New insights into the comorbid conditions of Turner syndrome: results from a long-term monocentric cohort study.

PURPOSE: Many questions concerning Turner syndrome (TS) remain unresolved, such as the long-term complications and, therefore, the optimal care setting for adults. The primary aim of this long-term cohort study was to estimate the incidence of comorbid conditions along the life course. METHODS: A total of 160 Italian patients with TS diagnosed from 1967 to 2010 were regularly and structurally monitored from the diagnosis to December 2019 at the University Hospital of Bologna using a structured multidisciplinary monitoring protocol. RESULTS: The study cohort was followed up for a median of 27 years (IQR 12-42). Autoimmune diseases were the comorbid condition with the highest incidence (61.2%), followed by osteoporosis and hypertension (23.8%), type 2 diabetes (16.2%) and tumours (15.1%). Median age of onset ranged from 22 years for autoimmune diseases to 39 years for type 2 diabetes. Malignant tumours were the most prominent type of neoplasm, with a cumulative incidence of 11.9%. Papillary thyroid carcinoma was the most common form of cancer, followed by skin cancer and cancer of the central nervous system. Only one major cardiovascular event (acute aortic dissection) was observed during follow-up. No cases of ischaemic heart disease, heart failure, stroke or death were recorded. CONCLUSIONS: This cohort study confirms the need for continuous, structured and multidisciplinary lifelong monitoring of TS, thus ensuring the early diagnosis of important comorbid conditions, including cancer, and their appropriate and timely treatment. In addition, these data highlight the need for the increased surveillance of specific types of cancer in TS, including thyroid carcinoma.

Microvascular dysfunction in pediatric patients with SARS-COV-2 pneumonia: report of three severe cases.

The coronavirus 19 (COVID-19) pandemic has affected hundreds of millions of people worldwide: in most of cases children and young people developed asymptomatic or pauci-symptomatic clinical pictures. However authors have showed that there are some categories of childhood more vulnerable to COVID-19 infection such as newborns or children with comorbidities. We report for the first time to the best of our knowledge about microvascular dysfunction in three pediatric clinical cases who developed COVID-19 infections with need of pediatric critical care. We found that sublingual microcirculation is altered in children with severe COVID-19 infection. Our findings confirmed most of data already observed by other authors in adult population affected by severe COVID-19 infection, but with distinct characteristics than microcirculation alterations previous observed in a clinical case of MIS-C. However we cannot establish direct correlation between microcirculation analysis and clinical or laboratory parameters in our series, by our experience we have found that sublingual microcirculation analysis allow clinicians to report directly about microcirculation dysfunction in COVID-19 patients and it could be a valuable bedside technique to monitor thrombosis complication in this population.

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.

Phenytoin intoxication associated with omeprazole administration in a child with defective CYP2C9.

Adverse drug reactions occur at a high rate in hospitalized children, frequently due to antiepileptic drug administration. Phenytoin is a commonly used drug, and its metabolism is mediated by a specific cytochrome-P450 isoform, CYP2C9, which is encoded by a polymorphic gene. It is worth noting that very frequently administered drugs, such as proton pump inhibitors, compete with phenytoin for CYP2C19-mediated metabolism. Here we describe a case of phenytoin intoxication in a child with defective CYP2C9, after omeprazole administration.

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.

Development of JAK2V617F-positive polycythemia vera after chemotherapy-induced remission of primary central nervous system diffuse large B cell non-Hodgkin's lymphoma: a case report and review of the literature.

The coexistence or the development of Philadelphia chromosome-negative myeloproliferative neoplasms after a lymphoproliferative disease in the same patient is an extremely rare event. We report the case of a 72-year-old man who developed JAK2V617F polycythemia vera 3 years after the diagnosis and treatment of primary diffuse large B cell non-Hodgkin's lymphoma of the central nervous system. We also review the literature regarding the pathogenesis underlying the association of myeloproliferative and lymphoproliferative chronic disorders.

Dynamics of self-generated, large amplitude magnetic fields following high-intensity laser matter interaction.

