Information about HAdV infection in SOT recipients is limited. We aimed to describe HAdV infection epidemiology and outcomes in a single‐center retrospective cohort during the era of PCR availability. SOT recipients transplanted at the CHOP 2004‐2013 were followed up for 180 days post‐transplant. HAdV infection was defined as a positive HAdV PCR from a clinical specimen. HAdV disease was defined by organ‐specific radiologic and/or laboratory abnormalities. No HAdV surveillance protocols were employed during the study period; testing was solely per clinician discretion. Progression of HAdV infection was defined as HAdV disease or ≥1‐log viral load increase since a corresponding site's first positive specimen. Of the assembled 425 SOT recipients, 227 (52.6%) had ≥1 HAdV PCR. Twenty‐four (10.6%) had ≥1 HAdV‐positive PCR. HAdV‐positive subjects were younger than uninfected subjects (2.0 years vs 6.5, P = 0.001). Infection incidence rates were highest in liver recipients (15.3%), followed by heart (8.6%), kidney (8.3%), and lung (4.2%). Four subjects (16.7%) met HAdV disease criteria at virus detection. Five subjects (20.8%) had progression of HAdV infection. All‐cause mortality rates in positive and negative subjects were 0% and 3.9%, respectively. HAdV infection was infrequently detected in SOT recipients. Over one‐third of HAdV‐positive patients met disease criteria at detection or had infection progression, but none died. This low all‐cause mortality raises questions about benefits of HAdV surveillance. Larger multicenter studies are needed to assess incidence variance by center and comparative effectiveness of therapeutic interventions.

Background Cytomegalovirus (CMV) is a significant source of morbidity and mortality among transplant recipients; the epidemiology is less understood in pediatric hematopoietic cell transplantation (HCT) cohorts. Furthermore, there is a paucity of data related to CMV prophylactic and preemptive strategies. Methods A single-center retrospective observational cohort of allogeneic HCT recipients at the Children’s Hospital of Philadelphia January 1, 2004–December 31, 2017 was constructed. Subjects were followed for 180 days after transplant to determine whether they had CMV infection or disease. Data on antiviral therapy were collected as were outcomes of CMV disease and adverse events (AEs) related to the antiviral therapy. Results Between January 2004 and March 2017, 345 allogeneic HCTs in 333 patients undergoing CMV surveillance testing were identified. CMV DNAemia was detected during the 180-day follow-up in 89 (25.8%) HCTs. CMV recipient-positive transplants were most likely to have CMV infection (47%). Infection rates were high for those receiving a CMV-specific prophylaxis regimen (50%). CMV DNAemia progressed to CMV disease 11.2% of the time. Of 224 subjects receiving CMV-specific prophylaxis, 19.2% experienced ≥1 AE. Of 53 receiving preemptive therapy during any CMV DNAemia episode, 32.1% experienced ≥1 AE. Conclusions CMV infection is common in pediatric allogeneic HCT recipients. The CMV-specific prophylaxis regimen employed in this cohort did not effectively prevent DNAemia, progression to CMV disease was uncommon, and AEs from prophylaxis and preemptive therapy were frequent. Novel approaches that reduce the impact of CMV on pediatric allogeneic HCT recipients are needed.

Background Cytomegalovirus (CMV) is an important cause of morbidity and mortality in pediatric solid organ transplant (SOT) recipients. However, the impact of asymptomatic CMV infections (ie, DNAemia) on clinical outcomes is not well established. Methods We performed a retrospective cohort study of children undergoing first SOT at our institution from January 2012 to June 2018. We evaluated the epidemiology of CMV infections and performed multivariable Cox regression to assess the association between CMV DNAemia without disease or CMV disease (syndrome or end‐organ disease) on negative outcomes (death, re‐transplantation, or moderate/severe rejection) within the first year after SOT. Results Among 271 individuals, 43 (15.9%) developed ≥1 CMV infection during the first year after SOT. There were 56 unique CMV infections including 14 episodes of CMV disease. In 167 patients offered CMV prophylaxis, only 8 (4.8%) developed their first CMV DNAemia episode while on prophylaxis 32 developed CMV DNAemia after prophylaxis completion; only 1 episode of CMV disease occurred while on antiviral prophylaxis. When accounting for receipt of ATG, oral steroids, and number of immunosuppressives on a given day, CMV disease was more strongly associated with negative outcomes (Hazard Ratio (HR): 3.28, 95% CI: 0.73–14.64; p = .12) than CMV DNAemia without disease (HR 1.42, 95% CI: 0.19– 10.79; p = .74), although not to a statistically significant degree. Conclusions Most CMV infections occurred after completion of antiviral prophylaxis. CMV disease was more strongly associated with negative outcomes than asymptomatic CMV DNAemia and should be the focus of CMV prevention practices.

