Acute liver failure secondary to toxic exposure in children.

INTRODUCTION: Acute liver failure (ALF) is a syndrome defined by jaundice, coagulopathy (INR > 1.5) and hepatic encephalopathy in patients with no evidence of prior liver disease. Toxins and drugs are a frequent cause of ALF in children. MATERIAL AND METHODS: The aim of our study was to establish the causes of toxic ALF in children followed up in our hospital in the period of January 2000 to August 2018. We retrospectively studied all hospital records of patients who developed ALF after mushroom/drug exposure and had been admitted to our hospital, the main pediatric toxicology center in north-western Romania. RESULTS: In the last 18 years, 123 patients were admitted to our clinic with toxic ALF (89 patients secondary to mushroom ingestion and 34 patients after drug exposure). In the 2000-2012 period accidental mushroom poisoning was the leading cause of toxic ALF. Unfortunately, during the last years, voluntary drug ingestions have increased dramatically. The most commonly incriminated drug was acetaminophen (52.94%). CONCLUSIONS: ALF in mushroom poisoning is associated with a high mortality in children, despite optimal medical therapy. This etiology was one of the most important causes of death in our cohort. The difficulty in accessing emergency liver transplantation is an obstacle common to many Eastern European pediatric centers. Fortunately, in the last 5 years the incidence of mushroom intoxications has decreased in our area. It is worrying that over the last few years there has been an increased incidence of toxic ALF after drug exposure (for suicidal purposes or due to lenient regulations for prescribing hepatotoxic medications).

The Role of Predictive Models in the Assessment of the Poor Outcomes in Pediatric Acute Liver Failure.

OBJECTIVES: In children, acute liver failure (ALF) is a severe condition with high mortality. As some patients need liver transplantation (LT), it is essential to predict the fatal evolution and to refer them early for LT if needed. Our study aimed to evaluate the prognostic criteria and scores for assessing the outcome in children with ALF. METHODS: Data of 161 children with ALF (54.66% female, mean age 7.66 ± 6.18 years) were analyzed based on final evolution (32.91% with fatal evolution or LT) and etiology. We calculated on the first day of hospitalization the PELD score (109 children), MELD, and MELD-Na score (52 children), and King's College Criteria (KCC) for all patients. The Nazer prognostic index and Wilson index for predicting mortality were calculated for nine patients with ALF in Wilson's disease (WD). RESULTS: PELD, MELD, and MELD-Na scores were significantly higher in patients with fatal evolution (21.04 ± 13.28 vs. 13.99 ± 10.07, p = 0.0023; 36.20 ± 19.51 vs. 20.08 ± 8.57, p < 0.0001; and 33.07 ± 8.29 vs. 20.08 ± 8.47, p < 0.0001, respectively). Moreover, age, bilirubin, albumin, INR, and hemoglobin significantly differed in children with fatal evolution. Function to etiology, PELD, MELD, MELD-Na, and KCC accurately predicted fatal evolution in toxic ALF (25.33 vs. 9.90, p = 0.0032; 37.29 vs. 18.79, p < 0.0001; 34.29 vs. 19.24, p = 0.0002, respectively; with positive predicting value 100%, negative predicting value 88.52%, and accuracy 89.23% for King's College criteria). The Wilson index for predicting mortality had an excellent predictive strength (100% sensibility and specificity), better than the Nazer prognostic index. CONCLUSIONS: Prognostic scores may be used to predict the fatal evolution of ALF in children in correlation with other parameters or criteria. Early estimation of the outcome of ALF is essential, mainly in countries where emergency LT is problematic, as the transfer to a specialized center could be delayed, affecting survival chances.

Laboratory Negative Predictive Factors for the Occurrence of Cardiac Complications in Children with Kawasaki Disease.

BACKGROUND: Patients with Kawasaki disease (KD) may develop cardiovascular complications in the presence of predictive factors, including young age < 6 months, male gender, unfavorable response to intravenous immunoglobulin (IVIG), low albuminemia, thrombocytosis, fever over 8 days, increased C-reactive protein (CRP), elevated levels of 25 OH vitamin D3, elevated levels of fibroblast growth factor 23 (FGF23), elevated D-dimers, elevated ferritin. The objectives of this study were to determine the laboratory negative predictive factors for the occurrence of cardiac complications in children with KD. Studies in the literature that dealt with these predictive factors were analyzed. METHODS: We followed the studies published in PubMed over a 10-year period. Seventy articles were reviewed and, after applying the inclusion and exclusion criteria, 20 articles were selected. RESULTS: We evaluated the population studies which showed factors can predict the occurrence of heart complications. These factors were different depending on age and depending on resistance to IVIG treatment. CONCLUSIONS: Some biological parameters such as low albumin, thrombocytosis, increased CRP, elevated levels of 25 OH vitamin D3, elevated levels of FGF23, elevated D-dimers, and elevated ferritin could be considered as laboratory negative predictive factors for CAL.

