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Iuliana Magdalena Starcea,1,2 Roxana Alexandra Bogos,1 Georgiana Scurtu,1 Mihaela Munteanu,2 Radu Russu,2 Vasile Valeriu Lupu,1 Ancuta Lupu,1 Laura Trandafir,1 Ingrith Crenguta Miron,1 Maria Adriana Mocanu1,2 1Pediatrics Department, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania; 2Nephrology Division, St. Mary’s Emergency Children Hospital, Iasi, RomaniaCorrespondence: Iuliana Magdalena Starcea, Pediatrics Department, “Grigore T. Popa” University of Medicine and Pharmacy, 16 University St, Iasi, 700115, Romania, Tel +40726704612, Email magdabirm@yahoo.com; magdalenastarcea@gmail.comBackground: Nephrotic syndrome (NS) is the term used for the association of edema and massive proteinuria. From a therapeutic point of view, it is important to distinguish between primitive and secondary kidney damage. The clinical evolution, prognosis and therapeutic response in the NS in children are directly determined by the anatomopathological aspect. Steroid resistant nephrotic syndrome was diagnosed in patients with idiopathic NS based on lack of complete remission despite treatment with steroids.Purpose: To analyse the anatomopathological aspects of steroid resistant nephrotic syndrome (SRNS) and their correlation with evolution.Materials and Methods: We made a retrospective study with the aim to analyze the anatomo-pathological aspects and their correlations with evolution in 68 cases of steroid resistant nephrotic syndrome (SRNS) hospitalized in the Pediatric Nephrology Department in Iaşi, Romania. We defined SRNS in all cases without response to corticosteroids after the first month of therapy. For all the cases selected, the period of follow-up was the minimal 6 months.Results and Discussions: A 36% case of nephrotic syndrome was corticoresistant, with the mean age at onset of patients with SRNS being 9.18 years, compared to KDIGO studies in which the corticosteroid resistance is 10– 20%. Renal biopsy was performed in 80.88% children with SRNS and was allowed the evaluation of the activity and chronicity index. Total remission was obtained in 44.01% children with SRNS. The correlation of the anatomopathological aspects with the evolution is not statistically significant (p = 0.76), observing different therapeutic responses to all the analyzed histological types.Conclusion: Almost half of NS in children are cortico resistant. Remission was obtained in 44% of cases of SRNS. Predicting the response to long-term treatment in SRNS is difficult using only renal biopsy; it is necessary to introduce genetic molecular analyses to establish a judicious therapeutic attitude.Keywords: nephrotic syndrome, children, steroid resistance, evolution

Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating adverse effect of bisphosphates, antiresorptive therapy or antiangiogenic agents that can potentially increase oxidative stress, leading to progressive osteonecrosis of the jaws. Despite the large number of published systematic reviews, there is a lack of potential MRONJ treatment protocols utilising photobiomodulation (PBM) as a single or adjunct therapy for preventive or therapeutic oncology or non-oncology cohort. Hence, this systematic review aimed to evaluate PBM laser efficacy and its dosimetry as a monotherapy or combined with the standard treatments for preventive or therapeutic approach in MRONJ management. The objectives of the review were as follows: (1) to establish PBM dosimetry and treatment protocols for preventive, therapeutic or combined approaches in MRONJ management; (2) to highlight and bridge the literature gaps in MRONJ diagnostics and management; and (3) to suggest rationalised consensus recommendations for future randomised controlled trials (RCTs) through the available evidence-based literature. This review was conducted according to the PRISMA guidelines, and the protocol was registered at PROSPERO under the ID CRD42021238175. A multi-database search was performed to identify articles of clinical studies published from their earliest records until 15 December 2023. The data were extracted from the relevant papers and analysed according to the outcomes selected in this review. In total, 12 out of 126 studies met the eligibility criteria. The striking inconsistent conclusions made by the various authors of the included studies were due to the heterogeneity in the methodology, diagnostic criteria and assessment tools, as well as in the reported outcomes, made it impossible to conduct a meta-analysis. PBM as a single or adjunct treatment modality is effective for MRONJ preventive or therapeutic management, but it was inconclusive to establish a standardised and replicable protocol due to the high risk of bias in a majority of the studies, but it was possible to extrapolate the PBM dosimetry of two studies that were close to the WALT recommended parameters. In conclusion, the authors established suggested rationalised consensus recommendations for future well-designed robust RCTs, utilising PBM as a monotherapy or an adjunct in preventive or therapeutic approach of MRONJ in an oncology and non-oncology cohort. This would pave the path for standardised PBM dosimetry and treatment protocols in MRONJ management.

Background/Objectives : Recurrent aphthous stomatitis (RAS) is one of the most common oral mucosal lesions and a very debilitating lesion, especially in paediatric and adolescent patients. The current pharmacotherapy offers a pain relief but not without side effects, and therefore photobiomodulation (PBM) can be an alternative therapy. To the authors' best knowledge, no published study has explored the efficacy of λ 980 nm laser PBM in the management of all RAS subtypes in paediatric and adolescent patients, and therefore, this prospective observational clinical study was conducted to bridge this gap by evaluating λ 980 nm laser PBM efficacy in symptomatic RAS management in paediatric and adolescent patients. The objectives were to evaluate (1) pain intensity alleviation; (2) wound healing rate; (3) wound size closure; (4) a complete resolution; (5) evidence of recurrence; and (6) patients' treatment satisfaction. Methods : The study's variables were assessed at the following timepoints: T0: pre-treatment; T1: immediately after first PBM session; T2: 5 hours (h) post first PBM session (via telephone call); T3: immediately after second PBM session (three days post first PBM session); T4: three-day follow-up (after complete PBM treatments); T5: two-week follow-up; and T6: three-month follow-up. The following PBM dosimetry and treatment protocols were employed: λ 980 nm; 300 mW; 60 s; 18 J; CW; flattop beam profile of 1 cm 2 spot size; 18 J/cm 2 ; and twice-a-week irradiation (72 h interval). Results : At T1, significant immediate pain intensity relief was reported. 33.33% recorded "4" and 66.67% reported "5" on the quantitative numeric pain intensity scale (NPIS), and this continued to improve significantly (83.33%) at T2. All the subjects reported "0" on the NPIS at T3, T4, T5 and T6. There was a significant reduction in the lesion surface area (>50% complete healing) at T3 compared to T0. Complete healing (100%) with no evidence of scarring and lesion recurrence observed at T4, T5 and T6. Very good patients' satisfaction was reported at all timepoints. Conclusions : This is the first report demonstrating λ980 nm efficacy in all RAS subtype management in paediatric and adolescent patients with a 3-month follow-up, whereby its PBM dosimetry and treatment protocols were effective from scientific and practical standpoints, and hence multicentre RCTs with large data are warranted to validate its reproducibility and to enrich the knowledge of PBM application in all RAS subtypes.

A prospective observational case series included six patients who presented with discoloured upper and lower teeth extending from the right second premolar to the left second premolar. The photoactivation dosimetry and treatment protocol were as follows: λ 450 nm, 1 W, CW; flattop beam profile; 1 cm 2 ; 15 J/spot; 10 irradiated spots; an irradiation time of 15 s/spot; three whitening cycles in a single session. Blanc One ULTRA + was the bleaching agent. A visual analogue scale (VAS) was utilised to evaluate the pain intensity and dental hypersensitivity during treatment immediately after complete treatment (T1), 24 h (T2), and 8 h (T3) postoperatively, and at an 8-month follow-up timepoint (T4), whereas the dental colour shade change was assessed using the VITA colour shade guide pre-treatment (T0), T1, and T4. The Gingival index and modified Wong Baker faces scale were utilised to evaluate gingival inflammation and patients' treatment satisfaction, respectively. Our findings revealed a reduction in the dental colour shade of the six cases between 2 and 10- fold (average of 3.5-fold) at T1 and maintained at T4, indicating significant improvement in the colour shade change with optimal outcomes. The percentage of this improvement for all the patients was ranged between 16.6% and 33.3%. At all timepoints, a "0" score was provided for pain intensity, dental hypersensitivity, and gingival inflammation. Our study demonstrates the feasibility and safety of a λ 450 nm laser delivered with a flattop handpiece to achieve optimal whitening outcomes without adverse effects. This offers a useful guide for dental clinicians for vital in-office tooth whitening. Extensive clinical studies with large data are warranted to validate our study protocol.

(1) Background: Immune thrombocytopenia (ITP) is an acute autoimmune blood disorder that is the main cause of thrombocytopenia in children. It is characterized by a decrease in platelets below 100 × 10 9 /L, and limited evolution with severe complications such as intracranial hemorrhage. The chronic form is defined by the persistence of thrombocytopenia more than 12 months after diagnosis. (2) Methods: We performed a retrospective study over a period of 10 years (1 January 2011-31 December 2020) at the Emergency Clinical Hospital for Children "Sf. Maria", Iasi. The aim of the study was to describe the clinical characteristics and to determine the prognostic factors in immune thrombocytopenia in children. (3) Results: In this study we included 271 children with ITP, comprising 123 females (45.4%) and 148 males (54.6%). The remission rate was higher in males, being 68.9% compared to 56.1% in females. Children with ITP under 9 years of age had a higher remission rate. Children with a platelet count > 10 × 10 9 /L at diagnosis had a higher likelihood-of-remission rate compared to patients who presented initial platelet count below this value. (4) Conclusions: The risk factors highly suggestive for chronicity are: age at diagnosis, female sex, and the number of platelets at the onset of the disease.

Sarcoidosis is a non-necrotizing granulomatous inflammatory multisystemic disorder of unknown etiology. In children, as in adults, it can involve a few or all organ systems to a varying extent and degree, entailing multisystemic manifestations. Kidney involvement in pediatric-onset adult-type sarcoidosis is rare, with a wide range of renal manifestations, most of them related to calcium metabolism. Children with renal sarcoidosis tend to be more symptomatic than adults, although male patients have a higher prevalence. We present the case of a 10-year-old boy who presented with advanced renal failure with nephrocalcinosis and important hepatosplenomegaly. The diagnosis was established by histopathological examination, with consequent cortisone therapy and hemodialysis. This review emphasizes that sarcoidosis should be considered in the differential diagnosis of pediatric patients with acute kidney insufficiency or chronic kidney disease of an unknown etiology. As far as we know, this is the first study regarding extrapulmonary sarcoidosis in children from Romania.

Thrombotic microangiopathy can present itself in the form of several clinical entities, representing a real challenge for diagnosis and treatment in pediatric practice. Our article aims to explore the evolution of two rare cases of pediatric thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome (aHUS) with extremely similar clinical pictures, which, coincidentally, presented at approximately the same time in our hospital. These cases and our literature review demonstrate the multiple facets of thrombotic microangiopathy, which can produce various determinations and salient manifestations even among the pediatric population. TTP and aHUS may represent genuine diagnostic pitfalls through the overlap of their clinical and biological findings, although they develop through fundamentally different mechanisms that require different therapeutic approaches. As a novelty, we underline that COVID-19 infection cannot be excluded as potential trigger for TTP and aHUS in our patients and we predict that other reports of such an association will follow, raising a complex question of COVID-19's implication in the occurrence and evolution of thrombotic microangiopathies. On this matter, we conducted literature research that resulted in 15 cases of COVID-19 pediatric infections associated with either TTP or aHUS. Taking into consideration the morbidity associated with TTP and aHUS, an elaborate differential diagnosis and prompt intervention are of the essence.

Over the past 40 years, the 5-years-overall survival rate of pediatric cancer reached 75-80%, and for acute lymphoblastic leukemia (ALL), exceeded 90%. Leukemia continues to be a major cause of mortality and morbidity for specific patient populations, including infants, adolescents, and patients with high-risk genetic abnormalities. The future of leukemia treatment needs to count better on molecular therapies as well as immune and cellular therapy. Advances in the scientific interface have led naturally to advances in the treatment of childhood cancer. These discoveries have involved the recognition of the importance of chromosomal abnormalities, the amplification of the oncogenes, the aberration of tumor suppressor genes, as well as the dysregulation of cellular signaling and cell cycle control. Lately, novel therapies that have already proven efficient on relapsed/refractory ALL in adults are being evaluated in clinical trials for young patients. Tirosine kinase inhibitors are, by now, part of the standardized treatment of Ph+ALL pediatric patients, and Blinatumomab, with promising results in clinical trials, received both FDA and EMA approval for use in children. Moreover, other targeted therapies such as aurora-kinase inhibitors, MEK-inhibitors, and proteasome-inhibitors are involved in clinical trials that include pediatric patients. This is an overview of the novel leukemia therapies that have been developed starting from the molecular discoveries and those that have been applied in pediatric populations.

Fabry disease is an X-linked lysosomal storage disease, second in prevalence after Gaucher disease. The onset of symptoms occurs in childhood or adolescence with palmo-plantar burning pains, hypo hidrosis, angiokeratomas, and corneal deposits. In the absence of diagnosis and treatment, the disease will progress to the late phase, characterized by progressive cardiac, cerebral and renal damage, and possible death. We present the case of an 11-year-old male boy who was transferred to the Pediatric Nephrology Department for palmo-plantar burning pain and end stage renal disease. Following the evaluations for the etiology of end stage renal disease we excluded the vasculitis, the neurologic diseases, extrapulmonary tuberculosis. Because of suggestive aspect at CT scan and lack of etiologic diagnosis of renal insufficiency we performed lymph node and kidney biopsy, with a surprising result for storage disease. The specific investigation confirmed the diagnosis.

Diamond-Blackfan anemia is a rare (6-7 million live births), inherited condition manifesting as severe anemia due to the impaired bone marrow production of red blood cells. We present the unusual case of a six month old infant with a de novo mutation of the RPS19 gene causing Diamond-Blackfan anemia who additionally suffers from severe sinus bradycardia. The infant was diagnosed with this condition at the age of four months; at the age of 6 months, she presents with severe anemia causing hypoxia which, in turn, caused severe dyspnea and polypnea, which had mixed causes (hypoxic and infectious) as the child was febrile. After correction of the overlapping diarrhea, metabolic acidosis, and severe anemia (hemoglobin < 3 g/dL), she developed severe persistent sinus bradycardia immediately after mild sedation (before central venous catheter insertion), not attributable to any of the more frequent causes, with a heart rate as low as 49 beats/min on 24 h Holter monitoring, less than the first percentile for age, but with a regular QT interval and no arrhythmia. The echocardiogram was unremarkable, showing a small interatrial communication (patent foramen ovale with left-to-right shunting), mild left ventricular hypertrophy, normal systolic and diastolic function, and mild tricuspid regurgitation. After red cell transfusion and appropriate antibiotic and supportive treatment, the child's general condition improved dramatically but the sinus bradycardia persisted. We consider this a case of well-tolerated sinus bradycardia and foresee a good cardiologic prognosis, while the hematologic prognosis remains determined by future corticoid response, treatment-related complications and risk of leukemia.

(1) Background: Although gastritis has been associated with multiple etiologies, in pediatrics the main etiology is idiopathic. Many studies have reported mild-to-severe gastritis Helicobacter pylori ( H. pylori ) as an etiological factor. We evaluated the distribution of the infection with H. pylori by age, gender and place of living; (2) Methods: A retrospective study was conducted over a period of 3 years, over a cohort of 1757 patients of both sexes, aged between 1 and 18 years, admitted to a regional gastroenterology center in Iasi, Romania, with clinical signs of gastritis which underwent upper gastrointestinal endoscopy. The research was based on the analysis of data from patient observation charts and hospital discharge tickets, as well as endoscopy result registers; (3) Results: Out of the 1757 children, in 30.8% of cases the H. pylori infection was present. Out of them, 26.8% were males and 73.2% females. The average age of children with an H. pylori infection was higher (14.1 + 2.8 DS), compared with children without H. pylori (12.8 + 3.7 SD), an average difference of 1.3 years (95% confidence interval 0.96 to 1.66; p < 0.001). By place of living, children with H. pylori infection were from urban areas at 24.7% and from rural areas at 75.3%; (4) Conclusions: H. pylori infection incidence is still high in children, especially in teenagers, so extensive prevention and treatment programs are needed.

Birth is a physiological act that is part of the morpho-functional economy of the maternal body. Each stage in the act of birth has a predetermined pathway that is neurohormonally induced and morpho-functionally established through specific and characteristic adaptations. Like maternity, childbirth also has an important impact on the maternal body as a biological structure and psycho-emotional behavior. Cesarean section performed at the request of the mother with no medical underlying conditions besides the prolonged hospitalization risk can also cause breathing problems in children, delayed breastfeeding, and possible complications in a future pregnancy. Vaginal birth remains the path of choice for a physiological evolution pregnancy. Although erroneously considered safe and easy today, cesarean section delivery must remain an emergency procedure or a procedure recommended for pregnancies where birth is a risk to the mother and to the child, as cesarean section itself is a risk factor for negative outcomes for both mother and baby. This review summarizes the impact that both cesarean section and natural birth have on mother and newborn in their attempt to adapt to postpartum events and extrauterine life., Competing Interests: The authors declare no conflict of interest.

Pediatric systemic lupus erythematosus is a chronic autoimmune disorder with a highly variable course and prognosis. It results in functional abnormalities in the immune system due to intrinsic factors and the use of immunosuppressive therapies associated with underlying comorbidities seem to increase the risk of severe COVID-19 and poor outcomes of the disease in pediatric systemic lupus erythematosus (SLE) patients. The aim of this review is to obtain a better understanding of the existing link between this new viral infection and pediatric lupus. We have analyzed the characteristics of newly diagnosed cases of pediatric SLE following COVID-19 which have been reported in the literature and which describe the impact that COVID-19 has on patients already suffering with pediatric SLE.

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.

(1) Background: The relationship between Helicobacter pylori (H. pylori) infection and liver disease has been discussed for many years, but the association between the infection and liver cytolysis in children has been insufficiently explored. In our study, we evaluate this relationship in a pediatric population from the northeast of Romania. (2) Methods: A retrospective study of children with H. pylori infection and liver cytolysis was conducted on a group of 1757 children, admitted to a pediatric gastroenterology regional center in northeast Romania over 3 years. (3) Results: Liver cytolysis syndrome was present in 112 children of both sexes. Of the 112 children, 20 children (17.9%) also had H. pylori infection. In the statistical analysis, we noted a significant association between liver cytolysis syndrome and H. pylori infection (χ2; p < 0.001). (4) Conclusions: This relationship requires further in-depth studies that also consider certain parameters that may influence the results of these correlations. In addition, we point out the need for further analyses evaluating, in terms of the histopathological changes in each liver disease, the efficacy of H. pylori eradication.

(1) Background: Many studies suggest that Helicobacter pylori ( H. pylori ) infection is associated with a higher prevalence of anemia. The aim of this study is to explore this fact for a pediatric population from the northeast of Romania; (2) Methods: A correlational retrospective study between infection with H. pylori and anemia was performed on a group of 542 children in a pediatric gastroenterology regional center in Northeast Romania; (3) Results: Out of 542 children with confirmed H. pylori infection, microcytic hypochromic anemia was present in 48 children, of whom 7 (14.5%) also had iron deficiency.; (4) Conclusions: The study results demonstrate a significant association of H. pylori infection with iron-deficiency anemia and iron deficiency in children in accordance with the results established in the published literature. Although the direct relationship between them it is not clear yet, prevention represents one of the first clinical measures that need to be implemented when encountering a refractory moderate to severe iron-deficiency anemia and, especially, when associated with gastrointestinal tract symptoms.

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.

(1) Background: The incidence of thromboembolic events is relatively low in the general population, but it increases in hospitalized children and those who underwent thrombogenic procedures. Although the evidence regarding direct oral anticoagulants (DOACs) in children with venous thromboembolism (VTE) is growing, DOACs were excluded from existing guidelines due to the lack of reliable data at that moment. Therefore, current evidence on VTE management in children needs to be critically reviewed. (2) Methods: We have conducted a literature search in the Scopus, EMBASE, and MEDLINE databases using prespecified keywords to retrieve studies published between 2010 and 2022. (3) Results: Clinical trials highlighted that rivaroxaban and dabigatran had predictable pharmacokinetic and pharmacodynamic profiles in children, similar to those observed in adults. Dabigatran and rivaroxaban had a similar safety profile to standard therapy but improved thrombotic burden and resolution during follow-up. Most studies involving apixaban and edoxaban are ongoing, and results are awaited. (4) Conclusions: Dabigatran and rivaroxaban could be valid therapeutic options for VTE management in children. In the case of apixaban and edoxaban, results from ongoing clinical studies are required before using them in pediatric VTE.

Intracardiac masses are unusual findings in infants, and most of them are benign. Nevertheless, they may be associated with a significant degree of hemodynamic instability and/or arrhythmias. Malignant tumors of the heart rarely occur in children. Rhabdoid tumors are aggressive tumors with a dismal prognosis even when diagnosed early. Although rhabdomyomas are common cardiac tumors in infants, they are mostly benign. The most common sites of involvement are the kidneys and central nervous system, but soft tissues, lungs, and ovaries may also be affected. The diagnosis can be challenging, particularly in sites where they do not usually occur. In the present paper, we report the case of a 2-year-old boy diagnosed with cardiac rhabdoid tumor highlighting the importance of molecular studies and recent genetic discoveries with the purpose of improving the management of such cases. The aim of this educational case report and literature review is to raise awareness of cardiac masses in children and to point out diagnostic hints toward a cardiac tumor on various imaging modalities. Given the rarity of all tumors involving the heart and the lack of symptom specificity, a high degree of suspicion is needed to arrive at the correct diagnosis.

Congenital heart defects are known causes of malnutrition. Optimal nutritional management is paramount in improving short and long-term prognosis for neonates and infants with congenital heart malformations, as current strategies target preoperative and postoperative feeding requirements. Standardized enteral and/or parenteral feeding protocols, depending on the systemic implications of the cardiac defect, include the following common practices: diagnosing and managing feeding intolerance, choosing the right formula, and implementing a monitoring protocol. The latest guidelines from the American Society for Parenteral and Enteral Nutrition and the European Society of Paediatric and Neonatal Intensive Care, as well as a significant number of recent scientific studies, offer precious indications for establishing the best feeding parameters for neonates and infants with heart defects.

Background: Pediatricians and pediatric surgeons often face children with cardiomegaly and dilatative or hypertrophic cardiomyopathies presenting with or without symptoms. Some of these patients have already been diagnosed and received medication, and some present with completely unrelated pathologies., Methods: We performed a 4-year retrospective study on the causes and mechanisms of death of children with cardiac pathology who died outside the cardiology clinic of our hospital by studying the hospital charts and necropsy reports. All children who were in this situation in our hospital were included., Results: Most children in our study group were infants (81.82%), most were boys (81.82%), and in most cases, the cause or mechanism of death was unrelated to their heart condition, whether it had already been diagnosed or not (one case probably died as a result of a malignant ventricular arrhythmia). Additionally, 27.27% of children died as a consequence of bronchopneumonia, the same percentage died as a consequence of an acquired non-pulmonary disease or after surgery, and 18.18% died as a consequence of congenital malformations., Conclusions: Cardiac disease needs to be thoroughly investigated using multiple tools for all children presenting with heart failure symptoms, those with heart murmurs, and children scheduled for surgery of any type. The intensive care specialist and surgeon need to be aware of any heart pathology before non-cardiac surgical interventions.

Abstract: Gastroesophageal reflux disease occurs when gastric contents flow back into the esophagus and produce symptoms. Recurrent wheezing affects the quality of life for the patient and family. The association of gastroesophageal reflux with recurrent wheezing is suggested by different studies. The purpose of this study was to explore this relationship and to evaluate the outcome after appropriate treatment.A retrospective study on 85 children with recurrent wheezing, admitted in a pediatric gastroenterology regional center in Romania was performed. 24-hour continuous esophageal pH monitoring was used to evaluate the presence of gastroesophageal reflux and the results were interpreted using the Boix Ochoa score. All patients with positive score received treatment with proton pump inhibitors and they were evaluated again after 2 months.Gastroesophageal reflux was present in 71 children (83.5%), while 14 (16.5%) had a negative score, with a statistic significance (χ2 = 6.88, P = .0086, 95% confidence interval). After 2 months treatment with proton pump inhibitors, the Boix Ochoa score was still positive in 15 patients (21.13%).Recurrent wheezing is a solid reason for evaluating the presence of gastroesophageal reflux by 24-hour continuous esophageal pH-metry. Adequate treatment of gastroesophageal reflux solves also the recurrent wheezing in the majority of patients., Competing Interests: The authors have no funding and conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: Children with Down syndrome (DS) have a higher risk of developing acute leukemia than do those without DS. There are few studies in the literature about outcome, survival, and difficulties of treating patients with DS and acute leukemia in a developing country. This study aimed to analyze the outcome, response to treatment, survival, treatment complications, and causes of death in patients with DS and acute leukemia compared with those in patients with acute leukemia without DS diagnosed in the same period of time.We conducted a retrospective observational analysis including a cohort of 21 patients with DS and acute leukemia diagnosed between 2009 and 2018 in 3 hemato-oncology centers (2 pediatric centers and 1 adult hematology center). A group of patients with DS-acute lymphoblastic leukemia (DS-ALL) was analyzed and compared with a group of 165 patients with acute lymphoblastic leukemia without DS, and a group of patients with DS-acute myeloid leukemia (DS-AML) was analyzed and compared with a group of 50 patients with acute myeloid leukemia without DS, which was diagnosed during the same period of time (2009-2018) and treated under similar conditions in terms of both treatment protocols and economic resources.The overall survival rates in children with DS-ALL and DS-AML were 35.7% and 57.1%, respectively (P = .438). The overall survival rate was significantly worse in children with DS-ALL than in those with acute lymphoblastic leukemia without DS (35.71% vs 75.80%, P = .001). We noted that treatment-related mortality in the patients with DS-ALL was high (50%) (infections and toxicities related to chemotherapy); this result was significantly different from that for patients with leukemia without DS (P < .0001). The relapse rate was higher in patients with DS-ALL but not significantly higher than that in patients without DS (P = .13).In contrast, the overall survival rate was better for patients with DS-AML than for those with acute myeloid leukemia without DS (57.1% vs 45.1%, P = .47).Because of the particularities of the host, we suggest that DS-ALL and DS-AML should be considered as independent diseases and treated according to specific protocols with therapy optimization per the minimal residual disease., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Asparaginase is a basic component of chemotherapy in pediatric acute lymphoblastic leukemia (ALL) and has played a crucial role in improving the long-term survival of this disease. The objectives of this retrospective study were to elucidate the toxicity profile associated with asparaginase in children and adolescents with ALL, to analyze the impact of each type of toxicity on long-term outcomes, and to identify risk factors. We analyzed the medical charts of 165 patients diagnosed with ALL at Sf. Maria Iasi Children's Hospital from 2010 to 2019 and treated according to a chemotherapeutic protocol containing asparaginase. The median duration of follow-up was 5 years (0.1-11.5 years). Groups of patients with specific types of toxicity were compared to groups of patients without toxicity. We found the following incidence of asparaginase-associated toxicity: 24.1% clinical hypersensitivity, 19.4% hepatotoxicity, 6.7% hypertriglyceridemia, 4.2% hyperglycemia, 3.7% osteonecrosis, 3% pancreatitis, 2.4% thrombosis, and 1.2% cerebral thrombosis. Overall, 82 patients (49.7%) had at least one type of toxicity related to asparaginase. No type of toxicity had a significant impact on overall survival or event-free survival. Being older than 14 years was associated with a higher risk of osteonecrosis ( p = 0.015) and hypertriglyceridemia ( p = 0.043) and a lower risk of clinical hypersensitivity ( p = 0.04). Asparaginase-related toxicity is common and has a varied profile, and its early detection is important for realizing efficient and appropriate management.

Rationale: Teratomas are solid tumors that may occur in both gonadal and extragonadal locations, depending on the age of the child. Benign cystic teratomas are relatively common tumors among women of reproductive age, but they can occur at any age. The clinical presentation is not specific. They can be found incidentally when patients are investigated for other conditions or they can present as emergencies when the ovarian teratoma is torsioned or ruptured., Patient Concerns: We present the case of a 17-year-old adolescent girl that was seen in our emergency department on several occasions for recurrent episodes of abdominal pain ongoing for 6 months., Diagnosis: An ultrasonography (US) was performed as an outpatient and a left ovarian mass was found along with right ureterohydronephrosis (UHN). Further assessment of the mass was done by abdominal and pelvic CT and tumoral markers. CT appearance was more suggestive of a teratoma., Interventions: She underwent laparotomy with complete excision of the tumor., Outcome: The patient had an uneventful recovery. A renal US follow up showed reduction of the dilatation, demonstrating that the condition was secondary to tumor compression., Lessons: In a teenager with nonspecific symptoms, a high suspicion index for tumors is mandatory. An early diagnosis and management avoid complications like UHN., Competing Interests: The authors have no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: This study evaluates the main (para)clinical aspects and outcomes in a group of Romanian children diagnosed with acute lymphoblastic leukemia (ALL), under the conditions of antileukemic treatment according to an adapted ALL IC Berlin-Frankfurt-Munster (BFM) 2002 protocol., Methods: We performed a retrospective single-center study of 125 children diagnosed with ALL between 2010 and 2016. Standard forms were used for data collection of variate clinical and paraclinical parameters., Results: The children were predominantly male (64.8%) and their median age at diagnosis was 5 years. A total of 107 patients were diagnosed with precursor B-cell acute lymphoblastic leukemia (BCP)-ALL and 18 with T-cell acute lymphoblastic leukemia T-ALL. Multiplex reverse transcription polymerase chain reaction RT-PCR assay for ETV6-RUNX1, BCR-ABL, E2A-PBX1, KMT2A-AFF1, and STIL-TAL1 fusion genes was performed in 111 patients. ETV6-RUNX1 translocation was detected in 18.9% of patients, while BCR-ABL1 and E2A-PBX1 rearrangements were seen in 2.7% and 3.6%, respectively. Complete remission at the end of induction phase was obtained in 89.6% of patients. The overall relapse rate was 11.2%, with 11 early and 3 late relapses. The 5-year overall survival rate in BCP-ALL was 81.6% and in T-ALL 71.4%., Conclusions: The 5-year overall and event-free survival rates in our study were slightly lower than those reported in developed countries, so the patients' outcomes are encouraging.

Endocardial fibroelastosis (EFE) signifies the pathological process by which collagen and elastin are focally or diffuse deposited in the endocardium of the left ventricle. The new layer causes left ventricular dysfunction sometimes with fulminant progression to heart failure. EFE is a major component in many congenital heart abnormalities but can also occur in the absence of heart malformations, either as a primary process or in response to cardiac injury. The endothelial-mesenchymal transition (EndMT) abnormalities seem to be main pathogenic factor in fibroelastosis development. The "gold standard" for diagnosis of primary EFE (pEFE) is the histological examination. Additionally, genetic studies may help to establish the natural course of the disease and to communicate prophylactic measures to family members of the affected child. Moreover, in the newborn, EFE takes the form of dilated cardiomyopathy (DCM) with unfavorable evolution. The proper management should be established considering negative prognostic factors, involving early transplantation, drug therapy and long-term follow-up.

Worldwide, nonalcoholic fatty liver disease (NAFLD) has emerged as the leading cause of chronic liver disease in children and adolescents, but also as a real public health issue. Over the last decades, the increase in the rates of obesity and overweight in children has led to the increase in the worldwide prevalence of pediatric NAFLD. Detection of a hyperechoic appearance of the liver at ultrasounds or elevated levels of transaminases, identified during a routine control in children, suggests NAFLD. The disorder can be diagnosed with either non-invasive strategies or through liver biopsy, which further allows the identification of specific histological aspects, distinct from those found in adults. Since NAFLD is a clinically heterogeneous disease, there is an imperative need to identify noninvasive biomarkers and screening techniques for early diagnosis in children, in order to prevent metabolic and cardiovascular complications later in adulthood. This review emphasizes the main diagnosis tools in pediatric NAFLD, a systemic disorder with multifactorial pathogenesis and varying clinical manifestations.

Infantile hemangiomas (IHs) are the most frequent pediatric benign vascular tumors, with a reported incidence of 5% to 10%. They have self-limiting evolution pattern divided into a growth phase in the first 12 months and a regression one, that may take up to 10 years. Occasionally, hemangiomas might lead to local or systemic complications, depending on their morphological characteristics. The first line of treatment is β-blockers, such as Propranolol, Timolol, Nadolol, administered either locally or systemically. Newer therapeutic strategies involving laser therapy and angiotensin-converting enzyme inhibitors are being studied, while older treatment modalities like corticosteroids, Imiquimod, Vincristine, Bleomycin and Interferon-α have become second line therapy options. Before establishing the appropriate treatment, clinical, histological, and imaging investigations are required.

Rationale: Erythema multiforme (EM) is an immune-mediated disease with mucocutaneous localization and plurietiologic determinism. The term "multiforme" refers to the variety of aspects that the lesions can take from patient to patient and during evolution in a single patient., Patient Concerns: We have selected 2 cases of small children diagnosed with different etiology of EM to illustrate the importance of a correct and fast diagnosis. Case 1 involves a 2-year-old girl from a rural area who presented with fever and pruritic erythematous papular eruption. The onset of the symptoms was 3 days before presentation with fever and ulcerative lesions on the oral and labial mucosa, followed by the appearance of erythematous macular lesions, with progressive confluence to intense pruritic patches. The 2nd involves a 2-year-old boy with fever, loss of appetite, productive cough, and petechiae. He had corticosensible immune thrombocytopenia from the age of 6 months, with many recurrences. The patient received treatment with ampicillin/sulbactam and symptomatics for an erythemato-pultaceous angina. During the 2nd day of treatment the patient developed an erythematous macular eruption on the face, scalp, trunk, and limbs, with bullae formation., Diagnoses: The 1st patient was diagnosed based on biologic findings: positive inflammatory syndrome, elevated level of anti-Mycoplasma pneumoniae immunoglobulin M antibodies and immunoglobulin E. Histopathologic examination described papillary dermal edema, inflammatory infiltrate, and lymphocyte exocytosis. In the 2nd case, the hemoleucogram identified 12,000/mm platelets and the medulogram aspect was normal. Serology for Epstein-Barr virus was negative. The diagnosis was EM secondary to M pneumoniae infection in case 1 and secondary to administration of ampicillin/sulbactam in case 2., Interventions: In both cases, etiopathogenic treatment consisting of steroidal antiinflammatory drugs, antihistamines was administered. Because of specific etiology, the 1st case received antibiotics., Outcomes: The evolution was favorable in 10 to 14 days; the patients were discharged after etiopathogenic treatment consisting of steroidal antiinflammatory drugs, antihistamines, and/or antibiotics., Lessons: Performing a detailed clinical examination, medical history of drug use, infection or general diseases can establish a good diagnosis of EM. Histopathologic examination can help. The treatment is etiologic, pathogenic, and symptomatic. EM usually has a self-limited evolution.

Aim: To investigate the influence of Montelukast (MK) in acute renal failure (ARF) experimentally induced by cisplatin (CIS)., Material and Methods: The experiment was carried out in male Wistar rats (280-320g), divided into 4 groups of 12 animals each, treated as follows: Group I (Control); Group II (CIS): CIS, 5 mg/kbw, single dose, i.p.; Group III (CISMK): CIS, 5 mg/kbw, single dose, i.p and MK 2 mg/kbw, p.o., 10 days; Group IV (MK): MK 2 mg/kbw, p.o., 10 days. Blood and urine (24 h) samples were taken before the start of experiment (Io) and at 3, 7, 10 and 14 days after CIS administration. The following were determined: urea, creatinine, Ca, Mg serum levels and creatinine, proteins, Ca and Mg urinary levels. For histological evaluation, 3 rats of each group were sacrificed at 3, 7, 10 and 14 days. The severity of histopathological changes was evaluated using scores on a 1-4 point scale., Results: Both in CIS and CISMK group, serum levels of urea and creatinine and urinary protein levels were significantly higher compared with Io values and control group at 3 and 7 days, (p < 0.01 and p < 0.05, respectively). Urinary creatinine levels were significantly decreased at 3 and 7 days, (p < 0.01) and (p < 0.05) in CIS and CISMK group compared to Io and control group. The degree of severity of histopathological changes was similar in CIS and CISMK group., Conclusions: The obtained results showed that MK at a dose of 2 mg/kbw had no protective effect in CIS-induced experimental acute renal failure.

Obesity and metabolic syndrome in association with an increased risk of cardiovascular disease and type II diabetes are significant problems that contribute to lower life expectancy of patients with schizophrenia. Understanding the pharmacological mechanisms of the current antipsychotic treatment is clearly the key to the improvement of pharmacotherapy, to avoid or to mitigate the metabolic adverse effects.