Pharmacokinetic effects of endoscopic gastric decontamination for multidrug gastric pharmacobezoars.

Introduction: Intentional multiple drugs overdose is an often-encountered method of self-harm in adolescence. Treatments include supportive therapy, antidotes (when available) and decontamination techniques with the aim of reducing drugs absorption by the gastrointestinal system to minimize toxicity. Nevertheless, the decontamination techniques currently used, such as gastric lavage (GL), activated charcoal or whole-bowel irrigation, have a questionable effectiveness. Endoscopic gastric decontamination (EGD) treatment for massive ingestion of drugs or formation of pharmacobezoars is currently described only in anecdotal cases. Here we describe the management of an intentional drug overdose in an adolescent patient treated with EGD and the effects of this therapy on drugs pharmacokinetics. Case report: A 15-year-old boy was admitted in an unconscious state (Glasgow Coma Scale: 7-8) to the pediatric intensive care unit after assuming an unspecified amount of quetiapine, aspirin, bisoprolol, fluoxetine, furosemide, alprazolam, and pregabalin pills. Rapid sequence intubation was immediately performed and then the patient was treated with symptomatic therapy and GL with minimal removal of gastric material. Accounting for the type of drugs, the time elapsed from oral assumption and the unknown quantity assumed, EGD was attempted with aim of removing potential aggregate of the drugs. Serial blood samples were taken before and after EGD to measure the plasma level of the drugs. A pharmacobezoar was found and was immediately removed with EGD. The results of the drug monitoring showed that quetiapine exceeded the toxic level reported in literature indicating that it may have been the drug assumed in higher quantity by our patient. PICU stay was uneventful, and the patient was transferred to the psychiatric ward after extubation. Discussion: Our case shows how GL is not effective in mitigating multidrug absorption especially drugs potentially inducing pharmacobezoars. Furthermore, based on our plasma drug monitoring, we believe that early EGD should be considered in all cases of massive pill intake, prolonged release drugs that can form pharmacobezoars or in cases where a life-threatening dose cannot be excluded.

Catheter salvage strategies in children with central venous catheter-related or -associated bloodstream infections: a systematic review and meta-analysis.

BACKGROUND: Optimal management of central venous catheter-related, or -associated, bloodstream infections (CRBSI or CLABSI) in children is not established. AIM: To evaluate success of catheter salvage strategies in paediatric patients. METHODS: Studies were retrieved from medical databases and article reference lists. Data were collected relating to clinical outcomes of two treatments: systemic antibiotics alone or in association with antimicrobial lock therapy (ALT). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from a mixed logistic effects model. Heterogeneity was summarized using I2 statistics. Publication bias was investigated by Egger's regression test and funnel plots. FINDINGS: From 345 identified publications, 19 met inclusion criteria (total of 914 attempted salvage strategies). To achieve successful catheter salvage, in CRBSI the addition of ALT was superior to systemic antibiotics alone (OR: -0.40; 95% CI: -1.41, 0.62): 77% (95% CI: 69, 85; I2 = 42.5%; P = 0.12) and 68% of success (95% CI: 59, 77; I2 = 0; P < 0.05), respectively. CRBSI recurrence was less common in studies that used ALT compared with systemic antibiotics alone: 5% (95% CI: 0, 13; I2 = 59.7%; P = 0.03) and 18% of recurrence (95% CI: 9, 28; I2 = 0; P < 0.05), respectively. Recurrences were low with both antibiotic locks and ethanol lock. No clear benefits of ALT addition compared to systemic antibiotic only were found in CLABSI (OR: -0.81; 95% CI: -0.80, 2.43). CONCLUSION: The addition of an antimicrobial lock solution to systemic antibiotic may be beneficial for successful catheter salvage in paediatric patients with CRBSI, depending on aetiology, whereas no statistically significant difference between systemic antibiotic with or without addition of an antimicrobial lock solution was found regarding CLABSI.

Acute toxic exposures in children: analysis of a three year registry managed by a Pediatric poison control Center in Italy.

