International myeloma working group immunotherapy committee recommendation on sequencing immunotherapy for treatment of multiple myeloma.

T-cell redirecting therapy (TCRT), specifically chimeric antigen receptor T-cell therapy (CAR T-cells) and bispecific T-cell engagers (TCEs) represent a remarkable advance in the treatment of multiple myeloma (MM). There are several products available around the world and several more in development targeting primarily B-cell maturation antigen (BCMA) and G protein-coupled receptor class C group 5 member D (GRPC5D). The relatively rapid availability of multiple immunotherapies brings the necessity to understand how a certain agent may affect the safety and efficacy of a subsequent immunotherapy so MM physicians and patients can aim at optimal sequential use of these therapies.

Translation of PET radiotracers for cancer imaging: recommendations from the National Cancer Imaging Translational Accelerator (NCITA) consensus meeting.

Background: The clinical translation of positron emission tomography (PET) radiotracers for cancer management presents complex challenges. We have developed consensus-based recommendations for preclinical and clinical assessment of novel and established radiotracers, applied to image different cancer types, to improve the standardisation of translational methodologies and accelerate clinical implementation.

Methods: A consensus process was developed using the RAND/UCLA Appropriateness Method (RAM) to gather insights from a multidisciplinary panel of 38 key stakeholders on the appropriateness of preclinical and clinical methodologies and stakeholder engagement for PET radiotracer translation.

Ravulizumab demonstrates long-term efficacy, safety and favorable patient survival in patients with paroxysmal nocturnal hemoglobinuria.

Ravulizumab is a second-generation complement component 5 (C5) inhibitor (C5i) approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) following positive results from two pivotal trials in patients with PNH originally naive to C5i treatment and eculizumab-experienced patients with PNH. In both trials, after the 26week primary evaluation period, all patients received ravulizumab for up to 6 years. To report ravulizumab treatment outcomes in patients with PNH originally naive to C5i treatment and eculizumab-experienced patients with PNH treated for up to 6 years.

Prevalence and potential implications of HPV infection in transgender women with gender reaffirming genital surgery: a systematic literature review and meta-analysis.

Background: Human papillomavirus (HPV) is a common infection of the anogenital tract. Although most infections clear, persistent infections with oncogenic types can predispose to cancer. While the natural history of anogenital HPV infection in cisgendered women is relatively well understood, there are significant knowledge gaps regarding HPV prevalence and clinical implications of genital HPV infection in transgender women (TGW) with neovagina(s).

Pharmacokinetic characterization and exposure-response relationship of crovalimab in the COMMODORE 1, 2 and 3 and COMPOSER trials of patients with paroxysmal nocturnal haemoglobinuria.

Aims: Crovalimab is a novel C5 inhibitor administered first intravenously and then subcutaneously in patients with paroxysmal nocturnal haemoglobinuria (PNH) naive to complement inhibition or switching from eculizumab or ravulizumab. Crovalimab showed efficacy and safety comparable to eculizumab in the pivotal COMMODORE 2 and supporting studies.

Methods: We characterized crovalimab pharmacokinetics and the relationship between exposure pharmacokinetic parameters and pharmacodynamic biomarkers, efficacy and safety endpoints using pooled data (healthy volunteers [n = 9], naive [n = 210] and switched [n = 211] patients).

Fluoxetine and fractures after stroke: an individual patient data meta-analysis of three large randomised controlled trials of fluoxetine for stroke recovery.

Background: Observational studies have shown that selective serotonin reuptake inhibitors are associated with an increased risk of bone fractures, but the association can be confounded by indication and other sources of systematic bias that can be minimised in randomised controlled trials (RCTs).

Aim: Our aim was to report the rate, site, context, and predictors of fractures after stroke, and whether the fractures modified the effect of fluoxetine on modified Rankin score (mRS) at six months in an individual patient data meta-analysis of 5907 patients enrolled in three RCTs of fluoxetine (20mg for six months) for stroke recovery.

Methods: We classified fractures by treatment allocation, site (and thus likelihood of osteoporosis) and context, then performed multivariable analyses to explore independent predictors of fractures.

Safety and humoral immunogenicity of the ChAdOx1 nCoV-19 vaccine administered as a fourth dose booster following two doses of ChAdOx1 nCoV-19 and a third dose of BNT162b2 (COV009): A prospective cohort study.

Objectives: Evaluation of the safety and humoral immunogenicity of ChAdOx1 nCoV-19 as a fourth dose booster in individuals who have had two initial doses of the vaccine and a third dose of BNT162b2.

Methods: COV009 is a safety follow-up study of volunteers enroled in the pivotal pre-licensure ChAdOx1 nCoV-19. In this sub-study, 149 eligible participants were given a fourth dose of ChAdOx1 nCoV-19.

Patient and public involvement in the design and protocol development for a platform randomised trial to evaluate diagnostic tests to optimise antimicrobial therapy (PROTECT).

