Thrombosis in Chronic Kidney Disease in Children.

Venous thromboembolism (VTE) in children is a rare condition. An increased incidence has been observed in the last few years due to several factors, such as increased survival in chronic conditions, especially chronic kidney disease (CKD), use of catheters, and increased sensitivity of diagnostic tools. VTE includes deep vein thrombosis (DVT) and pulmonary embolism (PE). VTE in children is associated with a two to six times higher mortality risk and a 5-10% prevalence of post-thrombotic syndrome. Overall, 5% of VTE episodes in children are associated with chronic kidney disease. The etiology of VTE in chronic kidney disease covers a wide range of pathologies. Various types of thrombotic complications may occur during long-term use of a chronic dialysis catheter. VTE occurs in 3% of children with nephrotic syndrome (NS). The risks for VTE and arterial thromboembolism (ATE) were particularly high in the first 6 months after the onset of NS. Other causes of VTE are graft rejection due to thrombosis of vascular anastomoses after kidney transplantation (3%) and autoimmune diseases (lupus nephritis, antiphospholipid syndrome). In this state-of-the-art overview, we have reviewed the physiologic and pathologic mechanisms underlying pediatric thrombosis and updated current diagnostic and treatment options, emphasizing personal experience as well.

TERT rs2853669 as a predictor for overall survival in patients with acute myeloid leukaemia.

INTRODUCTION: the aim of the study was to investigate the contribution of TERT rs2736100 and rs2853669 gene polymorphisms in defining the genetic predisposition to acute myeloid leukaemia (AML), their association with different prognostic markers, and their impact on survival, outcome, and the prognosis of affected patients. Also, we investigated the association of TERT SNPs in AML in the presence or absence of DNMT3A (R882), NPM1, and FLT3 mutations. MATERIAL AND METHODS: A total of 509 participants were enrolled in our study, consisting of 146 AML patients and 363 healthy participants, with no history of malignancy. TERT rs2736100 and rs2853669 polymorphisms were genotyped by using TaqMan SNP genotyping assay FLT3 (ITD, D835), DNMT3A (R882), and NPM1 c.863_864insTCTG (type A) mutations were analised in each AML case. RESULTS: TERT rs2736100 and rs2853669 were not associated with AML risk in the codominant, dominant, recessive, or allelic models. Multivariate Cox regression showed that TERT rs2853669 was a significant predictor for overall survival in AML patients. After adjusting for age, gender, cytogenetic risk group, ECOG status, FLT3, DNMT3A, NPM1 mutation, AML subtype, and treatment, the estimated adjusted hazard ratio (HR adjusted = 1.54, 95% CI: 1.01-2.35) showed that the TERT rs2853669 variant genotype had a negative influence on survival time. CONCLUSIONS: TERT rs2853669 and rs2736100 polymorphisms were not risk factors for developing AML in the Romanian population, but the TERT rs2853669 variant genotype had a negative effect on AML patients' overall survival in the presence of other known prognostic factors.

Innate immunity - the hallmark of Helicobacter pylori infection in pediatric chronic gastritis.

BACKGROUND: Innate immunity was found to be associated with both persistence of Helicobacter pylori (H. pylori) infection and increased risk of gastric cancer. AIM: To identify the risk factors associated with H. pylori infection and to establish the role of TLR9 rs352140 in suppressing or promoting inflammation related to this infection in children. METHODS: We performed a study of 155 children with digestive symptoms, who were divided into two groups according to the histopathological exam: Group 1 - 48 children with H. pylori-induced chronic gastritis, and Group 2 - control group. RESULTS: Rural area and poor living conditions were significantly associated with H. pylori chronic gastritis (P = 0.0042/P < 0.0001). Both positive immunoglobulin A anti H. pylori and the rapid urease test were significantly associated with H. pylori infection (P < 0.0001). Significantly higher values of leukocytes and neutrophils within the peripheral blood were found in children with H. pylori chronic gastritis (P = 0.111/P = 0.284). We found a significant positive correlation between the variant TT genotype of TLR9 rs352140 polymorphism and both leucocytes and neutrophils (P = 0.0225/P = 0.0292). CONCLUSION: Variant TT genotype carriers of the TLR9 rs352140 gene polymorphism might have a more severe degree of inflammation.

Nephrogenic diabetes insipidus in children (Review).

