A Phosphoramidate Prodrug Platform: One-Pot Amine Functionalization of Kinase Inhibitors with Oligoethylene Glycol for Improved Water-Solubility.

Small molecular kinase inhibitors play a key role in modern cancer therapy. Protein kinases are essential mediators in the growth and progression of cancerous tumors, rendering involved kinases an increasingly important target for therapy. However, kinase inhibitors are almost insoluble in water because of their hydrophobic aromatic nature, often lowering their availability and pharmacological efficacy.

Cardiac Health Assessment Using a Wearable Device Before and After Transcatheter Aortic Valve Implantation: Prospective Study.

Background: Due to aging of the population, the prevalence of aortic valve stenosis will increase drastically in upcoming years. Consequently, transcatheter aortic valve implantation (TAVI) procedures will also expand worldwide. Optimal selection of patients who benefit with improved symptoms and prognoses is key, since TAVI is not without its risks.

Nodal Metastases in Stage 3 Head and Neck Melanoma: Patterns of Metastases and Patterns of Failure.

Objective: Stage 3 patients with clinically positive nodal metastasis are treated with therapeutic neck dissection and adjuvant systemic therapy. The aim of our study was to examined the predictability of pre-operative CT as a nodal drainage assessment tool.

Methods: Retrospective review of all patients with clinically positive head and neck cutaneous melanoma between 2010 and 2019.

[An After-Action Review at Municipal Level in the Public Health Service - Lessons Learned at the Corona Unit of the Duesseldorf Public Health Authority after the end of the Covid-19 Pandemic, March 2023].

Background: After-Action Reviews (AARs) represent structured, qualitative evaluations of crisis interventions. Here, we describe the implementation of an AAR to assess the Corona Unit of the Duesseldorf Health Department.

Methods: We employed an after-action review (AAR) using the working group format supplemented by structured interviews with key personnel.

Mixed-method evaluation study of a targeted mass drug administration of long-acting anti-malarials among children aged 3 months to 15 years in the Bossangoa sub-prefecture, Ouham, Central African Republic, during the COVID-19 pandemic.

Background: In 2020, during the COVID-19 pandemic, Médecins Sans Frontières (MSF) initiated three cycles of dihydroartemisin-piperaquine (DHA-PQ) mass drug administration (MDA) for children aged three months to 15 years within Bossangoa sub-prefecture, Central African Republic. Coverage, clinical impact, and community members perspectives were evaluated to inform the use of MDAs in humanitarian emergencies.

Methods: A household survey was undertaken after the MDA focusing on participation, recent illness among eligible children, and household satisfaction.

Design and characterization of protective pan-ebolavirus and pan-filovirus bispecific antibodies.

Monoclonal antibodies (mAbs) are an important class of antiviral therapeutics. MAbs are highly selective, well tolerated, and have long in vivo half-life as well as the capacity to induce immune-mediated virus clearance. Their activities can be further enhanced by integration of their variable fragments (Fvs) into bispecific antibodies (bsAbs), affording simultaneous targeting of multiple epitopes to improve potency and breadth and/or to mitigate against viral escape by a single mutation.

LISA Eligibility and LISA Success in Extremely Preterm Infants: A Single-Center Experience.

Introduction: Less invasive surfactant application (LISA) is associated with improved short-term outcomes in preterm infants. Data on LISA eligibility and success for infants <28 weeks of gestation are lacking.

Methods: Preterm infants <28 weeks of gestation who were born and actively treated in our tertiary care center in 2018 were included in the retrospective study.

The Role of Adjuvant Radiotherapy for the Treatment of Resected High-Risk Stage III Cutaneous Melanoma in the Era of Modern Systemic Therapies.

Modern adjuvant systemic therapies (STs) have revolutionized the management of stage III melanoma. Currently, the role of adjuvant radiotherapy (RT) remains unclear. In this single-center retrospective study, patients with clinically detectable stage III melanoma with high-risk features for lymph node basin (LNB) recurrence and whose tumors were fully resected with complete lymphadenectomy (CLD) between 2010 and 2019 were assessed.

