Long-term mortality in pediatric solid organ recipients-A nationwide study.

BACKGROUND: The present study aimed at investigating long-term mortality of patients who underwent solid organ transplantation during childhood and at identifying their causes of death. METHODS: A cohort of 233 pediatric solid organ transplant recipients who had a kidney, liver, or heart transplantation between 1982 and 2015 in Finland were studied. Year of birth-, sex-, and hometown-matched controls (n = 1157) were identified using the Population Register Center registry. The Causes of Death Registry was utilized to identify the causes of death. RESULTS: Among the transplant recipients, there were 60 (25.8%) deaths (median follow-up 18.0 years, interquartile range of 11.0-23.0 years). Transplant recipients' risk of death was nearly 130-fold higher than that of the controls (95% CI 51.9-1784.6). The 20-year survival rates for kidney, liver, and heart recipients were 86.1% (95% CI 79.9%-92.3%), 58.5% (95% CI 46.2%-74.1%), and 61.4% (95% CI 48.1%-78.4%), respectively. The most common causes of death were cardiovascular diseases (23%), infections (22%), and malignancies (17%). There were no significant differences in survival based on sex or transplantation era. CONCLUSION: The late mortality is still significantly higher among pediatric solid organ recipients in comparison with controls. Cardiovascular complications, infections, and cancers are the main causes of late mortality for all studied transplant groups. These findings emphasize the cruciality of careful monitoring of pediatric transplant recipients in order to reduce long-term mortality.

Long-term outcome of biopsy-proven idiopathic tubulointersitial nephritis with or without uveitis in children-a nationwide follow-up study.

BACKGROUND: Only a few studies reporting the long-term outcome of children with idiopathic tubulointerstitial nephritis (TIN) and uveitis syndrome (TINU) are available. We studied the long-term kidney and ocular outcome in a nationwide cohort of children with TIN or TINU. METHODS: All patients followed up for a minimum of 1 year by a paediatrician and an ophthalmologist were enrolled. The data on plasma creatinine (P-Cr), estimated glomerular filtration rate (eGFR), proteinuria, hypertension and uveitis were collected retrospectively. RESULTS: Fifty-two patients were studied. Median age at time of diagnosis was 13.1 (1.8-16.9) years and median follow-up time was 5.7 (1.1-21.2) years. Forty-five (87%) patients were initially treated with glucocorticoids. The median of the maximum P-Cr was 162 µmol/l (47-1,016) and that of eGFR 47 ml/min/1.73m2 (8-124). Uveitis was diagnosed in 33 patients (63%) and 21 (40%) patients developed chronic uveitis. P-Cr normalised in a median of 2 months. Eleven (21%) patients had nephritis recurrence during or after discontinuation of glucocorticoids. At the latest follow-up, 13 (25%) patients had eGFR < 90 ml/min/1.73m2 (median 83; 61-89 ml/min/1.73m2). Six patients had tubular proteinuria; all presented with TIN without uveitis. Seven (13%) patients were hypertensive. Eleven (21%) patients had uveitis. One patient developed uraemia and was later transplanted. CONCLUSIONS: Our study questions the previously reported good long-term kidney and ocular outcome of patients with TIN/TINU. Decreased kidney function and/or ocular co-morbidities may persist for several years; thus, both kidney and ocular follow-up for at least 1 year is warranted. A higher resolution version of the Graphical abstract is available as Supplementary information.

Cancer morbidity and mortality after pediatric solid organ transplantation-a nationwide register study.

BACKGROUND: The prevalence of malignancies after pediatric solid organ transplantation was evaluated in a nationwide study. METHODS: All patients who had undergone kidney, liver, or heart transplantation during childhood between the years 1982 and 2015 in Finland were identified. The inclusion criteria were age under 16 years at transplantation and age over 18 years at the last follow-up day. A total of 233 (137 kidney, 53 liver, and 43 heart) transplant recipients were enrolled. Controls (n = 1157) matched by the year of birth, gender, and hometown were identified using the Population Register Center registry. The cancer diagnoses were searched using the Finnish Cancer Registry. RESULTS: Altogether 26 individuals diagnosed with cancer were found, including 18 transplant recipients. Cancer was diagnosed at a median of 12.0 (IQR 7.8-17.8) years after the transplantation. The transplant recipients' risk for cancer was significantly higher when compared with the controls (HR 14.7; 95% CI 6.4-33.9). There was no difference for different graft types. Sixty-one percent of cancers among the transplant recipients were diagnosed at age older than 18 years. CONCLUSION: The risk for cancer is significantly higher among young adults having undergone solid organ transplantation during childhood in comparison with population controls. Careful follow-up and attention to prevent cancers throughout adulthood are warranted.

