Paediatric Cushing’s disease: long-term outcome and predictors of recurrence

Paediatric Cushing’s disease (CD) is characterized by excess ACTH secretion from a pituitary adenoma, leading to hypercortisolism. It has approximately 5% of the incidence of adult CD and is a rare disorder in the paediatric age range. The four most specific presenting features of hypercortisolism are: change in facial appearance, weight gain, decreased linear growth and virilisation shown by advanced pubic hair for the stage of breast development or testicular volume. The main diagnostic priority is the demonstration of hypercortisolism followed by distinction between its ACTH-dependent and ACTH-independent origin, thus leading to identification of aetiology. All treatment options aim to resolve or control hypercortisolism. Consensus favours transsphenoidal (TSS) pituitary surgery with selective removal of the corticotroph adenoma. TSS in children with CD is now well established and induces remission in 70-100% of cases. External pituitary radiotherapy and bilateral adrenalectomy are second-line therapeutic approaches in subjects not responding to TSS. Long-term medical treatment is less frequently adopted. Recurrence in paediatric CD cases is low with factors predicting relapse being higher post-TSS cortisol and ACTH levels and rapid recovery of the hypothalamic-pituitary-adrenal axis after TSS. In summary, complete excision of the microadenoma with histological and biochemical evidence for this, predicts a low rate of recurrence of CD. Due to the need for rapid diagnosis and management to avoid the burden of prolonged exposure to hypercortisolism, tertiary university centres comprising both paediatric and adult endocrinology specialists together with experienced pituitary surgery and, eventually, radiotherapy units are recommended for referral of these patients

Spectral Formation in Accreting X-Ray Pulsars: Bimodal Variation of the Cyclotron Energy with Luminosity

Accretion-powered X-ray pulsars exhibit significant variability of the Cyclotron Resonance Scattering Feature (CRSF) centroid energy on pulse-to-pulse timescales, and also on much longer timescales. Two types of spectral variability are observed. For sources in group 1, the CRSF energy is negatively correlated with the variable source luminosity, and for sources in group 2, the opposite behavior is observed. The physical basis for this bimodal behavior is currently not understood. We explore the hypothesis that the accretion dynamics in the group 1 sources is dominated by radiation pressure near the stellar surface, and that Coulomb interactions decelerate the gas to rest in the group 2 sources. We derive a new expression for the critical luminosity such that radiation pressure decelerates the matter to rest in the supercritical sources. The formula for the critical luminosity is evaluated for 5 sources, using the maximum value of the CRSF centroid energy to estimate the surface magnetic field strength. The results confirm that the group 1 sources are supercritical and the group 2 sources are subcritical, although the situation is less clear for those highly variable sources that cross over the critical line. We also explain the variation of the CRSF energy with luminosity as a consequence of the variation of the characteristic emission height. The sign of the height variation is opposite in the supercritical and subcritical cases, hence creating the observed bimodal behavior.Comment: Accepted for publication in Astronomy & Astrophysic

The long helical jet of the Lighthouse nebula, IGR J11014-6103

Jets from rotation-powered pulsars have so far only been observed in systems moving subsonically trough their ambient medium and/or embedded in their progenitor supernova remnant (SNR). Supersonic runaway pulsars are also expected to produce jets, but they have not been confirmed so far. We investigated the nature of the jet-like structure associated to the INTEGRAL source IGR J11014-6103 (the "Lighthouse nebula"). The source is a neutron star escaping its parent SNR MSH 11-61A supersonically at a velocity exceeding 1000 km/s. We observed the Lighthouse nebula and its jet-like X-ray structure through dedicated high spatial resolution observations in X-rays (Chandra) and radio band (ATCA). Our results show that the feature is a true pulsar's jet. It extends highly collimated over >11pc, displays a clear precession-like modulation, and propagates nearly perpendicular to the system direction of motion, implying that the neutron star's spin axis in IGR J11014-6103 is almost perpendicular to the direction of the kick received during the supernova explosion. Our findings suggest that jets are common to rotation-powered pulsars, and demonstrate that supernovae can impart high kick velocities to misaligned spinning neutron stars, possibly through distinct, exotic, core-collapse mechanisms.Comment: 8 pages, 6 figures, 1 table. Discussion (sec.3) expanded and typos fixed; results unchanged. Published on A&

