Combination therapy of Epidermal Growth Factor and Growth Hormone-Releasing Hexapeptide in acute ischemic stroke: a phase I/II non-blinded, randomized clinical trial.

Objective: This study tested the hypothesis that a neuroprotective combined therapy based on epidermal growth factor (EGF) and growth hormone-releasing hexapeptide (GHRP6) could be safe for acute ischemic stroke patients, admitting up to 30% of serious adverse events (SAE) with proven causality. Methods: A multi-centric, randomized, open-label, controlled, phase I-II clinical trial with parallel groups was conducted (July 2017 to January 2018). Patients aged 18-80 years with a computed tomography-confirmed ischemic stroke and less than 12 h from the onset of symptoms were randomly assigned to the study groups I (75 µg rEGF + 3.5 mg GHRP6 i.v., n=10), II (75 µg rEGF + 5 mg GHRP6 i.v., n=10), or III (standard care control, n=16). Combined therapy was given BID for 7 days. The primary endpoint was safety over 6 months. Secondary endpoints included neurological (NIHSS) and functional [Barthel index and modified Rankin scale (mRS)] outcomes. Results: The study population had a mean age of 66 ± 11 years, with 21 men (58.3%), a baseline median NIHSS score of 9 (95% CI: 8-11), and a mean time to treatment of 7.3 ± 2.8 h. Analyses were conducted on an intention-to-treat basis. SAEs were reported in 9 of 16 (56.2%) patients in the control group, 3 of 10 (30%) patients in Group I (odds ratio (OR): 0.33; 95% CI: 0.06-1.78), and 2 of 10 (20%) patients in Group II (OR: 0.19; 95% CI: 0.03-1.22); only two events in one patient in Group I were attributed to the intervention treatment. Compliance with the study hypothesis was greater than 0.90 in each group. Patients treated with EGF + GHRP6 had a favorable neurological and functional evolution at both 90 and 180 days, as evidenced by the inferential analysis of NIHSS, Barthel, and mRS and by their moderate to strong effect size. At 6 months, proportion analysis evidenced a higher survival rate for patients treated with the combined therapy. Ancillary analysis including merged treated groups and utility-weighted mRS also showed a benefit of this combined therapy. Conclusion: EGF + GHRP6 therapy was safe. The functional benefits of treatment in this study supported a Phase III study. Clinical Trial Registration: RPCEC00000214 of the Cuban Public Registry of Clinical Trials, Unique identifier: IG/CIGB-845I/IC/1601.

Púrpura de Schõnlein-Henoch fulminante / Henoch-Schõnlein purpura fulminant

Se trata de paciente femenina de 51 años, con antecedentes patológicos personales de asma bronquial, hipertensión arterial y colitis ulcerativa e infección por el virus de la chikungunya desde hacía un mes. Ingresó con diarreas pastosas oscuras con moco y sangre, evolucionó desfavorablemente con paraplejia flácida y livedo reticularis, que se transformó en púrpura extensa; posteriormente flictenas y edema generalizado. Se mantuvo hipotensa con desequilibrio hidroelectrolítico y deterioro del estado de conciencia, se le realizaron complementarios, fue transfundida y se le realizó hemodiálisis; evolucionó al coma y a la muerte. Los hallazgos anatomopatológicos mostraron una forma adulta, fulminante y mortal de púrpura anafilactoide o de Schõnlein- Henoch. Se encontró proliferación mesangial con depósitos mesangiales fushinofílicos correspondientes a inmunoglobulina A con inmunofluorescencia, vasculitis leucocitoclástica y vasculitis necrotizante de pequeños vasos. La púrpura de Schõnlein-Henoch es una forma peculiar de vasculitis que tiende a la curación espontánea y, ocasionalmente, puede tener un curso mortal o proseguir hacia una nefritis crónica(AU)