INTRODUCTION: Acute pediatric poisoning is an emerging health and social problem. The aim of this study is to describe the characteristics of a large pediatric cohort exposed to xenobiotics, through the analysis of a Pediatric Poison Control Center (PPCc) registry. METHODS: This study, conducted in the Pediatric Hospital Bambino Gesù of Rome, a reference National Pediatric Hospital, collected data of children whose parents or caregivers contacted the PPCc by phone (group "P"), or who presented to the Emergency Department (group "ED"), during the three-year period 2014-2016. Data were prospectively and systematically collected in a pre-set electronic registry. Comparisons among age groups were performed and multivariable logistic regression models used to investigate associations with outcomes (hospital referral for "P", and hospital admission for "ED"group). RESULTS: We collected data of 1611 children on group P and 1075 on group ED. Both groups were exposed to both pharmaceutical and non-pharmaceutical agents. Pharmaceutical agent exposure increased with age and the most common route of exposure was oral. Only 10% among P group were symptomatic children, with gastrointestinal symptoms. Among the ED patients, 30% were symptomatic children mostly with gastrointestinal (55.4%) and neurologic symptoms (23.8%). Intentional exposure (abuse substance and suicide attempt), which involved 7.7% of patients, was associated with older age and Hospital admission. CONCLUSIONS: Our study describes the characteristics of xenobiotics exposures in different paediatric age groups, highlighting the impact of both pharmacological and intentional exposure. Furthermore, our study shows the utility of a specific PPCc, either through Phone support or by direct access to ED. PPCc phone counselling could avoid unnecessary access to the ED, a relevant achievement, particularly in the time of a pandemic.

Polystyrene nanoparticles may affect cell mitosis and compromise early embryo development in mammals.

A great interest surrounds the development of nanoparticles (NPs) for biomedical applications such as drug delivery and cancer therapy. However, the interplay between nanoscale materials and biological systems and the associated hazards have not been completely clarified yet. In this study, bovine oviductal epithelial cells (BOECs) and embryos were used as in vitro models to investigate whether cell mitosis and early mammalian embryo development could be affected by the exposure to polystyrene (PS) nanoparticles. Analysis of the karyotype performed on BOECs exposed to PS-NPs did not show chromosomal anomalies compared to the control, although more tetraploid metaphase plates were observed in the former. In vitro fertilization experiments designed to understand whether exposure to PS-NPs could affect pre-implantation development showed that incubation with PS-NPs decreased 8-cell embryo and blastocyst rate in dose-dependent fashion. The quality of the blastocysts in terms of mean cell percent blastomeres with fragmented DNA was the same in exposed blastocysts compared to controls. These results show that the exposure to PS-NPs may impair development. In turn, this may affect the rate of mitosis in embryos and yield a lower developmental competence to reach the blastocyst stage. This suggests that release in the environment and the subsequent accumulation of PS-NPs into living organisms should be carefully monitored to prevent cytotoxic effects that may compromise their reproduction rates.

Lifelong Aerobic Exercise Reduces the Stress Response in Rats.

The aim of this study was to analyze the effects of lifelong aerobic exercise (AE) on the adaptive response of the stress system in rats. It is well known that hypothalamic-pituitary-adrenal axis (HPA) activity differs when triggered by voluntary or forced exercise models. Male Wistar rats belonging to exercise (E) or control (C) groups were subjected to chronic AE, and two cutoff points were established at 8 (middle age) and 18 months (old age). Behavioral, biochemical and histopathological studies were performed on the main components/targets of the stress system. AE increased adrenal sensitivity (AS), brain corticosterone (CORT) and corticotropin-releasing factor (CRF), but had no effect on the thymus, adrenal glands (AGs) weight or plasma CORT. In addition, AE exerted no effect on the sympathetic tone, but significantly reduced anxiety-related behavior and emotionality. Aging decreased AS and deregulated neuroendocrine feedback, leading to an anxiogenic state which was mitigated by AE. Histopathological and morphometric analysis of AGs showed no alterations in middle-aged rats but adrenal vacuolization in approximately 20% old rats. In conclusion, lifelong AE did not produce adverse effects related to a chronic stress state. On the contrary, while AE upregulated some components of the HPA axis, it generated an adaptive response to cumulative changes, possibly through different compensatory and/or super compensatory mechanisms, modulated by age. The long-term practice of AE had a strong positive impact on stress resilience so that it could be recommended as a complementary therapy in stress and depression disease.

Management strategies in venovenous extracorporeal membrane oxygenation: a retrospective comparison from five European centres.