Complement activation predicts negative outcomes in COVID-19: The experience from Northen Italian patients

Coronavirus disease 19 (COVID-19) may present as a multi-organ disease with a hyperinflammatory and prothrombotic response (immunothrombosis) in addition to upper and lower airway involvement. Previous data showed that complement activation plays a role in immunothrombosis mainly in severe forms. The study aimed to investigate whether complement involvement is present in the early phases of the disease and can be predictive of a negative outcome. We enrolled 97 symptomatic patients with a positive RT-PCR for SARS-CoV-2 presenting to the emergency room. The patients with mild symptoms/lung involvement at CT-scan were discharged and the remaining were hospitalized. All the patients were evaluated after a 4-week follow-up and classified as mild (n. 54), moderate (n. 17) or severe COVID-19 (n. 26). Blood samples collected before starting any anti-inflammatory/immunosuppressive therapy were assessed for soluble C5b-9 (sC5b-9) and C5a plasma levels by ELISA, and for the following serum mediators by ELLA: IL-1β, IL-6, IL-8, TNFα, IL-4, IL-10, IL-12p70, IFNγ, IFNα, VEGF-A, VEGF-B, GM-CSF, IL-2, IL-17A, VEGFR2, BLyS. Additional routine laboratory parameters were measured (fibrin fragment D-dimer, C-reactive protein, ferritin, white blood cells, neutrophils, lymphocytes, monocytes, platelets, prothrombin time, activated partial thromboplastin time, and fibrinogen). Fifty age and sex-matched healthy controls were also evaluated. SC5b-9 and C5a plasma levels were significantly increased in the hospitalized patients (moderate and severe) in comparison with the non-hospitalized mild group. SC5b9 and C5a plasma levels were predictive of the disease severity evaluated one month later. IL-6, IL-8, TNFα, IL-10 and complement split products were higher in moderate/severe versus non-hospitalized mild COVID-19 patients and healthy controls but with a huge heterogeneity. SC5b-9 and C5a plasma levels correlated positively with CRP, ferritin values and the neutrophil/lymphocyte ratio. Complement can be activated in the very early phases of the disease, even in mild non-hospitalized patients. Complement activation can be observed even when pro-inflammatory cytokines are not increased, and predicts a negative outcome

A multi-model approach to X-ray pulsars: Connecting spectral and timing models to pin down the intrinsic emission characteristics of magnetized, accreting neutron stars

The emission characteristics of X-ray pulsars are governed by magnetospheric accretion within the Alfvén radius, leading to a direct coupling of accretion column properties and interactions at the magnetosphere. The complexity of the physical processes governing the formation of radiation within the accreted, strongly magnetized plasma has led to several sophisticated theoretical modelling efforts over the last decade, dedicated to either the formation of the broad band continuum, the formation of cyclotron resonance scattering features (CRSFs) or the formation of pulse profiles. While these individual approaches are powerful in themselves, they quickly reach their limits when aiming at a quantitative comparison to observational data. Too many fundamental parameters, describing the formation of the accretion columns and the systems' overall geometry are unconstrained and different models are often based on different fundamental assumptions, while everything is intertwined in the observed, highly phase-dependent spectra and energy-dependent pulse profiles. To name just one example: the (phase variable) line width of the CRSFs is highly dependent on the plasma temperature, the existence of B-field gradients (geometry) and observation angle, parameters which, in turn, drive the continuum radiation and are driven by the overall two-pole geometry for the light bending model respectively. This renders a parallel assessment of all available spectral and timing information by a compatible across-models-approach indispensable. In a collaboration of theoreticians and observers, we have been working on a model unification project over the last years, bringing together theoretical calculations of the Comptonized continuum, Monte Carlo simulations and Radiation Transfer calculations of CRSFs as well as a General Relativity (GR) light bending model for ray tracing of the incident emission pattern from both magnetic poles. The ultimate goal is to implement a unified fitting model for phase-resolved spectral and timing data analysis. We present the current status of this project

