Value of Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios in the Evaluation of Acute Rejection and Chronic Allograft Nephropathy in Children With Kidney Transplantation.

OBJECTIVES: Neutrophil-to-lymphocyte ratio and platelet (thrombocyte)-to-lymphocyte ratio have become accepted markers of inflammation in recent years and are used to assess disease activity in some diseases. In this study, we investigated the relationship between these values and acute rejection attacks, as well as their role in determining chronic allograft nephropathy, in follow-up of pediatric kidney transplant recipients. MATERIALS AND METHODS: Our study included 58 kidney transplant recipients (age 5-18 years) with at least 5-year follow-up at our center. Patients with history of secondary transplant, concomitant malignancy, and shorter follow-up were excluded. Medical history and laboratory parameters pretransplant and at 1, 3, and 6 months and 1, 2, 3, 4, and 5 years posttransplant, as well as kidney biopsy reports, were reviewed. RESULTS: Both neutrophil-to-lymphocyte (P = .003) and thrombocyte-to-lymphocyte (P = .002) ratios were significantly higher during acute rejection attacks. Although both values were higher in patients with chronic allograft nephropathy at 5 years posttransplant, differences were not statistically significant (P = .69 and P = .55). When patients with and without chronic allograft nephropathy within 5 years were compared, those who developed chronic allograft nephropathy had significantly higher neutrophil- tolymphocyte and thrombocyte-to-lymphocyte ratios at all periods in the first 2 and 4 years posttransplant, respectively. Among patients who had acute rejection attacks, those who subsequently developed chronic allograft nephropathy had higher neutrophil-tolymphocyte ratio in the first 3 years posttransplant, with higher thrombocyte-to-lymphocyte ratio at all posttransplant periods. CONCLUSIONS: This is the first study on neutrophil- tolymphocyte and thrombocyte-to-lymphocyte ratios in pediatric kidney transplant recipients. Our results indicated that both values can be useful and easily accessible markers in acute rejection diagnosis and determining chronic allograft nephropathy development risk, which are 2 major causes of kidney graft loss posttransplant. Pediatric studies with larger populations are needed to support our findings.

Evaluation of quality of life and its associations with clinical parameters in pediatric patients with familial Mediterranean fever.

OBJECTIVE: A favorable quality of life (QoL) is important in children with chronic disease, and it reflects successful disease management. The aim of our study was to evaluate QoL and its association with clinical parameters in pediatric patients with familial Mediterranean fever (FMF). METHODS: The Kinder Lebensqualität Fragebogen (KINDL®) questionnaires (kiddy: 4-7 years; kid: 8-16 years) for children and the proxy version for parents were implemented as a QoL measure. A total of 171 FMF patients, 69 healthy peers and their parents were enrolled in the study. RESULTS: The KINDL QoL scores of the FMF patients were significantly lower than their healthy peers. The physical and emotional well-being KINDL QoL scores of the FMF children were significantly lower than their healthy peers (p=0.017 and p=0.020, respectively). In the evaluation of the KINDL QoL scores between the kiddy and kid groups, only the self-esteem score was higher in the kiddy group (p=0.004), and the school functioning scores were higher in the kid group (p=0.002). The scores in the physical well-being and disease module had significant differences between patients who were adherent and those who were non-adherent to colchicine therapy (p=0.042 and p=0.047, respectively). The scores in the physical well-being and disease module were significantly higher in patients with fewer attacks than those who had many attacks per year (p=0.004 and p=0.014, respectively). CONCLUSION: This study suggests that FMF patients have significantly impaired QoL. The irregular use of colchicine and more frequent attacks affect QoL even more. A QoL assessment with multidisciplinary follow-up and control of the disease activity are essential, and if necessary, individualized support should be given to patients.

Evaluation of caregiver burden and coping strategies in parents of paediatric familial Mediterranean fever patients in relation to illness severity, therapy and health-related quality of life.

