Efficacy and safety of eliapixant in diabetic neuropathic pain and prediction of placebo responders with an exploratory novel algorithm: results from the randomized controlled phase 2a PUCCINI study.

Phase 2a of the PUCCINI study was a placebo-controlled, double-blind, parallel-group, multicenter, proof-of-concept study evaluating the efficacy and safety of the selective P2X3 antagonist eliapixant in patients with diabetic neuropathic pain (DNP) ( ClinicalTrials.gov NCT04641273). Adults with type 1 or type 2 diabetes mellitus with painful distal symmetric sensorimotor neuropathy of >6 months' duration and neuropathic pain were enrolled and randomized 1:1 to 150 mg oral eliapixant twice daily or placebo for 8 weeks.

Impact of Baseline Retinal Nonperfusion and Macular Retinal Capillary Nonperfusion on Outcomes in the COPERNICUS and GALILEO Studies.

Purpose: To evaluate the impact of baseline retinal capillary nonperfusion (RNP) and macular retinal capillary nonperfusion (MNP) status on outcomes at week 24 (W24).

Design: Post hoc analyses of 2 phase 3, randomized, double-masked, multicenter, sham-controlled studies.

Participants: Three hundred sixty-six patients with macular edema secondary to central retinal vein occlusion randomized in COPERNICUS and GALILEO.

The Developing Regorafenib Eye drops for neovascular Age-related Macular degeneration (DREAM) study: an open-label phase II trial.

Aims: This programme investigated topical regorafenib, a multikinase inhibitor, in patients with neovascular age-related macular degeneration (nAMD).

Methods: Topical regorafenib was investigated in an open-label, phase IIa/b study in which patients with choroidal neovascularization (CNV) secondary to nAMD received regorafenib (25 μl, 30 mg ml ) three times a day for 12 weeks. The primary endpoint of the phase II/a/b study was mean change in best-corrected visual acuity (BCVA) from baseline to weeks 4 and 12.

Integrated results from the COPERNICUS and GALILEO studies.

Objectives: To report on the efficacy and safety of intravitreal aflibercept in patients with macular edema secondary to central retinal vein occlusion (CRVO) in an integrated analysis of COPERNICUS and GALILEO.

Patients And Methods: Patients were randomized to receive intravitreal aflibercept 2 mg every 4 weeks or sham injections until week 24. From week 24 to week 52, all intravitreal aflibercept-treated patients in both studies and sham-treated patients in COPERNICUS were eligible to receive intravitreal aflibercept based on prespecified criteria.

Partial pharmacologic blockade shows sympathetic connection between blood pressure and cerebral blood flow velocity fluctuations.

Cerebral autoregulation (CA) dampens transfer of blood pressure (BP)-fluctuations onto cerebral blood flow velocity (CBFV). Thus, CBFV-oscillations precede BP-oscillations. The phase angle (PA) between sympathetically mediated low-frequency (LF: 0.

Predictors of disease activity in 857 patients with MS treated with interferon beta-1b.

Multiple sclerosis (MS) is a chronic demyelinating neurodegenerative disease of the CNS that requires long-term treatment. The identification of patient characteristics that can help predict disease outcomes could improve care for patients with MS. The objective of this study is to identify predictors of disease activity in patients from the BEYOND trial.

Intravitreal Aflibercept Injection in Patients with Myopic Choroidal Neovascularization: The MYRROR Study.

Purpose: To evaluate intravitreal aflibercept 2 mg in patients with myopic choroidal neovascularization (CNV).

Design: An international, phase III, multicenter, randomized, double-masked, sham-controlled study.

Participants: Patients aged ≥ 18 years with high myopia (≤-6.

Intravitreal aflibercept for macular edema secondary to central retinal vein occlusion: 18-month results of the phase 3 GALILEO study.

Purpose: To evaluate intravitreal aflibercept for treatment of macular edema secondary to central retinal vein occlusion (CRVO).

Design: Randomized, double-masked, phase 3 study.

Methods: A total of 177 patients with macular edema secondary to CRVO were randomized to receive 2 mg intravitreal aflibercept (n = 106) or sham (n = 71) every 4 weeks for 20 weeks.

Intravitreal aflibercept injection for macular edema due to central retinal vein occlusion: two-year results from the COPERNICUS study.

Purpose: To evaluate the efficacy and safety of intravitreal aflibercept injection (IAI) for the treatment of macular edema secondary to central retinal vein occlusion (CRVO).

Design: Randomized, double-masked, phase 3 trial.

Participants: A total of 188 patients with macular edema secondary to CRVO.

Music induces different cardiac autonomic arousal effects in young and older persons.

Background: Autonomic arousal-responses to emotional stimuli change with age. Age-dependent autonomic responses to music-onset are undetermined.

Objective: To determine whether cardiovascular-autonomic responses to "relaxing" or "aggressive" music differ between young and older healthy listeners.

Intravitreal Aflibercept Injection for Macular Edema Resulting from Central Retinal Vein Occlusion: One-Year Results of the Phase 3 GALILEO Study.

Purpose: To evaluate the efficacy and safety of intravitreal aflibercept injections for treatment of macular edema secondary to central retinal vein occlusion (CRVO).

Design: A randomized, multicenter, double-masked phase 3 study.

Participants: A total of 177 treatment-naive patients with macular edema secondary to CRVO were randomized in a 3:2 ratio.

