Susceptibility to Adrenal Crisis Is Associated With Differences in Cortisol Excretion in Patients With Secondary Adrenal Insufficiency

Objective: To compare cortisol pharmacokinetics and pharmacodynamics mapped through several glucocorticoid sensitive pathways in patients on hydrocortisone substitution with or without an adrenal crisis. Design: A post-hoc analysis of a previously conducted randomized controlled trial in patients with secondary adrenal insufficiency examining the effects of 2 weight-adjusted hydrocortisone doses. Methods: Comparisons were primarily made on a hydrocortisone dose of 0.2-0.3 mg/kg/day for plasma cortisol and cortisone, 24-hour urinary steroid profile, the glucocorticoid sensitive tryptophan-kynurenine pathway, the renin-angiotensin-aldosterone system and aspects of quality of life. Variables of interest were also analyzed on the hydrocortisone dose of 0.4-0.6 mg/kg/day. Results: Out of 52 patients, 9 (17%) experienced at least one adrenal crisis (AC+ group) and 43 did not develop an adrenal crisis (AC- group) during an observation period of 10 years. 24-hour urinary excretion of cortisol and cortisone were lower in the AC+ group (0.05 [IQR 0.03; 0.05] vs. 0.09 [0.05; 0.12] µmol/24h, P=0.01and 0.13 [0.10; 0.23] vs. 0.24 [0.19; 0.38] µmol/24h, P=0.04, respectively). No differences in pharmacokinetics of cortisol were observed. Kynurenine concentrations were higher in the AC+ group (2.64 [2.43; 3.28] vs. 2.23 [1.82; 2.38] µmol/L, P=0.03) as was general fatigue (Z-scores 1.02 [-0.11; 1.42] vs. -0.16 [- 0.80; 0.28], P=0.04). On the higher hydrocortisone dose urinary excretion of cortisol and cortisone was still significantly lower between the AC- and AC + group. The differences in glucocorticoid sensitive variables disappeared. Conclusion: Patients susceptible to an adrenal crisis demonstrated differences in cortisol and cortisone excretion as well as in pharmacodynamics when compared to patients who did not experience an adrenal crisis, suggesting a biological predisposition in certain patients for the development of an adrenal crisis

From thorium phosphate hydrogenphosphate hydrate to β\beta-thorium phosphate diphosphate: Structural evolution to a radwaste storage ceramic

$\beta$-Thorium phosphate diphosphate ($\beta$-TPD), considered as a very promising radwaste storage material, was obtained from thorium phosphate hydrogenphosphate hydrate (TPHPH) precursor through dehydration and hydrogen phosphate condensation. The structures of TPHPH, intermediate $\alpha$-thorium phosphate diphosphate ($\alpha$-TPD) and its hydrate ($\alpha$-TPDH) have been resolved ab initio by Rietveld analysis of their synchrotron diffraction patterns. All were found orthorhombic (space group Cmcm) and similarly composed of [ThPO$_4$]$_4^{4+}$ slabs alternating with disordered layers hosting either [HPO$_4$·H$_2$O]$_2^{4-}$ (TPHPH), [P$_2$O$_7$·2H$_2$O]$^{4-} ($\alpha$-TPDH), or [P$_2O_7$]$^{4-}$($\alpha$-TPD), unlike the 3D structure of$\beta$-TPD. The diphosphate groups of$\alpha$-TPD and$\alpha$-TPDH are strongly bent. The irreversible transition to the final$\beta$-TPD consists in a shearing of the slabs and a reduction of the interslabs cavities that explains the stability of this high-temperature form

Global Case Fatality of Bacterial Meningitis During an 80-Year Period: A Systematic Review and Meta-Analysis.

IMPORTANCE The impact of vaccination, antibiotics, and anti-inflammatory treatment on pathogen distribution and outcome of bacterial meningitis over the past century is uncertain. OBJECTIVE To describe worldwide pathogen distribution and case fatality ratios of community-acquired bacterial meningitis. DATA SOURCES Google Scholar and MEDLINE were searched in January 2022 using the search terms bacterial meningitis and mortality. STUDY SELECTION Included studies reported at least 10 patients with bacterial meningitis and survival status. Studies that selected participants by a specific risk factor, had a mean observation period before 1940, or had more than 10% of patients with health care-associated meningitis, tuberculous meningitis, or missing outcome were excluded. DATA EXTRACTION AND SYNTHESIS Data were extracted by 1 author and verified by a second author. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Random-effects models stratified by age (ie, neonates, children, adults), Human Development Index (ie, low-income or high-income countries), and decade and meta-regression using the study period's year as an estimator variable were used. MAIN OUTCOME AND MEASURE Case fatality ratios of bacterial meningitis. RESULTS This review included 371 studies performed in 108 countries from January 1, 1935, to December 31, 2019, describing 157 656 episodes. Of the 33 295 episodes for which the patients' sex was reported, 13 452 (40%) occurred in females. Causative pathogens were reported in 104 598 episodes with Neisseria meningitidis in 26 344 (25%) episodes, Streptococcus pneumoniae in 26 035 (25%) episodes, Haemophilus influenzae in 22 722 (22%), other bacteria in 19 161 (18%) episodes, and unidentified pathogen in 10 336 (10%) episodes. The overall case fatality ratio was 18% (95% CI, 16%-19%), decreasing from 32% (95% CI, 24%-40%) before 1961 to 15% (95% CI, 12%-19%) after 2010. It was highest in meningitis caused by Listeria monocytogenes at 27% (95% CI, 24%-31%) and pneumococci at 24% (95% CI, 22%-26%), compared with meningitis caused by meningococci at 9% (95% CI, 8%-10%) or H influenzae at 11% (95% CI, 10%-13%). Meta-regression showed decreasing case fatality ratios overall and stratified by S pneumoniae, Escherichia coli, or Streptococcus agalactiae (P < .001). CONCLUSIONS AND RELEVANCE In this meta-analysis with meta-regression, declining case fatality ratios of community-acquired bacterial meningitis throughout the last century were observed, but a high burden of disease remained

Defect-unbinding and the Bose-glass transition in layered superconductors

The low-field Bose-glass transition temperature in heavy-ion irradiated Bi_2Sr_2CaCu_2O_8+d increases progressively with increasing density of irradiation-induced columnar defects, but saturates for densities in excess of 1.5 x10^9 cm^-2. The maximum Bose-glass temperature corresponds to that above which diffusion of two-dimensional pancake vortices between different vortex lines becomes possible, and above which the ``line-like'' character of vortices is lost. We develop a description of the Bose-glass line that is in excellent quantitative agreement with the experimental line obtained for widely different values of track density and material parameters.Comment: 4 pages, 4 figures, submitted to Phys. Rev. Let