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Introduction COVID-19 convalescent plasma (CCP) is a possible treatment option for COVID-19. A comprehensive number of clinical trials on CCP efficacy have already been conducted. However, many aspects of CCP treatment still require investigations: in particular (1) Optimisation of the CCP product, (2) Identification of the patient population in need and most likely to benefit from this treatment approach, (3) Timing of administration and (4) CCP efficacy across viral variants in vivo. We aimed to test whether high-titre CCP, administered early, is efficacious in preventing hospitalisation or death in high-risk patients.Methods and analysis COVIC-19 is a multicentre, randomised, open-label, adaptive superiority phase III trial comparing CCP with very high neutralising antibody titre administered within 7 days of symptom onset plus standard of care versus standard of care alone. We will enrol patients in two cohorts of vulnerable patients [(1) elderly 70+ years, or younger with comorbidities; (2) immunocompromised patients]. Up to 1020 participants will be enrolled in each cohort (at least 340 with a sample size re-estimation after reaching 102 patients). The primary endpoint is the proportion of participants with (1) Hospitalisation due to progressive COVID-19, or (2) Who died by day 28 after randomisation. Principal analysis will follow the intention-to-treat principle.Ethics and dissemination Ethical approval has been granted by the University of Ulm ethics committee (#41/22) (lead ethics committee for Germany), Comité de protection des personnes Sud-Est I (CPP Sud-Est I) (#2022-A01307-36) (ethics committee for France), and ErasmusMC ethics committee (#MEC-2022-0365) (ethics committee for the Netherlands). Signed informed consent will be obtained from all included patients. The findings will be published in peer-reviewed journals and presented at relevant stakeholder conferences and meetings.Trial registration Clinical Trials.gov (NCT05271929), EudraCT (2021-006621-22)

A major limitation in the current topical treatment strategies for inflammatory skin disorders is the inability to selectively target the inflamed site with minimal exposure of healthy skin. Atopic dermatitis is one of the most prevalent types of dermatitis. The use of polymeric nanoparticles for targeting inflamed skin has been recently proposed, and therefore the aim of this proof-of-concept clinical study was to investigate the skin penetration and deposition of polymeric biodegradable nanoparticles in the atopic dermatitis lesions and compare the data obtained to the deposition of the particles into the healthy skin or lesion-free skin of the atopic dermatitis patients. For that, fluorescent PLGA nanoparticles in sizes of approximately 100 nm were prepared and applied to the skin of healthy volunteers and the lesional and non-lesional skin of atopic dermatitis patients. Skin biopsies were examined using confocal laser scanning microscopy to track the skin deposition and depth of penetration of the particles. Immunohistochemistry was performed to investigate the alteration in tight-junction protein distribution in the different types of skin. Results have shown that nanoparticles were found to have higher deposition into the atopic dermatitis lesions with minimal accumulation in healthy or non-lesional skin. This has been primarily correlated with the impaired barrier properties of atopic dermatitis lesions with the reduced production of Claudin-1. It was concluded that polymeric nanoparticles offer a potential tool for selective drug delivery to inflamed skin with minimal exposure risk to healthy skin.

