Roads to remission: evolving treatment concepts in type 2 inflammatory diseases.

Unlabelled: Non-communicable diseases (NCDs) characterised by type 2 inflammation, including asthma, allergic rhinitis, chronic rhinosinusitis with nasal polyps, atopic dermatitis, food allergies and eosinophilic esophagitis, are increasing in prevalence worldwide. Currently, there is a major paradigm shift in the management of these diseases, towards the concept of disease modification and the treatment goal remission, regardless of severity and age. Remission as a treatment goal in chronic inflammatory NCDs was first introduced in rheumatoid arthritis, and then adopted in other non-type 2 inflammatory diseases.

Medical Students' Acceptance of Tailored e-Mental Health Apps to Foster Their Mental Health: Cross-Sectional Study.

Background: Despite the high prevalence of mental health problems among medical students and physicians, help-seeking remains low. Digital mental health approaches offer beneficial opportunities to increase well-being, for example, via mobile apps.

Objective: This study aimed to assess the acceptance, and its underlying predictors, of tailored e-mental health apps among medical students by focusing on stress management and the promotion of personal skills.

The Intersection of Epigenetics and Senolytics in Mechanisms of Aging and Therapeutic Approaches.

The biological process of aging is influenced by a complex interplay of genetic, environmental, and epigenetic factors. Recent advancements in the fields of epigenetics and senolytics offer promising avenues for understanding and addressing age-related diseases. Epigenetics refers to heritable changes in gene expression without altering the DNA sequence, with mechanisms like DNA methylation, histone modification, and non-coding RNA regulation playing critical roles in aging.

Germline Single-Nucleotide Polymorphism Causes Alterations in Mitochondrial Metabolism and Leads to Increased ROS-Mediated DNA Damage in a Murine Model of Human Acute Myeloid Leukemia.

: GFI1-36N represents a single-nucleotide polymorphism (SNP) of the zinc finger protein Growth Factor Independence 1 (GFI1), in which the amino acid serine (S) is replaced by asparagine (N). The presence of the gene variant is associated with a reduced DNA repair capacity favoring myeloid leukemogenesis and leads to an inferior prognosis of acute myeloid leukemia (AML) patients. However, the underlying reasons for the reduced DNA repair capacity in leukemic cells are largely unknown.

Diurnal timing of physical activity in relation to obesity and diabetes in the German National Cohort (NAKO).

Background: Physical activity supports weight regulation and metabolic health, but its timing in relation to obesity and diabetes remains unclear. We aimed to assess the diurnal timing of physical activity and its association with obesity and diabetes.

Methods: We cross-sectionally analyzed hip-worn accelerometry data from 61,116 participants aged 20-75 in the German National Cohort between 2015 and 2019.

Consequences of COVID-19 for geriatric patients during a pandemic.

To investigate the outcomes of geriatric COVID-19 patients in a German academic setting during the pandemic. This study included 468 consecutive geriatric patients (≥ 70 years) who tested positive for SARS-CoV-2 and were treated at the University of Duisburg-Essen from 2/2020 to 3/2021. 74 patients were transferred to a geriatric hospital and a 12-month follow-up (prospective study) was performed in 51 patients.

Novel translational mouse models of Metabolic Dysfunction-associated steatotic liver disease comparable to human MASLD with severe obesity.

Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease, especially in patients with severe obesity. However, current mouse models for MASLD do not reflect the polygenetic background nor the metabolic changes in this population. Therefore, we investigated two novel mouse models of MASLD with a polygenetic background for the metabolic syndrome.

Phase 2 Randomised Study of Bulevirtide as Monotherapy or Combined With Peg-IFNα-2a as Treatment for Chronic Hepatitis Delta.

Background And Aim: Bulevirtide (BLV) leads to beneficial virologic and biochemical responses when given alone to treat hepatitis delta virus (HDV) infection, which causes the most severe form of chronic viral hepatitis. We evaluated 48 weeks of BLV monotherapy, BLV + tenofovir disoproxil fumarate (TDF) and BLV + pegylated interferon alfa-2a (Peg-IFNα-2a), with 24-week follow-up.

Methods: Ninety patients were enrolled into six arms of 15 each (A-F); 60 patients were included in the main randomisation (arms A-D), and 30 patients (arms E-F) were randomised to the extension phase: (A) Peg-IFNα-2a 180 μg once weekly (QW); (B) BLV 2 mg once daily (QD) + Peg-IFNα-2a 180 μg QW; (C) BLV 5 mg QD + Peg-IFNα-2a 180 μg QW; (D) BLV 2 mg QD; (E) BLV 10 mg QD + Peg-IFNα-2a 180 μg QW and (F) BLV 10 mg (5 mg twice daily) + TDF QD.

Artificial Intelligence in Cardiac Surgery: Transforming Outcomes and Shaping the Future.

Artificial intelligence (AI) has emerged as a transformative technology in healthcare, with its integration into cardiac surgery offering significant advancements in precision, efficiency, and patient outcomes. However, a comprehensive understanding of AI's applications, benefits, challenges, and future directions in cardiac surgery is needed to inform its safe and effective implementation. A systematic review was conducted following PRISMA guidelines.

Green Nuclear Medicine and Radiotheranostics.

There is a significantly growing interest in diagnostic and therapeutic radiopharmaceuticals, and it is foreseeable that an unprecedented number of patients will need to be treated with new nuclear medicine therapies. This predicted increase will have potentially significant environmental impacts. In this discussion, we show different areas of impact, as well as possible measures to reduce such impact.

