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Abstract Despite encouraging preclinical data, therapies to reduce ARDS mortality remains a globally unmet need, including during the COVID-19 pandemic. We previously identified extracellular nicotinamide phosphoribosyltransferase (eNAMPT) as a novel damage-associated molecular pattern protein (DAMP) via TLR4 ligation which regulates inflammatory cascade activation. eNAMPT is tightly linked to human ARDS by biomarker and genotyping studies in ARDS subjects. We now hypothesize that an eNAMPT-neutralizing mAb will significantly reduce the severity of ARDS lung inflammatory lung injury in diverse preclinical rat and porcine models. Sprague Dawley rats received eNAMPT mAb intravenously following exposure to intratracheal lipopolysaccharide (LPS) or to a traumatic blast (125 kPa) but prior to initiation of ventilator-induced lung injury (VILI) (4 h). Yucatan minipigs received intravenous eNAMPT mAb 2 h after initiation of septic shock and VILI (12 h). Each rat/porcine ARDS/VILI model was strongly associated with evidence of severe inflammatory lung injury with NFkB pathway activation and marked dysregulation of the Akt/mTORC2 signaling pathway. eNAMPT neutralization dramatically reduced inflammatory indices and the severity of lung injury in each rat/porcine ARDS/VILI model (~ 50% reduction) including reduction in serum lactate, and plasma levels of eNAMPT, IL-6, TNFα and Ang-2. The eNAMPT mAb further rectified NFkB pathway activation and preserved the Akt/mTORC2 signaling pathway. These results strongly support targeting the eNAMPT/TLR4 inflammatory pathway as a potential ARDS strategy to reduce inflammatory lung injury and ARDS mortality.

Global comparison of The outcome of surgical techniques for spondylodiscitis Jessica Burton@, Thamer Hamdan*, Bisola Ajayi#, Mohsen Raza$, Angelo Fragkakis&, Cristina Lupu^, Timothy Bishop%, Jason Bernard! & Darren Lui**. @MB,ChB student. *Professor of Orthopaedic Surgery at Basrah University, Visiting Professor at London Imperial College and Research Fellow as Saint George’s Hospital London. #Orthopaedic and Spine Physician Associate. $Orthopaedic Registrar. &Spine Fellow. ^ Spine CNS. %Orthopaedic Spinal Surgeon. !Orthopaedic Spinal Surgeon. **Orthopaedic Spinal Surgeon. Department of Trauma and Orthopaedics, Saint George’s University Hospital, London, UK. Abstract Spondylodiscitis is an infection of the intervertebral disc and neighbouring bone. It is treated conservatively or surgically using a range of techniques. The aim of this review is to determine whether the surgical techniques between different countries have an effect on clinical outcome: postoperative complications, relapse rate, treatment failure rate or mortality rate. Many articles were screened using Ovid and Pubmed databases for studies pertaining to the surgical treatment of spondylodiscitis. Paediatric studies, tubercular/brucellar/fungal/ postoperative infection and case reports were excluded from this review. The results shows that no differences in the outcome of surgery between countries was found, and reasons for this along with solutions for moving forward with comparing surgical techniques worldwide are noted. Key words: Spondylodiscitis, Surgery, Outcome, Comparison, Literature review