A convenient viral transduction based method for advanced multi-engineering of primary human (CAR) T-cells.

The past decades have illustrated the power of T-cell engineering in the development of new and successful cell therapies, such as chimeric antigen receptor (CAR) T-cells. Despite clinical success in hematological malignancies, it also becomes increasingly clear that additional T-cell engineering will be required to improve efficacy and safety and expand the application to solid tumors. Engineering is most often achieved by viral delivery of transgenes, however, viral vector capacity limitations make efficient and reproducible generation of multi transgene expressing T-cell therapeutics technically challenging.

Detecting Colorectal Neoplasia Using Specific Fecal Fluorogenic Protease-Sensitive Substrates: A Pilot Study.

Background: identification and removal of advanced adenomas (AA) reduce colorectal cancer (CRC) incidence and potentially mortality. CRC screening often uses fecal immunochemical testing to select high-risk individuals for colonoscopy, despite its low sensitivity for AA and relatively high false-positivity rate. Previous studies have linked proteases to CRC development through their ability to facilitate angiogenesis and immunoregulation.

Comparing the construct validity of measurement instruments for pain and stiffness in patients with axial spondyloartwhritis: cross-sectional analysis in the OASIS cohort.

Objectives: To compare the construct validity, including discrimination between known groups, of three pain and three morning stiffness (MS) measurement instruments.

Methods: Patients with radiographic axial spondyloarthritis with 8-year data from the Outcome in Ankylosing Spondylitis International Study cohort were assessed cross-sectionally. Three instruments for pain and three for MS, all self-reported and scored 0-10, were compared.

Lymph nodes as gatekeepers of autoimmune diseases.

Secondary lymphoid organs such as lymph nodes (LNs) are the home of peripheral tolerance mechanisms which control autoreactive T cells and prevent immune responses to self-antigen. In systemic autoimmunity, there is a clear failure of these peripheral tolerance mechanisms that leads to chronic inflammation and tissue destruction, highlighting the role for LNs as possible gatekeepers of autoimmunity. In recent years there has been a shift in research focus towards tissue sites in autoimmune diseases ranging from type 1 diabetes to rheumatoid arthritis in an effort to better characterise pathogenesis and guide diagnostic and therapeutic decisions.

Sex differences in the efficacy of angiotensin receptor blockers on kidney and cardiovascular outcomes among individuals with type 2 diabetes and diabetic kidney disease: post hoc analyses of the RENAAL and IDNT trials.

Aims/hypothesis: Our aim was to assess sex differences in the efficacy of angiotensin receptor blockers (i.e. losartan and irbesartan) on kidney and cardiovascular outcomes in individuals with type 2 diabetes and diabetic kidney disease.

Course of hand pain over four years in patients with hand osteoarthritis depends on BMI, employment and mental wellbeing: The Hand OSTeoArthritis in Secondary care cohort study.

Objective: We aimed to characterize hand osteoarthritis (OA) patients with deteriorating or improving hand pain, and to investigate patients achieving good clinical outcome after four years.

Methods: We used four year annual Australian/Canadian hand osteoarthritis index (AUSCAN) pain subscale (range 0-20) measurements from the HOSTAS cohort (hand OA patients). Pain changes were categorized as deterioration, stable and improvement using the Minimal Clinical Important Improvement (MCII).

Longitudinal assessment of immunoglobulin response and disease progression in critically ill patients with community acquired pneumonia.

Background: Low endogenous immunoglobulin(Ig)-levels are common in critically ill patients with sepsis, but it is unknown whether low Ig-levels are associated with poor outcome, and in which patients Ig-replacement therapy (IgRT) improves outcome. Given the crucial role of immunoglobulins in eliminating certain encapsulated pathogens, we examined the relationship between serial Ig-levels and disease course in critically ill patients with community acquired pneumonia (sCAP) caused by encapsulated or other pathogens.

Methods: We included a cohort of consecutive critically ill patients with CAP, and PaO/FiO-ratio < 200 with or without septic shock, from an existing biorepository where microbiological causes of infection had been adjudicated in a protocolized manner.

Predictors of dropping out from a home tele-exercise programme: A cohort study derived from a randomised controlled trial.

Background: Online home exercises represent opportunities to increase physical activity levels. However, high dropout rates are commonly reported in such programmes. This study aimed to investigate the predictors of dropping out from an online home exercise programme.

Impact of bimekizumab and certolizumab pegol on efficacy, safety and osteoblastic activity in radiographic axial spondyloarthritis: results from a phase IIa, multicentre, randomised, double-blind, exploratory study with PET-CT imaging.

Background: The efficacy and safety of bimekizumab (BKZ), an inhibitor of interleukin (IL)-17F in addition to IL-17A, has been established in axial spondyloarthritis (axSpA). Early assessment of new bone formation is possible using F-fluoride positron emission tomography-computerised tomography (PET-CT) imaging to quantitatively monitor osteoblastic activity.