Nephrogenic diabetes insipidus (NDI) is characterized by impaired urinary concentrating ability, despite normal or elevated plasma concentrations of the antidiuretic hormone, arginine vasopressin (AVP). NDI can be inherited or acquired. NDI can result from genetic abnormalities, such as mutations in the vasopressin V2 receptor (AVPR2) or the aquaporin-2 (AQP2) water channel, or acquired causes, such as chronic lithium therapy. Congenital NDI is a rare condition. Mutations in AVPR2 are responsible for approximately 90% of patients with congenital NDI, and they have an X-linked pattern of inheritance. In approximately 10% of patients, congenital NDI has an autosomal recessive or dominant pattern of inheritance with mutations in the AQP2 gene. In 2% of cases, the genetic cause is unknown. The main symptoms at presentation include growth retardation, vomiting or feeding concerns, polyuria plus polydipsia, and dehydration. Without treatment, most patients fail to grow normally, and present with associated constipation, urological complication, megacystis, trabeculated bladder, hydroureter, hydronephrosis, and mental retardation. Treatment of NDI consist of sufficient water intake, low-sodium diet, diuretic thiazide, sometimes in combination with a cyclooxygenase (COX) inhibitor (indomethacin) or nonsteroidal anti-inflammatory drugs (NSAIDs), or hydrochlorothiazide in combination with amiloride. Some authors note a generally favorable long-term outcome and an apparent loss of efficacy of medical treatment during school age.

Antibiotic resistance patterns of urinary tract pathogens in children from Central Romania.

One of the most frequent bacterial infections in children are urinary tract infections (UTIs). In recent years, an increasing incidence of UTIs caused by resistant bacterial strains has been observed, especially with extended-spectrum ß-lactamase-producing Enterobacteriaceae that represent about 15% of UTIs. A retrospective study was performed comprising 331 pediatric cases with UTI. Our study aimed to detect the resistance of the uropathogens to common drugs used in UTI treatment. High resistance rates have been recorded for ampicillin, amoxicillin, trimethoprim/sulfamethoxazole (TMP/SMX), cefuroxime, and ciprofloxacin, among E. coli and Klebsiella. The multidrug-resistance (MDR) rate was detected in one-third of the uropathogens, among which more than half were isolated in patients with urinary tract abnormalities. Our study highlighted that nitrofurantoin, ceftriaxone, amikacin and carbapenem may be used for the empirical treatment for febrile or complicated UTI in children. This is the first comprehensive study that evaluates antibiotic resistance in UTIs in children, and their association with urinary tract abnormalities in Romania. As a result of this research, the protocol for initial empiric treatment of infants with febrile or complicated UTI should be modified considering a detailed and ongoing monitoring of local sensitivity of uropathogens to antimicrobial agents.

Presence of copy number aberration and clinical prognostic factors in patients with acute myeloid leukemia: an analysis of effect modification.

INTRODUCTION: Acute myeloid leukemia (AML) is characterized by multiple acquired genetic events, chromosomal abnormalities such as copy number aberrations (CNAs), disease progression, and low survival rates. OBJECTIVES: We assessed the utility of a multiplex ligation-dependent probe amplification (MLPA) assay in AML as well as correlations of CNAs with various biological and clinical features of patients with AML, including somatic mutations in the FLT3, NPM1, and DNMT3A genes and survival. PATIENTS AND METHODS: The study included 283 patients with AML. The MLPA was used for investigation of CNAs. The status of somatic mutations was analyzed in all cases. RESULTS: The presence of CNAs was associated with the adverse (high) risk category according to the European LeukemiaNet (ELN) classification (PFDR <0.0001). The significant predictors of mortality were age of 65 years or older (hazard ratio [HR], 2.30; 95% CI, 1.71-3.09), ELN high­risk category (HR, 1.71; 95% CI, 1.15-2.56), and the Eastern Cooperative Oncologic Group Scale (ECOG) performance status grade of 3 or higher (HR, 2.43; 95% CI, 1.80-3.30), but not the presence of CNA. An interaction between CNAs and the ECOG performance status was shown (HRinteraction, 2.24; 95% CI, 1.09-4.57, P = 0.02). The presence of CNAs was positively correlated with the risk of death in patients with an ECOG grade of 3 or higher (HR, 2.02; 95% CI, 1.30-3.12), while for patients with the performance status of 2 or lower, the presence of CNAs was a protective factor against the risk of death. CONCLUSIONS: The presence of CNAs may modify the effect of the ECOG performance status on survival. Independent predictors of mortality in patients with AML include age, ELN adverse risk category, and the ECOG grade of at least 3.

Cytokine rs361525, rs1800750, rs1800629, rs1800896, rs1800872, rs1800795, rs1800470, and rs2430561 SNPs in relation with prognostic factors in acute myeloid leukemia.

