ABSTRACT
Background: Valganciclovir is the only approved antiviral for cytomegalovirus (CMV) prevention in pediatric solid organ transplantation (SOT). Additional approaches may be needed to improve outcomes. Methods: A multicenter retrospective study from 2016 to 2019 was conducted of pediatric SOT recipients in whom at least 3 months of valganciclovir prophylaxis was planned. Episodes of CMV DNA in blood (DNAemia), CMV disease, drug-related toxicities, as well as other infections in the first year posttransplant and demographic and clinical data were collected. CMV DNAemia in the first year after prophylaxis or during prophylaxis (breakthrough) was analyzed by multivariate hazard models. Results: Among the 749 patients enrolled, 131 (17.5%) had CMV DNAemia at any time in the first year; 85 (11.4%) had breakthrough DNAemia, and 46 (6.1%) had DNAemia after prophylaxis. CMV disease occurred in 30 (4%). In a multivariate model, liver transplantation compared to kidney or heart, intermediate or high risk based on donor/recipient serologies, neutropenia, and valganciclovir dose modifications attributed to toxicity were associated with increased risk of total and/or breakthrough DNAemia. Bacteremia was also associated with increased hazard ratio for CMV DNAemia. In a separate multivariate analysis, rejection occurred more often in those with breakthrough CMV DNAemia (P = .002); liver transplants, specifically, had increased rejection if CMV DNAemia occurred in the first year (P = .004). These associations may be bidirectional as rejection may contribute to infection risk. Conclusions: CMV DNAemia in the first year posttransplantation occurs despite valganciclovir prophylaxis and is associated with medication toxicity, bacteremia, and rejection. Pediatric studies of newer antivirals, especially in higher-risk subpopulations, appear to be warranted.
ABSTRACT
Optimal dosing of valganciclovir (VGCV) for cytomegalovirus (CMV) prevention in pediatric solid organ transplantation recipients (SOTR) is controversial. Dosing calculated based on body surface area (BSA) and creatinine clearance is recommended but simplified body weight (BW) dosing is often prescribed. We conducted a retrospective 6-center study to compare safety and efficacy of these strategies in the first-year posttransplant There were 100 (24.2%) pediatric SOTR treated with BSA and 312 (75.7%) with BW dosing. CMV DNAemia was documented in 31.0% vs 23.4% (P = .1) at any time during the first year and breakthrough DNAemia in 16% vs 12.2% (P = .3) of pediatric SOTR receiving BSA vs BW dosing, respectively. However, neutropenia (50% vs 29.3%, P <.001), lymphopenia (51% vs 15.0%, P <.001), and acute kidney injury causing treatment modification (8.0% vs 1.8%, P <.001) were documented more frequently during prophylaxis in pediatric SOTR receiving BSA vs BW dosing. The adjusted odds ratio of VGCV-attributed toxicities comparing BSA and BW dosing was 2.3 (95% confidence interval [CI], 1.4-3.7] for neutropenia, 7.0 (95% CI, 3.9-12.4) for lymphopenia, and 4.6 (95% CI, 2.2-9.3) for premature discontinuation or dose reduction of VGCV, respectively. Results demonstrate that BW dosing is associated with significantly less toxicity without any increase in CMV DNAemia.
Subject(s)
Cytomegalovirus Infections , Lymphopenia , Neutropenia , Organ Transplantation , Child , Humans , Valganciclovir/therapeutic use , Antiviral Agents/therapeutic use , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/etiology , Cytomegalovirus Infections/prevention & control , Body Surface Area , Retrospective Studies , Cytomegalovirus , Neutropenia/etiology , Neutropenia/drug therapy , Organ Transplantation/adverse effects , Body Weight , Ganciclovir/therapeutic useABSTRACT
We describe the successful treatment of a 10-month-old female with respiratory distress secondary to Coronavirus disease 2019 (COVID-19) with the nebulized investigational drug, DAS181. Therapy was well tolerated, and the patient had minimal side effects. The patient's respiratory distress and positive viral polymerase chain reaction rapidly resolved after initiation of therapy.