Quality of Life in Children with Juvenile Idiopathic Arthritis.

Background: The depressive syndrome is commonly found in children suffering from chronic diseases, which is also present in patients with juvenile idiopathic arthritis (JIA). Objective: This study proposed to analyze depression's incidence in children with JIA. We also monitored the evolution of depression with the improvement of the disease under treatment. Material and methods: We followed 145 patients suffering from JIA according to ILAR and Edmonton classification in 2001. The study was conducted over three years between 2015 and 2017. The assessment of depression was made using the Hamilton scale adapted for children by us. This scale consists of 11 fields with multiple questions, the evaluation was made by counting the score. The scale assesses overall depression intensity. It has a maximum score of 28 points, and one with eight points defines depression. Results: The results obtained using the Hamilton scale showed that, from the total of 145 patients suffering from JIA, 35 (24%) experienced mild depression, 10 (7%) moderate depression and 26 were borderline; 74 children did not experience the depressive syndrome. In the control group, depression was found in only 5% of subjects. After administering the most appropriate treatment, symptoms of depression have been improved and the depression score has decreased. Conclusion: The Hamilton questionnaire adapted for children is easy to apply and it is an important tool for assessing depression. Depression has been present in one-third of patients with JIA selected for this study. The symptoms of depression have been correlated with disease activity. Depression does not influence the disease, but the disease induces depression.

Prevalence of Serum Specific Antibodies to TORCH Agents in a Cohort of Children Using DiaSorin "Flash" Chemiluminescence Technology.

BACKGROUND: Our study was undertaken to detect the prevalence of serum specific antibodies to TORCH agents in children by establishing the presence of the specific IgM antibodies with DiaSorin "Flash" chemiluminescence technology. MATERIALS AND METHODS: A total of 804 blood samples were collected for the detection of the Toxoplasma IgM; 2,048 cases were collected for CMV IgM, and 337 cases were collected for HSV-1/2 IgM, over a period of 9 months (from January 2019 to September 2019). RESULTS: In our cohort, a total of 103 samples (12.8%) were found to be seropositive for Toxoplasma, 1,551 samples (75.7%) were positive for CMV and 174 samples (51.6%) were positive for the HSV-1/2 infections. The perinatal CMV infection was observed in 11.9% of the patients with positive serology for CMV. CONCLUSIONS: The routine antenatal screening with chemiluminescence technology should be recommended in general population to avoid congenital malformations, as long as the prevalence of serum specific antibodies to TORCH agents is high and seropositivity rate increases with age.

Guillain-Barré Syndrome With a Peculiar Course: A Case Report.

Guillain-Barré syndrome (GBS) or acute inflammatory demyelinating polyradiculoneuropathy (AIDP) is a rare autoimmune disorder in which the body's immune system mistakenly attacks the nerves. In this report, we present a case of a 15-month-old girl who presented with an inability to walk and support the vertical and sitting positions, pain in the lower limbs accompanied by grimaces, muscular weakness, and agitation due to gait disturbances. This is a unique case in that GBS affected a previously healthy girl and was associated with pneumonia and anemia as the disease progressed, causing an intriguing diagnosis. Also, another remarkable aspect of our case is that complete recovery was achieved following intravenous immunoglobulin (IVIG) and anti-inflammatory treatment; our patient was able to walk again after receiving the first dose of IVIG.

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

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

A Mutation in the SCN1A Gene With a Peculiar Course: A Case Report.

In this report, we present the case of a one-year-old female patient with a history of febrile seizures, which was characterized by multiple seizures during hot baths and more than one episode of status epilepticus. Dravet syndrome was suspected due to the clinical context of the seizures and was confirmed by genetic testing. The brain MRI was found to be normal. Throughout the course of disease progression, the patient showed no signs of neurological degradation. The patient was found to have a mutation in the SCN1A gene with a peculiar course, which had not been reported previously. The normal psychomotor development, as seen in this case, highlights the different possibilities related to disease progression in Dravet syndrome.

