In vivo dendritic cell reprogramming for cancer immunotherapy.

Immunotherapy can lead to long-term survival for some cancer patients, yet generalized success has been hampered by insufficient antigen presentation and exclusion of immunogenic cells from the tumor microenvironment. Here, we developed an approach to reprogram tumor cells in vivo by adenoviral delivery of the transcription factors PU.1, IRF8, and BATF3, which enabled them to present antigens as type 1 conventional dendritic cells.

A survey of experts to identify methods to detect problematic studies: stage 1 of the INveStigating ProblEmatic Clinical Trials in Systematic Reviews project.

Background And Objective: Randomized controlled trials (RCTs) inform health-care decisions. Unfortunately, some published RCTs contain false data, and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesize all RCTs which have been conducted on a given topic.

Therapeutic Effects of Heart Failure Medical Therapies on Standardized Kidney Outcomes: Comprehensive Individual Participant-Level Analysis of 6 Randomized Clinical Trials.

Background: Kidney outcomes have been variably defined using nonstandardized composite end points in key heart failure trials, thus introducing complexity in their interpretation and cross-trial comparability. We examined the effects of steroidal mineralocorticoid receptor antagonists, the angiotensin receptor-neprilysin inhibitor sacubitril/valsartan, and SGLT2 (sodium-glucose cotransporter-2) inhibitors on composite kidney end points using uniform definitions in 6 contemporary heart failure trials.

Methods: Individual participant-level data from trials of steroidal mineralocorticoid receptor antagonists (EMPHASIS-HF [Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure], TOPCAT [Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist] Americas), angiotensin receptor-neprilysin inhibitor (PARADIGM-HF [Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure], PARAGON-HF [Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin-Receptor Blockers Global Outcomes in HF With Preserved Ejection Fraction]), and SGLT2 inhibitors (DAPA-HF [Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure], DELIVER [Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure]) were included.

Nutrient Status and Intakes of Adults with Phenylketonuria.

A phenylalanine-restricted diet, supplemented with protein substitutes (PSs), remains the cornerstone of phenylketonuria (PKU) management. However, adherence is challenging in adulthood, and data on the nutritional status of early and continuously treated adults with PKU (ETAwPKU) are scarce. A total of 34 ETAwPKU (16 females; mean ± SD, age: 28 ± 9 years, phenylalanine concentration: 847 ± 285 µmol/L) and 34 age- and sex-matched control subjects were compared regarding their blood nutrient status, self-reported dietary intake, and cognitive wellbeing.

Nucleoside/nucleotide reverse transcriptase inhibitor-associated weight gain in people living with HIV: data from the Copenhagen Comorbidity in HIV Infection (COCOMO) study.

Weight gain effects of Nucleoside/Nucleotide Reverse Transcriptase Inhibitors in people with HIV (PWH) have been sparsely studied.Participants were enrolled in the Copenhagen Comorbidity in HIV Infection (COCOMO) study. PWH receiving a backbone of emtricitabine, or lamivudine combined with abacavir, tenofovir disoproxil, or tenofovir alafenamide were analysed.

Quality of Life and Exercise Capacity in Early Stage and Subclinical Hypertrophic Cardiomyopathy: A Secondary Analysis of the VANISH Trial.

Background: The health-related quality of life (HRQOL) and cardiopulmonary exercise testing (CPET) performance of individuals with subclinical and early stage hypertrophic cardiomyopathy (HCM) have not been systematically studied. Improved understanding will inform the natural history of HCM and factors influencing well-being.

Methods: VANISH trial (Valsartan for Attenuating Disease Evolution in Early Sarcomeric HCM) participants with early stage sarcomeric HCM (primary analysis cohort) and subclinical HCM (sarcomere variant without left ventricular hypertrophy comprising the exploratory cohort) who completed baseline and year 2 HRQOL assessment via the pediatric quality of life inventory and CPET were studied.

Effect of ghrelin on glucose tolerance, gut hormones, appetite, and food intake after sleeve gastrectomy.

Ghrelin is an appetite-stimulating hormone secreted from the gastric mucosa in the fasting state, and secretion decreases in response to food intake. After sleeve gastrectomy (SG), plasma concentrations of ghrelin decrease markedly. Whether this affects appetite and glucose tolerance postoperatively is unknown.

Aryl hydrocarbon receptor repressor ( AHRR ) methylation predicts risk of vascular disease: A cohort study of the general population.

Aims: Smoking is a risk factor for cardiovascular disease, but there is currently no clinically established biomarker for its cardiovascular damage. We aimed to investigate the hypothesis that aryl hydrocarbon receptor repressor ( AHRR ) methylation at CpG site cg05575921, a biomarker of smoking behavior, is associated with the risk of peripheral artery disease (PAD) and aortic aneurysm (AA) in the general population.