Background: Our patient and public involvement activities were part of a project aiming to develop a master protocol and National Institute for Health and Care research application for the PROTECT trial aiming to assess the effectiveness, implementation, and efficiency of antimicrobial stewardship interventions, to safely reduce unnecessary antibiotic usage by excluding severe bacterial infection in acutely unwell patients.

Methods: Three public involvement sessions were held with representation from young people and parents, people from diverse backgrounds and people with experience of presenting to the emergency department with undifferentiated illness. The teleconference meetings lasted between 60-90 minutes, were recorded, notes were subsequently taken, and findings summarised.

Baricitinib dose reduction in patients with rheumatoid arthritis achieving sustained disease control: Final results from the RA-BEYOND study.

Objective: This study examines the impact of dose step-down in patients with rheumatoid arthritis (RA) who achieved sustained disease control with baricitinib 4-mg once-daily up to 96-weeks.

Methods: Patients who completed a baricitinib phase 3 study could enter a long-term extension (LTE). In the LTE, patients who received baricitinib 4-mg for ≥15 months and maintained clinical disease activity index (CDAI) low disease activity (LDA) or remission (REM) were blindly randomized to continue 4-mg or taper to 2-mg.

International Society of Sports Nutrition Position Stand: Long-Chain Omega-3 Polyunsaturated Fatty Acids.

Position Statement: The International Society of Sports Nutrition (ISSN) presents this position based on a critical examination of the literature surrounding the effects of long-chain omega-3 polyunsaturated fatty acid (ω-3 PUFA) supplementation on exercise performance, recovery, and brain health. This position stand is intended to provide a scientific foundation for athletes, dietitians, trainers, and other practitioners regarding the effects of supplemental ω-3 PUFA in healthy and athletic populations. The following conclusions represent the official position of the ISSN: Athletes may be at a higher risk for ω-3 PUFA insufficiency.

Evaluation of a novel malaria anti-sporozoite vaccine candidate, R21 in Matrix-M adjuvant, in the UK and Burkina Faso: two phase 1, first-in-human trials.

Background: Malaria remains a substantial public health burden among young children in sub-Saharan Africa and a highly efficacious vaccine eliciting a durable immune response would be a useful tool for controlling malaria. R21 is a malaria vaccine comprising nanoparticles, formed from a circumsporozoite protein and hepatitis B surface antigen (HBsAg) fusion protein, without any unfused HBsAg, and is administered with the saponin-based Matrix-M adjuvant. This study aimed to assess the safety and immunogenicity of the malaria vaccine candidate, R21, administered with or without adjuvant Matrix-M in adults naïve to malaria infection and in healthy adults from malaria endemic areas.

R21 in Matrix-M adjuvant in UK malaria-naive adult men and non-pregnant women aged 18-45 years: an open-label, partially blinded, phase 1-2a controlled human malaria infection study.

Background: R21 is a novel malaria vaccine, composed of a fusion protein of the malaria circumsporozoite protein and hepatitis B surface antigen. Following favourable safety and immunogenicity in a phase 1 study, we aimed to assess the efficacy of R21 administered with Matrix-M (R21/MM) against clinical malaria in adults from the UK who were malaria naive in a controlled human malaria infection study.

Methods: In this open-label, partially blinded, phase 1-2A controlled human malaria infection study undertaken in Oxford, Southampton, and London, UK, we tested five novel vaccination regimens of R21/MM.

Procalcitonin-guided duration of antibiotic treatment in children hospitalised with confirmed or suspected bacterial infection in the UK (BATCH): a pragmatic, multicentre, open-label, two-arm, individually randomised, controlled trial.

Background: Procalcitonin is a rapid response biomarker specific for bacterial infection, which is not routinely used in the UK National Health Service. We aimed to assess whether using a procalcitonin-guided algorithm would safely reduce the duration of antibiotic therapy compared with usual care, in which C-reactive protein is the commonly used biomarker.

Methods: The BATCH trial was a pragmatic, multicentre, open-label, parallel, two-arm, individually randomised, controlled trial conducted in 15 hospitals in England and Wales.

Autologous macrophage therapy for liver cirrhosis: a phase 2 open-label randomized controlled trial.

Cirrhosis is a major cause of morbidity and mortality; however, there are no approved therapies except orthotopic liver transplantation. Preclinical studies showed that bone-marrow-derived macrophage injections reduce inflammation, resolve fibrosis and stimulate liver regeneration. In a multicenter, open-label, parallel-group, phase 2 randomized controlled trial ( ISRCTN10368050 ) in n = 51 adult patients with compensated cirrhosis and Model for End-Stage Liver Disease (MELD) score ≥10 and ≤17, we evaluated the efficacy of autologous monocyte-derived macrophage therapy (n = 27) compared to standard medical care (n = 24).

Novel digital leakage notification system can promote better stoma management routines: a multicentre clinical trial.

Background: Most people with a stoma are anxious about stoma-related leakage.

Aims: To investigate the impact of a novel digital leakage notification system on worry related to stoma leakage, and to evaluate the effect on overall stoma care management.

