Objectives To determine the frequency and characteristics of clinical signs, symptoms, laboratory findings, and medication use in children with pediatric systemic lupus erythematosus (pSLE) at ...presentation and during the course of the disease, and to examine correlations among disease manifestations, disease activity, and damage over time. Study design The study involved an analysis of medical records and the SLE database of an inception cohort of 256 patients with pSLE (female:male ratio, 4.7:1). Results The most common clinical manifestations were arthritis (67%), malar rash (66%), nephritis (55%), and central nervous system (CNS) disease (27%). At diagnosis, patients with both renal and CNS disease had the highest SLE Disease Activity Index (SLEDAI) scores ( P < .0001), but these scores were similar to those of the total group at 1 year ( P = .11). Patients who developed renal and CNS disease more than 1 year after diagnosis had higher SLEDAI scores at disease onset. Some 34% of patients had Systemic Lupus International Collaborative Clinics Damage Index (SLICC-DI) scores >1 at a mean follow-up of 3.5 years. A greater proportion of patients with renal and CNS disease had SLICC-DI scores of >1, and these patients had higher mean scores compared with patients without major organ involvement (70% vs 11% P < .0001 and 1.4 vs 0.1 P < .0001, respectively). Conclusions Most of the patients in our cohort exhibited major organ involvement. These patients had the highest SLEDAI scores at diagnosis, which normalized at 1 year but preceded development of renal and CNS disease. The average SLICC-DI score was lower than that previously reported in patients with pSLE.
Ethnic differences in outcomes among children with nephrotic syndrome are unknown.
We conducted a longitudinal study at a single regional pediatric center comparing ethnic differences in incidence ...from 2001 to 2011 census data and longitudinal outcomes, including relapse rates, time to first relapse, frequently relapsing disease, and use of cyclophosphamide. Among 711 children, 24% were European, 33% were South Asian, 10% were East/Southeast Asian, and 33% were of other origins.
Over 10 years, the overall incidence increased from 1.99/100,000 to 4.71/100,000 among children ages 1-18 years old. In 2011, South Asians had a higher incidence rate ratio of 6.61 (95% confidence interval, 3.16 to 15.1) compared with Europeans. East/Southeast Asians had a similar incidence rate ratio (0.76; 95% confidence interval, 0.13 to 2.94) to Europeans. We determined outcomes in 455 children from the three largest ethnic groups with steroid-sensitive disease over a median of 4 years. South Asian and East/Southeast Asian children had significantly lower odds of frequently relapsing disease at 12 months (South Asian: adjusted odds ratio; 0.55; 95% confidence interval, 0.39 to 0.77; East/Southeast Asian: adjusted odds ratio; 0.42; 95% confidence interval, 0.34 to 0.51), fewer subsequent relapses (South Asian: adjusted odds ratio; 0.64; 95% confidence interval, 0.50 to 0.81; East/Southeast Asian: adjusted odds ratio; 0.47; 95% confidence interval, 0.24 to 0.91), lower risk of a first relapse (South Asian: adjusted hazard ratio, 0.74; 95% confidence interval, 0.67 to 0.83; East/Southeast Asian: adjusted hazard ratio, 0.65; 95% CI, 0.63 to 0.68), and lower use of cyclophosphamide (South Asian: adjusted hazard ratio, 0.82; 95% confidence interval, 0.53 to 1.28; East/Southeast Asian: adjusted hazard ratio, 0.54; 95% confidence interval, 0.41 to 0.71) compared with European children.
Despite the higher incidence among South Asians, South and East/Southeast Asian children have significantly less complicated clinical outcomes compared with Europeans.
Takayasu arteritis (TAK) is a large vessel vasculitis that rarely affects children. Data on childhood TAK are scarce. The aim of this study was to analyze the presenting features, course and outcome ...of children with TAK, compare efficacy of treatment regimens and identify high-risk factors for adverse outcome.
