The Role of Urinary NGAL in the Management of Primary Vesicoureteral Reflux in Children.

Vesicoureteral reflux (VUR) is the most frequent congenital urinary tract malformation and an important risk factor for urinary tract infections (UTIs). Up to 50% of children with VUR may develop reflux nephropathy (RN), and the diagnosis and monitoring of renal scars are invasive and costly procedures, so it is paramount to find a non-invasive and accurate method to predict the risk of renal damage. Neutrophil gelatinase-associated lipocalin (NGAL) has already proven to be a good predictive biomarker in acute kidney injuries, but there are few studies that have investigated the role of NGAL in primary VUR in children. Our aim is to review the predictive value of urine NGAL (uNGAL) as a non-invasive biomarker of RN in children with primary VUR, as well as its ability to predict the evolution of chronic kidney disease (CKD). Based on our analysis of the available original studies, uNGAL can be an accurate and reliable biomarker of RN and its progression to CKD. Some studies suggested a good correlation between VUR severity and uNGAL levels, but other studies found no significant correlation. The relationship between VUR severity and uNGAL levels is likely complex and influenced by factors such as UTIs, the timing of the urine sample collection, and the age and overall health of the patient.

Watchful Waiting in Pediatric Acute Otitis Media: A Real Practice Approach or an Intangible Desideratum?

Acute otitis media (AOM) in children is one of the leading causes of health care visits and antibiotic prescriptions worldwide. The overall aim of the current study is twofold: 1. to analyze and discuss the antibiotic prescription patterns in AOM in children without complications or risk factors and 2. to assess to what extent the watchful-waiting approach is a real practice or a mere desideratum. We performed an electronic search in the PubMed and Embase databases from 2013 to 2023 to capture original research studies investigating antibiotic prescribing patterns for AOM in children. Among the 12 papers included in the analysis, the antibiotic prescription rate ranged from 44.8% to 98%. Our study reveals similarities regarding the use of amoxicillin as a first-line antibiotic in pediatric AOM, but also discrepancies in the watchful-waiting approach attitude and in the choice of second or third-line antimicrobial agents. The proportion of cases managed with the watchful-waiting approach ranged from 7.5% (Australia) to 55.2% (Finland). Denmark was the only country reporting penicillin V as a first-choice regimen for children with AOM, which fulfils the guidelines' recommendations. The most unsatisfying rate of amoxicillin use was recorded in Japan, contrary to the recommendations of local guidelines. The use of quinolones was reported in two out of twelve studies, with the highest proportion in Japan, where tosufloxacin was used in 21.4% of the total number of cases. The duration of the antibiotic regimens was analyzed in three out of twelve papers. Since global antibiotic overuse contributes to the emergence of antibiotic resistant bacteria, new strategies are needed to increase the rate of watchful waiting and to promote the judicious use of antibiotics.

Acute Otitis Media in Children-Challenges of Antibiotic Resistance in the Post-Vaccination Era.

Acute otitis media (AOM) is a leading cause of antibiotic prescriptions in children worldwide, even in the era of pneumococcal conjugate vaccines. We aimed to assess the bacterial spectrum of AOM in children and to investigate the antimicrobial resistance profile in culture-positive cases. We performed a retrospective, tympanocentesis-based analysis of antimicrobial resistance patterns in children with AOM hospitalized in "St Mary" Emergency Hospital for Children Iasi, Romania, between January 2013 and December 2021. A total of 147 samples have been assessed, 97 (65.98%) of which had positive cultures, with Streptococcus pneumoniae and Haemophilus influenzae as the most common microorganisms. A worrying proportion, 82.85% (58/70), of the Streptococcus pneumoniae strains were multidrug-resistant. The World Health Organization included Streptococcus pneumoniae and Haemophilus influenzae on the medium priority group due to penicillin non-susceptibility and ampicillin-resistant strains, respectively. Consequently, strategies to address the threats of antimicrobial resistance are needed to reduce the potential negative effects on hospitalization costs.

uNGAL Predictive Value for Serum Creatinine Decrease in Critically Ill Children.

Acute kidney injury (AKI) occurs frequently in critically ill children, having an incidence of up to 26.9% and is associated with high morbidity and mortality in pediatric intensive care units (PICU). Currently, the decrease in the glomerular filtration rate is calculated using the serum creatinine levels. Nevertheless, there may be a 48 h delay between the renal injury and measurable increase in creatinine. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) has been validated in relation to cardiopulmonary bypass in children, being able to detect AKI before the functional change proven by the rise in serum creatinine. Our aim was to study the utility of using uNGAL in the management of critical pediatric patients admitted to our hospital in a six month period, more specifically, its capacity to predict AKI development, alone and in the association with the renal angina index (RAI). Twenty-eight critically ill children aged from 1 day to 15 years have been included. We found that an increase in uNGAL in day 1 of admission in the PICU was significantly correlated with a decrease in creatinine clearance but not anymore in day 3. However, in our sample uNGAL did not show a significant predictability for AKI development nor the supplementary incorporation of RAI into the prediction model. Therefore, apart from cardiac surgery, the efficacy and utility or uNGAL in the management of critically ill children is still questionable. For the best prediction, we will need to incorporate not only the RAI or other PICU scores, but other biomarkers such as KIM-1, urinary cystatin, and IL 18 in larger samples.

