HCT and SOT recipients, compromising approximately 1% of total cases among adult patients. Given the relatively lower number of pediatric transplant recipients, the incidence of CNS disease amongst in this population remains unknown. Although infections comprise a small percentage of the neurological complications that occur post-transplant, the associated morbidity and mortality in an immunosuppressed state makes it imperative to promptly evaluate and aggressively treat a pediatric transplant patient with suspicion for viral meningoencephalitis. This manuscript guides the reader through a broad infectious and non-infectious diagnostic differential in a transplant recipient presenting with altered mentation and fever and thereafter, elaborates on diagnostics and management of viral meningoencephalitis. Hypothetical SOT and HCT patient cases have also been constructed to illustrate the diagnostic and management process in select viral etiologies. Given the unique risk for various opportunistic viral infections resulting in CNS disease among transplant recipients, the manuscript will provide a contemporary review of the epidemiology, risk factors, diagnosis, and management of viral meningoencephalitis in these patients.

Routine Repeat Imaging of Pediatric Blunt Solid Organ Injuries Is Not Necessary.

Nonoperative management of hemodynamically stable patients with blunt splenic and/or hepatic injury has been widely accepted in the pediatric population. However, variability exists in the utilization and timing of repeat imaging to assess for delayed complications during index hospitalization. Recent level-IV evidence suggests that repeat imaging in children should be performed based on a patient's clinical status rather than on a routine basis. The aim of this study is to examine the rate of delayed complications and interventions in pediatric trauma patients with blunt splenic and/or hepatic injuries who undergo repeat imaging prompted either by a clinical change (CC) or non-clinical change (NCC). A 9-year (2011-2019), retrospective, dual-institution study was performed of children (0-17years) with blunt splenic and/or hepatic injuries. Patients were grouped based on reason for repeat imaging: CC or NCC. The rate of organ-specific delayed complications and interventions was examined by reason for scan. A total of 307 injuries were included in the study period (174 splenic, 113 hepatic, and 20 both). Of 194 splenic injuries, 30(15.5%) underwent repeat imaging (CC = 19; NCC = 11). Of 133 hepatic injuries, 27(20.3%) underwent repeat imaging (CC = 21; NCC = 6). There was no difference in the incidence of organ-specific delayed complications between the CC and NCC groups. Of the 4 patients with complications necessitating intervention, only one was identified based on NCC. Our data suggest routine repeat imaging is unnecessary in children with blunt splenic and/or hepatic injuries; therefore, practitioners may rely on a patient's clinical change.

#50: Cytomegalovirus Retinitis Among Pediatric Hematopoietic Stem Cell and Solid Organ Transplantation Recipients: A Contemporary Review

Abstract Background Cytomegalovirus infection can cause significant morbidity and mortality after transplantation. Cytomegalovirus retinitis (CMVR) can be a major complication of tissue invasive CMV disease in transplant recipients. There are little data regarding the contemporary incidence and outcomes of CMVR among pediatric transplant recipients. Methods We performed a retrospective cohort analysis of allogeneic hematopoietic (allo-HCT) and solid organ transplant (SOT) recipients who received medical care at Nationwide Children’s Hospital (NCH) from 1/1/10–11/30/20 and had a diagnosis of CMVR to describe the incidence, timing post-transplant, ocular manifestations, management, and outcomes. Basic demographic and clinical data, pre-transplant donor/recipient CMV serostatus, and post-transplant CMV infection data were collected. Graft-specific CMV surveillance and prophylaxis strategies were performed according to NCH hospital guidelines. During the study period, quantitative plasma CMV PCR assays included copies/mL (2010–2013) and WHO international standard IU/mL (2013–2020). Results During the 10-year study period, 347 patients underwent allo-HCT (N=214) or SOT (N=133; heart N=46, liver N=36, kidney N= 52; 1 patient had concomitant kidney and liver transplantation); median age was 8.6 years [range 0.1–25.9] and 198 (56.5%) were male. In total, 98 patients had CMV DNAemia post-transplant, and CMVR was diagnosed in 3 (HCT=2, SOT=1), for an overall CMVR incidence of 0.86% among all transplant recipients and occurring in 3% of patients with CMV DNAemia. No CMVR was diagnosed in patients without CMV DNAemia. An ophthalmologic examination was performed in 58 (59%) of patients with any DNAemia compared with 67 (27%) of patients without DNAemia. CMVR was diagnosed on funduscopic examination a median of 183 days [range 34–512] post-transplant based on visual symptomatology (N=2) or by routine eye screening prompted by DNAemia (N=1). CMV DNAemia at the time of CMVR was 1,463 copies/mL, 3,000, and 14,204 IU/mL; all patients had prolonged (>3 months) CMV detection before CMVR. One SOT recipient had concomitant pathology confirming CMV gastrointestinal tract disease. Two of the 3 CMVR cases occurred in the setting of genotypic UL94 CMV resistance mutations (A594V, H520Q)(Figure 1). Two patients were already receiving CMV antiviral therapy (maribavir N=1; valganciclovir=1) at the time of CMVR diagnosis. After the CMVR diagnosis, all patients were prescribed systemic foscarnet. Adjunctive therapies included concurrent intravitreal antiviral therapy (ganciclovir N=1; foscarnet N=1) and adoptive immunotherapy with CMV antiviral specific T-cells (N=1, HCT). Improvement of ocular symptoms occurred in 2 patients at 15 and 20 days after starting targeted CMV antiviral therapy; one patient developed permanently impaired vision. Conclusion CMVR remains as an important complication in transplant recipients. Although CMVR incidence was low in our cohort of transplant recipients, it occurred most frequently in cases of CMV resistance, prolonged DNAemia, and led to permanent visual impairment in 1 of 3 patients. The development of resistant CMV may have a role in the occurrence, progression, and severity of CMVR. Additional pediatric-specific data are needed to better characterize CMVR and inform optimal prevention strategies.

