SARS-CoV-2-specific T cell therapy for severe COVID-19: a randomized phase 1/2 trial.

Despite advances, few therapeutics have shown efficacy in severe coronavirus disease 2019 (COVID-19). In a different context, virus-specific T cells have proven safe and effective. We conducted a randomized (2:1), open-label, phase 1/2 trial to evaluate the safety and efficacy of off-the-shelf, partially human leukocyte antigen (HLA)-matched, convalescent donor-derived severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells (CoV-2-STs) in combination with standard of care (SoC) in patients with severe COVID-19 compared to SoC during Delta variant predominance. After a dose-escalated phase 1 safety study, 90 participants were randomized to receive CoV-2-ST+SoC (n = 60) or SoC only (n = 30). The co-primary objectives of the study were the composite of time to recovery and 30-d recovery rate and the in vivo expansion of CoV-2-STs in patients receiving CoV-2-ST+SoC over SoC. The key secondary objective was survival on day 60. CoV-2-ST+SoC treatment was safe and well tolerated. The study met the primary composite endpoint (CoV-2-ST+SoC versus SoC: recovery rate 65% versus 38%, P = 0.017; median recovery time 11 d versus not reached, P = 0.052, respectively; rate ratio for recovery 1.71 (95% confidence interval 1.03-2.83, P = 0.036)) and the co-primary objective of significant CoV-2-ST expansion compared to SοC (CoV-2-ST+SoC versus SoC, P = 0.047). Overall, in hospitalized patients with severe COVID-19, adoptive immunotherapy with CoV-2-STs was feasible and safe. Larger trials are needed to strengthen the preliminary evidence of clinical benefit in severe COVID-19. EudraCT identifier: 2021-001022-22 .

Dexmedetomidine as an adjuvant to scalp block in patients undergoing elective craniotomy: A prospective randomized controlled trial.

OBJECTIVE: Regional techniques minimize anesthetic requirements and their effects may be beneficial. There is a lack of consensus and evidence concerning alternative analgesia strategies for cranial neurosurgery. This study was designed to evaluate the effect of scalp block with or without dexmedetomidine combined with general anesthesia on hemodynamic stability, opioid consumption and postoperative pain in patients undergoing elective craniotomy. METHODS: One hundred five patients undergoing elective craniotomy for tumor dissection were randomly divided into three groups to receive scalp block as an adjuvant to general anesthesia: with either 40 ml ropivacaine 0.5 % (Group R), 40 ml ropivacaine 0.5 % plus dexmedetomidine 1 µg/kg (Group RD) or 40 ml saline as a placebo (Group C). After a standard induction sequence using propofol, fentanyl and a single dose of rocuronium, patients were intubated. Bilateral scalp block was given immediately after induction. Anesthesia was maintained with propofol and remifentanil infusion. Five minutes before head pinning scalp block was performed by blocking the supraorbital, supratrochlear, auriculotemporal, occipital, and postauricular branches of the greater auricular nerves. All patients were monitored with electrocardiogram, invasive blood pressure, pulse oximetry and BIS monitoring. Primary outcomes measures were overall hemodynamic variables during surgery and intravenous fentanyl and remifentanil consumption. Mean arterial pressure (MAP) and heart rate (HR) were recorded at seven time-points: scalp block (T1-baseline), pin fixation (T2), skin incision (T3), drilling (T4), dura matter incision (T5), dura matter closure (T6) and skin closure (T7). For all time points it was recorded the mean value after 3 consecutive measures with 5 min interval. Secondary outcome was postoperative pain intensity using visual analog scale 24 and 48 h after surgery. VAS scores, fentanyl and remifentanil were evaluated using Kruskal-Wallis test. MAP and HR were compared by One-Way repeated measures Anova (GLMM) using time as random efect and by One-Way Anova using time as fxed efect. RESULTS: Mean arterial pressure was significant lower at skin closure compared to baseline in group R (p < 0,001) and in group RD (p < 0,001). Patients in group RD showed significant lower heart rate at dura matter incision, dura matter closure and skin closure compared to baseline, pin fixation and skin incision time points (p < 0,001) and reported significantly less heart rate than group C (p < 0,001) and group R (p < 0,001) during dura matter incision, dura matter closure and skin closure time points. Patients in group RD receive significant lower fentanyl than group R (p < 0,01). The intraoperative consumption of remifentanil was significant higher in control group compared to group R (p < 0,01) and to group RD (p < 0,001). Additionally, remifentanil consumption was significant lower in group RD as compared to group R (p < 0,001). Postoperative pain had no statistically differences between the three groups at 24 h and 48 h after craniotomy (Preop VAS: p = 0,915, VAS 24: p = 0,284, VAS 48, p = 0,385). No adverse effects were noted. CONCLUSION: Our study indicated that addition of dexmedetomidine to scalp block with ropivacaine 0.5% provided significantly better perioperative hemodynamic stability during elective craniotomy. Moreover, scalp block with or without dexmedetomidine reduced fentanyl and remifentanil consumption, but it didn't significantly prolonged analgesia in patients undergoing elective craniotomy.

Blood and fluid management during scoliosis surgery: a single-center retrospective analysis.

AIM: In the present retrospective study in scoliosis surgery, we hypothesized that application of a protocol for blood and fluid management, based on goal-directed fluid therapy, cell salvage and tranexamic acid, could lead to reduced allogeneic red blood cells transfusion. METHODS AND MATERIAL: Thirty-five patients, with American Society of Anesthesiologists physical status I/III, between 14 and 18 years scheduled for elective orthopedic surgery of scoliosis, with a planned intensive care unit admission, were enrolled in a retrospective observational study. Patients were divided in two groups. Patients in no-protocol group (Group noPro, n = 18) received a liberal intraoperative fluid therapy and patients in protocol group (Group Pro, n = 17) received fluid therapy managed according to a stroke volume variation-based protocol. The protocol included fluid therapy according to SVV monitor, permissive hypotension, tranexamic acid infusion, restrictive RBC trigger and use of perioperative cell savage. STATISTICAL ANALYSIS USED: Student's t test (2-tailed), Mann-Whitney test, Chi square test were used for statistical analysis of the data. RESULTS: There were no significant differences between the two groups in demographic data and clinical characteristics. Infused crystalloids (p = .003) and transfused allogeneic red blood cells (p = .015) were lesser in Group Pro compared to Group noPro. On the other hand, diuresis (p < .001) and vasopressors administration (p = .042) were higher in Group Pro than in Group noPro. CONCLUSION: The application of a protocol for blood and fluid management, based on goal-directed fluid therapy, cell salvage and tranexamic acid, was associated with less crystalloid fluid administration, less perioperative RBC transfusions and significantly better diuresis than patients in the no-protocol group in scoliosis surgery. REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT03814239.