Objectives: This exploratory study, initiated before phase IIb/III studies, assessed the efficacy and safety of BKZ in patients with radiographic (r-)axSpA and its effect on new bone formation.

Expert consensus recommendations for the diagnosis and treatment of chronic non-bacterial osteitis (CNO) in adults.

Background: There is considerable practice variation in labelling, diagnosis and treatment of adults with sterile bone inflammation. We developed a expert consensus recommendations on the disease definition, diagnosis and treatment of this rare condition.

Methods: Systematic literature review and Grading of Recommendations, Assessment, Development and Evaluations-based appraisal of evidence, two Delphi surveys and three digital and in-person consensus meetings with a multidisciplinary expert panel and patient representatives.

Computerized decision support to optimally funnel patients through the diagnostic pathway for dementia.

Background: The increasing prevalence of dementia and the introduction of disease-modifying therapies (DMTs) highlight the need for efficient diagnostic pathways in memory clinics. We present a data-driven approach to efficiently guide stepwise diagnostic testing for three clinical scenarios: 1) syndrome diagnosis, 2) etiological diagnosis, and 3) eligibility for DMT.

Methods: We used data from two memory clinic cohorts (ADC, PredictND), including 504 patients with dementia (302 Alzheimer's disease, 107 frontotemporal dementia, 35 vascular dementia, 60 dementia with Lewy bodies), 191 patients with mild cognitive impairment, and 188 cognitively normal controls (CN).

Utilization of hematopoietic cell transplantation and cellular therapy technology in Europe and associated Countries. Using the 2022 activity survey data to correlate with economic and demographic factors. A report from the EBMT.

We looked at treatment rates and center density across countries for patients treated in 2022; 46,143 HCTs (19,011 (41.2%) allogeneic, 27,132 (58.8%) autologous) reported by 689 centers.

Heterozygous BTNL8 variants in individuals with multisystem inflammatory syndrome in children (MIS-C).

Multisystem inflammatory syndrome in children (MIS-C) is a rare condition following SARS-CoV-2 infection associated with intestinal manifestations. Genetic predisposition, including inborn errors of the OAS-RNAseL pathway, has been reported. We sequenced 154 MIS-C patients and utilized a novel statistical framework of gene burden analysis, "burdenMC," which identified an enrichment for rare predicted-deleterious variants in BTNL8 (OR = 4.

Implications of the microbiome after pancreatic cancer resection with regard to morbidity and mortality.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with an extremely poor prognosis. The most common complications after a pancreaticoduodenectomy (PD) include surgical site infection (SSI), postoperative pancreatic fistula (POPF), and delayed gastric emptying (DGE). The potential role and mechanisms of microbial colonization of key surgical sites resulting in perioperative complications after PD remain to be fully elucidated.

Type I interferon biomarker in idiopathic inflammatory myopathies: associations of Siglec-1 with disease activity and treatment response.

Objectives: Novel biomarkers are needed to guide therapy in idiopathic inflammatory myopathies (IIM). Expression of Siglec-1, a type I interferon biomarker, was examined in adult patients with IIM in relation to disease activity and treatment response.

Methods: We analysed PBMC samples from 19 newly diagnosed adult IIM patients who participated in a phase-2 pilot study on efficacy of intravenous immunoglobulin (IVIG) monotherapy, and from 9 healthy controls.

Autoantibodies against a subunit of mitochondrial respiratory chain complex I in inclusion body myositis.

Background: Autoantibodies are found in up to 80 % of patients with idiopathic inflammatory myopathies (IIM) and are associated with distinct clinical phenotypes. Autoantibodies targeting cytosolic 5'-nucleotidase 1A (anti-NT5C1A) are currently the only known serum biomarker for the subgroup inclusion body myositis (IBM), although detected even in other autoimmune diseases. The aim of the study was to identify new autoimmune targets in IIM.

International study to develop a patient-reported outcome measure to evaluate outcomes of gender-affirming care - the GENDER-Q.

Background: To meaningfully understand outcomes of gender-affirming care, patient-reported outcome measures (PROMs) that are grounded in what matters to individuals seeking care are urgently needed. The objective of this study was to develop a comprehensive PROM to assess outcomes of gender-affirming care in clinical practice, research, and quality initiatives (the GENDER-Q).

Methods: Internationally established guidelines for PROM development were used to create a field test version of the GENDER-Q.

Use of Adaptive Conjoint Analysis-Based Values Clarification in a Patient Decision Aid Is Not Associated with Better Perceived Values Clarity or Reduced Decisional Conflict but Enhances Values Congruence.

Background: Evidence is lacking on the most effective values clarification methods (VCMs) in patient decision aids (PtDAs). We tested the effects of an adaptive conjoint analysis (ACA)-based VCM compared with a ranking-based VCM and no VCM on several decision-related outcomes, with the decisional conflict and its subscale "perceived values clarity" as primary outcomes.

Design: Online experimental study with 3 conditions: no VCM versus ranking-based VCM versus -based VCM ( = 282; = 63.