PURPOSE: The study aimed to determine the caregiver burden and coping strategies in caregivers of familial Mediterranean fever (FMF) patients in relation to illness severity, therapy and health-related quality of life (HRQoL). METHODS: The study included 171 paediatric FMF patients and their caregivers (parents). The caregivers were asked to complete a socio-demographic form, the Zarit caregiver burden interview (ZCBI) and the Brief COPE. The patients and their caregivers were asked to complete the KINDer Lebensqualitätsfragebogen questionnaire (self-report and proxy report, respectively) for assessing HRQoL. The patients were categorised according to their disease activity (mild, moderate or severe) and the presence or absence of anti-IL-1 therapy. RESULTS: The mean ZCBI score of the caregivers was 44.7 ± 13.5. ZCBI and COPE scores did not differ significantly between the caregivers of FMF patients receiving and not receiving anti-IL-1 therapy. However, dysfunctional COPE (p = 0.039) and ZCBI (p = 0.021) scores showed a significant difference between the caregivers in relation to patient's disease severity. ZCBI scores were positively correlated with dysfunctional coping (p = 0.01). Self-reported HRQoL disease module scores were lower for the patients who received anti-IL-1 therapy than for those did not (p = 0.009). Proxy-reported (p < 0.001) and self-reported (p = 0.043) HRQoL disease module scores were lower for the patients with severe disease activity. CONCLUSIONS: As the caregiver burden increases, parents tend to use a dysfunctional coping strategy. Good control of disease activity with administration of medical therapy can reduce the disease severity, thereby decrease the caregiver burden, and secondly help to reduce the usage of dysfunctional coping in caregivers.

Hypophosphatasia: is it an underdiagnosed disease even by expert physicians?

INTRODUCTION: Hypophosphatasia (HPP) is caused by mutations in the ALPL that encodes the tissue-nonspecific isoenzyme of alkaline phosphatase (ALP). Clinical manifestations range from extreme life-threatening lethal forms to no signs or symptoms at all. MATERIALS AND METHODS: Consecutive 30,000 outpatients and inpatients with ALP data were screened retrospectively, out of which 1000 patients were found to have low levels of ALP more than once. Then, patients were evaluated for the symptoms and signs of HPP with further biochemical and genetic analyses. RESULTS: Thirty-seven patients who had severe musculoskeletal pain, recurrent fractures, and tooth anomalies were then screened with substrate and DNA sequencing analyses for HPP. It was determined that eight patients had variants in the ALPL gene. A total of eight different ALPL variants were identified in eight patients. The variants, namely c.244G > C (p.Gly82Arg), c.1444C > T (p.His482Tyr), c.1487A > G (p.Asn493Ser), and c.675_676insCA (p.Met226GlnfsTer52), had not been previously reported. DISCUSSION: Considering the wide spectrum of clinical signs and symptoms, HPP should be among the differential lists of bone, muscle, and tooth abnormalities at any age.

Parental knowledge about familial Mediterranean fever: a cross-sectional study.

BACKGROUND: The life-long course, long-term complications, necessity for regular treatment, and potential side effects of the medications must be well understood by parents of pediatric familial Mediterranean fever (FMF) patients. The aim of this study was to assess parental knowledge and to investigate how parents obtained scientific information about FMF. METHODS: One hundred and seventy-one pediatric FMF patients and their parents were enrolled in this crosssectional study. Three-part questionnaires, including forms on socio-demographics, knowledge and perceptions of FMF, and how to get information about FMF, were administered to parents. RESULTS: In the analysis of the knowledge questions, 90.1% of parents were aware of colchicine as an effective drug for FMF, but only 39.2% of them were aware that there is no vital risk during FMF attacks. Caregivers preferred to obtain information from physicians (98.8%), websites (47.9%), seminars (3.5%), and books (1.7%). The knowledge scores of parents were significantly higher among those whose children were using antiinterleukin- 1 therapy in addition to colchicine relative to those on colchicine alone (p = 0.04). There was a positive correlation between knowledge level and parental educational status (p = 0.0001). CONCLUSIONS: Knowledge scores among parents of pediatric FMF patients are unsatisfactory. The parents whose children have a severe disease course and a need for anti-interleukin-1 therapy are more knowledgeable. For parents, continuing education programs including books, seminars and web-sites giving information about the course, prognosis, complications and treatments of FMF should be employed immediately after the diagnosis and thereafter.

Disease activity and outcomes in juvenile Behçet's disease: 10 years' experience of a single centre.

