[Emotional and physical aftereffects of cancer Utility and impact of a rehabilitation program]. / Séquelles émotionnelles et physiques du cancer. Utilité et impact d'un programme de réadaptation.

An increasing number of people are surviving cancer in Switzerland : 163,450 people were still alive in 2006 after a cancer diagnosis less than ten years prior, compared to 210,350 in 2016. However, most have to cope with debilitating emotional and physical aftereffects. A new 12-week rehabilitation program aims to restore patients' abilities. It consists of group-led therapies: adapted physical activity, psycho-oncology, dietetics, management of cognitive disorders, and integrative medicine. The first 116 patients who benefited from the program reported a general reduction in symptoms at the end of the program, an improvement that lasts even after 9 months, although fatigue and mood become concerning again. Some express a desire for post-rehabilitation follow-up.

De plus en plus de personnes survivent au cancer en Suisse : 163 450 personnes étaient encore en vie après un diagnostic de cancer remontant à moins de dix ans en 2006, contre 210 350 en 2016. La plupart doivent toutefois faire face à des séquelles émotionnelles et physiques invalidantes. Un nouveau programme de réadaptation de 12 semaines vise à restaurer les capacités des patients. Il est composé de thérapies menées en groupe : activité physique adaptée, psycho-oncologie, diététique, gestion des troubles cognitifs et médecine intégrative. Les 116 premiers patients bénéficiaires expriment une diminution générale des symptômes à l'issue du programme, une amélioration qui perdure après 9 mois, même si la fatigue et le moral redeviennent préoccupants. Certains expriment le souhait d'un suivi post-réadaptation.

Von Willebrand factor antigen as a marker of disease activity in childhood-onset antineutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVE: Von Willebrand Factor (VWF) antigen plays a role in vascular inflammation and thrombosis, both important in the pathogenesis of Antineutrophil Cytoplasmic Antibody-associated vasculitis (AAV). Previous work found that VWF correlates with disease activity in childhood-onset primary CNS vasculitis. We sought to determine the relationship between VWF and disease activity over time in children with AAV. METHODS: AAV patients with more than one VWF level measured were included in this retrospective stuy, and the relationship between active vasculitis, VWF and other disease measures were analyzed. Generalized estimating equations (GEE) analysis was used to account for repeated VWF measurements within a patient. Repeated measures correlation was used to determine associations of paired laboratory observations. Diagnostic performance was evaluated using receiver operating curve (ROC) analysis. RESULTS: 732 total VWF measurements were collected in 33 AAV patients. VWF antigen levels were higher during active disease (median = 2.03 IU/ml, IQR = [1.35, 2.55]) compared with inactive disease (median = 1.18 IU/ml, IQR = [0.94, 1.53). VWF antigen was the only variable that was significantly associated with active disease (OR 3.01, p< 0.001, 95CI [2.3, 3.93]). The effect of VWF did not show a substantial difference between the disease subtypes. There was a moderate positive correlation between VWF antigen and disease activity, with an acceptable sensitivity and specificity rates. CONCLUSION: Increased VWF antigen levels correlate with active vasculitis in this paediatric-onset AAV cohort and may be used as an additional biomarker in childhood AAV.

Immunogenicity of a quadrivalent human papillomavirus vaccine in pediatric kidney and liver transplant recipients.

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.

Incidence and Risk Factors of Obesity in Childhood Solid-Organ Transplant Recipients.

BACKGROUND: Obesity is a significant public health concern; however, the incidence post solid-organ transplantation is not well reported. METHODS: This study determined the incidence and risk factors of obesity among pediatric solid-organ transplant recipients (heart, lung, liver, kidney, multiorgan) at The Hospital for Sick Children (2002-2011), excluding prevalent obesity. Follow-up occurred from transplantation until development of obesity, last follow-up, or end of study. Incidence of obesity was determined overall, by baseline body mass index, and organ group. Risk factors were assessed using Cox proportional-hazards regression. RESULTS: Among 410 (55% male) children, median transplant age was 8.9 (interquartile range [IQR]: 1.0-14.5) years. Median follow-up time was 3.6 (IQR: 1.5-6.4) years. Incidence of obesity was 65.2 (95% confidence interval [CI]: 52.7-80.4) per 1000 person-years. Overweight recipients had a higher incidence, 190.4 (95% CI: 114.8-315.8) per 1000 person-years, than nonoverweight recipients, 56.1 (95% CI: 44.3-71.1). Cumulative incidence of obesity 5-years posttransplant was 24.1%. Kidney relative to heart recipients had the highest risk (3.13 adjusted hazard ratio [aHR]; 95% CI: 1.53-6.40) for obesity. Lung and liver recipients had similar rates to heart recipients. Those with higher baseline body mass index (z-score; 1.72 aHR; 95% CI: 1.39-2.14), overweight status (2.63 HR; 95% CI: 1.71-4.04), and younger transplant age (y; 1.18 aHR; 95% CI: 1.12-1.25) were at highest risk of obesity. Higher cumulative steroid dosage (per 10 mg/kg) was associated with increased risk of obesity after adjustment. CONCLUSIONS: Among all transplanted children at The Hospital for Sick Children, 25% developed obesity within 5-years posttransplant. Kidney recipients, younger children, those overweight at transplant, and those with higher cumulative steroid use (per 10 mg/kg) were at greatest risk. Early screening and intervention for obesity are important preventative strategies.