A major limitation in the current topical treatment strategies for inflammatory skin disorders is the inability to selectively target the inflamed site with minimal exposure of healthy skin. Atopic dermatitis is one of the most prevalent types of dermatitis. The use of polymeric nanoparticles for targeting inflamed skin has been recently proposed, and therefore the aim of this proof-of-concept clinical study was to investigate the skin penetration and deposition of polymeric biodegradable nanoparticles in the atopic dermatitis lesions and compare the data obtained to the deposition of the particles into the healthy skin or lesion-free skin of the atopic dermatitis patients. For that, fluorescent PLGA nanoparticles in sizes of approximately 100 nm were prepared and applied to the skin of healthy volunteers and the lesional and non-lesional skin of atopic dermatitis patients. Skin biopsies were examined using confocal laser scanning microscopy to track the skin deposition and depth of penetration of the particles. Immunohistochemistry was performed to investigate the alteration in tight-junction protein distribution in the different types of skin. Results have shown that nanoparticles were found to have higher deposition into the atopic dermatitis lesions with minimal accumulation in healthy or non-lesional skin. This has been primarily correlated with the impaired barrier properties of atopic dermatitis lesions with the reduced production of Claudin-1. It was concluded that polymeric nanoparticles offer a potential tool for selective drug delivery to inflamed skin with minimal exposure risk to healthy skin. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockade has proven its efficacy in hypermutated subtypes of metastatic colorectal cancers (mCRC). Immunogenic potential can also be observed with conventional chemotherapies, but this property has never been explored thoroughly in CRC patients. The CRC therapeutic arsenal includes oxaliplatin, a well‐characterized platinum drug already described as immunogenic. Here, we investigated the impact of the oxaliplatin‐based treatment on mCRC immunopeptidome. We demonstrated that oxaliplatin‐resistant CRC cell lines overexpressed telomerase reverse transcriptase (TERT), colorectal‐associated‐tumor antigen‐1 (COA‐1) and mesothelin tumor‐associated antigens. We identified new HLA class‐II‐restricted and promiscuous peptides derived from COA‐1 and mesothelin. The two naturally processed peptides COA‐1331‐345 and Meso366‐380 appear to be the most immunogenic in mCRC patients. A prospective cohort of 162 mCRC patients enabled us to explore the impact of oxaliplatin exposure on the antitumor‐specific immune response. Interestingly, chemotherapy‐naive mCRC patients present high immune CD4 T‐cell responses directed against TERT, COA‐1 and mesothelin‐derived peptides. These antitumor T‐cell responses were maintained after 3 months of oxaliplatin‐based treatment. Altogether, these findings highlight the interest of immunostimulatory agents to improve the management of chemoresistant mCRC patients. Finally, the high frequency of immune responses targeting the new immunogenic peptides derived from COA‐1 and mesothelin support their use in immunomonitoring strategies. What's new? Oxaliplatin, like other platinum drugs, kills cancer cells through induction of DNA damage, but immunomodulatory properties have also been described. Here the authors examined the immunopeptidome in oxaliplatin‐resistant colon cancer cell lines. They identified novel MHC class II‐restricted peptides derived from overexpressed tumor antigens and show that these are immunogenic in metastatic colorectal cancer patients treated with oxaliplatin. These findings may lead to new immunotherapeutic approaches to oxaliplatin‐resistant colon cancer. [ABSTRACT FROM AUTHOR]

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Purpose: The aim of the study was to examine the effects of a post-prandial 20 min nap on a short-term physical exercise and subsequent sleep in athletes keeping their usual sleep schedules and in 5-h phase-advance condition. Methods: Sixteen healthy young male athletes (age 22.2 ± 1.7 years, non-habitual nappers) participated in the study. After a baseline 8-h time in bed in normal and 5-h advanced sleep schedules, a standardized morning and lunch in a laboratory environment, subjects underwent either a nap (20 min of sleep elapsed from 3 epochs of stage 1 or 1 epoch of stage 2), or a rest without sleep by lying in a bed, between 13:00 and 14:00 hours in non-shifted condition or 08:00 and 09:00 hours in shifted condition, after which anaerobic exercises were performed twice 2 h apart. Core body temperature was recorded throughout the study period. Results: The nap extended sleep onset latency from 6.72 ± 3.83 to 11.84 ± 13.44 min, after shifted condition but did not modify sleep architecture of the post-trial night among athletes, whether shifted or not. Moreover, napping did not improve physical performance but it delayed acrophase and batyphase of core body temperature rhythm parameters. Conclusion: Napping showed no reliable benefit on short-term performances of athletes exercising at local time or after a simulated jet lag. [ABSTRACT FROM AUTHOR]