Tuberculosis in Pediatric Solid Organ and Hematopoietic Stem Cell Recipients.

Children undergoing solid organ and hematopoietic stem cell transplantation are at high risk of morbidity and mortality from tuberculosis (TB) disease in the post-transplant period. Treatment of TB infection and disease in the post-transplant setting is complicated by immunosuppression and drug interactions. There are limited data that address the unique challenges for the management of TB in the pediatric transplant population. This review presents the current understanding of the epidemiology, clinical presentation, diagnosis, management, and prevention for pediatric transplant recipients with TB infection and disease. Further studies are needed to improve diagnosis of TB and optimize treatment outcomes for these patients.

Effectiveness of immunosuppression minimisation, conversion or withdrawal strategies in paediatric solid organ and haematopoietic stem cell transplantation: a protocol of a systematic review and meta-analysis

IntroductionPaediatric transplantation is the only curative therapeutic procedure for several end-stage rare diseases affecting different organs and body systems, causing altogether great impact in European children’s health and quality of...

Cross-cutting view of current challenges in paediatric solid organ and haematopoietic stem cell transplantation in Europe: the European Reference Network TransplantChild

The low prevalence of European paediatric transplanted patients and scarcity of resources and expertise led to the need for a multidisciplinary network able to improve the quality of life of paediatric patients and families requiring a solid organ or haematopoietic stem cell transplantation. The European Reference Network (ERN) TransplantChild is one of the 24 ERNs established in a European legal framework to improve the care of patients with rare diseases. ERN TransplantChild is the only ERN focused on both solid organ and haematopoietic stem cell paediatric transplantation, based on the understanding of paediatric transplantation as a complex and highly specialised process where specific complications appear regardless the organ involved, thus linking the skills and knowledge of different organ disciplines. Gathering European centres of expertise in paediatric transplantation will give access to a correct and timely diagnosis, share expertise and knowledge and collect a critical mass of patients and data that increases the speed and value of clinical research outcomes. Therefore, the ERN TransplantChild aims for a paediatric Pan-European, Pan-transplant approach.

Non-Operative Management of Pediatric Blunt Abdominal Solid Organ Injuries : Our Experience at Queen Rania Al-Abdullah Hospital for Children

Non-Operative Management of Pediatric Blunt Abdominal Solid Organ Injuries : Our Experience at Queen Rania Al-Abdullah Hospital for Children

Sex and gender considerations in transplantation research: protocol for a scoping review

BackgroundDespite the growing appreciation of the importance of sex and gender considerations in transplantation research, there is currently no framework or good practice guidelines for the appropriate handling of sex and gender issues in human allotransplantation research.MethodsWe will conduct a scoping review to synthesize the evidence on how matters of sex and gender have been handled in human allotransplantation research. We will survey the literature discussing sex and gender in relation to transplantation, including adult and pediatric patients, hematopoietic and solid organ transplant recipients as well as organ donors. We will search MEDLINE and Embase for literature discussing sex and gender in relation to transplantation. Two reviewers will independently evaluate the eligibility of all identified titles and abstracts for inclusion in the full text review, as well as data extraction. Descriptive data and information on how sex and gender have been considered in human transplantation research will be reported.DiscussionThis scoping review will be an important stepping stone towards the development of good practice guidelines on study design and analysis considerations when handling sex and gender issues in human transplantation research. This scoping review can also help identify methodological issues that restrict the translation of transplantation research findings into clinical practice related to underestimation of sex/gender differences. This review will ultimately identify major gaps, inform donor-recipient selection, guide personalized interventions, and prioritize research recommendations in human transplantation research.