Prophylaxis with valganciclovir (VGCV) is used routinely to prevent cytomegalovirus (CMV) infections in at‐risk pediatric solid organ transplant (SOT) recipients. However, the rate and factors associated with toxicities in this population are not well‐described. We conducted a retrospective cohort study of children undergoing SOT at our hospital from January 2012–June 2018. We evaluated the frequency of hematologic and renal toxicities from day 15 through 1‐year post‐SOT in relation to antiviral exposures, focused on VGCV prophylaxis. Marginal rate models were used to determine the risk of kidney injury and neutropenia in relation to VGCV prophylaxis. Among 281 SOTs, VGCV prophylaxis was administered on 20.1% of all follow‐up days. The incidence rates of kidney injury, leukopenia, and neutropenia were significantly higher during VGCV prophylaxis compared to when no antiviral agents were given. Using multivariable marginal rate models, receipt of VGCV prophylaxis was associated with development of kidney injury (rate ratio [RR] 1.79, 95% confidence interval [CI]: 1.22–2.65) and neutropenia (RR 4.82, 95% CI: 3.08–7.55). VGCV dosing did not impact the development of kidney injury or neutropenia. Toxicities are common with VGCV prophylaxis in pediatric SOT recipients.

Introduction: Hyperglycemic emergencies in children with diabetes traditionally include diabetic ketoacidosis (DKA) predominantly associated with T1DM, whereas hyperosmolar hyperglycemic state (HHS) that is associated with relative insulin deficiency in T2DM, rarely occurs (2%). There have been increasing reports of mixed DKA-HHS affecting up to 27%. The purpose of this study is to identify clinical features, risk factors, complications and outcomes among minority children presenting with hyperglycemic emergencies at our center. Methods: This is a retrospective chart review of children and adolescents (ages 1-21 years) admitted for hyperglycemic emergencies including DKA [defined as glucose >200 mg/dL, metabolic acidosis (pH <7.3 or serum bicarbonate <15 mmol/L) and ketonemia (ß-hydroxybuyrate ≥3 mmol/L) or moderate to large ketonuria], or HHS [defined as glucose >600 mg/dL, effective serum osmolality >320 mOsm/kg, venous pH >7.25 or arterial pH >7.30 or serum bicarbonate >15 mmol/L, absent to mild ketonemia] or mixed DKA-HHS between 2004 and 2019. Descriptive statistics, chi-squared analysis and t-tests were used. Results: Of 322 patients, 92% were African American with mean age 13.6 ± 3.5 years, 39% males, consisting of 266 (83%) with DKA, 52 (16%) mixed DKA-HHS, and 4 (1%) HHS. Ninety-eight of the DKA and DKA-HHS groups had T1DM. All 4 patients with HHS had T2DM. Compared to the DKA group, the mixed DKA-HHS group required higher IV fluids rates (p<0.0001), 4.3-fold greater odds of acute kidney injury (AKI, mean serum creatinine of 1.6 mg/dl vs 1.1 mg/dl; ref 0.5-1.0 mg/dL) and 3.3-fold greater odds of developing altered mental status (AMS). Risk factors such as insulin adherence, and precipitating factors like infection or stress were not different between both groups (p=0.06). There was no significant difference in insulin rates or time to resolution (p=0.4) in both groups. Among the HHS group, 50% presented with AMS and AKI (mean Cr 1.1 mg/dl ± 0.31) due to severe dehydration and required higher IV fluids rates (≥2 x maintenance). Creatinine kinase in 2 patients were slightly elevated (mean 1643 units/L, ± 77; ref 39-309). Insulin drip at 0.05 u/kg/hour was started in all 4 patients. None had venous thrombosis, rhabdomyolysis, cerebral edema, or death. Average time of resolution was 10 ±1.63 hours. Conclusion: In this study, 16% of patients with hyperglycemic emergencies presented with mixed DKA-HHS which was associated with more complications compared to the DKA group. Serum osmolality should be calculated and checked at diagnosis. Identification of hyperosmolality whether with or without DKA in the emergency setting is important because treatment should be focused on the degree of dehydration (usually moderate to severe) and other complications such as AKI and mental status changes.