Posttransplant Lymphoproliferative Disorder in Pediatric Patients: Characteristics of Disease in EBV-seropositive Recipients.

BACKGROUND: Patients at greatest risk of posttransplant lymphoproliferative disorder (PTLD) are those who acquire primary Epstein-Barr virus (EBV) infection after solid organ transplantation. The incidence of PTLD among patients who are EBV-seropositive before transplant is lower, and little is known about the differences in presentation and outcome of this population. We describe the characteristics of EBV-seropositive transplant recipients (R+) who developed PTLD and compare survival outcomes with EBV-seronegative recipients (R-). METHODS: A hospital-based registry was used to identify all patients with biopsy-proven PTLD for the period 2000-2014. Characteristics and outcomes were compared between R+ and R- patients with PTLD. RESULTS: Sixty-nine patients were included, among which 20 (29.0%) were R+ and 49 (71.0%) were R-. Multiorgan transplant patients accounted for 25% of PTLD cases in R+ patients, while accounting for only 2.1% of all transplants during the study period. There was no difference in PTLD site between R+ and R- patients. PTLD among R+ individuals occurred during the second year after transplant (median: 1.92; range: 0.35-3.09 y) compared with during the first year for R- individuals (median: 0.95; range: 0.48-2.92 y; P = 0.380). There was a trend for a higher overall mortality among R+ individuals (log rank: 0.09). PTLD-related mortality did not differ between R+ and R- individuals (log rank: 0.17). CONCLUSIONS: PTLD among R+ individuals was more likely to occur among multiorgan recipients, and there was a tendency for poorer outcomes at 1 and 5 years after the diagnosis of PTLD.

Posttransplant lymphoproliferative disorder in pediatric patients: Survival rates according to primary sites of occurrence and a proposed clinical categorization.

Posttransplant lymphoproliferative disorder (PTLD) is a devastating complication of organ transplant. In a hospital-based registry, we identified biopsy-proven cases of PTLD among children during a 15-year period and reviewed trends in PTLD rates, the sites of involvement, and the associated survival rates. Cases that were included had at least 1 year of follow-up after the diagnosis of PTLD. We studied 82 patients with first-episode PTLD. Median age at diagnosis was 6.4 years (IQR 3.2-12.3 years). The most frequent PTLD sites were tonsillar/adenoidal (T/A [34%]) and gastrointestinal (32%), followed by miscellaneous (defined as less common sites including central nervous system, kidney, lung, and soft tissue [12%]), lymph node (11%), and multisite (11%). Kaplan-Meier survival curves showed that T/A PTLD was associated with decreased all-cause mortality compared with PTLD at other sites (log-rank 0.004), even after adjustment for histological subtype (P = .047). PTLD-related mortality was also decreased among T/A PTLD (log-rank 0.012) but showed a trend toward significance only after adjustment for histological subtype (P = .09). Among first episodes of PTLD, T/A PTLD was associated with a survival advantage compared with PTLD at other sites, even after adjustment for potential confounders. Based on our observations, we propose a clinical categorization of PTLD according to anatomical site of occurrence.

Epstein-Barr virus latent gene EBNA-1 genetic diversity among transplant patients compared with patients with infectious mononucleosis.

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.

Elevated Risk of Cancer After Solid Organ Transplant in Childhood: A Population-based Cohort Study.

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.

Biallelic mutations in EXOC3L2 cause a novel syndrome that affects the brain, kidney and blood.