OBJECTIVES: The aims of this study were to investigate the development of new events (new clinical signs related to Behçet's disease) and to evaluate outcomes in juvenile Behçet's disease (jBD) patients over a 10-year follow-up. METHODS: We included 57 patients diagnosed with jBD according to International Behçet's Study Group (ISG) criteria and/or the International Criteria for BD (ICBD) and/or Paediatric BD (PEDBD) group criteria, followed-up between 2008 and 2018. Any new organ system involvement during follow-up was defined as an event in event-free survival analysis. RESULTS: The patients' female/male ratio was 33/24. The most prevalent clinical feature was recurrent oral aphthosis (100%), followed by musculoskeletal symptoms (63%), genital ulcers (56%), ocular manifestations (47%) and cutaneous manifestations (46%). Vascular, neurological, gastrointestinal and genitourinary manifestations were observed in 4-17% of the patients. Fifty-four (95%) cases fulfilled the ICBD, while 31 (54%) and 34 (60%) fulfilled ISG and PEDBD criteria, respectively. The median Iranian Behçet's disease dynamic activity measure (IBDDAM) score at diagnosis was 5 (range: 3-14) and decreased to 1 (range: 0-6) at the last visit. One to three events occurred in 21 (37%) cases. One fifth (19%) of these events were severe. The event-free survival rate was 95% at one year, 70% at three years and 50% at eight years. CONCLUSIONS: This study shows that with effective treatment, jBD has favourable outcome and a remarkable event-free survival. Underdiagnosed cases according to ISG and PEDBD criteria could be diagnosed using the ICBD.

An adolescent case of extensive Behçet`s disease successfully treated with Infliximab.

Isiyel E, Bakkaloglu S, Oguz D, Yenicesu I, Boyunaga Ö, Özdemir Y, Damar Ç, Kandur Y, Akçaboy M, Aslan AT, Sismanlar T, Hasanoglan E, Buyan N. An adolescent case of extensive Behçet`s disease successfully treated with Infliximab. Turk J Pediatr 2019; 61: 585-588. Cardiac involvement is an uncommon and life-threatening complication of Behçet`s Disease. We present a 14-year-old boy, admitted to our hospital for recurrent hemoptysis. In his radiologic evaluation, a right ventricular thrombus and pulmonary arterial aneurysm were identified. He was diagnosed with Behçet`s Disease, and then he received prednisone and cyclophosphamide. However, his cardiac thrombus enlargened. After his treatment was replaced with infliximab, the pulmonary aneurysms regressed, and the cardiac thrombus disappeared. In conclusion, infliximab should be considered as a reliable option for vascular Behçet`s Disease resistant to conventional treatment.

What triggered massive hemoptysis in Goodpasture syndrome with isolated pulmonary involvement in a 14-year-old boy?

Sismanlar-Eyüboglu T, Aslan AT, Gezgin-Yildirim D, Buyan N, Emeksiz S, Kalkan G. What triggered massive hemoptysis in Goodpasture syndrome with isolated pulmonary involvement in a 14-year-old boy? Turk J Pediatr 2019; 61: 611-614. Goodpasture syndrome is a rare, autoimmune disease associated with the development of antibodies against a specific antigen both in glomerular basement membrane and alveolar basement membrane. It is very rare in childhood and its incidence is not known. Although the mechanism of the disease is the same in lung as in the kidney, sometimes it presents with involvement of only one organ. Pulmonary involvement may be lifethreatening in patients with massive hemoptysis. Herein we report a 14-yearold boy with isolated lung involvement. He had massive hemoptysis following bronchoscopy and recovered succesfully with treatment.

Protracted febrile myalgia as a challenging manifestation of familial Mediterranean fever: case-based review.

