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INTRODUCTION: Riluzole, a sodium-glutamate antagonist which is FDA approved for ALS has shown promising pre-clinical results and is clinically safe in SCI patients. METHOD(S): The RISCIS trial is an international, multi-center, prospective, double-blinded, randomized, placebo-controlled Phase II/ III trial. Patients with ASIA A-C, C4-C8 SCI and <12 hours from injury were randomized between Riluzole, at an oral dose of 100mg BID for the first 24 hours followed by 50mg BID for the following 13 days, and placebo control. RESULT(S): Due to the impact of the global COVID-19 pandemic this trial was terminated prior to completion. 193 patients were randomized with a follow-up rate of 82.7% at 180-days. No statistical difference was noted in the demographics and baseline injury characteristics between the two groups. At 6 months there was a median gain in total motor scores (TOTM) of 30.0 in the Riluzole group compared to 20.0 for the Placebo group. The improved motor outcomes did not reach statistical significance. Given the decreased sample size, additional sensitivity analyses were conducted. In the ASIA-C population, Riluzole was a significant improver of total motor scores (coefficient estimate: 14.10, p = 0.020) and upper motor scores (CE: 7.68, p = 0.040) at 6 months. ASIA B patients had higher reported independence, as measured by the SCIM score (45.3 vs. 27.3;p = 0.071) and change in mental health scores as measured by the SF-36 mental health domain (2.01 vs. -11.58;p: 0.0205) at 180 days. CONCLUSION(S): Despite the premature termination of the RISCIS trial due to the COVID-19 pandemic, 193 subjects were recruited into this trial. Primary analysis showed a 10-motor point gain in riluzoletreated subjects which did not reach significance. However, on secondary analysis, incomplete cervical SCI subjects (AIS B and C) showed significant gains in functional recovery.
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Objectives: The exposure risks to front-line health care workers (HCWs) who are in close proximity for prolonged periods of time, caring for COVID-19 patients undergoing surgery or obstetrical delivery, is unclear. Understanding of sample types that may harbour virus is important for evaluating risk. The objectives are as follows: to determine if SARS-CoV-2 viral RNA from patients with COVID-19 undergoing surgery or obstetrical delivery is present in: 1) the peritoneal cavity of males and females 2) the female reproductive tract, 3) the environment of the surgery or delivery suite (surgical instruments, equipment used, air or floors) and 4) inside the masks of the attending health care workers. Methods: In this cross-sectional study, conducted at 2 Toronto hospitals, 32 patients with COVID-19 underwent urgent surgery or obstetrical delivery and the presence of SARS-CoV-2 viral RNA in patient, environmental and air samples was identified by real time reverse transcriptase polymerase chain reaction. Air samples were collected using both active and passive sampling techniques. The primary outcome was the proportion of HCW masks positive for SARS-CoV-2 RNA. Results: SARS-CoV-2 RNA was detected in 20/332 (6%) patient and environmental samples collected: 4/24 (16.7%) patient, 5/60 (8.3%) floor, 1/5 (1.9%) air, 10/23 (43.5%) surgical instruments/equipment, 0/24 cautery filters and 0/143 (95% CI 0–0.026) inner surface of mask samples. Conclusions: While there is evidence of SARS-CoV-2 RNA in the surgical and obstetrical operative environment, the finding of no detectable virus inside the masks worn by the medical teams would suggest a low risk of infection for our health care workers using appropriate personal protective equipment. Keywords: SARS-CoV-2 viral RNA;PPE;exposure risk;health care workers;real time RT-PCR;environmental and air sampling;operating room exposure;delivery room exposure