A single-center cohort study of consecutive children fulfilling the EULAR/PRINTO/PReS criteria for childhood TAK between 1986 and 2015 was performed. Clinical phenotypes, laboratory markers, imaging features, disease course and treatment were documented. Disease activity was assessed using the Pediatric Vasculitis Disease Activity Score at each visit.
disease flare defined as new symptoms and/or increased inflammatory markers necessitating therapy escalation and/or new angiographic lesions, or death.
logistic regression tested relevant variables for flare. Kaplan-Meier analyses compared treatment regimens.
Twenty-seven children were included; 74% were female, median age at diagnosis was 12.4 years. Twenty-two (81%) children presented with active disease at diagnosis. Treatment regimens included corticosteroids alone (15%), corticosteroids plus methotrexate (37%), cyclophosphamide (19%), or a biologic agent (11%). Adverse outcomes were documented in 14/27 (52%) children: two (7%) died within 6 months of diagnosis, and 13 (48%) experienced disease flares. The 2-year flare-free survival was 80% with biologic treatments compared to 43% in non-biologic therapies (p = 0.03); at last follow-up, biologic therapies resulted in significantly higher rates of inactive disease (p = 0.02). No additional outcome predictor was identified.
Childhood TAK carries a high disease burden; half of the children experienced flares and 7% died. Biologic therapies were associated with better control of disease activity.
BACKGROUND.Cancer risk is elevated among adult transplant recipients, but there is limited data regarding long-term cancer risk and mortality in pediatric recipients.
METHODS.We conducted a ...population-based retrospective cohort study in Ontario, Canada. We included pediatric recipients of solid organ transplants at the Hospital for Sick Children, Toronto, from 1991 to 2014, and compared rates of new cancers and cancer-specific mortality to nontransplanted Ontario children born in the same year. We constructed standard and time-dependent Cox proportional hazards models accounting for competing risk of death.
RESULTS.A total of 951 recipients (kidney, n = 400; liver, n = 283; heart, n = 218; lung, n = 36; multiorgan/small bowel, n = 14) were compared with 5.3 million general population children. Mean (SD) age was 8.2 (6.4) years; 50% were male. Over a mean (SD) follow-up of 10.8 (7.1) years, cumulative incidence of cancer was 20% in recipients and 1.2% in the general population (incidence rate ratio, 32.9; 95% confidence interval CI, 26.6–40.8). Risk was highest in the first year posttransplant (adjusted hazard ratio aHR,176; 95% CI, 117–264), but remained elevated beyond 10 years (aHR, 10.8; 95% CI, 6.3–18.6). Lymphoproliferative disorders were predominant (77%); however, solid cancers (renal, sarcomas, genital, thyroid) were seen. Recipients of lung or multiorgan transplants were at highest risk. Cancer-specific mortality was also higher among recipients (HR, 93.1; 95% CI, 59.6–145.2).
CONCLUSIONS.Childhood transplant recipients have a 30 times greater cancer incidence versus the general population. Further investigation is needed to guide screening strategies in this at-risk population.
Prevalence and severity of systemic lupus erythematosus (SLE) in adults is suggested to be distinctly different between ethnic groups. The impact of ethnicity is not as well delineated in pediatric ...SLE (pSLE). We compared prevalence and extent of major organ involvement, disease activity, and damage in pSLE between different ethnic groups.
Ethnic demographic profiles of an inception cohort of 265 patients with pSLE followed at Sick Kids Hospital in Toronto were determined and compared to the Metropolitan Toronto at-risk population. Patients were categorized into ethnic subsets based on self-designated ethnic origins. Disease characteristics including major organ involvement, disease activity, and damage measures were longitudinally determined and compared among ethnic groups.
