Spatial and temporal characteristics of set-related inhibitory and excitatory inputs from the dorsal premotor cortex to the ipsilateral motor cortex assessed by dual-coil transcranial magnetic stimulation

The capacity to produce movements only at appropriate times is fundamental in successful behavior and requires a fine interplay between motor inhibition and facilitation. Evidence in humans indicates that the dorsal premotor cortex (PMCd) is involved in such preparatory and inhibitory processes, but how PMCd modulates motor output in humans is still unclear. We investigated this issue in healthy human volunteers, using a variant of the dual-coil transcranial magnetic stimulation (TMS) technique that allows testing the short-latency effects of conditioning TMS to the left PMCd on test TMS applied to the ipsilateral orofacial primary motor cortex (M1). Participants performed a delayed cued simple reaction time task. They were asked to produce a lip movement cued by an imperative GO-signal presented after a predictable SET-period, during which TMS was applied at different intervals. Results showed that the area of motor evoked potentials (MEPs) to test TMS was modulated by conditioning TMS. A transient inhibition cortico-bulbar excitability by PMCd stimulation was observed around the middle of the SET-period. Conversely, a ramping excitatory effect of PMCd stimulation appeared towards the end of the SET-period, as the time of the predicted GO-signal approached. The time-course of PMCd-M1 activity scaled to the varying SET-period duration. Our data indicate that inhibition and excitation of motor output during a delayed reaction time task are two distinct neural phenomena. They both originate in PMCd and are conveyed via cortico-cortical connections to the ipsilateral M1, where they are integrated to produce harmonic fluctuations of motor output

Tocilizumab for treatment of severe covid-19 patients: Preliminary results from smatteo covid19 registry (smacore)

Objective: This study aimed to assess the role of Tocilizumab therapy (TCZ) in terms of ICU admission and mortality rate of critically ill patients with severe COVID-19 pneumonia. Design: Patients with COVID-19 pneumonia were prospectively enrolled in SMAtteo COvid19 REgistry (SMACORE). A retrospective analysis of patients treated with TCZ matched using propensity score to patients treated with Standard Of Care (SOC) was conducted. Setting: The study was conducted at IRCCS Policlinico San Matteo Hospital, Pavia, Italy, from March 14, 2020 to March 27, 2020. Participants: Patients with a confirmed diagnosis of COVID-19 hospitalized in our institution at the time of TCZ availability. Interventions: TCZ was administered to 21 patients. The first administration was 8 mg/kg (up to a maximum 800 mg per dose) of Tocilizumab intravenously, repeated after 12 h if no side effects were reported after the first dose. Main Outcomes and Measures: ICU admission and 7-day mortality rate. Secondary outcomes included clinical and laboratory data. Results: There were 112 patients evaluated (82 were male and 30 were female, with a median age of 63.55 years). Using propensity scores, the 21 patients who received TCZ were matched to 21 patients who received SOC (a combination of hydroxychloroquine, azithromycin and prophylactic dose of low weight heparin). No adverse event was detected following TCZ administration. This study found that treatment with TCZ did not significantly affect ICU admission (OR 0.11; 95% CI between 0.00 and 3.38; p = 0.22) or 7-day mortality rate (OR 0.78; 95% CI between 0.06 and 9.34; p = 0.84) when compared with SOC. Analysis of laboratory measures showed significant interactions between time and treatment regarding C-Reactive Protein (CRP), alanine aminotransferase (ALT), platelets and international normalized ratio (INR) levels. Variation in lymphocytes count was observed over time, irrespective of treatment. Conclusions: TCZ administration did not reduce ICU admission or mortality rate in a cohort of 21 patients. Additional data are needed to understand the effect(s) of TCZ in treating patients diagnosed with COVID-19