Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

<i>Cucumeropsis mannii</i> seed oil protects against bisphenol A-induced hepatotoxicity by mitigating inflammation and oxidative stress in rats

From Crossref journal articles via Jisc Publications RouterHistory: epub 2023-10-20, issued 2023-10-20Article version: AMPublication status: PublishedOBJECTIVES This study looked at how CMSO affected male Wistar albino rats' liver damage caused by bisphenol A. METHODS The standard HPLC method was used to assess the CMSO's phenolic content. Then, six (n = 8) groups of forty-eight (48) male Wistar rats (150 20 g) each received either CMSO or olive oil before being exposed to BPA for 42 days. Groups: A (one milliliter of olive oil, regardless of weight), B (BPA 100 mg/kg body weight (BW)), C (CMSO 7.5 mg/kg BW), D (CMSO 7.5 mg/kg BW + BPA 100 mg/kg BW), E (CMSO 5.0 mg/kg BW + BPA 100 mg/kg BW), and F (CMSO 2.5 mg/kg BW + BPA 100 mg/kg BW). KEY FINDINGS A surprising abundance of flavonoids, totaling 17.8006 10.95 g/100 g, were found in the HPLC data. Malondialdehyde, liver enzymes, reactive oxygen species, total bilirubin, and direct bilirubin levels were all significantly elevated by BPA (p 0.05). Additionally, nuclear factor-B, interleukin-6, interleukin-1, tumor necrosis factor, and histological alterations were all considerably (p 0.05) caused by BPA. The altered biochemical markers and histology were, however, noticeably recovered by CMSO to a level that was comparable to the control. CONCLUSION Due to the abundance of flavonoid components in the oil, CMSO protects the liver from BPA-induced hepatotoxicity by lowering oxidative stress and inflammatory reactions

Cucumeropsis mannii seed oil protects against bisphenol A-induced hepatotoxicity by mitigating inflammation and oxidative stress in rats

From Oxford University Press via Jisc Publications RouterHistory: received 2023-07-05, accepted 2023-10-11, epub 2023-10-20, cover 2024-01, collection 2024-01-01, corrected-typeset 2024-03-05Acknowledgements: We appreciate the management of the Department of Biochemistry Institutional Research Ethics Committee, Ebonyi State University, Abakaliki, Nigeria.Publication status: PublishedObjectives: This study looked at how Cucumeropsis mannii seed oil (CMSO) affected male Wistar albino rats’ liver damage caused by bisphenol A (BPA). Methods: The standard HPLC method was used to assess the CMSO’s phenolic content. Then, six (n = 8) groups of 48 male Wistar rats (150 20 g) each received either CMSO or olive oil before being exposed to BPA for 42 days. Groups: A (1 ml of olive oil, regardless of weight), B (BPA 100 mg/kg body weight (BW)), C (CMSO 7.5 mg/kg BW), D (CMSO 7.5 mg/kg BW + BPA 100 mg/kg BW), E (CMSO 5.0 mg/kg BW + BPA 100 mg/kg BW), and F (CMSO 2.5 mg/kg BW + BPA 100 mg/kg BW). Key findings: A surprising abundance of flavonoids, totalling 17.8006 10.95 g/100 g, were found in the HPLC data. Malondialdehyde, liver enzymes, reactive oxygen species, total bilirubin, and direct bilirubin levels were all significantly elevated by BPA (P = 0.05). Additionally, nuclear factor-B, interleukin-6, interleukin-1, tumour necrosis factor, and histological alterations were all considerably (P = 0.05) caused by BPA. The altered biochemical markers and histology were, however, noticeably recovered by CMSO to a level that was comparable to the control. Conclusions: Due to the abundance of flavonoid components in the oil, CMSO protects the liver from BPA-induced hepatotoxicity by lowering oxidative stress and inflammatory reactions

Cucumeropsis mannii seed oil protects against Bisphenol A‐induced testicular mitochondrial damages

Abstract There has been increasing search for the ameliorative properties of seed oils against toxicants. bisphenol A acts as an estrogenic endocrine‐disrupting chemical capable of causing male infertility. This study aimed to explore Cucumeropsis mannii seed oil effects against mitochondrial damage in rats using bisphenol A. Forty‐eight rats were randomly assigned to six groups (n = 6) of eight rats each and fed the same food and water for 6 weeks. The group A rats were given 1 mL olive oil, while the ones in group B were given bisphenol A at 100 mL/kg body weight via oral route. Group C received C. mannii seed oil 7.5 mL/kg body weight C. mannii seed oil, while group D, group E, and group F were pre‐administered bisphenol A at 100 mL/kg body weight, followed by treatment with C. mannii seed oil at 7.5, 5, and 2.5 mL/kg body weight, respectively. Antioxidant enzymes, glutathione, reactive oxygen species, testicular volume, malondialdehyde, body weight, and testicular studies were done using standard methods. The results of the bisphenol A‐administered group showed a significant decrease in the antioxidant enzymes, glutathione, body weight, and testicular volume with elevation in the levels of reactive oxygen species, malondialdehyde, and testicular indices. BPA + CMSO‐treated group showed a significant increase in GPx activity compared with BPA‐exposed rats. CMSO treatment significantly increased catalase activity in comparison with that of rats exposed to BPA. Remarkably, C. mannii seed oil and bisphenol A co‐administration significantly reversed the abnormalities observed in the dysregulated biochemical biomarkers. Our findings suggest that C. mannii seed oil has considerable antioxidant potential which can be explored in therapeutic development against systemic toxicity induced by exposure to bisphenol A. Cucumeropsis mannii seed oil protects against bisphenol A‐induced testicular mitochondria damages