Complete Response to Donor Lymphocyte Infusion for Primary Hemophagocytic Lymphohistiocytosis Relapse after Allogeneic Hematopoietic Cell Transplantation.

Introduction: Primary hemophagocytic lymphohistiocytosis (HLH) is a hyper-inflammatory disorder characterized by dysregulation of inflammatory cells and cytokine signaling. Although first-line treatment consisting of immunosuppressive therapy and allogeneic hematopoietic cell transplantation (HCT) is often curative, it remains unknown whether any effective therapies exist for disease relapse/progression after HCT.

Case Presentation: Here we present a case of a 29-year-old male with primary HLH who failed HLH-94 protocol and subsequently underwent myeloablative HCT.

Minimally invasive management of vital teeth requiring root canal therapy.

The present study aimed to investigate the possible use of a non-instrumentation technique including blue light irradiation for root canal cleaning. Extracted human single rooted teeth were selected. Nine different groups included distilled water, NaOCl, intra-canal heated NaOCl, and NaOCl + EDTA irrigation after either instrumentation or non-instrumentation, and a laser application group following non-instrumentation technique.

Low incidence of acute kidney injury in VLBW infants with restrictive use of mechanical ventilation.

Background: We assessed the incidence of and risk factors for acute kidney injury (AKI) in very low birthweight infants (VLBW) in a center with a specific neonatal management protocol focusing on avoidance of early mechanical ventilation (MV).

Methods: This retrospective single center analysis includes 128 infants born in 2020 with a gestational age ≥ 22 weeks who were screened for AKI using the nKDIGO criteria.

Results: AKI was identified in 25/128 patients (19.

Estimating the cost impact of atrial fibrillation using a prospective cohort study and population-based controls.

Aims: Atrial fibrillation (AF) costs are expected to be substantial, but cost comparisons with the general population are scarce. Using data from the prospective Swiss-AF cohort study and population-based controls, we estimated the impact of AF on direct healthcare costs from the Swiss statutory health insurance perspective.

Methods: Swiss-AF patients, enrolled from 2014 to 2017, had documented, prevalent AF.

Assessment of Comfort during Less Invasive Surfactant Administration in Very Preterm Infants: A Multicenter Study.

Introduction: This study was set up to investigate if and to what extent non-pharmacological analgesia is able to provide comfort to very preterm infants (VPI) during less invasive surfactant administration (LISA).

Methods: This was a prospective non-randomized multicenter observational study performed in level IV NICUs. Inborn VPI with a gestational age between 220/7 and 316/7 weeks, signs of respiratory distress syndrome, and the need for surfactant replacement were included.

Microgels as Platforms for Antibody-Mediated Cytokine Scavenging.

Therapeutic antibodies are the key treatment option for various cytokine-mediated diseases, such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease. However, systemic injection of these antibodies can cause side effects and suppress the immune system. Moreover, clearance of therapeutic antibodies from the blood is limiting their efficacy.

Advanced Radio Frequency Applicators for Thermal Magnetic Resonance Theranostics of Brain Tumors.

Thermal Magnetic Resonance (ThermalMR) is a theranostic concept that combines diagnostic magnetic resonance imaging (MRI) with targeted thermal therapy in the hyperthermia (HT) range using a radiofrequency (RF) applicator in an integrated system. ThermalMR adds a therapeutic dimension to a diagnostic MRI device. Focused, targeted RF heating of deep-seated brain tumors, accurate non-invasive temperature monitoring and high-resolution MRI are specific requirements of ThermalMR that can be addressed with novel concepts in RF applicator design.

A UK-wide survey of healthcare professionals' awareness, knowledge and skills of the impact of food insecurity on eating disorder treatment.

Objective: Food insecurity (FI) is associated with significant adverse effects on health and well-being and increasingly recognised as a global problem. The current study explored the impact of FI on eating disorder (ED) clinical practice in the UK, aiming to assess healthcare professionals' (HCPs) knowledge, skills and views on the topic of FI in their patients.

Design: This study was an exploratory, mixed-methods, descriptive analysis of online survey data collected from ED HCPs in the UK between September and October 2022.