Method: A 12-week interventional, single-arm, multicentre study was conducted in the UK to evaluate the novel digital leakage notification system, including a telemedicine-based support service (=test product), as part of routine stoma care in patients with a recent stoma formation (ClinicalTrials.

Kinetic Oscillation Stimulation for the Preventive Treatment of Chronic Migraine: A Randomized, Double-Blind, Sham-Controlled Trial.

Background And Objectives: The Chordate System administers kinetic oscillation stimulation (K.O.S) into the nasal cavity thereby potentially modulating the activity of trigemino-autonomic reflex.

Risk-Based Screening of Atrial Fibrillation in General Practice (R-BEAT): A randomised Cross-over Trial.

Background: The optimal approach to the diagnosis of atrial fibrillation in primary care is unclear.

Aim: To determine if external loop recorder (ELR) screening improves atrial fibrillation detection in community dwelling adults with a CHA2DS2-VASc score of greater than two.

Design: Randomised cross-over clinical trial.

Developing an adaptive paediatric intensive care unit platform trial with key stakeholders: a qualitative study.

Objectives: Platform trials were used successfully in adult populations during the COVID-19 pandemic. By testing multiple treatments within a single trial, platform trials can help identify the most effective treatments (and any interactions between treatments) for patients more quickly and with less burden for patients and their families. The aim of this qualitative research was to inform the design of the first adaptive platform trial for paediatric intensive care in the UK with young people, parents/carers and paediatric intensive care unit (PICU) staff.

Association of real life postural transitions kinematics with fatigue in neurodegenerative and immune diseases.

Fatigue is prevalent in immune-mediated inflammatory and neurodegenerative diseases, yet its assessment relies largely on patient-reported outcomes, which capture perception but not fluctuations over time. Wearable sensors, like inertial measurement units (IMUs), offer a way to monitor daily activities and evaluate functional capacity. This study investigates the relationship between sit-to-stand and stand-to-sit transitions and self-reported physical and mental fatigue in participants with Parkinson's, Huntington's, rheumatoid arthritis, systemic lupus erythematosus, primary Sjögren's syndrome and inflammatory bowel disease.

Experimental medicine study with stabilised native-like HIV-1 Env immunogens drives long-term antibody responses, but lacks neutralising breadth.

Background: We report findings from an experimental medicine study of rationally designed prefusion stabilised native-like HIV envelope glycoprotein (Env) immunogens, representative of global circulating strains, delivered by sequential intramuscular injection.

Methods: Healthy adult volunteers were enrolled into one of five groups (A to E) each receiving a different schedule of one of two consensus Env immunogens (ConM SOSIP, ConS UFO, either unmodified or stabilised by chemical cross-linking, followed by a boost with two mosaic Env immunogens (Mos3.1 and Mos3.

Molecular and spatial analysis of tertiary lymphoid structures in Sjogren's syndrome.

Tertiary lymphoid structures play important roles in autoimmune and non-autoimmune conditions. While many of the molecular mechanisms involved in tertiary lymphoid structure formation have been identified, the cellular sources and temporal and spatial relationship remain unknown. Here we use combine single-cell RNA-sequencing, spatial transcriptomics and proteomics of minor salivary glands of patients with Sjogren's disease and Sicca Syndrome, with ex-vivo functional studies to construct a cellular and spatial map of key components involved in the formation and function of tertiary lymphoid structures.

Review of methodology and re-analysis of lipidomic data focusing on specialised pro-resolution lipid mediators (SPMs) in a human model of resolving inflammation.

Using a model of UV-killed E. coli driven dermal inflammation in healthy human volunteers, we originally reported that following inflammatory resolution there was infiltration of macrophages, which, through prostanoids including prostaglandin (PG) E, imprints long-term tissue immunity. In addition to the prostanoids, data on levels of Specialised Pro-Resolution Lipid Mediators (SPMs) throughout inflammatory onset, resolution and post-resolution phases of this model were presented, but as illustrations rather than as primary data.

Triangulating evidence from the GALENOS living systematic review on trace amine-associated receptor 1 (TAAR1) agonists in psychosis.

Background: Trace amine-associated receptor 1 (TAAR1) agonists offer a new approach, but there is uncertainty regarding their effects, exact mechanism of action and potential role in treating psychosis.

Aims: To evaluate the available evidence on TAAR1 agonists in psychosis, using triangulation of the output of living systematic reviews (LSRs) of animal and human studies, and provide recommendations for future research prioritisation.

Method: This study is part of GALENOS (Global Alliance for Living Evidence on aNxiety, depressiOn and pSychosis).

Effect of time and temperature on the stability of HPV and cellular nucleic acid using simulated dry self-samples.

Background: Self-sampling is now a key component within HPV-based cervical screening programmes to engage individuals and enhance participation. As self-sampling is relatively new, information on the influence of pre-analytical parameters such as transit-temperature and time between sampling and testing on HPV test results requires detailed investigation.

Methods: FLOQSwabs® and Evalyn Brushes® were used to assess HPV and cellular stability over a 30-week period (0w,4w,12w,30w) at 4 °C, ambient, and 37 °C.