Ethnicity data were available on 259/265 pSLE patients (99.6%); the majority were non-Caucasian (60%) compared to the Metropolitan Toronto at-risk population (40%) (p < 0.0001). Non-Caucasian patients were younger at diagnosis than Caucasian patients, Black patients being the youngest at diagnosis (12.6 vs 14.6 yrs; p = 0.007). Renal disease was significantly more common in non-Caucasian than in Caucasian pSLE patients (62% vs 45%; p = 0.01). There was a trend toward increased prevalence of central nervous system disease in Black patients compared to Asian patients (p = 0.108). There was no difference in gender ratio, SLE Disease Activity Index, or damage scores between ethnic groups.
Non-Caucasian ethnicity is associated with increased pSLE disease prevalence. Non-Caucasian pSLE patients were significantly younger and more likely to have nephritis. However, disease activity and damage were strongly associated with major organ disease independent of the patient's ethnicity.
Background
Solid‐organ transplant recipients are at increased risk of developing human papillomavirus‐related diseases.
Methods
To evaluate the immunogenicity of a quadrivalent vaccine, a prospective ...observational study included females aged 12–19 years who had received kidney or liver transplants, or were otherwise healthy volunteers. With the three‐dose vaccination, serum antibodies were measured.
Results
The study included 17 transplant recipients (seven kidney and 10 liver) and 16 healthy participants. Six of seven kidney transplant recipients were on three immunosuppressive medications, whereas 9 of the 10 liver transplant recipients were on one. For the serology within 6 months from the last vaccine dose, the geometric mean titers of human papillomavirus types 6, 11, 16, and 18 were 26.7, 8.6, 35.7, and 42.4 (kidney transplant); 579.2, 569.3, 3097.3, and 835.7 (liver transplant); and 860.5, 638.8, 4391.6, and 902.6 milli‐Merck Units/ml (healthy). The seropositivity rates of kidney transplant recipients for the four serotypes ranged from 50% to 75%, while all liver transplant recipients and healthy participants had 100% seropositivity rates for all four types. While there were no statistical differences of titers between liver transplant recipients and healthy participants, the titers of kidney transplant recipients were lower than those of healthy participants for type 6 (p = .034), type 11 (p = .032), and type 16 (p = .032).
Conclusions
The results support the recommendation of human papillomavirus vaccination in pediatric transplant recipients given the significant risk of human papillomavirus‐related diseases in this population, though immunogenicity was lower in kidney transplant recipients on multiple immunosuppressive medications.
: This summary of the NAPRTCS 2006 Annual Report of the Transplant Registry highlights the significant impact the registry has had in advancing knowledge in pediatric renal transplantation ...worldwide. This cooperative group has collected clinical information on children undergoing a renal transplantation since 1987 and now includes over 150 participating medical centers in the USA, Canada, Mexico, and Costa Rica. Currently, the NAPRTCS transplant registry includes information on 9837 renal transplants in 8990 patients (NAPRTCS 2006 Annual Report). Since the first data analysis in 1989, NAPRTCS reports have documented marked improvements in outcome after renal transplantation in addition to identifying factors associated with both favorable and poor outcomes. The registry has served to document and influence practice patterns, clinical outcomes, and changing trends in renal transplantation.
It is unknown whether steroid sensitivity and other putative risk factors collected at baseline can predict the disease course of idiopathic nephrotic syndrome in childhood. We determined whether ...demographic, clinical, and family reported factors at presentation can predict outcomes in idiopathic nephrotic syndrome.
An observational cohort of 631 children aged 1 to 18 years diagnosed with idiopathic nephrotic syndrome between 1993 and 2016 were followed up until clinic discharge, 18 years of age, end-stage kidney disease (ESKD), or the last clinic visit. Baseline characteristics were age, sex, ethnicity, and initial steroid sensitivity. Of these, 287 (38%) children also reported any family history of kidney disease, preceding infection, microscopic hematuria, and history of asthma/allergies. The outcomes were complete remission after initial steroid course, need for a second-line agent, frequently relapsing disease, and long-term remission. The discriminatory power of the models was described using the c-statistic.
