Objectives: Convalescent plasma (CP) as a passive source of neutralizing antibodies and immunomodulators is a century-old therapeutic option used for the management of viral diseases. We investigated its effectiveness for the treatment of COVID-19. Design: Open-label, parallel-arm, phase II, multicentre, randomized controlled trial. Setting: Thirty-nine public and private hospitals across India. Participants: Hospitalized, moderately ill confirmed COVID-19 patients (PaO2/FiO2: 200-300 or respiratory rate > 24/min and SpO2 ≤ 93% on room air). Intervention: Participants were randomized to either control (best standard of care (BSC)) or intervention (CP + BSC) arm. Two doses of 200 mL CP was transfused 24 hours apart in the intervention arm. Main Outcome Measure: Composite of progression to severe disease (PaO2/FiO2<100) or all-cause mortality at 28 days post-enrolment. Results: Between 22 nd April to 14 th July 2020, 464 participants were enrolled; 235 and 229 in intervention and control arm, respectively. Composite primary outcome was achieved in 44 (18.7%) participants in the intervention arm and 41 (17.9%) in the control arm [aOR: 1.09; 95% CI: 0.67, 1.77]. Mortality was documented in 34 (13.6%) and 31 (14.6%) participants in intervention and control arm, respectively [aOR) 1.06 95% CI: -0.61 to 1.83]. Interpretation: CP was not associated with reduction in mortality or progression to severe COVID-19. This trial has high generalizability and approximates real-life setting of CP therapy in settings with limited laboratory capacity. A priori measurement of neutralizing antibody titres in donors and participants may further clarify the role of CP in management of COVID-19.

Background: CrossFit is an increasingly popular, rapidly growing exercise regimen. Few studies have evaluated CrossFit-associated musculoskeletal injuries on a large scale. This study explores such injuries and associated risk factors in detail. Objective: To identify the most common musculoskeletal injuries endured during CrossFit training among athletes at different levels of expertise. Design: Survey-based retrospective cross-sectional study. Setting: Distribution at CrossFit gyms in the United States and internationally. Also published on active online forums. Participants: A total of 885 former and current CrossFit athletes. Methods: Institutional review board-approved 33-question Web-based survey focused on CrossFit injuries and associated risk factors. Survey submissions were accepted for a period of 6 months. Main outcome measurements: Specific injuries with associated workouts, risk factors that affected injury including (1) basic demographics, (2) regional differences in reported injuries, (3) training intensity, and (4) expertise level at time of injury. Results: Of the 885 respondents, 295 (33.3%) were injured. The most common injuries involved the back (95/295, 32.2%) and shoulder (61/295, 20.7%). The most common exercises that caused injury were squats (65/295, 22.0%) and deadlifts (53/295, 18.0%). Advanced-level (64/295, 21.7%) athletes were more significantly injured than beginner-level (40/295, 13.6%) athletes. International participants were 2.2 times more likely than domestic US participants to suffer injury. Individuals with 3+ years of CrossFit experience were 3.3 times more likely to be injured than those with 2 or less years of experience. Participants who trained for 11+ h/week were significantly more likely to be injured than those who trained less than or equal to 10 h/week. Conclusions: As CrossFit becomes more popular, it is important to monitor the safety of its practitioners. Further studies are needed to explore how to lower this injury prevalence of 33.3%. Areas to focus on include factors that have caused the regional (international vs US states) differences, level of expertise/experience differences (advanced level vs intermediate and beginner levels), and stretching routine modifications.

A large proportion of cerebral strokes disrupt descending commands from motor cortical areas to the spinal cord which can results in permanent motor de cits of the arm and hand1,2. However, below the lesion, the spinal circuits that control movement5 remain intact and could be targeted by neurotechnologies to restore movement6-9. Here we demonstrate that by engaging spinal circuits with targeted electrical stimulation we immediately improved voluntary motor control in two participants with chronic post-stroke hemiparesis. We implanted a pair of 8-contact percutaneous epidural leads on the lateral aspect of the cervical spinal cord to selectively target the dorsal roots that provide excitatory inputs to motoneurons controlling the arm and hand10,11. With this strategy, we obtained independent activation of shoulder, elbow and hand muscles. Continuous stimulation through selected contacts at speci c frequencies enabled participants to perform movements that they had been unable to perform for many years. Overall, stimulation improved strength, kinematics, and functional performance.Unexpectedly, both participants retained some of these improvements even without stimulation, suggesting that spinal cord stimulation could be a restorative as well as an assistive approach for upper limb recovery after stroke.

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Over 90% of the COVID-19 patients manifest mild/moderate symptoms or are asymptomatic. Although comorbidities and dysregulation of immune response have been implicated in severe COVID-19, the host factors that associate with asymptomatic or mild infections have not been characterized. We have collected serial samples from 23 hospitalized COVID-19 patients with mild symptoms and measured the kinetics of SARS-CoV-2 viral load in respiratory samples and markers of inflammation in serum samples. We monitored seroconversion during the acute phase of illness and quantitated the amount of total IgG against the receptor-binding domain of SARS-CoV-2 and estimated the virus neutralization potential of these antibodies. Viral load decreased by day 8 in all the patients but the detection of viral RNA in saliva samples did not correlate well with viral RNA detection in nasopharyngeal/oropharyngeal swab samples. 25% of the virus-positive patients had no detectable neutralizing antibodies in the serum and in other cases, the efficiency of antibodies to neutralize SARS-CoV-2 B1.1.7 strain was lower as compared to the circulating virus isolate. Decrease in viral load coincided with increase in neutralizing antibodies and interferon levels in serum. Most patients showed no increase in inflammatory cytokines such as IL-1β or IL-6, however, elevated levels of IL-7 and other inflammatory mediators such as TNF-α and IL-8 was observed. These data suggest that most mild infections are associated with absence of inflammation coupled with an active innate immune response, T-cell activation and neutralizing antibodies.

The purpose of this study was to examine the biomechanical effects of bone-patellar tendonbone (BPTB) grafts subject to repeat freeze-thaw cycles in a cyclic loading model. We hypothesized that repeat freeze-thaw cycles have deleterious effects on the tensile properties of BPTB grafts.Thirty BPTB composite grafts were harvested from porcine knee specimens. Tendons were randomized into 3 groups: fresh, 1 freeze-thaw cycle (280°C), or 2 freeze-thaw cycles. The grafts were cyclically loaded to simulate the forces on the anterior cruciate ligament during walking and running, prior to single cycle loadto-failure testing.All tendon failures were mid-substance and occurred during the single cycle load-to-failure testing. There was no statistically significant difference in ultimate stress or strain between the groups. Repeat freezethaw cycles do not have deleterious effects on the tensile properties of BPTB grafts in a cyclic loading model. Potential influence on biologic graft healing or integration remains unknown. [J Knee Surg. 2009;22:111-113.]