OBJECTIVE: To investigate contemporary clinical practice in the management of venovenous (VV) extracorporeal membrane oxygenation (ECMO) in critically ill patients with bacterial pneumonia. METHODS: In this multicentre retrospective study, 48 patients with severe respiratory failure due to bacterial pneumonia receiving VV ECMO therapy in five experienced European ECMO centres were included. Ventilator and ECMO settings were analysed. RESULTS: Ventilator settings showed great variability between participating centres, particularly relating to positive end-expiratory pressure, peak inspiratory pressure and driving pressure. Different strategies in cannulation, ECMO setting and weaning procedures were also observed. CONCLUSION: There is great diversity in management modalities for ventilator and ECMO settings for patients with bacterial pneumonia. Our study emphasises the lack of clinical consensus in VV ECMO management.

[GnRH agonists and antagonists in the preoperative therapy of uterine fibroids: literature review]. / Agonisti e antagonisti del GnRH nella terapia pre-chirurgica della fibromiomatosi uterina.

Uterine leiomyomas are the most frequent gynecological benign tumors. Their growth is regulated by ovarian steroids, therefore a hypoestrogenic state, like menopause or pharmacologically induced pseudo-menopause by GnRH-agonists or GnRH-antagonists, is associated with the decrease of their volume. This volume reduction allows a less invasive surgical procedure and may reduce the amount of blood loss during surgery. Therefore, GnRH-agonists and antagonists are used in presurgical treatment of uterine fibromatosis. This review analyses the effects of GnRH-agonists and GnRH-antagonists therapies. GnRH-agonists produce a down-regulation of GnRH receptor, while GnRH-antagonists compete with endogenous GnRH for pituitary binding sites. Due to the lack of any intrinsic activity of GnRH-antagonists, the characteristic initial flare-up observed with GnRH-agonist treatment is absent. So, GnRH-antagonists rapidly suppress gonadotropin release within 4-8 h, while GnRH-agonists show clinical effects after 2 or 3 weeks of treatment. GnRH-antagonist activity is dose-dependent so it is possible to adjust the dose to obtain the proper levels of inhibition. The GnRH-agonist presurgical treatment usually is a short-term therapy (3-6 months), because it causes side-effects like menopause symptoms. GnRH-antagonist clinical effects can be achieved with a short-time therapy too. Their side-effects include flushes and head-ache. After stopping therapy with both drugs, leiomyomas rapidly achieve their original size while side-effects disappear. Further studies are necessary to establish the use of GnRH-antagonists in leiomyomas therapy, but in Italy this is not possible because their use is not approved.

Antitoxin use and pediatric intensive care for viper bites in Rome, Italy.

In Italy viper bites represent an uncommon event, though envenomation can cause severe complications, more in children than adults, because of dose/body size ratio. We present a case series within a selected population: 10 Italian cases (from Rome surroundings) of viperbites requiring PICU admission, over a 5-year interval. Five children showed a systemic involvement, whereas the remaining patients showed a damage. All were managed and closely monitored in an ICU setting. Relevant clinical findings and therapeutic approach, ICU course and complications have been recorded. Age range was 3-15 years with mean age of 6,9 (SD±4,58) years; 2 patients needed respiratory support beyond oxygen supplementation. Most patients underwent fluid loading, while hemodynamic support was given to4/10. Median PICU stay was 60 hours (IQR=24.0-75.5). No mortality was reported. Indications and precautions for administration of antivenom in the last years have been reviewed: early treatment seems to reduce mortality/morbidity, though representing a threat for children. Current recommendations for the treatment of viper envenomation have been described, based on a literature's review and the application of these knowledges to clinical reality of our PICUs. Therefore, paediatric patients with systemic or rapidly evolving symptoms should be monitored carefully for the development of bite-related complications in an ICU setting mostly in younger children.

Neurogenic pulmonary edema and variations of hemodynamic volumetric parameters in children following head trauma.