Protracted febrile myalgia syndrome (PFMS) in familial Mediterranean fever (FMF) patients is a vasculitic condition characterized by severe myalgia, fever, abdominal pain, diarrhea, and arthralgia/arthritis episodes lasting 4-6 weeks. Symptoms typically resolve with corticosteroid treatment. However, in recent years, corticosteroid-resistant PFMS patients have been reported. We herein report five pediatric FMF patients complicated with PFMS. In addition, demographic findings, Mediterranean fever (MEFV) gene analysis, symptoms at disease onset, time interval between the diagnoses of FMF and PFMS, co-existent diseases, and treatment responses were evaluated. Resolution of all PFMS symptoms was accepted as complete response, while decreased symptoms without full recovery as partial response. We searched PubMed using the keywords 'protracted febrile myalgia' and 'anakinra', and reviewed the literature. There were three male and two female patients. Median age at the diagnosis of FMF was 6 (3-10) years. The time from diagnosis of FMF to the development of PFMS was changed from 0 to 8 (median: 2) years. All of the patients, except one, had homozygous M694V mutation. All patients were treated with corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs) first. Two out of five patients were exhibited partial response, while others exhibited complete response. Patients with partial response to the conventional therapies were treated with anakinra, and achieved a great response after the first dose. Anti-interleukin-1 (IL-1) therapy may be a beneficial and a reasonable treatment option, when there is insufficient response to NSAID and corticosteroid therapies in pediatric PFMS patients.

Isolated acute lupus pneumonitis as the initial presentation of systemic lupus erythematosus in an 8-year-old girl.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease which has broad pleuropulmonary manifestations. One of the rare and mortal complications is acute lupus pneumonitis, which is reported very rarely, especially in childhood. Herein, we report an 8-year-old girl with isolated acute lupus pneumonitis as the initial presentation that required a lung biopsy for diagnosis. Although she had improvement with the administration of steroids, steroid treatment was reduced due to the drug's side effects resulting in the addition of azathioprine and mycophenolate mofetil to the treatment regimen. After the new regimen failed to result in clinical improvement, hydroxychloroquine treatment was started and a significant improvement was observed. Acute lupus pneumonitis is an uncommon manifestation of SLE and diagnosis may be difficult in patients without other organ involvement.

Whole blood viscosity and cerebral blood flow velocities in obese hypertensive or obese normotensive adolescents.

BACKGROUND: Obesity affects all major organ systems and leads to increased morbidity and mortality. Whole blood viscosity is an important independent regulator of cerebral blood flow. The aim of the present study was to evaluate the effect of whole blood viscosity on cerebral artery blood flow velocities using transcranial Doppler ultrasound in pediatric patients with obesity compared to healthy controls and analyze the effect of whole blood viscosity and blood pressure status to the cerebral artery blood flow velocities. METHODS: Sixty patients with obesity diagnosed according to their body mass index (BMI) percentiles aged 13-18 years old were prospectively enrolled. They were grouped as hypertensive or normotensive according to their ambulatory blood pressure monitoring. Whole blood viscosity and middle cerebral artery velocities by transcranial Doppler ultrasound were studied and compared to 20 healthy same aged controls. RESULTS: Whole blood viscosity values in hypertensive (0.0619±0.0077 poise) and normotensive (0.0607±0.0071 poise) groups were higher than controls (0.0616±0.0064 poise), with no significance. Middle cerebral artery blood flow velocities were higher in the obese hypertensive (73.9±15.0 cm/s) and obese normotensive groups (75.2±13.5 cm/s) than controls (66.4±11.5 cm/s), but with no statistical significance. CONCLUSIONS: Physiological changes in blood viscosity and changes in blood pressure did not seem to have any direct effect on cerebral blood flow velocities, the reason might be that the cerebral circulation is capable of adaptively modulating itself to changes to maintain a uniform cerebral blood flow.

Successful treatment of a childhood synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome with subcutaneous methotrexate: A case report.

Akçaboy M, Bakkaloglu-Ezgü SA, Büyükkaragöz B, Isiyel E, Kandur Y, Hasanoglu E, Buyan N. Successful treatment of a childhood synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome with subcutaneous methotrexate: A case report. Turk J Pediatr 2017; 59: 184-188. SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis and osteitis) is defined as a syndrome that is related to various osteoarticular manifestations and chronic dermatological conditions especially severe acne. SAPHO syndrome is a rare and unusual clinical entity in childhood and treatment choices are variable. We report an 11-year-old girl who suffered from SAPHO syndrome and successfully treated with subcutaneous methotrexate. We report our case in order to take attention to this rare clinical condition in evaluating patients and also to point out that treatment options beyond biologic agents should be the first line treatment in childhood.