Interleukin 8 as predictive factor for response to chemotherapy in colorectal cancer patients.

Background: Colorectal cancer (CRC) represents a major public health problem owing to the fact that many patients are diagnosed in locally advanced or metastatic stage when chemotherapy is the only remaining option. However, treatment response is still unpredictable and depends upon a diversity of factors such as tumor inherited or acquired drug resistance and the host immune response to the malignant cells. The aim of this study was to evaluate the serum levels of interleukin 6, 8, 10 (IL-6, 8, 10) as possible predictive factors for response to chemotherapy and the correlation between the cytokines and the psychological distress.Methods: Forty-nine patients undergoing chemotherapy for locally advanced or metastatic CRC were included, for each patient IL-6, 8 and 10 were assessed through ELISA. Depression and anxiety were quantified through questionnaires. Statistical data were performed with GraphPad.Results: Patients with CRC had high serum levels of IL-8 and IL-6 compared to the healthy control group. High levels of IL-8 before treatment were correlated with progressive disease. There was a high incidence of psychological complication in CRC patients, especially in young male patients, from an urban area, with a positive correlation between serum levels of IL-8 and depression.Conclusions: These results indicate that high serum levels of IL-8 are predictive factors in CRC patients that undergo chemotherapy, but also could be useful in identifying psychological distress associated with this pathology.

The evaluation of heavy metals in transylvania, as predictor for the health status of the exposed population.

It is well known and proven that heavy metal contamination of the soils can severely affect the health of the people living in the contaminated areas given the ease with which trace elements can enter the human body. In addition-to agricultural crop depreciation as well as soil erosion, soil pollution can negatively affect the natural function of ecosystems. While certain heavy metals in high doses can be harmful to the body, others such as cadmium, mercury, lead, chromium, silver and arsenic in minimal amounts have delusional effects on the body, causing acute and chronic intoxication. Our research is focused on the identification of heavy metals from the soil (O, Al, Ca, Cu, Fe, K, Mg, Na, P, Pb, Si, Ti, Zn) in 3 areas in Transylvania where factories were in operation, using 4 methods: UV-VIS spectrometry, AAS, SEM-EDAX and X-ray diffractions. High levels of very toxic trace elements such as lead, aluminum, cadmium were found near the studied areas, especially using SEM-EDAX and AAS methods. Knowledge on the soil concentration of TEs, the time exposure and the side effects can lead us to predict the health status of the exposed population. In our study, by determinating the concentration of TEs we set out to formulate a prediction on the health status of the exposed population using literature data.

Etiology and Outcome of Acute Liver Failure in Children-The Experience of a Single Tertiary Care Hospital from Romania.

BACKGROUND: Acute liver failure (ALF) is a rare disease, associated with high mortality, despite optimal medical therapy without emergency liver transplantation. Knowing the possible cause of ALF plays a vital role in the management, as the child could benefit from effective specific therapies in emergencies. METHODS: We have analyzed the etiology and outcome of ALF in children followed-up in a tertiary care hospital between January 2012-December 2018. The patients were grouped into different age categories: neonates (0-1 month), infants (1-12 months), children (1-14 years), and teenagers (14-18 years). RESULTS: 97 children (46 males, 47.42%, the mean age of 7.66 ± 8.18 years) were admitted with ALF. The most important causes of ALF were in neonates and infants, infections (72.72%), and metabolic disorders (43.47%), in children and adolescents were the toxic causes (60% and 79.41%). The mortality rate was 31.95% (31 patients), mainly in ALF due to infections or metabolic disorders. CONCLUSIONS: In neonates and infants, the main causes of ALF were infections and metabolic diseases, while in older children and teenagers, were toxin-induced liver injuries. The mortality among neonates and infants was significantly higher than in other ages. Early recognition and immediate therapeutic intervention could improve the outcome of these patients.

Megacystis-microcolon-intestinal hypoperistalsis syndrome associated with cystic fibrosis and meconium peritonitis in a female neonate 4 days of age - case report and review of the literature.