BACKGROUND: Cytokines were correlated with survival and disease progression in acute myeloid leukemia (AML). We aimed to evaluate the multivariate effect of TNF-α rs361525, rs1800750, rs1800629, IL-10 rs1800896, rs1800872, IL-6 rs1800795, TGF-ß1 rs1800470, IFN-γ rs2430561 single nucleotide polymorphisms (SNPs) on AML risk, the multivariate effect of SNPs on overall survival (OS) in AML and the association between the investigated SNPs and prognostic factors in AML. METHODS: All SNPs were genotyped in 226 adult AML cases and 406 healthy individuals. AML patients were investigated for FLT3 (ITD, D835), DNMT3A (R882), and NPM1 type A mutations. RESULTS: Univariate analysis revealed that age above 65 years had a negative influence on survival (P < .001). The presence of the rs1800750 variant genotype (P = .005) or FLT3-ITD mutation (P = .009) in a cytogenetic high-risk group (P = .003) negatively influenced OS. A negative association was observed between Eastern Cooperative Oncologic Group Scale status > 2, lactate dehydrogenase (LDH) level, platelet (PLT) count <40 000 cells/mm3 , and OS. Multivariate Cox regression analysis showed that the presence of the rs1800750 variant genotype was a risk factor for death (P = .007), and that blast percentage, LDH level (≥600 IU/L), and cytogenetic high-risk were independent significant predictors for death in AML (P = .04, corrected HR = 1.20; P = .022, corrected HR = 1.24; P = .021, corrected HR = 1.34, respectively). CONCLUSIONS: Age above 65 years, PLT count, TNF-α rs1800750 variant genotype, blast percentage, LDH level, and cytogenetic high-risk may be used as independent risk factors to assess AML mortality.

Long term follow-up in a patient with prune-belly syndrome - a care compliant case report.

RATIONALE: Malformative uropathies represent a major cause of Chronic Kidney Disease (CKD) in children. Genitourinary system is the most frequent and sever affected in Prune-Belly syndrome cases. That is why the findings of early diagnosis and vigilant monitoring for these situations remain a major challenge for the medical team. PATIENT CONCERNS: We present the clinical course of a 10 years old child with diagnosis of Prune-Belly syndrome. A urinary tract abnormality was suspected starting 25 weeks of gestation, when a routine ultrasound showed oligohydramnios, increased size urinary bladder, bilateral hydronephrosis and megaureters, thin abdominal wall. DIAGNOSIS: Prenatal suspicion of Prune-Belly syndrome plays a deciding role in renal disease progression. A detailed clinical exam at birth established the diagnosis of Prune-Belly syndrome. Renal ultrasound confirmed bilateral grade III hydronephrosis and megaureters, with empty bladder, suggesting an obstruction at this level. A persistent urachus was confirmed by catheterization. Later it was used for imaging study that showed bilateral high grade reflux. INTERVENTIONS: The main goal of any treatment is to preserve kidney function. Treatment options depend on the clinical picture. The pregnancy was closely monitorized, but fetal distress appeared so early labor was induced at 32 weeks. At beginning a temporary catheter was placed into the urachus which expressed urine. The urachus drain was left in place until the age of 6 weeks, when a bilateral ureterostomy was performed. Skeletal and genital malformations were present too; the child has undergone several surgeries to solve these abnormalities. OUTCOMES: At the age of 10 years, he is a well-adapted child. He has had fewer than 3 urinary tract infections per year. Long term follow-up showed a relatively slow decline in the estimated Glomerular Filtration Rate in our child (62 ml/1.73m/min). LESSONS: This case suggests that induced early labor could prove beneficial for early upper urinary tract decompression through earlier access to surgery. This is an option especially in situations or region where vesicoureteric or vesicoamniotic shunt placement is not available.

Acute Pulmonary Embolism in a Teenage Female - A Case Report.

Thrombophilia represents a tendency towards excessive blood clotting and the subsequent development of venous thromboembolism (VTE). VTE is a rare condition in children that comprises both deep venous thrombosis (DVT) and pulmonary embolism (PE). This paper reports the case of a 16-year-old girl, admitted to the Pediatrics Clinic No. 1, Tîrgu Mureș, Romania, for dyspnea, chest pain and loss of consciousness. Her personal history showed that she had had two orthopedic surgical interventions in infancy, two pregnancies, one spontaneous miscarriage and a recent caesarian section at 20 weeks of gestation for premature detachment of a normally positioned placenta associated with a deceased fetus. Laboratory tests showed increased levels of D-dimers. Angio-Computed Tomography (Angio-CT) showed multiple filling defects in both pulmonary arteries, establishing the diagnosis of PE. The laboratory tests were undertaken to assist in the diagnoses of a possible thrombophilia underlined a low level of antithrombin III. Antiphospholipid syndrome was ruled out and genetic tests revealed no specific mutation. Anticoagulant therapy was initiated with unfractionated heparin and afterwards subcutaneously low molecular heparin was prescribed for three months. Later it has been changed to oral therapy with acenocoumarol. The patient was discharged in good general status with the recommendation of life-long anticoagulation therapy. Thrombophilia is a significant risk factor for PE, and it must be ruled out in all cases of repeated miscarriage.