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Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50-64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.

Aims/hypothesis Obesity surgery (OS) and diet-induced weight loss rapidly improve insulin resistance. We aim to investi-gate the impact of either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) surgery compared with a diet lowin energy (low-calorie diet; LCD) on body composition, glucose control and insulin sensitivity, assessed both at the globaland tissue-specific level in individuals with obesity but not diabetes. Methods In this parallel group randomised controlled trial, patients on a waiting list for OS were randomised (no blinding,sealed envelopes) to either undergo surgery directly or undergo an LCD before surgery. At baseline and 4 weeks after surgery(n=15, 11 RYGB and 4 SG) or 4 weeks after the start of LCD (n=9), investigations were carried out, including an OGTTand hyperinsulinaemic–euglycaemic clamps during which concomitant simultaneous whole-body [ 18 F]fluorodeoxyglucose-positron emission tomography (PET)/MRI was performed. The primary outcome was HOMA-IR change. Results One month after bariatric surgery and initiation of LCD, both treatments induced similar reductions in body weight(mean ± SD: −7.7±1.4 kg and −7.4±2.2 kg, respectively), adipose tissue volume (7%) and liver fat content (2% units).HOMA-IR, a main endpoint, was significantly reduced following OS (−26.3% [95% CI −49.5, −3.0], p=0.009) and non-significantly following LCD (−20.9% [95% CI −58.2, 16.5). For both groups, there were similar reductions in triglyceridesand LDL-cholesterol. Fasting plasma glucose and insulin were also significantly reduced only following OS. There was anincrease in glucose AUC in response to an OGTT in the OS group (by 20%) but not in the LCD group. During hyperinsuli-naemia, only the OS group showed a significantly increased PET-derived glucose uptake rate in skeletal muscle but a reduceduptake in the heart and abdominal adipose tissue. Both liver and brain glucose uptake rates were unchanged after surgery orLCD. Whole-body glucose disposal and endog

BACKGROUND: Fatty acids may influence lean tissue volume and skeletal muscle function. We previously reported in young lean participants that overfeeding polyunsaturated fat (PUFA) compared with saturated fat (SFA) induced greater lean tissue accumulation despite similar weight gain. OBJECTIVE: In a double-blind randomized controlled trial (RCT), we aimed to investigate if the differential effects of overfeeding SFA and PUFA on lean tissue accumulation could be replicated in individuals with overweight, and identify potential determinants. Further, using substitution models, we investigated associations between SFA and PUFA levels with lean tissue volume, in a large population-based sample (UK Biobank). METHODS: Sixty-one males and females with overweight (BMI 27.3 (interquartile range 25.4 to 29.3), age 43 (interquartile range 36 to 48)) were overfed SFA (palm oil) or n-6 PUFA (sunflower oil) for 8 weeks. Lean tissue was assessed by magnetic resonance imaging (MRI). We had access to n=13849 participants with data on diet, covariates and MRI measurements of lean tissue, as well as 9119 participants with data on circulating fatty acids, in the UK Biobank. RESULTS: Body weight gain (mean±SD) was similar in PUFA (2.01±1.90 kg) and SFA (2.31±1.38 kg) groups. Lean tissue increased to a similar extent (0.54±0.93 L and 0.67±1.21 L for PUFA and SFA group, respectively, with a difference between groups of 0.07 (-0,21, 0,35)). We observed no differential effects on circulating amino acids, myostatin or interleukin-15 and no clear determinants of lean tissue accumulation. Similar non-significant results for SFA and PUFA were observed in UK Biobank, but circulating fatty acids demonstrated ambiguous and sex-dependent associations. CONCLUSION: Overfeeding SFA or PUFA does not differentially affect lean tissue accumulation during 8 weeks in individuals with overweight. A lack of dietary fat type-specific effects on lean tissue is supported by specified substitution models in a la