We present a case of megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) in a four days old female infant who presented with abdominal distension, bilious vomiting, massive hematuria and feeding intolerance which was first interpreted as Prune Belly Syndrome (PBS), referred to our department after iatrogenic gastric and colonic perforation. Berdon syndrome or MMIHS is a rare congenital anomaly characterized by a massive enlarged bladder, distended abdomen, microcolon, functional obstruction of the gastrointestinal tract, and malrotation.

Papillary thyroid carcinoma in children with Hashimoto's thyroiditis - a review of the literature between 2000 and 2020.

OBJECTIVES: Thyroid cancer is the most common pediatric endocrine neoplasm representing 3% of all malignancies in children. Hashimoto's thyroiditis (HT) is also a common disorder in the pediatric age range. Patients with HT frequently develop enlarged thyroid with nodules. We aimed to provide a literature review on the frequency of papillary thyroid carcinoma (PTC) in patients with HT. CONTENT: A literature search of the PubMed database between 2000 and 2020 was performed, using the relevant keywords "papillary thyroid carcinoma," "Hashimoto's thyroiditis" and "children". We followed the PRISMA statement guidelines during the preparation of this review. Six studies (n=2,065 patients with HT) were retained for the final analysis. The follow-up of the patients with HT was from 2 to 10 years. PTC was diagnosed in 0.67-7.87% of the HT patients included in these studies. In patients with HT and nodules, the percentage of PTC varied between 5.13 and 35%. The overall occurrence of PTC in patients with HT was 3.07%. SUMMARY AND OUTLOOK: The number of patients developing thyroid nodules in relation to HT was increased. The development of PTC in children with HT appeared to be higher than in the normal population.

Vitamin D-Binding Protein (Gc-Globulin) in Acute Liver Failure in Children.

This study aimed to analyse vitamin d-binding protein (Gc-globulin) serum levels in acute liver failure (ALF) in children in relation to disease outcomes and correlations with other known markers used to evaluate the severity of ALF. Our study included 34 children (mean age 4.87 ± 5.30 years) with ALF of different causes (metabolic, 26.47%; autoimmune, 23.53%; toxic, 20.59%; infection, 17.65%; unknown, 11.76%) and 30 children without any liver injury (mean age 6.11 ± 4.26 years). The outcome was poor in 14 patients (41.18%), including one child with liver transplantation (2.94%). Serum Gc-globulin levels were significantly lower in ALF patients compared to the control group (151.57 ± 171.8 mg/L vs. 498.63 ± 252.50 mg/L; p < 0.000001), with an optimum cut-off of 163.5 mg/L (Area Under the Curve, AUC, 0.8921; sensitivity, 76.50%; specificity, 100%). Levels were also lower in patients with poor outcomes compared to survivors (59.34 ± 33.73 mg/L vs. 216.12 ± 199.69 mg/L; p < 0.0001), with an optimum cut-off 115 mg/L (AUC, 0.7642; sensitivity, 100%; specificity, 50%). Gc-globulin serum levels were variable according to ALF aetiology, i.e., lower in metabolic, infectious, or unknown causes compared to autoimmune and toxic causes. Gc-globulin serum levels were decreased in children with ALF and lower in those with poor outcomes compared with survivors. Gc-globulin serum levels were correlated with other known parameters used to evaluate the severity of ALF and could help to identify patients at high risk for poor outcomes.

Neonatal polycystic kidney disease, a potential life-threatening condition at this age: A case report.

RATIONALE: Autosomal recessive polycystic kidney disease (ARPKD) is a severe rare genetic condition, with high mortality rates and autosomal recessive pattern of transmission similar to most early onset cystic kidney diseases. The mortality rates can reach up to 30% during the neonatal period. PATIENT CONCERNS: We report a case of a 27-day-old male neonate admitted in our clinic for fever, foul-smelling urine, and diarrhea. A previous abdominal ultrasound at the age of 2 weeks revealed enlarged, hyperechoic kidneys, no abnormalities of the urinary exam. Clinical examination revealed poor general status, ill-looking face, diminished cutaneous turgor, distended abdomen, and palpable kidneys. Laboratory tests pointed out leukopenia, anemia, border-line platelet count, elevated inflammatory biomarker level, hyponatremia, hypoalbuminemia, proteinuria, leukocyturia, and hematuria. Both urine and blood cultures were positive for E. coli. DIAGNOSES: Abdominal ultrasound revealed bilateral nephromegaly, diminished parenchymatous index, with the absence of differentiation between the cortex and medulla. Abdominal MRI described bilateral nephromegaly, the hypertrophy comprising especially the structures of Malpighi pyramids, with multiple cystic lesions disseminated within both kidneys, projected also in Malpighi pyramids, their diameters ranging between 2 and 7 mm. Thus, our final diagnoses were polycystic kidney disease and sepsis due to urinary tract infection with E. coli. INTERVENTIONS: After treating the infection, the patient was referred to a more experienced center for appropriate management of polycystic kidney disease. OUTCOMES: The progress of the patient until the age of 1 year and 2 months has been remarkably favorable, presenting first-degree chronic kidney disease, with normal blood parameters and controlled blood pressure values, no other episodes of urinary infection, and without supplementary pathological changes in ultrasound. LESSONS: Despite the poor prognosis of PKD reported in the literature, our case had an outstandingly favorable evolution during the first 2 years of life most-likely due to the early diagnosis and treatment, but also proper monitoring.

