Prospective Randomized Open-label Multicenter Phase I/II Dose Escalation Trial of Visilizumab (HuM291) in Severe Steroid-refractory Ulcerative Colitis

Background: Visilizumab is a humanized IgG(2) monoclonal anti-CD3 antibody. We evaluated its safety and dose response in severe intravenous steroid-refractory ulcerative colitis (UC). Methods: In all, 104 patients were treated. In Stage 1, 73 patients were randomly assigned to receive intravenous visilizumab 5, 7.5, 10, or 12.5 mu g/kg/day for 2 consecutive days. In Stage II, 33 patients received visilizumab at the optimal clinical dose (OCD) of 5 mu g/kg/day for 2 days. Symptomatic response and remission were defined by the modified Truelove-Witts severity index. Clinical response and remission were defined by the Mayo score. Results: The rates of symptomatic response at day 15 in the 5, 7.5, 10, or 12.5 mu g/kg dose groups were 71%, 70%, 50%, and 61%. respectively, in Stage I and in 54% in Stage II. The symptomatic remission rates were 3.5%, 5%, 22%, and 11% in Stage I and 18% in Stage II. The rates of clinical response at day 30 in the 5, 7.5, 10, or 12.5 mu g/kg dose groups were 71%, 65%, 50%, and 67%, respectively, in Stage I and 55% in Stage II. The clinical remission rates were 6%, 5%, 0%, and 11% in Stage I and 6% in Stage II. All patients experienced adverse events. Serious adverse events included abdominal abscess, cytomegalovirus infection, atrial fibrillation, herpes zoster, and esophageal candidiasis. Conclusions: Treatment with visilizumab induced symptomatic response and clinical response. Results with 5 mu g/kg/day were similar to those observed with higher doses (NCT00267306 at www.clinicaltrials.gov).Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Global Impact of COVID-19 on Stroke Care and IV Thrombolysis

OBJECTIVE: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods. METHODS: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. RESULTS: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] -11.7 to -11.3, p < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI -13.8 to -12.7, p < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI -13.7 to -10.3, p = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2-9.8, p < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions. CONCLUSIONS: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months. © 2021 American Academy of Neurology

Combined Measurement and QCD Analysis of the Inclusive e+- p Scattering Cross Sections at HERA

A combination is presented of the inclusive deep inelastic cross sections measured by the H1 and ZEUS Collaborations in neutral and charged current unpolarised ep scattering at HERA during the period 1994-2000. The data span six orders of magnitude in negative four-momentum-transfer squared, Q^2, and in Bjorken x. The combination method used takes the correlations of systematic uncertainties into account, resulting in an improved accuracy. The combined data are the sole input in a NLO QCD analysis which determines a new set of parton distributions HERAPDF1.0 with small experimental uncertainties. This set includes an estimate of the model and parametrisation uncertainties of the fit result