BACKGROUND: Dandy-Walker malformation features agenesis/hypoplasia of the cerebellar vermis, cystic dilatation of the fourth ventricle and enlargement of posterior fossa. Although Dandy-Walker malformation is relatively common and several genes were linked to the syndrome, the genetic cause in the majority of cases is unknown. OBJECTIVE: To identify the mutated gene responsible for Dandy-Walker malformation, kidney disease and bone marrow failure in four patients from two unrelated families. METHODS: Medical assessment, sonographic, MRI and pathological studies were used to define phenotype. Chromosomal microarray analysis and whole-exome sequence were performed to unravel the genotype. RESULTS: We report four subjects from two unrelated families with homozygous mutations in the Exocyst Complex Component 3-Like-2 gene (EXOC3L2).EXOC3L2 functions in trafficking of post-Golgi vesicles to the plasma membrane. In the first family a missense mutation in a highly conserved amino acid, p.Leu41Gln, was found in three fetuses; all had severe forms of Dandy-Walker malformation that was detectable by prenatal ultrasonography and confirmed by autopsy. In the second family, the affected child carried a nonsense mutation, p.Arg72*, and no detected protein. He had peritrigonal and cerebellar white matter abnormalities with enlargement of the ventricular trigones, developmental delay, pituitary hypoplasia, severe renal dysplasia and bone marrow failure. CONCLUSION: We propose that biallelic EXOC3L2 mutations lead to a novel syndrome that affects hindbrain development, kidney and possibly the bone marrow.

Pathogenesis and treatment of ANCA-associated vasculitis-a role for complement.

The antineutrophil cytoplasm autoantibody (ANCA)-associated vasculitides (AAV), although rare in childhood, can have devastating effects on affected organs, especially the kidney. In this review we present an update on the pathogenesis and treatment of ANCA vasculitis, with a particular emphasis on the role of the alternative pathway of complement. The rationale and evidence for the current treatment strategies are summarized. Targeting the activation of neutrophils by the anaphylatoxin C5a may serve as an additional therapeutic strategy, however the results of clinical studies are awaited.

A curious case of growth failure and hypercalcemia: Questions.

BACKGROUND: Sarcoidosis is a multisystem granulomatous disease of unknown etiology that rarely presents in childhood. Here, we report a case of pediatric sarcoidosis presenting with renal failure and hypercalcemia. CASE DIAGNOSIS/TREATMENT: A previously well 14-year-old Caucasian boy was admitted to the Hospital for Sick Children, Canada, for hypertension and renal failure following work-up by his family physician for initial concerns of growth failure. On admission, his weight was 35 kg (<3rd percentile), his height was 148 cm (≪3rd percentile), and his blood pressure was 154/116 mmHg (>99th percentile for height). Laboratory findings showed elevated creatinine (218 µmol/L), hypercalcemia (3.21 mmol/L), and normocytic anemia (hemoglobin 105 g/L). His further assessment showed a urinary concentrating defect with hypercalciuria (calcium/creatinine 1.76 mmol/mmol) and nephrocalcinosis on ultrasound. His eye examination showed uveitis with conjunctival biopsy remarkable for granulomas, which led to pursuit of a diagnosis of possible sarcoidosis. Angiotensin-converting enzyme was found to be high at 96 U/L, and he had a renal biopsy that was consistent with interstitial nephritis with granulomas. Treatment was started with prednisone leading to resolution of his hypercalcemia but persistence of his mild chronic kidney disease. CONCLUSIONS: This case represents an atypical presentation of a rare pediatric disease and highlights the spectrum of renal manifestations and treatment options in sarcoidosis.

A curious case of growth failure and hypercalcemia: Answers.

BACKGROUND: Sarcoidosis is a multisystem granulomatous disease of unknown etiology that rarely presents in childhood. Here, we report a case of pediatric sarcoidosis, presenting with renal failure and hypercalcemia. CASE DIAGNOSIS/TREATMENT: A previously well 14-year-old Caucasian boy was admitted to the Hospital for Sick Children, Canada, for hypertension and renal failure following work-up by his family physician for initial concerns of growth failure. On admission, his weight was 35 kg (<3rd percentile), his height was 148 cm (<<3rd percentile), and his blood pressure was 154/116 mmHg (>99th percentile for height). Laboratory findings showed elevated creatinine (218 umol/L), hypercalcemia (3.21 mmol/L), and normocytic anemia (hemoglobin 105 g/L). His further assessment showed a urinary concentrating defect with hypercalciuria (calcium/creatinine 1.76 mmol/mmol) and nephrocalcinosis on ultrasound. His eye examination showed uveitis with conjunctival biopsy remarkable for granulomas, which led to pursuit of a diagnosis of possible sarcoidosis. Angiotensin Angiotensin-converting enzyme was found to be high at 96 U/L, and he had a renal biopsy that was consistent with interstitial nephritis with granulomas. Treatment was started with prednisone leading to resolution of his hypercalcemia but persistence of his mild chronic kidney disease. CONCLUSIONS: This case represents an atypical presentation of a rare pediatric disease and highlights the spectrum of renal manifestations and treatment options in sarcoidosis.

Outcome of kidney transplantation in pediatric patients with ANCA-associated glomerulonephritis: a single-center experience.

OBJECTIVES: Data on kidney transplant outcomes for pediatric patients with end-stage renal disease (ESRD) secondary to anti-neutrophil cytoplasmic antibody glomerulonephritis (ANCA GN), particularly granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), is limited. We describe our experience of kidney transplantation in pediatric ANCA GN patients. METHODS: We performed a retrospective review of patients with ANCA GN who developed ESRD and were transplanted at a single center between the years 2000 and 2014. RESULTS: Since 2000, there were seven pediatric patients with ANCA GN (four MPA) transplanted. Mean age at ANCA GN diagnosis was 11.8 ± 2.8 (range, 7.2-15.4) years. All seven were ANCA (three anti-PR3/four anti-MPO) positive. Estimated glomerular filtration rate (eGFR) at diagnosis was 11.7 ± 6.3 ml/min/1.73 m2. All received steroids and cyclophosphamide and three (23.3%) received plasma exchange. Six were dialysis dependent by 6 months post diagnosis. Time from diagnosis to transplant was 30 ± 12 (range, 17-48) months. Six of the seven received a deceased donor transplant. All patients received induction therapy and standard maintenance immunosuppression post transplant. Median duration of follow-up post transplantation was 27 months (range, 13-88 months). Median eGFR at last follow-up was 77 ml/min/1.73 m2 (range, 7.9-83.5). One patient lost her transplant to acute cellular rejection following non-adherence to immunosuppression after 21 months of stable transplant function. No patient had recurrence of vasculitis, either renal or extra-renal. CONCLUSIONS: Short-term patient and allograft survival in pediatric patients with ESRD secondary to ANCA GN seems excellent, with no recurrence of vasculitis post transplant in this small cohort.

The genetic diversity of Epstein-Barr virus in the setting of transplantation relative to non-transplant settings: A feasibility study.

This study examines EBV strains from transplant patients and patients with IM by sequencing major EBV genes. We also used NGS to detect EBV DNA within total genomic DNA, and to evaluate its genetic variation. Sanger sequencing of major EBV genes was used to compare SNVs from samples taken from transplant patients vs. patients with IM. We sequenced EBV DNA from a healthy EBV-seropositive individual on a HiSeq 2000 instrument. Data were mapped to the EBV reference genomes (AG876 and B95-8). The number of EBNA2 SNVs was higher than for EBNA1 and the other genes sequenced within comparable reference coordinates. For EBNA2, there was a median of 15 SNV among transplant samples compared with 10 among IM samples (p = 0.036). EBNA1 showed little variation between samples. For NGS, we identified 640 and 892 variants at an unadjusted p value of 5 × 10(-8) for AG876 and B95-8 genomes, respectively. We used complementary sequence strategies to examine EBV genetic diversity and its application to transplantation. The results provide the framework for further characterization of EBV strains and related outcomes after organ transplantation.

Presentation and outcome of paediatric membranous non-proliferative lupus nephritis.

BACKGROUND: Studies of paediatric patients with membranous lupus nephritis (MLN) have yielded variable results, mostly due to the inclusion of mixed, i.e. proliferative nephritis. The aim of this study was to describe clinical and laboratory findings at the diagnosis of paediatric non-proliferative MLN, report the outcome and identify predictors of remission. METHODS: A single-center cohort study of consecutive children diagnosed with non-proliferative MLN was performed. Clinical and laboratory measures and treatment regimens were obtained in prospective standardized assessments. Renal outcome was measured by renal parameters and steroid requirement. Predictors for remission and time to remission were determined. RESULTS: A total of 30 children were identified with a median follow-up time 4.1 years. Of 21 patients followed for more than 2 years, 19 (90 %) achieved clinical remission, and 16 (76 %) achieved a state of maintained clinical remission on low-dose prednisone. Three patients developed proliferative nephritis on subsequent renal biopsy. Lower albumin at the time of biopsy was correlated with a lower rate of remission and longer time to remission. CONCLUSIONS: Among our paediatric patient cohort the outcome of non-proliferative MLN in systemic lupus erythematosus was good. The majority of patients did not require aggressive immunosuppressive treatment to reach a stable disease state on low-dose steroid treatment.

The new histopathologic classification of ANCA-associated GN and its association with renal outcomes in childhood.

BACKGROUND AND OBJECTIVES: A proposed histopathologic classification for ANCA-associated GN is predictive of long-term renal outcome in adult populations. This study sought to validate this system in a pediatric cohort. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a retrospective, single-center, cohort study of 40 children diagnosed and followed until their transition to adult care at one institution between 1987 and 2012. Renal biopsy specimens were reviewed by a pathologist blinded to patient outcome and were classified using the new histopathologic classification system of focal, crescentic, mixed, and sclerotic groups. Time to the composite outcome of CKD stages 3 and 4 (determined by eGFR with repeated creatinine measures using the Schwartz equation) or ESRD (defined as dialysis dependence or transplantation) were ascertained. RESULTS: The study population consisted of 40 children (70% female), followed for a median of 2.4 years. The biopsy specimens were categorized as focal in 13 patients (32.5%), crescentic in 20 (50%), mixed in two (5%), and sclerotic in five (12.5%). Mixed and crescentic were combined for analyses. Survival analysis of time to the composite renal endpoint of at least 3 months of eGFR<60 ml/min per 1.73 m(2) or ESRD differed significantly among the three biopsy groups log-rank P<0.001), with an adjusted hazard ratio of 3.14 (95% confidence interval, 0.68 to 14.4) in the crescentic/mixed group and 23.6 (95% confidence interval, 3.9 to 144.2) in the sclerotic category compared with the focal category. The probability of having an eGFR>60 ml/min per 1.73 m(2) at 2 years was 100% for the focal, 56.5% for the crescentic/mixed, and 0% for the sclerotic biopsy categories. CONCLUSIONS: This study showed the clinical utility of this histopathologic classification system and its ability to discriminate renal outcomes among children with ANCA GN.

The effect of oral acetazolamide on weight gain in children.

OBJECTIVE: Oral acetazolamide is a potent medical treatment for pediatric glaucoma, but ophthalmologists may have concerns that it retards weight gain in children and may choose surgical management instead. DESIGN: Retrospective chart review. PARTICIPANTS: Twenty-two well children with glaucoma taking acetazolamide orally for >or=3 months. METHODS: Abnormal weight gain was determined using downward crossing of 2 percentile lines on growth charts and change in z score for weight using a hierarchical linear model. RESULTS: One patient with Sturge-Weber syndrome and growth failure was excluded when growth hormone deficiency was diagnosed. Two patients crossed 2 lines downward; both showed metabolic acidosis. The trend for the 2 reversed after medication was discontinued. The other 20 tracked steadily on growth curves. Eleven patients (11/22, 50%) showed a decline in z score for weight over the follow-up period, and the remainder showed an increase, for an overall estimate of slope in this sample of 0.01, which was not significant (p = 0.8). CONCLUSIONS: Oral acetazolamide may cause poor weight gain in a small subset of children on treatment. Metabolic acidosis may be a mediating factor for growth failure. Our data suggest that acetazolamide does not cause significant weight changes in cases of pediatric glaucoma. Growth parameters should be followed. Growth hormone deficiency should be considered in Sturge-Weber syndrome. Prospective study is needed.

Gene expression using microarrays in transplant recipients at risk of EBV lymphoproliferation after organ transplantation: preliminary proof-of-concept.

We hypothesized that aspects of the virus-host interaction could be measured to help predict progression to EBV-PTLD. We examined the spectrum of host genes differentially expressed and any relevant clustering in children at risk of EBV lymphoproliferation after organ transplantation. We compared the genes expressed among patients with different levels of viral loads. Gene expression was measured by microarray analysis of RNA from CD19+ B lymphocytes using the Human Genome U133 Plus 2.0 GeneChip. Among 27 samples from 26 transplant recipients, the viral load categories were: low or undetectable loads (LU), n = 14; high or intermediate loads (HI), n = 13. There were seven healthy EBV-seropositive (P) and -seronegative controls (N). Median time of post-transplantation was 0.5 yr (range 0.1-3.8). We identified 24-54 differentially expressed genes in each of four comparisons of HI vs. P, LU vs. P, HI vs. LU, and P vs. N. We identified patterns of 563 gene expressions, creating five clusters aligned with levels of viral load. PTLD occurred in four of five clusters. In summary, we demonstrated varying degrees of alignment between levels of VL and gene clusters. Analyses for differential expression of genes showed genes that could be implicated in the pathogenesis of EBV-PTLD.