The brightest gamma-ray flaring blazar in the sky: AGILE and multi-wavelength observations of 3C 454.3 during November 2010

Since 2005, the blazar 3C 454.3 has shown remarkable flaring activity at all frequencies, and during the last four years it has exhibited more than one gamma-ray flare per year, becoming the most active gamma-ray blazar in the sky. We present for the first time the multi-wavelength AGILE, SWIFT, INTEGRAL, and GASP-WEBT data collected in order to explain the extraordinary gamma-ray flare of 3C 454.3 which occurred in November 2010. On 2010 November 20 (MJD 55520), 3C 454.3 reached a peak flux (E>100 MeV) of F_gamma(p) = (6.8+-1.0)E-5 ph/cm2/s on a time scale of about 12 hours, more than a factor of 6 higher than the flux of the brightest steady gamma-ray source, the Vela pulsar, and more than a factor of 3 brighter than its previous super-flare on 2009 December 2-3. The multi-wavelength data make a thorough study of the present event possible: the comparison with the previous outbursts indicates a close similarity to the one that occurred in 2009. By comparing the broadband emission before, during, and after the gamma-ray flare, we find that the radio, optical and X-ray emission varies within a factor 2-3, whereas the gamma-ray flux by a factor of 10. This remarkable behavior is modeled by an external Compton component driven by a substantial local enhancement of soft seed photons.Comment: Accepted for publication in ApJ Letters. 18 Pages, 4 Figures, 1 Tabl

The variable XMM-Newton spectrum of Markarian 766

The narrow-line Seyfert 1 galaxy Markarian 766 was observed for 60 ks with the XMM-Newton observatory. The source shows a complex X-ray spectrum. The 2-10 keV spectrum can be adequately represented by a power law and broad Fe Ka emission. Between 0.7 and 2 keV the spectrum is harder and exhibits a flux deficit with respect to the extrapolated medium energy slope. Below 0.7 keV, however, there is a strong excess of emission. The RGS spectrum shows an edge-like feature at 0.7 keV; the energy of this feature is inconsistent with that expected for an OVII edge from a warm absorber. Markarian 766 varies by a factor of ~ 2 in overall count rate in the EPIC and RGS instruments on a timescale of a few thousand seconds, while no significant flux changes are observed in the ultraviolet with the OM. The X-ray variability is spectrally dependent with the largest amplitude variability occurring in the 0.4-2 keV band. The spectral variability can be explained by a change in flux and slope of the medium energy continuum emission, superimposed on a less variable (or constant) low energy emission component.Comment: 6 pages, 6 figures, Accepted by A&A for publication in the Special Issue on 1st science with XMM Newto

Accretion, Outflows, and Winds of Magnetized Stars

Many types of stars have strong magnetic fields that can dynamically influence the flow of circumstellar matter. In stars with accretion disks, the stellar magnetic field can truncate the inner disk and determine the paths that matter can take to flow onto the star. These paths are different in stars with different magnetospheres and periods of rotation. External field lines of the magnetosphere may inflate and produce favorable conditions for outflows from the disk-magnetosphere boundary. Outflows can be particularly strong in the propeller regime, wherein a star rotates more rapidly than the inner disk. Outflows may also form at the disk-magnetosphere boundary of slowly rotating stars, if the magnetosphere is compressed by the accreting matter. In isolated, strongly magnetized stars, the magnetic field can influence formation and/or propagation of stellar wind outflows. Winds from low-mass, solar-type stars may be either thermally or magnetically driven, while winds from massive, luminous O and B type stars are radiatively driven. In all of these cases, the magnetic field influences matter flow from the stars and determines many observational properties. In this chapter we review recent studies of accretion, outflows, and winds of magnetized stars with a focus on three main topics: (1) accretion onto magnetized stars; (2) outflows from the disk-magnetosphere boundary; and (3) winds from isolated massive magnetized stars. We show results obtained from global magnetohydrodynamic simulations and, in a number of cases compare global simulations with observations.Comment: 60 pages, 44 figure