The dynamics of magnetic fields with an amplitude of several tens of megagauss, generated at both sides of a solid target irradiated with a high-intensity (~10(19) W/cm(2)) picosecond laser pulse, has been spatially and temporally resolved using a proton imaging technique. The amplitude of the magnetic fields is sufficiently large to have a constraining effect on the radial expansion of the plasma sheath at the target surfaces. These results, supported by numerical simulations and simple analytical modeling, may have implications for ion acceleration driven by the plasma sheath at the rear side of the target as well as for the laboratory study of self-collimated high-energy plasma jets.

Comparison of times of intervention during pediatric CPR maneuvers using ABC and CAB sequences: a randomized trial.

BACKGROUND: The proposed introduction of the CAB (circulation, airway, breathing) sequence for cardiopulmonary resuscitation has raised some perplexity within the pediatric community. We designed a randomized trial intended to verify if and how much timing of intervention in pediatric cardiopulmonary resuscitation is affected by the use of the CAB vs. the ABC (airway, breathing, circulation) sequence. PATIENTS AND METHODS: 340 volunteers, paired into 170 two-person teams, performed 2-rescuer healthcare provider BLS with both a CAB and ABC sequence. Their performances were audio-video recorded and times of intervention in the two scenarios, cardiac and respiratory arrest, were monitored. RESULTS: The CAB sequence compared to ABC prompts quicker recognition of respiratory (CAB vs. ABC=17.48 ± 2.19 vs. 19.17 ± 2.38s; p<0.05) or cardiac arrest (CAB vs. ABC=17.48 ± 2.19 vs. 41.67 ± 4.95; p<0.05) and faster start of ventilatory maneuvers (CAB vs. ABC=19.13 ± 1.47s vs. 22.66 ± 3.07; p<0.05) or chest compressions (CAB vs. ABC=19.27 ± 2.64 vs. 43.40 ± 5.036; p<0.05). CONCLUSIONS: Compared to ABC the CAB sequence prompts shorter time of intervention both in diagnosing respiratory or cardiac arrest and in starting ventilation or chest compression. However, this does not necessarily entail prompter resumption of spontaneous circulation and significant reduction of neurological sequelae, an issue that requires further studies.

Focusing dynamics of high-energy density, laser-driven ion beams.

The dynamics of the focusing of laser-driven ion beams produced from concave solid targets was studied. Most of the ion beam energy is observed to converge at the center of the cylindrical targets with a spot diameter of 30 µm, which can be very beneficial for applications requiring high beam energy densities. Also, unbalanced laser irradiation does not compromise the focusability of the beam. However, significant filamentation occurs during the focusing, potentially limiting the localization of the energy deposition region by these beams at focus. These effects could impact the applicability of such high-energy density beams for applications, e.g., in proton-driven fast ignition.

Spatially resolved measurements of laser filamentation in long scale length underdense plasmas with and without beam smoothing.

The onset of filamentation, following the interaction of a relatively long (τ(L)≃1 ns) and intense (I(L)≃5×10(14) W/cm(2)) laser pulse with a neopentane filled gas bag target, has been experimentally studied via the proton radiography technique, in conditions of direct relevance to the indirect drive inertial confinement fusion scheme. The density gradients associated with filamentation onset have been spatially resolved yielding direct and unambiguous evidence of filament formation and quantitative information about the filamentation mechanism in agreement with previous theoretical modelings. Experimental data confirm that, once spatially smoothed laser beams are used, filamentation is not a relevant phenomenon during the heating laser beams propagation through typical hohlraum gas fills.

Proton radiography of a shock-compressed target.

In this paper we report on the radiography of a shock-compressed target using laser produced proton beams. A low-density carbon foam target was shock compressed by long pulse high-energy laser beams. The shock front was transversally probed with a proton beam produced in the interaction of a high intensity laser beam with a gold foil. We show that from radiography data, the density profile in the shocked target can be deduced using Monte Carlo simulations. By changing the delay between long and short pulse beams, we could probe different plasma conditions and structures, demonstrating that the details of the steep density gradient can be resolved. This technique is validated as a diagnostic for the investigation of warm dense plasmas, allowing an in situ characterization of high-density contrasted plasmas.