BACKGROUND: Currently there is no clear evidence of how changes in hemodynamic parameters are involved in the onset of neurogenic pulmonary edema. Aim of the study has been to correlate the principal variations of the intracranial pressure and volumetric hemodynamic parameters with the variations of extravascular lung water following severe head trauma in children. METHODS: We studied 28 children, 16 males and 12 females, mean ± SD age 71±29 months (range 24-130 months), admitted for traumatic head injury with Glasgow Coma scale ≤8. All patients received volumetric hemodynamic, and intracranial pressure monitoring following initial resuscitation and every four hours thereafter or whenever a hemodynamic deterioration was suspected. All readings were divided in 2 groups: with intracranial pressure (ICP) >15 mmHg or ≤15 mmHg. RESULTS: During the cumulative in hospital stay a total 508 sets of measurements were done. In the group with ICP >15 mmHg vs. that with ICP ≤15 mmHg we observed increased Extravascular Lung Water Index (EVLWi) (11.05±2.28 vs. 6.96±0.87 P<0.0001) and pulmonary permeability (8.50±1.19 vs. 5.08±0.90, P<0.0001), and decreased systemic vascular resistances, (1,451±371 vs. 1,602±447 P<0.0001) cerebral perfusion (48.87±18.67 vs. 69.72±11.36 P<0.0001) and PaO2/FiO2 ratio (349±122 vs. 490±96 P<0.0001). There was a significant correlation between EVLWi and pulmonary permeability (R2=0.83, P<0.0001). Fluid overload and cardiac functional index did not change significantly. CONCLUSION: The increased EVLWi observed in children following severe head trauma seems mainly related with pulmonary vascular permeability which is significantly increased when ICP is >15 mmHg.

Echocardiographic evaluation and clinical management of ductal shunting in hemodynamically unstable preterm neonates without congenital heart disease in the pediatric intensive care unit.

Although significant steps have been taken to monitor complex hemodynamics in neonatal and pediatric intensive care units, cardiovascular function in neonates is still evaluated by measuring blood pressure, heart rate, diuresis, central venous pressure (if a central venous catheter was placed), capillary refill time and oxygen saturation measurement in the upper and lower extremities. The use of other non-invasive or invasive technologies (for example, continuous impedance cardiography, transesophageal Doppler and continuous pulse contour methods) is, in fact, quite problematic in neonates in whom relevant hemodynamic changes are common during the transition to postnatal life. For these reasons, use of transthoracic echocardiography, performed by skilled pediatric intensivists, is increasing in several dedicated centers to guide treatment choices in hemodynamically unstable neonates.

Treatment of severe diabetic acidosis with tris-hydroxymethyl aminomethane in a thirteen-year-old child.

Diabetic ketoacidosis is a severe complication of type I diabetes. A 13-year-old female (40 kg) patient was admitted to our Intensive Care Unit with severe metabolic acidosis (pH: 6.8), hyperglycemia (835 mg/dL) and coma. Her hemodynamic conditions were unstable and, even though a large amount of plasma expanders, crystalloids, and inotropic support were supplied, the patient went into cardiac arrest in the first hour of treatment. After resuscitation, a better hemodynamic balance was achieved and metabolic acidosis was treated with fluid replacement therapy, continuous insulin infusion, and Tris-hydroxymethyl aminomethane (THAM) as a buffering agent. This therapy rapidly improved her metabolic conditions. The patient was discharged 5 days after Intensive Care Unit admission in good condition and without neurological sequelae.

Molecular screening of the ghrelin gene in Italian obese children: the Leu72Met variant is associated with an earlier onset of obesity.

OBJECTIVE: To test whether ghrelin variants could play a role in modulating some aspects of the obese phenotype during childhood. DESIGN: We screened the ghrelin gene in 300 Italian obese children and adolescents (mean age 10.5+/-3.2 y; range 4-19 y) and 200 controls by using the single-strand conformation polymorphism and the restriction fragment length polymoprhism analysis. RESULTS: No mutations were detected with the exception of two previously described polymorphisms, Arg51Gln and Leu72Met. For both variations, allelic frequencies were similar between patients and controls. Interestingly, we showed that the Leu72Met polymorphism was associated with differences in the age at obesity onset. Patients with the Met72 allele became obese earlier than homozygous patients for the wild Leu72 allele. The logrank test comparing the plots of the complement of Kaplan-Meier estimates between the two groups of patients was statistically significant (P<0.0001). CONCLUSION: It is unlikely that ghrelin variations cause the obesity due to single-gene mutations. The Leu72Met polymorphism of the ghrelin gene seems to play a role in anticipating the onset of obesity among children suggesting, therefore, that ghrelin may be involved in the pathophysiology of human adiposity.