Overall, 25.7% of children had no further disease after their initial steroid course. In addition, 31.2% developed frequently relapsing disease; however, 77.7% were disease-free at 18 years of age. Furthermore, 1% of children progressed to ESKD. Logistic regression modeling using the different baseline exposures did not significantly improve the prediction of outcomes relative to the observed frequencies (maximum c-statistic, 0.63; 95% confidence interval CI, 0.59–0.67). The addition of steroid sensitivity did not improve outcome prediction of long-term outcomes (c-statistic, 0.63; 95% CI, 0.54–0.70).
Demographic, clinical, and family reported characteristics, specifically steroid sensitivity, are not useful in predicting relapse rates or long-term remission in idiopathic nephrotic syndrome. Further studies are needed to address factors that contribute to long-term health.
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Introduction
As a step toward evaluating the association between Epstein‐Barr virus genetic diversity and post‐transplant lymphoproliferative disorder (PTLD), we conducted a preliminary study to ...compare the genetic diversity of the EBNA‐1 gene among transplant patients and patients with infectious mononucleosis (IM).
Methods
We sequenced the EBNA‐1 gene in blood samples from study subjects using Sanger methodology. The sequences were aligned with a reference strain and compared with publicly available sequences.
Results
We analyzed 33 study samples and 25 publicly available sequences along with the reference strain B95‐8. The evaluable samples were from sixteen patients with IM (median age 14.0 years, range 2‐24) and 17 transplant patients. There were six children without PTLD (median age 1.93 years, range 0.79‐7.46) and 11 who developed PTLD (median age 5.67 years, range 0.96‐17.45). A predominant EBNA‐1 variant (P‐thr) was identified across the study groups. Differences were observed between the samples from the IM patients compared with the transplant samples.
Conclusion
The predominant EBNA‐1 strain is in contrast to reports of the predominant strain in North America. The results suggest differences between the EBNA‐1 strains among the study groups. Further studies will examine the relationship between EBNA‐1 strains and PTLD occurrence and outcomes.
Nephrotic syndrome represents a condition in pediatric nephrology typified by a relapsing and remitting course, proteinuria and the presence of edema. The PROMIS measures have previously been studied ...and validated in cross-sectional studies of children with nephrotic syndrome. This study was designed to longitudinally validate the PROMIS measures in pediatric nephrotic syndrome.
One hundred twenty seven children with nephrotic syndrome between the ages of 8 and 17 years participated in this prospective cohort study. Patients completed a baseline assessment while their nephrotic syndrome was active, a follow-up assessment at the time of their first complete proteinuria remission or study month 3 if no remission occurred, and a final assessment at study month 12. Participants completed six PROMIS measures (Mobility, Fatigue, Pain Interference, Depressive Symptoms, Anxiety, and Peer Relationships), the PedsQL version 4.0, and two global assessment of change items.
Disease status was classified at each assessment: nephrotic syndrome active in 100% at baseline, 33% at month 3, and 46% at month 12. The PROMIS domains of Mobility, Fatigue, Pain Interference, Depressive Symptoms, and Anxiety each showed a significant overall improvement over time (p < 0.001). When the PROMIS measures were compared to the patients' global assessment of change, the domains of Mobility, Fatigue, Pain Interference, and Anxiety consistently changed in an expected fashion. With the exception of Pain Interference, change in PROMIS domain scores did not correlate with changes in disease activity. PROMIS domain scores were moderately correlated with analogous PedsQL domain scores.
This study demonstrates that the PROMIS Mobility, Fatigue, Pain Interference, and Anxiety domains are sensitive to self-reported changes in disease and overall health status over time in children with nephrotic syndrome. The lack of significant anchoring to clinically defined nephrotic syndrome disease active and remission status may highlight an opportunity to improve the measurement of HRQOL in children with nephrotic syndrome through the development of a nephrotic syndrome disease-specific HRQOL measure.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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