Effects of whole blood viscosity and plasma NOx on cardiac function and cerebral blood flow in children with chronic kidney disease

Background/aim: The aim of the study was to investigate the effects of whole blood viscosity and plasma nitric oxide on cerebral and cardiovascular risks associated with chronic kidney disease. Materials and methods: The study group consisted of 40 pediatric patients and 21 healthy control subjects. Hematologic and biochemical variables, viscosity and plasma nitric oxide levels, echocardiographic findings, and middle cerebral artery blood flow velocity were examined. Results: Viscosity values of patients were significantly lower than those of the control group. Lower values of hematocrit, total protein, and albumin and higher values of ferritin in all patient groups resulted in significantly low viscosity levels. Plasma nitric oxide levels were higher in all patient groups than those in the controls. No statistically significant difference was present in middle cerebral artery blood flow velocity between the patient and control groups. Even when systolic functions were normal, the patient group had significant deterioration in diastolic functions, suggesting morbidity and mortality risks. Conclusions: Cerebral blood flow velocities were not affected by viscosity and nitric oxide levels, suggesting that cerebral circulation has the ability to make adaptive modulation. The metabolism of nitric oxide levels needs further investigation and studies in patients with chronic renal disease.

Results of native and transplant kidney biopsies of children in a single center over a 15 years period.

Renal biopsy is an important diagnostic procedure in pediatric nephrology. This study retrospectively investigates the indications, results and complications in a single tertiary children's hospital in Turkey. We evaluated the native and transplant kidney biopsies in Gazi University Pediatric Nephrology Department between 2001 and 2015. A total of 196 biopsies (144 natives and 52 transplants) were included into the study. The mean age of the patients was respectively 10.8 ± 3.5, 13.9 ± 1.5 years. The main indication for a biopsy was non-nephrotic proteinuria with or without hematuria (n= 35), followed by steroid-resistance nephrotic syndrome (SRNS) (n = 34) and Henoch-Schönlein purpura (HSP)-related proteinuria (n = 20) for native kidneys. We found that focal segmental glomerulosclerosis (FSGS) (11.7%) was the most common histopathologic diagnosis for native kidneys, but acute cellular rejection (7.6%) was the most common histopathologic diagnosis for transplant kidneys. The complication rate in our study was founded 6.6% totally. Different complication rates were found in other studies; however, we think that this difference comes from the inspecting methodology of the complications. Hence, we wanted to share our own experience in the context of other studies in the literature.

Cerebral Vasculitis in Henoch-Schönlein Purpura: A Case Report.

Henoch-Schönlein purpura is a common form of systemic small vessel vasculitis in childhood. Although headache and behavioral changes have been described in a significant proportion of children with Henoch-Schönlein purpura, severe neurological complications are rare. In this article, we report a case of central vasculitis in a four-year-old boy who presented with hemiplegia and aphasia. The treatment options for cerebral vasculitis of Henoch-Schönlein purpura are numerous but controversial in pediatric patients. Our patient was successfully treated by pulse methylprednisolone and pulse cyclophosphamide. The patient was followed-up for four years without any sequel.

Micronuclei and other nuclear anomalies in buccal epithelial cells of children with chronic kidney disease.

The objective of this study was to reveal the likely genomic instability in children with chronic kidney disease (CKD) using micronucleus (MN) assay on buccal epithelial cells (BEC). We investigated the frequencies of micronuclei and other nuclear anomalies, such as nuclear buds, binucleated cells, condensed chromatin, and karyorrhectic and pyknotic cells in BEC. Children with CKD were grouped as follows: children in the pre-dialysis (PreD) stage (N=17), children on regular haemodialysis (HD) (N=14), and children who have undergone transplantation (Tx) (N=17). As a control group, twenty age- and gender-matched healthy children were selected. The MN frequency in BEC of all groups of children with CKD was significantly elevated (5- to 7-fold) as compared to the control group (p<0.001). In contrast, the frequencies of nuclear buds were not significantly higher in the study groups compared to the control group. The frequencies of binucleated cells and condensed chromatin cells were significantly higher in all subgroups of children with CKD relative to the control group (p<0.001). Our results show that the BEC of pediatric PreD, HD, and Tx patients with CKD display increased cytogenetic, cytokinetic, and cytotoxic effects. They also point to the sensitivity and usefulness of the BEC MN assay in the assessment of genetic susceptibility of patients with CKD.