Interferon beta-1b reduces black holes in a randomised trial of clinically isolated syndrome.

Background: Multiple sclerosis (MS) is characterised by inflammatory lesions of the central nervous system. Interferon beta-1b (IFNB-1b) has been shown to improve clinical and magnetic resonance imaging (MRI) measures for patients with MS.

Objective: To evaluate whether IFNB-1b in patients presenting with clinically isolated syndromes (CIS) prevented persisting T1 hypointensities on MRI (persistent black holes (PBHs)).

Autonomic blockade during sinusoidal baroreflex activation proves sympathetic modulation of cerebral blood flow velocity.

Background And Purpose: Pharmacological blockade showed sympathetic origin of 0.03 to 0.15 Hz blood pressure (BP) oscillations and parasympathetic origin of 0.

Variability in detection and quantification of interferon β-1b-induced neutralizing antibodies.

Background: Interferon-beta (IFNB) therapy for multiple sclerosis can lead to the induction of neutralizing antibodies (NAbs) against IFNB. Various methods are used for detection and quantification of NAbs.

Methods: Blood samples from 125 IFNB-1b-treated patients, which were tested NAb negative or NAb positive after conclusion of a clinical study, were retested three years after first being assessed in four different laboratories that offer routine NAb testing to practicing neurologists.

Effects of interferon beta-1b on cognitive performance in patients with a first event suggestive of multiple sclerosis.

Background: Cognitive dysfunction occurs at the earliest stages of multiple sclerosis (MS), including the stage of clinically isolated syndrome (CIS).

Methods: We evaluated the impact of interferon beta-1b (IFNβ-1b) 250 µg on cognitive performance during the CIS stage in the BENEFITstudy. Cognition was assessed by Paced Auditory Serial Addition Test-3" (PASAT-3") scores.

Metronomic breathing shows altered parasympathetic baroreflex function in untreated Fabry patients and baroreflex improvement after enzyme replacement therapy.

Objective: In untreated Fabry patients without overt autonomic dysfunction and normal baroreflex sensitivity (BRS) at rest, BRS is impaired during orthostatic, sympathetic challenge but normalizes after enzyme-replacement therapy (ERT) (Hilz et al., J Hypertens 2010; 28:1438-1448). This study evaluated BRS during parasympathetic challenge with six cycles per minute metronomic deep breathing (MDB) in Fabry patients before and after ERT.

Enzyme replacement therapy improves cardiovascular responses to orthostatic challenge in Fabry patients.

Objective: Fabry patients have autonomic dysfunction but usually do not present clinically overt signs of orthostatic dysregulation. This study evaluated orthostatic regulation and baroreflex sensitivity (BRS) in untreated Fabry patients and possible baroreflex improvement with enzyme replacement therapy (ERT).

Methods: In 22 Fabry patients (aged 28W8 years), we assessed electrocardiographic RR intervals (RRIs), SBP, DBP and respiratory frequency, in supine and standing position, before and after 18 (11 patients) or 23 months (11 patients) of biweekly alpha-galactosidase A infusions (1.

Isolated corticosteroid myopathy of the gluteal muscles.

Corticosteroid myopathy is a severe side effect of corticosteroid application. Although the risk usually increases with drug dosage, even a single dose can lead to substantial muscular damage. Usually the tissue recovers over time after discontinuation of the responsible drug.

Assessing function and pathology in familial dysautonomia: assessment of temperature perception, sweating and cutaneous innervation.

This study was performed to assess cutaneous nerve fibre loss in conjunction with temperature and sweating dysfunction in familial dysautonomia (FD). In ten FD patients, we determined warm and cold thresholds at the calf and shoulder, and sweating in response to acetylcholine iontophoresis over the calf and forearm. Punch skin biopsies from calf and back were immunostained and imaged to assess nerve fibre density and neuropeptide content.

Reduced cerebral blood flow velocity and impaired cerebral autoregulation in patients with Fabry disease.

In Fabry disease, there is glycosphingolipid storage in vascular endothelial and smooth muscle cells and neurons of the autonomic nervous system. Vascular or autonomic dysfunction is likely to compromise cerebral blood flow velocities and cerebral autoregulation. This study was performed to evaluate cerebral blood flow velocities and cerebral autoregulation in Fabry patients.

Postischemic cutaneous hyperperfusion in the presence of forearm hypoperfusion suggests sympathetic vasomotor dysfunction in Fabry disease.

In Fabry disease, deficiency of alpha-galactosidase A induces glycolipid storage that accounts for neuropathy, renal failure, myocardial infarction and stroke. Vascular crises may be precipitated by stressful conditions. To evaluate pathomechanisms of overall organ versus microvessel perfusion in response to ischemic challenge, we assessed resting and postischemic forearm and skin blood flow in Fabry patients.

Comprehensive imaging of ischemic stroke with multisection CT.

Computed tomography (CT) is an established tool for the diagnosis of ischemic or hemorrhagic stroke. Nonenhanced CT can help exclude hemorrhage and detect "early signs" of infarction but cannot reliably demonstrate irreversibly damaged brain tissue in the hyperacute stage of ischemic stroke. Further evaluation of patients with ischemic stroke should include differentiation between reversible and irreversible brain damage, which is essential for choosing an appropriate therapy.