Hypercholesterolemia triggers innate immune imbalance and transforms brain infarcts after ischemic stroke.

Post-stroke early activation of neutrophils contributes to intensive neuroinflammation and worsens disease outcomes. Other pre-existing patient conditions can modify the extent of their activation during disease, especially hypercholesterolemia. However, whether and how increased circulating cholesterol amounts can change neutrophil activation responses very early after stroke has not been studied.

The Importance of Preserving the Posterior Ligament Complex in Elective Lumbar Fusion Surgery: Early Results from a Single-Center Experience.

Background:  Adjacent segment disease (ASD) is a degenerative condition at the segment adjacent to a previously fused segment. Potential risk factors for ASD, such as posterior ligamentous complex (PLC) integrity between the upper instrumented vertebra (UIV) and the first unfused segment (UIV+1), have not been addressed. The objective of this study is to assess the PLC integrity between the UIV and UIV+1 following posterior lumbar decompression and fusion (PLDF).

Impact of visual presentation of atherosclerotic carotid plaque on cardiovascular risk profile using mHealth technologies.

This randomized, controlled trial evaluated the impact of plaque visualization combined with daily tasks on cardiovascular risk profile and included 240 participants with coronary arterial disease. The intervention group received the PreventiPlaque app during the 12-month study period in addition to standard care. The app contained daily tasks that promoted lifestyle modifications and adherence to prescribed medication.

Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

Evaluation of colour vision impairment during acute hypobaric hypoxia in aviation medicine: a randomized controlled trial.

The digitization of aircraft cockpits places high demands on the colour vision of pilots. The present study investigates colour vision changes upon acute exposure to hypobaric hypoxia. The digital Waggoner Computerized Color Vision Test and the Waggoner D-15 were performed by 54 healthy volunteers in a decompression chamber.

Disease-modifying strategies: Targeting protein kinases in multiple sclerosis and other autoimmune disorders.

A wide variety of immunomodulatory therapies are already available for the treatment of multiple sclerosis (MS). Through fundamental insights from basic research with a gain of knowledge in the pathological processes underlying MS, the exploration of additional medical compounds within clinical trials has been ignited. Emerging novel medications with innovative mechanisms of action are being introduced.

Perioperative Chemotherapy or Preoperative Chemoradiotherapy in Esophageal Cancer.

Background: The best multimodal approach for resectable locally advanced esophageal adenocarcinoma is unclear. An important question is whether perioperative chemotherapy is preferable to preoperative chemoradiotherapy.

Methods: In this phase 3, multicenter, randomized trial, we assigned in a 1:1 ratio patients with resectable esophageal adenocarcinoma to receive perioperative chemotherapy with FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) plus surgery or preoperative chemoradiotherapy (radiotherapy at a dose of 41.

Triiodothyronine treatment in mice improves stroke outcome and reduces blood-brain barrier damage.

Objective Thyroid hormones (TH) control a variety of processes in the central nervous system and influence its response to different stimuli, such as ischemic stroke. Post-stroke administration of 3,3',5-triiodo-L-thyronine (T3) has been reported to substantially improve outcomes, but the optimal dosage and time window remain elusive. Methods Stroke was induced in mice by transient middle cerebral artery occlusion (tMCAO) and T3 was administered at different doses and time points before and after stroke.

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.

Gemcitabine and ATR inhibitors synergize to kill PDAC cells by blocking DNA damage response.

The DNA-damaging agent Gemcitabine (GEM) is a first-line treatment for pancreatic cancer, but chemoresistance is frequently observed. Several clinical trials investigate the efficacy of GEM in combination with targeted drugs, including kinase inhibitors, but the experimental evidence for such rationale is often unclear. Here, we phenotypically screened 13 human pancreatic adenocarcinoma (PDAC) cell lines against GEM in combination with 146 clinical inhibitors and observed strong synergy for the ATR kinase inhibitor Elimusertib in most cell lines.

The Co-IMPACT Consortium: Integrating Prostate-specific Membrane Antigen Positron Emission Tomography and Radiotherapy in Prostate Cancer Care.

The Co-IMPACT consortium addresses knowledge gaps in prostate-specific membrane antigen positron emission tomography-guided radiotherapy for prostate cancer by establishing a global database (46 centres from 16 countries) to standardise and analyse data across four distinguished clinical scenarios. A collaborative model with the Advanced Prostate Cancer Consensus Conference aligns urgent clinical needs with actionable research insights.

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).

SILAC-based quantification reveals modulation of the immunopeptidome in BRAF and MEK inhibitor sensitive and resistant melanoma cells.

Background: The immunopeptidome is constantly monitored by T cells to detect foreign or aberrant HLA peptides. It is highly dynamic and reflects the current cellular state, enabling the immune system to recognize abnormal cellular conditions, such as those present in cancer cells. To precisely determine how changes in cellular processes, such as those induced by drug treatment, affect the immunopeptidome, quantitative immunopeptidomics approaches are essential.

Comprehensive Phenotyping of Extracellular Vesicles in Plasma of Healthy Humans - Insights Into Cellular Origin and Biological Variation.

Despite immense interest in biomarker applications of extracellular vesicles (EVs) from blood, our understanding of circulating EVs under physiological conditions in healthy humans remains limited. Using imaging and multiplex bead-based flow cytometry, we comprehensively quantified circulating EVs with respect to their cellular origin in a large cohort of healthy blood donors. We assessed coefficients of variations to characterize their biological variation and explored demographic, clinical, and lifestyle factors contributing to observed variation.