MiRNAs roles in the diagnosis, prognosis and treatment of colorectal cancer.

Introduction: The liver is the main location for metastasization in stage IV colorectal cancers. Areas covered: This review intends to comprehensively present the most important studies conducted in the past few years concerning the role of miRNAs in colorectal cancer liver metastases, trying to clarify some aspects regarding tumor biology and favorite liver metastasization site. Expert commentary: Recent advances in tissue and serum RNA extraction has considerably improved the field of microRNAs studies. These molecules known to play a crucial role in the metastatic stage indicate a starting point in the development of clinical biomarkers with a possible role in the stratification of high-risk patients for adequate treatment.

Ganglioneuroblastoma in children.

INTRODUCTION: Neuroblastoma ranks third among pediatric malignancies. CASE REPORT: The case of a 3-year-old child is presented, who suddenly had frequent, unproductive, emetic cough; fever; and weight loss. Lung X-ray showed an opacity situated in the posterior superior mediastinum. Thoracic ultrasound revealed a slightly inhomogeneous, hypoechoic mass located in the posterior superior mediastinum. Computed tomography evidenced a tumor mass with homogeneous appearance in the costo-vertebral groove. Histological examination confirmed the diagnosis of ganglioneuroblastoma. CONCLUSION: Although history and clinical examination provided few elements, diagnosis was made based on imaging and histopathological examination.

Liquid biopsy challenge and hope in colorectal cancer.

INTRODUCTION: Colorectal cancer is an important global health burden marked by a high mortality rate. Medical attention is drawn more often by the new targeted therapies, but also by the concept of liquid biopsy. Tumor's genetic profile is the major indicator of the response to targeted therapies and the risk for metastatic relapse. Therefore, analysis of tumor-linked genetic alterations holds a great importance, both for diagnostic and prognostic purposes. Areas covered: The present paper highlights the molecular basis of the liquid biopsy concept and its major clinical applications in colorectal cancer. This consists in circulating tumor cells (CTC) and cell-free tumor DNA (cfDNA) and is described in manuscripts as an alternative to tissue samples, providing more information about tumor heterogeneity and tumor evolution in dynamic. Expert opinion: Liquid biopsy is an innovative, minimally invasive method which enables real-time monitoring of tumor's genetic heterogeneity, being an important step towards personalized medicine. However, despite the large number of detection methods available, it is necessary to standardize them regarding the blood collection processing and sample storage, analysis in order to be implemented in clinical guidelines.

A Rare Case of Double-System With Ectopic Ureteral Openings Into Vagina.

The presence of an ectopic ureter may be indicated by continuous wetting, despite a normal voiding pattern, especially in girls. In most cases, an ectopic ureter is associated with a duplex collecting system and complete ureteral duplication. A 5-year-old girl presented with urinary incontinence regardless of the successful toilet training and a suspicion of left duplex kidney on a previous ultrasound. Contrast-enhanced computed tomography revealed a double left kidney with double ureters, both inserting together into the vagina. The surgical treatment consisted in the "en block" reimplantation of the ectopic ureters into the bladder, with complete resolution of the symptoms. The reported case does not represent just a typical presentation of a single ectopic ureter, as the duplex kidney system had ectopic both ipsilateral ureters (with insertion into the vagina). This case reminds us that congenital abnormalities of the genito-urinary tract should be considered in case of urinary incontinence and recurrent urinary tract infections.