Respiratory Viral Infections in Pediatric Solid Organ and Hematopoietic Stem Cell Transplantation

Respiratory viruses are common in children, including pediatric recipients of both solid organ transplantation and hematopoietic stem cell transplantation. The prevalence and risk factors in each of these groups are reviewed. Furthermore, associated morbidity and mortality in pediatric transplant recipients with respiratory viral infections are addressed. The literature on specific prevention and treatment options for respiratory syncytial virus, adenovirus, influenza, and other respiratory viruses in pediatric solid organ and hematopoietic stem cell transplant recipients is reported.

Anti-adenoviral substances isolated from medicinal plants: current status and future prospects

Development of safe and commonly approved antiviral therapy and/or immunotherapy for infections caused by human double-stranded DNA adenoviruses (HAdVs) in a variety of immunocompromised hosts as AIDS patients, hereditary immunodeficient subjects, pediatric solid organ or haematopoietic steam cell transplant recipients, is still a challenging issue. Thus, the recently reported advances in the development of extraction, identification, cytotoxicity evaluation, proteomic profiling and antiviral activity assays protocols used for search of substances with medicinal plant origin which indicated selective and potent activity against human adenoviruses causing a number of self-limiting mild respiratory, gastrointestinal, genitourinary, ocular and obesity-related [1,2] infectious disease has been reviewed. The performed meta-analysis of these research showed that a still limited set of the plant derived active compounds as some catechins, hydroxyflavones, metoxyflavones, polyphenol acids, depsides, pentacyclic triterpenes, and terpene alcohols has been identified to cause in vitro and in vivo effects on specific human adenovirus inactivation and growth. A significant anti-HAdV activity at non-toxic concentration for some fractions of ethanolic- or water-type extracts obtained from a restrained number of medicinal plants with ethno-medical background and belonging to different plant families have been also described. However, further and more intensified research is needed to elucidate the active constituents of these plants and to establish detailed mechanism of their anti-adenoviral and virucidal effects to enable development of effective and marketable anti-HAdVs agents.

Parvovirus B19 in Solid Organ Transplant Recipients

Parvovirus B19 is a common, ubiquitous human pathogen.It is a small, single-stranded linear, nonenveloped DNAvirus classified into three different genotypes (genotype1, Au and Wi strains; genotype 2, LaLi and A6 strains; andgenotype 3, V9 strains). Its worldwide genetic variability islow, and there is no clear correlation between genotypeand distinctive clinical manifestation. Parvovirus B19 repli-cates most efficiently and preferentially in human erythro-cyte precursors; thus, the virus is classified as a memberof the Erythrovirus genus of the Parvoviridae family. Mostpeople are infected between the ages of 5 and 15 years;by adulthood, up to 80% are seropositive (1). Infection ap-pears to confer lifelong immunity to immunocompetenthosts, but reinfection is possible in a minority of cases(2). It has been hypothesized that Parvovirus B19 can per-sist in the bone marrow and other tissues (3), support-ing possible reactivation rather than reinfection in certainseropositive patients. Parvovirus B19 infection can be ei-ther symptomatic or asymptomatic, depending on the age,hematologic and immunologic status of the host. Whilemostpatientsrecollectonlynonspecificflu-likesymptoms,distinctive clinical entities have been associated with Par-vovirus B19 infection in both immunocompetent hosts (4)and solid organ transplant (SOT) recipients (5). The mostcommonclinicalmanifestationsofParvovirusB19aresum-marizedinTable1.Although large, prospective surveillance studies are lack-ing, earlier studies reported an incidence of Parvovirus B19disease of