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.

Observation of magnetized soliton remnants in the wake of intense laser pulse propagation through plasmas.

Slowly evolving, regularly spaced patterns have been observed in proton projection images of plasma channels drilled by intense (≳10¹9 W cm⁻²) short (∼1 ps) laser pulses propagating in an ionized gas jet. The nature and geometry of the electromagnetic fields generating such patterns have been inferred by simulating the laser-plasma interaction and the following plasma evolution with a two-dimensional particle-in-cell code and the probe proton deflections by particle tracing. The analysis suggests the formation of rows of magnetized soliton remnants, with a quasistatic magnetic field associated with vortexlike electron currents resembling those of magnetic vortices.

Modified proton radiography arrangement for the detection of ultrafast field fronts.

The experimental arrangement for the investigation of high-field laser-induced processes using a broadband proton probe beam has been modified to enable the detection of the ultrafast motion of field fronts. It is typical in such experiments for the target to be oriented perpendicularly with respect to the principal axis of the probe beam. It is demonstrated here, however, that the temporal imaging properties of the diagnostic arrangement are altered drastically by placing the axis (or plane) of the target at an oblique angle to the transverse plane of the probe beam. In particular, the detection of the motion of a laser-driven field front along a wire at a velocity of (0.95+/-0.05)c is described.

Experiencia clínica de monitorización hemodinámica del shock mediante el sistema PiCCO® / Preliminary clinical experience with PiCCO® system in children with shock

Objetivo: Evaluar la utilidad clínica del empleo del sistema de monitorización PiCCO® (pulse induced contour cardiac output ‘gasto cardíaco por análisis del contorno de la onda de pulso’) en pacientes pediátricos en situación de shock. Pacientes y métodos: Estudio analítico prospectivo y multicéntrico en niños de un mes a 18 años en situación de shock ingresados en 5 unidades de cuidados intensivos pediátricos. Se realizaron mediciones antes y después de 3 tipos de intervenciones: a) expansión volumétrica; b) aumento de dosis en fármacos vasoactivos, y c) cambio de dosis en fármacos que pudieran disminuir las resistencias periféricas. Los parámetros que se recogieron incluyeron los datos obtenidos de las termodiluciones junto con los parámetros hemodinámicos habituales. Resultados: Se realizaron 120 mediciones en 35 pacientes de edad de 36 (2,6 a 156) meses y peso de 15 (5,8 a 72) kg. La etiología del shock fue séptica (37%), cardiogénica (26%), hipovolémica (20%) y neurogénica (17%). No se registraron complicaciones en relación con el procedimiento. Se registraron 22 expansiones volumétricas en 17 pacientes, que produjeron una elevación significativa del ITBI (intrathoracic blood volume index ‘índice de volumen de sangre intratorácico’) de 501(235 a 763) a 584 ml/m2 (418 a 810), del CI (cardiac index ‘índice cardíaco’) de 4,04 (2,58 a 6,25) a 4,48 l/min/m2 (2,86 a 8,71) y de la presión arterial media de 74 (53 a 99) a 87 mmHg (59 a 112). Los cambios en el CI se correlacionaron con el incremento del ITBI (coeficiente de correlación = 0,678; p = 0,001). Las 13 intervenciones destinadas a incrementar el tono vasomotor se asociaron a un incremento del índice de resistencia vascular sistémica del 18%. Conclusiones: La monitorización hemodinámica mediante el sistema PiCCO® es factible y parece segura en pacientes pediátricos en shock. Los datos de monitorización obtenidos podrían añadir información relevante sobre el estado de precarga y la respuesta hemodinámica a sus modificaciones (AU)