Prophylactic Administration of the Monoclonal Antibody Adintrevimab Protects against SARS-CoV-2 in Hamster and Non-Human Primate Models of COVID-19.

Adintrevimab is a human immunoglobulin G1 monoclonal antibody engineered to have broad neutralization against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and other SARS-like coronaviruses with pandemic potential. In both Syrian golden hamster and rhesus macaque models, prophylactic administration of a single dose of adintrevimab provided protection against SARS-CoV-2/WA1/2020 infection in a dose-dependent manner, as measured by significant reductions in lung viral load and virus-induced lung pathology, and by inhibition of viral replication in the upper and lower respiratory tract.

Patient clusters and cost trajectories in the Swiss Atrial Fibrillation cohort.

Objective: Evidence on long-term costs of atrial fibrillation (AF) and associated factors is scarce. As part of the Swiss-AF prospective cohort study, we aimed to characterise AF costs and their development over time, and to assess specific patient clusters and their cost trajectories.

Methods: Swiss-AF enrolled 2415 patients with variable duration of AF between 2014 and 2017.

Causal analyses with target trial emulation for real-world evidence removed large self-inflicted biases: systematic bias assessment of ovarian cancer treatment effectiveness.

Background And Objectives: Drawing causal conclusions from real-world data (RWD) poses methodological challenges and risk of bias. We aimed to systematically assess the type and impact of potential biases that may occur when analyzing RWD using the case of progressive ovarian cancer.

Methods: We retrospectively compared overall survival with and without second-line chemotherapy (LOT2) using electronic medical records.

Serum dihydrotestosterone levels are associated with adverse myocardial remodeling in patients with severe aortic valve stenosis before and after aortic valve replacement.

Animal studies show a pivotal role of dihydrotestosterone (DHT) in pressure overload-induced myocardial hypertrophy and dysfunction. The aim of our study was to evaluate the role of DHT levels and myocardial hypertrophy and myocardial protein expression in patients with severe aortic valve stenosis (AS). Forty-three patients [median age 68 (41-80) yr] with severe AS and indication for surgical aortic valve replacement (SAVR) were prospectively enrolled.

Effect of transcatheter edge-to-edge repair device position on diastolic hemodynamic parameters: An echocardiography-based simulation study.

Background: Transcatheter edge-to-edge repair (TEER) has developed from innovative technology to an established treatment strategy of mitral regurgitation (MR). The risk of iatrogenic mitral stenosis after TEER is, however, a critical factor in the conflict of interest between maximal reduction of MR and minimal impairment of left ventricular filling. We aim to investigate systematically the impact of device position on the post treatment hemodynamic outcome by involving the patient-specific segmentation of the diseased mitral valve.

Oral Premalignant and Malignant Lesions in Fanconi Anemia Patients.

Objective: There is a lack of data supporting cancer surveillance in pediatric Fanconi Anemia patients. We sought to describe the rates of upper aerodigestive lesions and malignancy in this population to augment current management guidelines.

Methods: A retrospective cohort study of patients with Fanconi Anemia from a quaternary referral center between 2007-2021 was completed for head and neck cancer risk.

Virtual treatment planning in three patients with univentricular physiology using computational fluid dynamics-Pitfalls and strategies.

Background: Uneven hepatic venous blood flow distribution (HFD) to the pulmonary arteries is hypothesized to be responsible for the development of intrapulmonary arteriovenous malformations (PAVM) in patients with univentricular physiology. Thus, achieving uniform distribution of hepatic blood flow is considered favorable. However, no established method for the prediction of the post-interventional hemodynamics currently exists.

Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects.

Growing interest has been seen in using lysergic acid diethylamide (LSD) and psilocybin in psychiatric research and therapy. However, no modern studies have evaluated differences in subjective and autonomic effects of LSD and psilocybin or their similarities and dose equivalence. We used a double-blind, randomized, placebo-controlled, crossover design in 28 healthy subjects (14 women, 14 men) who underwent five 25 h sessions and received placebo, LSD (100 and 200 µg), and psilocybin (15 and 30 mg).