Latest Insights into Mechanisms behind Atrial Cardiomyopathy: It Is Not always about Ventricular Function.

Atrial cardiomyopathy (ACM) represents a constantly evolving concept, with increasing importance in contemporary research and clinical practice. A better understanding of the mechanisms involved in atrial remodeling and its clinical correlations especially with atrial fibrillation (AF) and other cardiometabolic comorbidities may induce a significant impact on the diagnosis, prognosis, and therapeutic approach of ACM-related comorbidities. Although initially described several decades ago, investigators have only recently highlighted that several renal, metabolic, and cardiovascular diseases are determining factors for atrial remodeling and subsequent ACM. Based on data from multiple recent studies, our research emphasizes the correlations between ACM and other coexisting pathologies including cardiovascular, respiratory, or metabolic diseases, with fibrosis being the most incriminated pathophysiological mechanism. In addition to the usual tests, the paraclinical assessment of ACM is increasingly based on the use of various cardiac biomarkers, while the cardiac magnetic resonance (CMR) has become an increasingly tempting diagnostic too for describing morphofunctional aspects of the heart chambers, with the gadolinium contrast enhanced CMR (LGE-CMR) emerging as a commonly used technique aiming to identify and quantify the precise extent of atrial fibrosis. Further research should be conducted in order to clarify our knowledge regarding atrial remodeling and, therefore, to develop new and improved therapeutic approaches in these patients.

Treatment with Cyclophosphamide for steroid-resistant nephrotic syndrome in children.

The management of patients with steroid-resistant nephrotic syndrome remains difficult. We repport our experience with Cyclophosphamide therapy, in an attempt to compare the results between an oral protocol and two i.v. protocols. The complete and sustained general remission rate was 43.1%, which confirms the efficacy of the treatment, especially for children with minimal change nephrotic syndrome. For the i.v. administration we recommend only 6 month of therapy, due to severe side-effects in longer courses.

[Factors influencing responsiveness to treatment in children with renal anemia in end stage renal disease]. / Factorii care limiteaza raspunsul la tratament la copiii cu anemie secundara insuficientei renale cronice terminale.

UNLABELLED: Human recombined erythropoietin had proven its efficiency in the treatment of anemia in chronic dialyzed patients and allows the elimination of complete necessity of transfusion. PURPOSE: We proposed ourselves to identify the factors that limit the answer to the combined treatment with iron and erythropoietin in a group study of 71 children diagnosed with ESRD in the IVth Pediatrics Clinic and included in the chronic dialysis program. MATERIAL AND METHOD: We divided the patients in three groups, in relation to the time in which the patients had reached and maintained the hemoglobin value of 10.5 g/dl under sustained iron treatment, combined with EPO. We analyzed the correlations established between responsively/non-responsively to treatment and the medium value of Hb, Ht, reticulocytes number, plasma value of iron and ferritin, the parameters of phospho-calcium metabolism, malnutrition as presence and degree, the age of entrance in dialysis and the duration of renal function support. RESULTS: We observed that Hb and Ht have low medium values (Hb-8.44 g/dl, Ht-25.65%) in the non-responsive group, by comparison to the responsive patients group (Hb-10.98 g/dl, Ht -32.31%). The most elevated values of iPTH around 420 pg/ml and the most frequent cases of protein-caloric malnutrition (26.8%) are seen in the non-responsive group to EPO treatment. The age of 13 years old at the entrance in the chronic dialysis program and the time of support of renal function over 21 months are seen in the non-responder group. CONCLUSION: We consider the secondary hyperparathyroidism, the protein-caloric malnutrition, the older age in the moment of entrance in dialysis and the long time of support of renal function factors that are able to influence, in a negative manner, the response to this treatment.

[A preliminary clinical study of the metabolic syndrome in children]. / Studiu clinic preliminar asupra sindromului metabolic la copil.

UNLABELLED: The aim of the study was to identify and evaluate the metabolic syndrome of overweight children admitted in last 12 month at the 4th Department of Paediatrics. MATERIAL AND METHODS: The study included 21 overweight children aged between 5 to 18 years old. The parameters that we considered were demographics, anthropometrics, biochemical and cardiovascular. RESULTS: Metabolic syndrome was present in 11 of 21 cases (52.38%). The female gender, children with BMI > 95 percentile and people with low level of socioeconomic status were predominantly affected. A pathologic body mass index (BMI) is highly associated with borderline hypertension in 47% of cases, impaired glucose tolerance in 42% of patients and less with the presence of dyslipidemia (just 23% of patients had abnormal level of HDL-cholesterol, 14% the level of triglycerides above normal and all of them had normal value of the LDL-cholesterol). The obese and overweight children had abdominal obesity (81% of cases). The patients with abnormal value of the IMT had low level of HDL-cholesterol, impaired glucose tolerance and borderline hypertension. CONCLUSION: The determination of the carotid intima-media thickness (IMT) is a valuable method for the management of the children with metabolic syndrome and it has to be performed to all overweight children. Because the strong correlations between the different components of the metabolic syndrome, all of these patients have to be evaluated correct and complete.

[The TB infection in children with chronic renal diseases]. / Infectia TBC la copiii cu boli renale cronice.

UNLABELLED: The incidence of tuberculosis in the general population has risen in Romania over the past years. It is, therefore, presumable that this incidence is higher in the immuno-compromised hosts than in the general population. METHODS: We analysed the tuberculosis incidence in children with a chronic renal disease, the favourable factors, and also the tuberculosis impact on the evolution of the renal disease. The tracing period was of 12 years, the lot being composed of 168 patients: 96 with primitive or secondary chronic renal diseases who were treated with immunosuppressive agents and 72 with ESRD, undergoing chronic dialysis. The study traced: the main disease, the immunosuppressive therapy received at the time of the TB diagnosis, the age of the main disease at the time of the TB diagnosis and its evolution stage, the proper framing within the disease type. RESULTS: There were 22 cases of tuberculosis diagnosed (22.03%), 2 ending in deaths. 10 were TB-infected (positive tuberculin skin test-TST) and 12 had TB-disease (5 cases of pulmonary and 6 of extra-pulmonary TB). The period between the diagnosing of the renal disease and that of the TB was, in average, around 6 months (between 0-48 months). Contact with other ill persons existed in only one case. Out of the cases diagnosed with TB, immunosuppression was present as a favouring factor in 9 cases (75%)--2 cases with ESRD and 7 cases with immunosuppressive therapy for the active renal disease. 4 cases with cortico-resistant nephritic syndrome (3 cases with mesangioproliferative glomerulonephritis and one case which did not undergo biopsy) responded to the immunosuppressive treatment after the tuberculostatic treatment. CONCLUSION: The tracing of the TB infection is compulsory in the groups of patients presenting risks, even in the absence of suggestive epidemiologic data. Tuberculosis induces resistance to the immunosuppressive therapy, the remission being dependent on the efficiency of the tuberculostatic treatment.

[A possible prognosis score in corticosteroid-resistant nephrotic syndrome]. / Un posibil scor prognostic în sindromul nefrotic corticorezistent.

Chronic glomerular nephropathies in children are marked by an often unfavourable evolution, so that the establishing of a prognosis at the time of the diagnosis is both a professional and a moral duty for the pediatric nephrologists. The estimation of the current practice renal survival prognosis in children with chronic glomerular nephropathies, by using clinical and laboratory elements in different histological forms of primitive chronic glomerulonephritis (CGN), with a minimum period of observation of one year. We analyzed parameters that may intervene in the duration of renal survival: type of CGN, age at the debut of the illness, histological scores of activity and chronicity, the presence of tubular atrophy lesions and that of interstitial fibrosis, renal failure (RF) installment time, in cases with normal renal function at the beginning, the time until the initiation of dialysis in cases with ESRF, respectively. The statistic analysis of data has been carried out with Epi soft (Fischer test). The results have been as follows: unfavourable evolution has been taken into consideration in the cases which have presented fixed nitric retention or which required the initiation of dialysis. The initiation of dialysis was necessary in 19 cases (76%), out of which 11 (44%) having associated between 4 and 6 of the considered risk factors. If the histological type (SFGS, DGS, MPGN) is added to the obtained score, the accuracy of the estimation increases to 89%. In conclusion, the usage of prognosis scores composed of current elements of diagnosis that have proven to have statistical significance, as far as the renal survival prognosis is concerned, may allow the invoking of a medium-term prognosis in the evolution of children with CGN.

[Treatment outcome using prednisone in corticosteroid-responsive primary nephrotic syndrome in children]. / Rezultatele tratamentului cu prednison in sindromul nefrotic primitiv cortico-sensibil la copil.

In children, the nephrotic syndrome is usually corticoid-responsive; approximately 70% of patients experience relapses, frequently triggered by infections. Our paper presents the results obtained using a 4 month prednisone regimen. This retrospective study included 83 children afflicted with nephrotic syndrome over a 10 year span. We analyzed: age at diagnosis, boys/girls ratio, response to corticoid treatment - after one month of prednisone and at the completion of the treatment course, number of relapses and their frequency, complications of prednisone treatment. The median age at diagnosis was 4.8 years, males predominating M:F = 1.5:1. Complete response after 4 weeks of prednisone therapy was noted in 98.79% of cases. We had 116 episodes of relapses during the first year of follow-up, occurring in 67.4% of children (27.9% were frequent relapsers, 11.62% subsequently became corticoid-dependent). Late relapses, after the first year, occurred in 32.55% of cases. We noted mostly mild adverse effects of the prednisone treatment: occurrence of infections during therapy (16.27%), cushingoid facies (37.2%), hirsutism (4.6%), high blood pressure (4.65%), stretch marks (2.32%). In conclusion, the 4 month prednisone treatment regimen is efficient in inducing and maintaining a remission. The incidence of relapses is 32.55%, comparable to the figure cited in larger studies. Serious adverse effects are significantly lower with this regimen compared to other corticoid treatment schemes. Key wo