Methods And Results: In this prospective cohort study of the general population, we measured AHRR methylation in individuals from three visits to the Copenhagen City Heart Study.

NSGO-OV-UMB1/ENGOT-OV30: A phase II study of durvalumab in combination with the anti-CD73 monoclonal antibody Oleclumab in patients with relapsed ovarian cancer.

Objectives: In patients with epithelial ovarian cancer (EOC), the clinical efficacy of monotherapy with immune checkpoint inhibitors (ICIs) against PD-1/PD-L1 is modest. To enhance response rates to these immunotherapeutic agents and broaden the indications for their use, new approaches involving combinational therapy are needed. The immune regulator CD73 is a potential target, as it promotes tumor escape by producing immunosuppressive extracellular adenosine in the tumor microenvironment.

Acute Effects of Hallucinogens on Functional Connectivity: Psilocybin and Salvinorin-A.

The extent of changes in functional connectivity (FC) within functional networks as a common feature across hallucinogenic drug classes is under-explored. This work utilized fMRI to assess the dissociative hallucinogens Psilocybin, a classical serotonergic psychedelic, and Salvinorin-A, a kappa-opioid receptor (KOR) agonist, on resting-state FC in nonhuman primates. We highlight overlapping and differing influence of these substances on FC relative to the thalamus, claustrum, prefrontal cortex (PFC), default mode network (DMN), and DMN subcomponents.

No Effect of Methylnaltrexone on Acute Pancreatitis Severity: A Multicenter Randomized Controlled Trial.

Introduction: Opioids used to manage severe pain in acute pancreatitis (AP) might exacerbate the disease through effects on gastrointestinal and immune functions. Methylnaltrexone, a peripherally acting µ-opioid receptor antagonist, may counteract these effects without changing analgesia.

Methods: This double-blind, randomized, placebo-controlled trial included adult patients with AP and systemic inflammatory response syndrome at 4 Danish centers.

Accuracy of gross tumour volume delineation with [68Ga]-PSMA-PET compared to histopathology for high-risk prostate cancer.

Background: The delineation of intraprostatic lesions is vital for correct delivery of focal radiotherapy boost in patients with prostate cancer (PC). Errors in the delineation could translate into reduced tumour control and potentially increase the side effects. The purpose of this study is to compare PET-based delineation methods with histopathology.

Phenotypic Spectrum of Subclinical Sarcomere-Related Hypertrophic Cardiomyopathy and Transition to Overt Disease.

Genetic hypertrophic cardiomyopathy (HCM) is classically caused by pathogenic/likely pathogenic variants in sarcomere genes (G+). Currently, HCM is diagnosed if there is unexplained left ventricular (LV) hypertrophy with LV wall thickness ≥15 mm in probands or ≥13 mm in at-risk relatives. Although LV hypertrophy is a key feature, this binary metric does not encompass the full constellation of phenotypic features, particularly in the subclinical stage of the disease.

Impact of leaflet splitting on coronary access after redo-TAVI for degenerated supra-annular self-expanding platforms.

Background: Coronary access (CA) is a major concern in redo-transcatheter aortic valve implantation (TAVI) for failing supra-annular self-expanding transcatheter aortic valves (TAVs).

Aims: This ex vivo study evaluated the benefit of leaflet splitting (LS) on subsequent CA after redo-TAVI in anatomies deemed at high risk of unfeasible CA.

Methods: Ex vivo, patient-specific models were printed three-dimensionally.

Quantifying the relative importance of genetics and environment on the comorbidity between mental and cardiometabolic disorders using 17 million Scandinavians.

Mental disorders are leading causes of disability and premature death worldwide, partly due to high comorbidity with cardiometabolic disorders. Reasons for this comorbidity are still poorly understood. We leverage nation-wide health records and near-complete genealogies of Denmark and Sweden (n = 17 million) to reveal the genetic and environmental contributions underlying the observed comorbidity between six mental disorders and 15 cardiometabolic disorders.

Association of Cortical Lesions With Regional Glutamate, GABA, -Acetylaspartate, and Myoinositol Levels in Patients With Multiple Sclerosis.

Background And Objectives: Cortical lesions contribute to disability in multiple sclerosis (MS), but their impact on regional neurotransmitter levels remains to be clarified. We tested the hypothesis that cortical lesions are associated with regional glutamate and gamma-aminobutyric acid (GABA) concentrations within the affected cortical region.

Methods: In this cross-sectional study, we used structural 7T MRI to segment cortical lesions and 7T proton MR-spectroscopy of the bilateral sensorimotor hand areas to quantify regional GABA, glutamate, -acetylaspartate, and myoinositol concentrations in patients with MS (inclusion criteria: diagnosis of relapsing-remitting [RR] or secondary progressive MS [SPMS]; age 18-80 years) and age and sex-matched healthy controls.

Acromegaly management in the Nordic countries: A Delphi consensus survey.

Objective: Acromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist.