Predictor Factors for Chronicity in Immune Thrombocytopenic Purpura in Children.

(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 × 109/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 × 109/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.

The Overlap of Kidney Failure in Extrapulmonary Sarcoidosis in Children-Case Report and Review of Literature.

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.

Pitfalls of Thrombotic Microangiopathies in Children: Two Case Reports and Literature Review.

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.

Pediatric Acute Lymphoblastic Leukemia Emerging Therapies-From Pathway to Target.

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.

Palm-Plant Pain, Sign of a Severe Systemic Disease? Case Report and Review of Literature.

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.

Unusual Association of Diamond-Blackfan Anemia and Severe Sinus Bradycardia in a Six-Month-Old White Infant: A Case Report and Literature Review.

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.

Pediatric Systemic Lupus Erythematous in COVID-19 Era.

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.

Epidemiological Characteristics of Helicobacter pylori Infection in Children in Northeast Romania.

(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.

Difficulties in Adaptation of the Mother and Newborn via Cesarean Section versus Natural Birth-A Narrative Review.

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.

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.

The Prevalence of Liver Cytolysis in Children with Helicobacter pylori Infection.

(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.

The Relationship between Anemia and Helicobacter Pylori Infection in Children.

(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 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.

Current Antithrombotic Therapy Strategies in Children with a Focus on Off-Label Direct Oral Anticoagulants-A Narrative Review.

(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.

Pathological and Evolutive Correlations in Steroid Resistant Nephrotic Syndrome in Children.

Background: 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 Iasi, 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.

Non-Cardiac Cause of Death in Selected Group Children with Cardiac Pathology: A Retrospective Single Institute Study.

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.

The relationship between gastroesophageal reflux disease and recurrent wheezing in children.

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.

Outcomes of patients with Down syndrome and acute leukemia: A retrospective observational study.

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.

L-Asparaginase Toxicity in the Treatment of Children and Adolescents with Acute Lymphoblastic Leukemia.

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.

Ovarian teratoma in a teenager causing ureterohydronephrosis: Case report and literature review.

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.