Purpose: To evaluate the PiCCO® hemodynamics monitor in terms of clinical usefulness in children with shock. Methods: Prospective multicenter analytical study in children aged from one month to 18 years with shock admitted to five pediatric intensive care units. Measurements were made before and after three interventions: a) volume load; b) increases in vasoactive drugs; c) dosage changes of drugs that could lessen vascular resistance. Recorded parameters included thermodilution data, along with the usual hemodynamic parameters. Results: A total of 120 measurements were performed on 35 patients: mean age 36 (2.6–156) months, mean weight 15 (5.8–72)kg. Shock etiology was septic in 37% of cases, cardiogenic in 26%, hypovolemic in 20% and neurogenic in 17%. No procedure related complication was noticed. Twenty-two volume challenges in 17 patients were registered. Volume load induced a significant intrathoracic blood volume index (ITBI) increase from 501(235–763) to 584 (418–810)ml/m2, cardiac index (CI) 4.04 (2.58–6.25) to 4.48 (2.86–8.71)lmin-1m2, and mean blood pressure from 74 (53–99) to 87 (59–112)mmHg. CI changes correlated with ITBI increase (r=0.678, p=0.001). 13 interventions to increase vasomotor tone were associated with an increase in contractility of 18% in systemic vascular resistance index (SVRI). Conclusions: Hemodynamic monitoring with the PiCCO® system is feasible and seems safe in children with shock. PiCCO® derived parameters could add clinically important information to assess preload state and its modifications with therapy (AU)

[Preliminary clinical experience with PiCCO system in children with shock]. / Experiencia clínica de monitorización hemodinámica del shock mediante el sistema PiCCO.

PURPOSE: To evaluate the PiCCO hemodynamics monitor in terms of clinical usefulness in children with shock. METHODS: Prospective multicenter analytical study in children aged from one month to 18 years with shock admitted to five pediatric intensive care units. Measurements were made before and after three interventions: a) volume load; b) increases in vasoactive drugs; c) dosage changes of drugs that could lessen vascular resistance. Recorded parameters included thermodilution data, along with the usual hemodynamic parameters. RESULTS: A total of 120 measurements were performed on 35 patients: mean age 36 (2.6-156) months, mean weight 15 (5.8-72) kg. Shock etiology was septic in 37% of cases, cardiogenic in 26%, hypovolemic in 20% and neurogenic in 17%. No procedure related complication was noticed. Twenty-two volume challenges in 17 patients were registered. Volume load induced a significant intrathoracic blood volume index (ITBI) increase from 501(235-763) to 584 (418-810) ml/m(2), cardiac index (CI) 4.04 (2.58-6.25) to 4.48 (2.86-8.71) lmin-1m(2), and mean blood pressure from 74 (53-99) to 87 (59-112) mmHg. CI changes correlated with ITBI increase (r = 0.678, p = 0.001). 13 interventions to increase vasomotor tone were associated with an increase in contractility of 18% in systemic vascular resistance index (SVRI). CONCLUSIONS: Hemodynamic monitoring with the PiCCO system is feasible and seems safe in children with shock. PiCCO derived parameters could add clinically important information to assess preload state and its modifications with therapy.

Laser-driven ultrafast field propagation on solid surfaces.

The interaction of a 3x10;{19} W/cm;{2} laser pulse with a metallic wire has been investigated using proton radiography. The pulse is observed to drive the propagation of a highly transient field along the wire at the speed of light. Within a temporal window of 20 ps, the current driven by this field rises to its peak magnitude approximately 10;{4} A before decaying to below measurable levels. Supported by particle-in-cell simulation results and simple theoretical reasoning, the transient field measured is interpreted as a charge-neutralizing disturbance propagated away from the interaction region as a result of the permanent loss of a small fraction of the laser-accelerated hot electron population to vacuum.

Hot and cold electron dynamics following high-intensity laser matter interaction.

The characteristics of fast electrons laser accelerated from solids and expanding into a vacuum from the rear target surface have been measured via optical probe reflectometry. This allows access to the time- and space-resolved dynamics of the fast electron density and temperature and of the energy partition into bulk (cold) electrons. In particular, it is found that the density of the hot electrons on the target rear surface is bell shaped, and that their mean energy at the same location is radially homogeneous and decreases with the target thickness.

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.