Telomere length regulators are activated in young men after pediatric kidney transplantation compared to healthy controls and survivors of childhood cancer-A cross-sectional study.

Chronic diseases are known to cause premature aging and frailty. Data about telomere length and telomere length-regulating proteins after pediatric KTx are scarce. Leukocyte telomere length and gene expression level of eight telomere-binding proteins were analyzed in 20 KTx recipients, eight childhood NBL survivors, and nine healthy controls. The influence of key clinical parameters on telomere length and on regulators of telomere length was evaluated. The telomere length in the KTx recipients tended to be shorter (0.53 AU) than in the healthy controls (0.64 AU) but longer than in the NBL survivors (0.38 AU). There was no significant difference in telomere length between the NBL survivors and the KTx recipients (P = .110). The gene expression level of telomere length-preserving protein RPA1 was significantly higher in the KTx recipients than among the NBL survivors or healthy controls, while the expression of TRF2 and the tumor suppressor gene p16 was significantly higher in the KTX recipients when compared to the controls. TRF2 and TIN2 correlated significantly with hsCRP; additionally, TRF2 showed significant correlation with plasma creatinine and eGFR. KTx recipients have near to normal telomere length, but they have significantly higher gene expression levels of telomere regulatory proteins compared with healthy controls, suggesting activation of mechanisms preserving telomere length among KTx recipients. Our results suggest that declined graft function and consequent inflammatory response may have influence on telomerase activity.

Methylprednisolone or cyclosporine a in the treatment of Henoch-Schönlein nephritis: a nationwide study.

BACKGROUND: Optimal treatment of Henoch-Schönlein purpura nephritis (HSN) remains unclear. We evaluated outcome of pediatric HSN patients treated initially with either methylprednisolone (MP) or cyclosporine A (CyA) in Finland between 1996 and 2011. METHODS: Outcome of 62 HSN patients was evaluated by screening urine and blood samples (n = 51) or by collecting clinical parameters from medical charts until last follow-up visit (n = 11). Sixty (97%) patients had nephrotic-range proteinuria and/or ISKDC grade ≥ III before initial treatment. Patients were initially treated with either MP pulses (n = 42) followed by oral prednisone or with CyA (n = 20). Fifty-nine (95%) patients received angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers. RESULTS: Mean follow-up time was 10.8 years (range 3.2-21.2 years). One patient developed end-stage renal disease and another had decreased renal function (eGFR < 60 mL/min/1.73m2), both initially treated with MP (3%). Six patients (5 MP, 1 CyA) had eGFR between 60 and 89 mL/min/1.73m2 (10%). Eighteen patients (13 MP, 5 CyA) had proteinuria and/or hematuria (29%) and four of them had proteinuria > 0.5 g/day at end of follow-up. Sixteen (38%) MP-treated and two (10%) CyA-treated patients needed additional immunosuppressive treatment (RR 3.81, 95% CI 1.16-14.3, p = 0.035). Late initiation of treatment was associated with an increased risk for persistent proteinuria. CONCLUSIONS: Long-term outcome was relatively good in both treatment groups. However, since urinary abnormalities may persist or develop, long-term follow-up of HSN patients is mandatory. Early initiation of treatment had a favorable effect on proteinuria.

Lower quality of life in young men after pediatric kidney transplantation when compared to healthy controls and survivors of childhood leukemia-a cross-sectional study.

Data about health-related quality of life (HRQOL) in adult recipients after pediatric kidney transplantation (KTx) are scarce. In this nationwide questionnaire-based study, HRQOL and social status in young adult men having undergone KTx during childhood (n = 29) were studied and compared to age- and gender-matched healthy controls (n = 56) and survivors of childhood acute lymphoblastic leukemia (n = 52) comprising controls with another chronic disease of childhood. Altogether 41% of the KTx recipients, 50% of the leukemia survivors and 80% of the healthy controls lived in a permanent relationship. When compared with leukemia survivors, the KTx recipients reported significantly more bodily pain and worse general health (RAND-36). Older age at time of study, longer duration of dialysis, multiple transplantations and diminished graft function correlated with lower scores. The KTx recipients had a significantly higher mean Beck Depression Inventory (BDI) score than the leukemia survivors (P = 0.000) or the healthy controls (P = 0.006). BDI scores were highest in patients who lived without a partner or children had lower educational level or were unemployed. KTx recipients had significantly lower HRQOL scores than their healthy and controls with childhood chronic disease. Early detection of psychosocial problems and poor physical functioning among these patients is warranted.

FOXP3+ T cells are present in kidney biopsy samples in children with tubulointerstitial nephritis and uveitis syndrome.

BACKGROUND: Tubulointerstitial nephritis (TIN) is an inflammatory disease of unknown pathogenesis. To evaluate a possible role of regulatory T cells (Tregs) in the pathophysiology of TIN with (TINU) and without uveitis, we investigated the presence and quantity of FOXP3+ T regulatory lymphocytes in diagnostic kidney biopsies from pediatric patients. METHODS: A total of 33 patients (14 TIN and 19 TINU) were enrolled. The quantity of CD4+, FOXP3+ and double-positive T cells in formalin-fixed kidney biopsies was determined using double label immunohistochemistry with anti-human CD4 and FOXP3 antibodies. RESULTS: FOXP3 staining was successful in all 33 patients. In patients with chronic uveitis, the density of FOXP3+ cells was significantly lower (p = 0.046) than in TIN patients without uveitis or with uveitis lasting <3 months. CD4+ staining was successful in 23 patients. The density of all lymphocytes (CD4+, CD4+FOXP3+ and FOXP3+ cells) was significantly lower (p = 0.023) in patients with chronic uveitis than in other patients. CONCLUSIONS: FOXP3+ T cells are present in kidney biopsy samples from TIN and TINU patients. In patients with chronic uveitis, the density of FOXP3+ T cells is significantly lower than in other patients, suggesting a different pathomechanism for these clinical conditions.

Subaxial cervical vertebrae in patients with juvenile idiopathic arthritis--something special?

OBJECTIVES: To describe the main dimensions of the cervical vertebrae and spinal canal in two groups with juvenile idiopathic arthritis (JIA) and a non-inflammatory control group. METHODS: There were altogether 158 female patients in three different groups included in the study: a group with severe, complicated JIA (sJIA), a population based JIA group (pJIA), and fibromyalgia patients as a non-inflammatory control group (pFM). The patients' clinical records and cervical spine radiographs taken in adult age (>17 years) were evaluated. RESULTS: The patients with sJIA had the mean area of the 3rd-6th cervical vertebrae bodies and the average width and height of the 3rd-6th cervical vertebrae bodies significantly smaller than the patients in the pJIA and pFM groups. The mean value of the maximal difference between the successive vertebral body areas of each individual was significantly larger in the sJIA group than the other groups (p=0.047; the body height adjusted). There were no significant differences in the mean diameter of the sagittal spinal canal between study groups. CONCLUSIONS: Inflammatory changes of the cervical spine are common, and growth disturbances of cervical vertebrae in patients with JIA have been described previously. We found that patients with severe complicated JIA have a smaller cervical vertebral body size in general. They also have more differences in the sizes of their own vertebrae, representing growth disturbances of individual vertebral bodies. This is probably caused by the inflammatory disease and/or its more aggressive pharmacotherapy. The spinal canal diameter was only slightly smaller in the sJIA group. Thus the disturbed growth of the vertebral body in sJIA does not, in general, increase the risk of spinal canal compression.

[Evidence-based methods of medicine in specialization training: a neonatologic problem as an example]. / Näyttöön perustuvan lääketieteen menetelmät erikoistumiskoulutuksessa: esimerkkinä neonatologinen ongelma.

One of the objectives of the qualification of medical specialists is familiarization to the scientific literature of the future special field. We describe a training project, in which doctors specializing in pediatrics collected and evaluated the current scientific data on the closure of the arterial duct in premature infants. Main emphasis in the article is put on the setting of the questions to be elucidated, acquisition of the required information, evaluation of the degree of evidence, and how reliably these questions can be answered on the basis of the current information. We recommend arranging evidence-based medical training for specializing doctors.