Subject(s)
Antiviral Agents/therapeutic use , COVID-19 Drug Treatment , Neuraminidase/therapeutic use , Recombinant Fusion Proteins/therapeutic use , COVID-19/diagnostic imaging , COVID-19/physiopathology , Female , Humans , Infant , SARS-CoV-2/isolation & purificationABSTRACT
MRSA infection following SOT is an important cause of morbidity and mortality, but epidemiology and risk factors for colonization prior to pediatric SOT remain unclear. A retrospective cohort of SOT patients ≤21 years of age from 2009 to 2014 was evaluated. Demographics, MRSA screens, timing of transplantation, and MRSA infection were abstracted. From 2013 to 2014, 130 SOT candidates were screened or had known prior MRSA infection. Seventeen patients (13%) were MRSA colonized. Liver transplant candidates were least likely to be colonized (OR 0.22, CI:0.06-0.81, P = .02); greatest risk of colonization was in lung (OR 18.7, CI:1.9-182.3, P = .03), abdominal multivisceral (OR 7.5, CI:1.5-38.6, P = .02), and cardiac patients with history of cardiothoracic surgery (OR 8.0, CI:1.7-36.0, P = .007). In univariable analysis, African American patients were more likely to be colonized (OR 7.1, CI:2.49-19.41, P = .0005). There were 3 early MRSA infections in screened patients, incidence of 3.9%; only one in a colonized patient. Thirteen percent of screened pediatric SOT candidates were MRSA colonized, with greatest risk in lung, multivisceral and cardiac patients with prior cardiothoracic surgery. Early MRSA infection occurred in 3.9% of transplanted patients. Cardiothoracic and multivisceral organ transplant candidates may benefit the most from targeted MRSA screening.
ABSTRACT
OBJECTIVE: To identify the incidence of endocrine dysfunction in children following traumatic brain injury (TBI). STUDY DESIGN: This was a prospective evaluation of 31 children after TBI. Inclusion criteria included Glasgow Coma Scale score ≤ 12 and age 1.5-18 years. We evaluated thyroid function, insulin-like growth factor I, insulin-like growth factor-binding protein 3, and cortisol at 1, 3, 6, and 12 months after injury, and assessed prolactin at 3 and 6 months. At 6 months, we also assessed overnight spontaneous growth hormone secretion, nocturnal thyrotropin surge, adrenal reserve, and serum and urine osmolarity. RESULTS: The average patient age was 11.6 years, and mean Glascow Coma Scale score was 6. The incidence of endocrine dysfunction was 15% at 1 month, 75% at 6 months, and 29% at 12 months. At 12 months after injury, 14% had precocious puberty, 9% had hypothyroidism, and 5% had growth hormone deficiency. Endocrine dysfunction at 1 year did not correlate with the severity of injury. CONCLUSIONS: Endocrine dysfunction after TBI is common in children, but most cases resolve by 1 year. We recommend endocrine surveillance at both 6 and 12 months following moderate or severe TBI to ensure early intervention for persistent or late-occurring endocrine sequelae.
Subject(s)
Brain Injuries/complications , Endocrine System Diseases/epidemiology , Endocrine System Diseases/etiology , Adolescent , Child , Child, Preschool , Disease Progression , Female , Humans , Incidence , Male , Prospective StudiesABSTRACT
BACKGROUND: Children with Fanconi anemia (FA) tend to have short stature, mild thyrotropin (TSH) elevation, and borderline low free thyroxine (FT4). Objective was to examine whether thyroid hormone therapy improves linear growth in children with FA and borderline thyroid function tests PROCEDURE: Thyroid function tests were performed in 63 children with FA. Eight subjects participated in a random order, double-blind, cross-over treatment for 7 months with levothyroxine and for 7 months with placebo. Monitoring included growth measurements and laboratory assays at 1, 4 and 7 months of each phase. A 1 month lead in/wash out period was excluded from analysis of each treatment phase. RESULTS: The majority (63%) of FA children had borderline thyroid function tests. All eight FA subjects enrolled in the treatment study had FT4 in the lowest third of the normal range of 0.8-1.8 ng/dL (10.3-23.2 pmol/L) [FT4 0.9 +/- 0.1 ng/dL (mean +/- SD), range 0.8-1.2 ng/dL (10.3-15.4 pmol/L)]. TSH (optimal range 0.5-3 mU/L) was borderline elevated in six of eight subjects (4.0 +/- 1.5 mU/L, 1.9-7.3 mU/L). Growth velocity was slow at baseline and improved significantly during the thyroid phase compared to the placebo phase (2.1 +/- 1.2 cm/year vs. 5.4 +/- 1.7 cm/year, P < 0.05). CONCLUSIONS: Thyroid hormone therapy is safe and may improve linear growth velocity in children with FA who have borderline thyroid function. Subtle hypothyroidism has importance for growth in children. Whether thyroid hormone treatment improves adult height in these children remains to be elucidated.