RNA Respiratory Viral Infections in Solid Organ Transplant Recipients

A wide range of RNA respiratory viruses have been identi-fiedascausesofsignificantmorbidityandmortalityamongtransplant recipients, including influenza, respiratory syn-cytial virus (RSV), parainfluenza virus (PIV), rhinovirus, hu-manmetapneumovirus(hMPV),coronavirus,bocavirusandpolyomaviruses (1) (Table 1). Several features are commonamong all of these viruses in the transplant population:1. The seasonality of respiratory viral infections amongtransplant recipients usually follows that of the generalpopulation (2,3).2. The viruses all cause a range of disease, from mild con-gestion and rhinorrhea to more severe tracheobronchi-tis, bronchiolitis and pneumonia. No one virus is ex-clusively associated with one clinical syndrome (i.e.influenza-like illness, croup, etc.). As such, diagnosticstrategiesshouldinitiallybebroad,attemptingtoscreenfor all recognized viruses (3,4) with particular emphasison ones that might be amenable to therapy. Symptomscommonly associated with a respiratory viral infectioninclude fevers, nasal congestion, rhinorrhea, wateryeyes, cough, sore throat, sputum production, wheez-ing, shortness of breath and fevers.3. Transplant recipients often present with mild or atypi-cal symptoms. Lung transplant recipients, for example,may initially only have subjective symptoms of short-ness of breath or subtle changes in pulmonary functiontesting without more typical symptoms (5). Fever maybe absent in transplant recipients with pneumonia ormay be the sole presenting sign or symptom (1,4). Assuch, any fever or respiratory symptom should promptthe consideration of a respiratory viral infection as thepotential cause.4. Viral shedding is usually prolonged among transplantrecipients. Prolonged shedding is seen even with theuse of antivirals and therefore may contribute to theincreased risk of resistant variant emergence (1,6).5. Transplant recipients are at higher risk of infectiouscomplications compared to immunocompetent hosts.In the older studies, initial evidence of or progressionto lower tract involvement with viruses occurred fre-quently, but may in part be due to ascertainment biasesas sicker patients were more likely to be seen by physi-cians and have specimens sent for viral assays (1). Res-piratory viral infections are a significant risk factor forsubsequent development of fungal and bacterial pneu-monia (1). Other infections, such as CMV viremia, maycomplicate respiratory viral infections as well.6. Respiratory viral infections appear to be a risk factor forboth acute and chronic rejection with the greatest riskin lung transplant recipients (5,7–9) (II-2). Concurrentrejection and graft dysfunction has been documentedwith other solid organ transplant recipients as well, al-though at a lower frequency than in lung transplant re-cipients (1) (III). The pathogenesis of the link betweenrespiratory viral infections and rejection is not clearlyunderstood.7. All pediatric solid organ and lung transplant recipientsappear to have the greatest risk of both RNA viral in-fections and more severe courses and complications(1).8. All are potential nosocomial pathogens which can bepotentially spread by staff or visitor with mild upperrespiratory illness.9. There are few prospective studies of respiratory virusinfections in most solid organ transplant populations,withtheexceptionoflungtransplantrecipients.Mostofthese studies were retrospective in nature and focusedonindividualswhowerehospitalizedwithinfections(1).Inaddition,moststudiesevaluatedpatientsclosetothetime of transplantation when specimens were morelikely to be obtained for diagnosis. This likely leads toan overestimation of the severity and underestimationof the incidence of these infections among transplantrecipients.

54 A prospective study of Parvovirus B19 infections in pediatric solid-organ and bone marrow transplant recipients and pediatric solid tumor patients: Preliminary results

54 A prospective study of Parvovirus B19 infections in pediatric solid-organ and bone marrow transplant recipients and pediatric solid tumor patients: Preliminary results

Human Parvovirus B19

Human Parvovirus B19

Parvovirus B19 infection in pediatric solid-organ and bone marrow transplantation.

The clinical significance of parvovirus B19 infection in pediatric solid-organ and bone marrow transplanted patients is unclear. The overall prevalence of parvovirus B19 infection in these patients is about 1-2% during the first year after transplantation. The most common symptom is anemia, but leukopenia and thrombocytopenia have also been observed. Rare cases of hepatic dysfunction, myocarditis, vasculitis and respiratory failure have also been reported. Whereas serology is of limited value around the time of transplantation, it is recommended that a search for B19 DNA is included in first-line investigations in any transplanted patient with unexplained anemia. Specific antiviral therapy is not available, however, intravenous immunoglobulin produces rapid improvement in most cases. Although relatively rare, the severe complications following parvovirus B19 infection in the transplant setting can be avoided by early diagnosis and treatment.