Purpose: Although CD19 chimeric antigen receptor T cells (CAR-T) therapy has shown remarkable success in B-cell malignancies, a substantial fraction of patients do not obtain a long-term clinical response. This could be influenced by the quality of the individual CAR-T infusion product. To shed some light on this, clinical outcome was correlated to characteristics of CAR-T infusion products. Patients and Methods: In this phase II study, patients with B-cell lymphoma (n ¼ 23) or leukemia (n ¼ 1) received one or two infusions of third-generation CD19-directed CAR-Ts (2 × 108/m2). The clinical trial was registered at clinicaltrials. gov: NCT03068416. We investigated the transcriptional profile of individual CD19 CAR-T infusion products using targeted single-cell RNA sequencing and multicolor flow cytometry. Results: Two CAR-T infusions were not better than one in the settings used in this study. As for the CAR-T infusion products, we found that effector-like CD8þCAR-Ts with a high polyfunctionality, high cytotoxic and cytokine production profile, and low dysfunctional signature were associated with clinical response. An extended ex vivo expansion time during CAR-T manufacturing negatively influenced the proportion of effector CD8þCAR-Ts in the infusion product. Conclusions: We identified cell-intrinsic characteristics of effector CD8þCAR-Ts correlating with response that could be used as an indicator for clinical outcome. The results in the study also serve as a guide to CAR-T manufacturing practices. ©2023 The Authors; Published by the American Association for Cancer Research., Funding Agencies|Swedish Research Council [2019-01326, 2019-01721]; Swedish Cancer Society [19 0184Pj, 20 0756 PjF, 20 1303 PjF]; AFA Insurance for regenerative medicine; Lions Cancer Fund at Uppsala University Hospital; Swedish State Support for Clinical Research; Barncancerfonden [TJ 2019-0014]; Knut and Alice Wallenberg Foundation, National Bioinformatics Infrastructure Sweden at SciLifeLab [KAW 2017.0003]

Diffusion weighted magnetic resonance imaging (DW-MRI) technique probing the microscopic movement of water molecules in tissue, allows for the quantification of water diffusivity and the contribution of perfusion to the total amount of water. In the last decades, its use in organs other than the brain has increased and it has successfully been applied to abdominal organs; otherwise the use of DWI for the assessment of perfusion (by measuring perfusion fraction and edema (by measuring the apparent diffusion coefficient-ADC) of entire organs is not a clinical standard. The aim of this paper is to assess whether DWI, specifically IVIM, can accurately assess edema (the amount of water contained in a tissue) and perfusion in abdominal organs (liver, spleen, intestine and kidneys) in an endotoxemic porcine model. Endotoxemia was induced in 20 piglets and they were divided into three groups: HM group (HighMAP, mean arterial pressure was maintained >65 mmHg by noradrenaline infusion), LM group (LowMAP, MAP was maintained between 50 and 60 mmHg) and LTD (the thoracic duct was ligated to increase abdominal edema). In addition, a fourth group of healthy controls (four animals) underwent MRI. Edema was also assessed by wet-dry weight in liver, spleen and intestine; and perfusion was assessed by hemodynamics, lactate concentration and SvO(2). ADC was found to be higher in the intestine of the LTD group compared with the other groups, in accordance with wet-dry weight. In addition, ADC in kidneys was found to be correlated to glomerular filtration rate. f was correlated with hemodynamics in kidneys and liver. The presented data show that there is a potential for clinical use of the technique in septic patients.

The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote the science, technology, and practical application of nuclear medicine. The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association that facilitates communication worldwide between individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. The merged International Society for Magnetic Resonance in Medicine (ISMRM) is an international, nonprofit, scientific association whose purpose is to promote communication, research, development, and applications in the field of magnetic resonance in medicine and biology and other related topics and to develop and provide channels and facilities for continuing education in the field.The ISMRM was founded in 1994 through the merger of the Society of Magnetic Resonance in Medicine and the Society of Magnetic Resonance Imaging. SNMMI, ISMRM, and EANM members are physicians, technologists, and scientists specializing in the research and practice of nuclear medicine and/or magnetic resonance imaging. The SNMMI, ISMRM, and EANM will periodically define new guidelines for nuclear medicine practice to help advance the science of nuclear medicine and/or magnetic resonance imaging and to improve the quality of service to patients throughout the world. Existing practice guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated. Each practice guideline, representing a policy statement by the SNMMI/EANM/ISMRM, has undergone a thorough consensus process in which it has been subjected to extensive review. The SNMMI, ISMRM, and EANM recognize that the safe and effective use of diagnostic nuclear medicine imaging and magnetic resonance imaging requires specific training, skills, and techniques, as described in each document. Reproduction or modification