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BACKGROUND: Multiple myeloma (MM) and Waldenström macroglobulinemia (WM) are associated with significant immunoparesis. Based on the ongoing COVID-19 pandemic, there is an urgent need to understand whether patients are able to mount a sufficient response to COVID-19 vaccines. METHODS: MM and WM patients are vaccinated with mRNA-1273 (Moderna), BNT162b2 mRNA (Pfizer/BioNTech), or JNJ-78436735 (Johnson & Johnson) in a prospective clinical trial. Primary endpoint is SARS-CoV-2 spike protein (S) antibody (Ab) detection 28 days after final vaccination. Secondary endpoints include functional serologic assessments and T-cell responses at 28 days, 6 months, 9 months, and 12 months following vaccination. S Abs were detected by Elecsys assay (Roche Diagnostics), with 3 0.80 U/mL defined as positive and titers > 250 U/mL considered stronger correlates of neutralization. SARS-CoV-2 wildtype and variant S-specific Ab isotypes and FcγR binding profiles were quantified by custom Luminex assay. Antibody-dependent neutrophil and cellular phagocytosis (ADNP and ADCP) were assessed using flow cytometry. RESULTS: To date 141 patients have been enrolled, 137 (91 MM and 46 WM) of whom had an S Ab assessment. Median Ab titer was 178.0 (IQR, 16.10-1166.0) for MM and 3.92 (IQR, 0-278.9) for WM. S Ab response rate was 91% (83/91) in MM and 56% (27/46) in WM. However, responses achieving S Ab >250 U/mL were 47.3% (43/91) in MM and 26.1% (12/46) in WM. In patients 375 years, responses >250 u/mL were 13.3% (2/15;p<0.05). Vaccine-specific S Ab responses >250 u/mL following mRNA-1273, BNT162b2, and JNJ-78436735 were 67.6% (23/34;p<0.05), 38.3% (18/47;p=NS), and 20% (2/10;p=NS) in MM and 50.0% (8/16;p<0.05), 14.8% (4/27;p<0.05), and 0% (0/3;p=NS) in WM. Among MM patients with progressive disease, S Ab response >250 u/mL occurred in 30% (6/20) as opposed to 55.6% (30/54) for VGPR+ (p<0.05). MM patients having autologous stem cell transplant within 12 months demonstrated 100% (5/5;p<0.05) S Ab responses. For MM patients actively receiving an anti-CD38 monoclonal Ab or an immunomodulatory drug, S Ab response occurred in 38.9% (14/36;p=NS) and 50.9% (28/55;p<0.05). Among WM patients, S Ab responses >250 U/mL occurred in 63.6% (7/11;p<0.05) previously untreated;0% (0/9;p<0.05) who received rituximab within 12 months;10% (2/20);p<0.05) on an active Bruton Tyrosine Kinase (BTK) inhibitor;and 20% (3/15;p=NS) who received other therapies. Functional Ab studies were performed on 14 MM patients, 14 WM, patients, and 14 healthy donors (HD) (Figure 1). All patients were assessed 28 days following their final vaccination and myeloma patients had an additional assessment 28 days following initial vaccination. MM and WM patients demonstrated less IGG1 and IGG3 S Ab production than HD. MM patients showed increased IgA and IgM S Ab production as well as increased FcgR2A binding following a second vaccine in contrast to HD. Both ADNP and ADCP were reduced in MM and WM patients. MM patients demonstrated improved ADCP in SARS-CoV-2 variants B.1.351, B.1.117, and P.1 versus wildtype (p<0.05). CONCLUSIONS: We report the first known evidence of impaired functional humoral responses following COVID-19 vaccines in patients with MM and WM. Overall, WM patients showed more severe impairment of COVID-19 S Ab responses. Most previously untreated WM patients achieved S Ab responses, however the most significant reduction in S Ab responses were seen in WM patients who received rituximab within 12 months or active BTK inhibitors. For MM patients, being in disease remission associated with improved S Ab response. Among MM and WM patients, age 375 years associated with significantly lower rates and vaccination with MRNA-1273 (Moderna) elicited significantly higher S Ab response rates than other vaccines. A defect in ADNP and more profound defect in ADCP suggests overall compromised opsinophagocytic activity among MM and WM patients. Data comparing first and second vaccine responses in MM patients, suggest less efficient class switching to IGG as well as incomple e maturation of their FcgR2A binding profiles but normal maturation of FcgR3A. Interestingly, ADCP was improved in several emerging SARS-CoV-2 variants. T-cell studies are pending and will be updated. Further understanding of the immunological response to COVID19 vaccination is needed to clarify patients risks, and necessity for booster or alternative protective measures against COVID-19. (Figure Presented).