Atypical Post-Injection Reactions with Delayed Onset Following Glatiramer Acetate 40 mg: Need for Titration?

BACKGROUND: Glatiramer acetate (GA) 20 mg/day (GA20) is associated with immediate post-injection reactions (PIRs). For convenience of use, approved GA 40 mg three times weekly (GA40) delivers a similar weekly dose. The dose and concentration of a single GA40 injection are, however, twice as high as for GA20, and post-injection adverse events may differ. Cases of atypical PIRs to GA40 prompted us to systematically monitor such events. OBJECTIVE: The aim was to characterize atypical PIRs in multiple sclerosis (MS) patients treated with GA40. METHODS: Clinical practice data were prospectively collected in consecutive relapsing-remitting MS patients. Descriptive statistics for categorical and continuous variables, Mann-Whitney and Chi-squared tests for baseline comparisons, and Cox regression models for association of variables to first atypical PIRs were applied. RESULTS: Forty-six out of 173 patients (26.6%) given GA40 experienced any PIRs. Of those, 38 (22.0%) had atypical, 14 (8.1%) had combined typical and atypical, and 26 (15.0%) had recurrent atypical PIRs, most frequently shivering (13.3%) and nausea/vomiting (8.1%). Compared to typical PIRs, onset of atypical PIRs was significantly delayed (median 30 vs 1 min, p < 0.0001), and their median duration longer (median 120 vs 6 min, p = 0.00013). Previous exposure to GA20 was associated with a lower risk of atypical PIRs [hazard ratio (HR) = 0.35, 95% confidence interval (CI) 0.17-0.72, p = 0.0039]. Patients experiencing PIRs with GA20 were at elevated risk for atypical PIRs with GA40 (HR = 5.75, 95% CI 1.66-19.94, p = 0.0059). CONCLUSIONS: Atypical PIRs with GA40, especially gastrointestinal symptoms and/or fever/shivering, had a delayed onset and occurred in a significant proportion of our patients. Their real prevalence should be assessed in appropriately designed studies accounting for  nocebo responses. Initial dose titration might reduce PIR frequency.

Automated double-cone-beam CT fusion technique. Enhanced evaluation of glue distribution in cases of spinal dural arteriovenous fistula (SDAVF) embolisation.

OBJECTIVES: Spinal dural arteriovenous fistulas (SDAVFs) are acquired diseases that represent the majority of all arteriovenous spinal shunts, leading to progressive and disabling myelopathy. Treatment is focused on accurately disconnecting the fistula point. We present our experience with the double-cone-beam CT fusion technique successfully applied to evaluate treatment results in a series of SDAVFs. METHODS: Between November 2011 and December 2015 we performed double-DynaCT acquisition (pre- and post-embolisation) in 12 cases of SDAVF. RESULTS: A successful DynaCT fusion technique was only achieved in the group of patients with pre- and post-treatment images acquired at the same time as the treatment session, under general anaesthesia (4/12). DynaCT performed on different days proved to be inadequate for the automated fusion technique because of changes in the body position (8/12). CONCLUSIONS: A pre-treatment flat-panel cone-beam CT with contrast, at the time of diagnostic angiography, can be very helpful to detect the correct level of the fistula and the relationship between the fistula and the surrounding structures. In case of the endovascular approach, additional post-treatment native acquisition merged with the pre-treatment acquisition (double-cone-beam CT fusion technique) permits to immediately evaluate the distribution of the glue cast and to confirm the success of the procedure. KEY POINTS: • SDAVF treatment must be aimed to occlude the fistula point shunt. • Native post-operative cone-beam CT permits high-spatial-resolution imaging of the embolic cast. • The automated double-cone-beam CT fusion technique (pre/post) accurately demonstrates intravascular glue distribution after embolisation. • Patient movements should be avoided to obtain good technical results.

Simulation of the neutron flux in the irradiation facility at RA-3 reactor.

A facility for the irradiation of a section of patients' explanted liver and lung was constructed at RA-3 reactor, Comisión Nacional de Energía Atómica, Argentina. The facility, located in the thermal column, is characterized by the possibility to insert and extract samples without the need to shutdown the reactor. In order to reach the best levels of security and efficacy of the treatment, it is necessary to perform an accurate dosimetry. The possibility to simulate neutron flux and absorbed dose in the explanted organs, together with the experimental dosimetry, allows setting more precise and effective treatment plans. To this end, a computational model of the entire reactor was set-up, and the simulations were validated with the experimental measurements performed in the facility.

Triterpene saponins from Tupidanthus calyptratus.

Five new bisdesmosidic saponins (1--5) were isolated from the aerial parts of Tupidanthus calyptratus. Their structures were determined by (1)H--(1)H correlation spectroscopy (COSY, TOCSY, ROESY) and (1)H--(13)C correlation (HSQC, HMBC) NMR experiments, FABMS, and chemical data.

Antiproliferative triterpene saponins from Trevesia palmata.

During the course of a study of plants of the family Araliaceae, antiproliferative activity was demonstrated by the crude saponin fraction of Trevesia palmata. After chromatographic purification, six new bisdesmosidic saponins (1-6), along with two known triterpenoid saponins, (7 and 8), were isolated. The structures of 1-6 were determined by (1)H-(1)H correlation spectroscopy (COSY-DQF, 1D TOCSY, 2D HOHAHA, 1D ROESY) and (1)H-(13)C (HSQC, HMBC) spectroscopy. The antiproliferative activity of compounds 1-8 and of their prosapogenins (2a-7a) prepared by alkaline hydrolysis, was evaluated using three continuous culture cell lines.

Triterpenoid saponins from Trevesia sundaica.

Six new bisdesmosidic saponins 1-6, along with four known triterpenoid saponins were isolated from the aerial parts of Trevesia sundaica (Araliaceae). Their structures were determined by 1H-1H correlation spectroscopy (COSY, TOCSY, ROESY) and 1H-13C heteronuclear correlation (HSQC, HMBC) NMR experiments, FABMS, and chemical data.

Three acylated flavone glycosides from Sideritis syriaca.

From the aerial parts of Sideritis syriaca a new flavone glycoside, 5,8,3'-trihydroxy-4'-methoxyflavone 7-(6"'-O-acetylsophoroside) was identified together with apigenin 7-(6"-p-coumaroylglucoside) and apigenin 7-(4"-p-coumaroylglucoside) which are reported for the first time in the genus Sideritis. The compounds were characterized using 1H NMR, 13C NMR, MS and chemical methods.

T-lymphocyte subpopulation changes during hemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient children.

Lymphocyte subpopulations were studied by means of sheep red blood cell (SRC)-rosetting technique and OKT11, OKT3, OKT4, and OKT8 monoclonal antibodies in ten Sicilian glucose-6-phosphate dehydrogenase-deficient children during the hemolytic crisis due to fava bean ingestion. The number of SRC-rosetting lymphocytes was significantly reduced, while the number of OKT3-positive cells was normal. An inversion of the OKT4/OKT8 ratio was observed, due to a decrease of OKT4-positive cells and an increase of OKT8-positive cells. All these abnormalities reverted to normal in the four children studied after recovery.