Resistance of HNSCC cell models to pan-FGFR inhibition depends on the EMT phenotype associating with clinical outcome.

Background: Focal adhesion signaling involving receptor tyrosine kinases (RTK) and integrins co-controls cancer cell survival and therapy resistance. However, co-dependencies between these receptors and therapeutically exploitable vulnerabilities remain largely elusive in HPV-negative head and neck squamous cell carcinoma (HNSCC).

Methods: The cytotoxic and radiochemosensitizing potential of targeting 10 RTK and β1 integrin was determined in up to 20 3D matrix-grown HNSCC cell models followed by drug screening and patient-derived organoid validation.

Treatment of Femoropopliteal Artery Disease with Polymer-Coated Drug-Eluting Stent: 5-Year Results of a Prospective, Non-Randomized Study Including the Halo Phenomenon.

Purpose: To investigate the long-term results of the Eluvia drug-eluting stent (DES) implantation for femoropopliteal arterial disease, including the 'halo' phenomenon. Long-term data of DES is scarce. A focal reaction ('halo') following Eluvia DES deployment has been described.

The definition of treatment resistance in anxiety disorders: a Delphi method-based consensus guideline.

Anxiety disorders are very prevalent and often persistent mental disorders, with a considerable rate of treatment resistance which requires regulatory clinical trials of innovative therapeutic interventions. However, an explicit definition of treatment-resistant anxiety disorders (TR-AD) informing such trials is currently lacking. We used a Delphi method-based consensus approach to provide internationally agreed, consistent and clinically useful operational criteria for TR-AD in adults.

Female sex and burden of depressive symptoms predict insufficient response to telemedical treatment in adult attention-deficit/hyperactivity disorder: results from a naturalistic patient cohort during the COVID-19 pandemic.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a chronic neuropsychiatric disorder, that typically manifests itself during childhood and persists in a majority of the affected individuals into adulthood, negatively affecting physical and mental health. Previous studies have shown detrimental effects of the COVID-19 pandemic on mental health in individuals with ADHD. Thus, telemedicine could be a useful tool for optimizing treatment-outcomes in adult ADHD by improving treatment adherence and persistence.

Case report: Beneficial long-term effect of the atrial-flow-regulator device in a pediatric patient with idiopathic pulmonary arterial hypertension and recurring syncope.

We report the long-term effect after successfully implanting an 8 mm Atrial-flow-regulator (AFR) device in a 7-year-old girl with idiopathic pulmonary hypertension with persistent syncope under triple therapy with significant improvement after implantation and absence of any further syncope. Early Implantation of the AFR device (Occlutech, Germany) can be efficient and safe interventional therapy option for pulmonary arterial hypertension with a history of syncope.

mpMRI-targeted biopsy of the prostate in men ≥ 75 years. 7-year report from a high-volume referral center.

Objective: Multiparametric magnetic resonance imaging (mpMRI) -Ultrasound- fusion guided biopsy of the prostate (FBx) is the new gold standard for the detection of prostate cancer. Hallmark studies showing superior detection rates of FBx over randomized biopsies routinely excluded patients≥75 years and information on outcome of FBx on this patient cohort is sparse. As a large referral center, we have performed FBx on a substantial number of patients this age.

Unbiased chemokine receptor screening reveals similar efficacy of lymph node- and tumor-targeted T cell immunotherapy.

Localization is a crucial prerequisite for immune cell function and solid tumors evade immune control by modulating immune cell infiltration into the tumor stroma. Immunosuppressive cells like regulatory T cells are attracted, while cytotoxic CD8 T cells are excluded. Engineering CD8 T cells with chemokine receptors is a potent strategy to turn this mechanism of directed immune cell recruitment against the tumor.

Formation of Amorphous Iron-Calcium Phosphate with High Stability.

Amorphous iron-calcium phosphate (Fe-ACP) plays a vital role in the mechanical properties of teeth of some rodents, which are very hard, but its formation process and synthetic route remain unknown. Here, the synthesis and characterization of an iron-bearing amorphous calcium phosphate in the presence of ammonium iron citrate (AIC) are reported. The iron is distributed homogeneously on the nanometer scale in the resulting particles.

2023 Update on European Atherosclerosis Society Consensus Statement on Homozygous Familial Hypercholesterolaemia: new treatments and clinical guidance.

This 2023 statement updates clinical guidance for homozygous familial hypercholesterolaemia (HoFH), explains the genetic complexity, and provides pragmatic recommendations to address inequities in HoFH care worldwide. Key strengths include updated criteria for the clinical diagnosis of HoFH and the recommendation to prioritize phenotypic features over genotype. Thus, a low-density lipoprotein cholesterol (LDL-C) >10 mmol/L (>400 mg/dL) is suggestive of HoFH and warrants further evaluation.

A transcriptomic pan-cancer signature for survival prognostication and prediction of immunotherapy response based on endothelial senescence.

Background: The microvascular endothelium inherently controls nutrient delivery, oxygen supply, and immune surveillance of malignant tumors, thus representing both biological prerequisite and therapeutic vulnerability in cancer. Recently, cellular senescence emerged as a fundamental characteristic of solid malignancies. In particular, tumor endothelial cells have been reported to acquire a senescence-associated secretory phenotype, which is characterized by a pro-inflammatory transcriptional program, eventually promoting tumor growth and formation of distant metastases.

Radical Prostatectomy without Prior Biopsy in Patients with High Suspicion of Prostate Cancer Based on Multiparametric Magnetic Resonance Imaging and Prostate-Specific Membrane Antigen Positron Emission Tomography: A Prospective Cohort Study.

Modern risk stratification of prostate cancer (PCa) allows for prediction of advanced disease with a high level of certainty. We aimed to evaluate a prospective series of patients undergoing radical prostatectomy without prior biopsy based solely on clinical criteria and imaging results. The patients were divided into three groups.

Development of hemodynamically relevant acquired arterio-venous fistulae in patients with venous malformations.

Background: Venous malformations tend to retain their slow-flow behavior, even in progressive disease or regression following therapy.

Objective: The aim of this study is to analyze the development of acquired hemodynamic relevant arterio-venous fistulae in patients with slow-flow malformations.

Methods: This study is a retrospective analysis based on a consecutive local registry at a tertiary care Interdisciplinary Center for Vascular Anomalies.

Patients with affective disorders profit most from telemedical treatment: Evidence from a naturalistic patient cohort during the COVID-19 pandemic.

Background: During the COVID-19 pandemic telemedicine became essential in maintaining diagnostic procedures and treatment in psychiatry. However, it is still an open question if telemedicine is a feasible treatment option for all groups of psychiatric patients alike. This prospective monocentric observational trial was conducted to assess the general applicability of telemedical treatment in a naturalistic psychiatric outpatient cohort and to identify groups of disorders and clusters of psychopathology that respond particularly well to telemedical treatment considering sociodemographic characteristics and patients' perspectives.

The OTUD6B-LIN28B-MYC axis determines the proliferative state in multiple myeloma.

Deubiquitylases (DUBs) are therapeutically amenable components of the ubiquitin machinery that stabilize substrate proteins. Their inhibition can destabilize oncoproteins that may otherwise be undruggable. Here, we screened for DUB vulnerabilities in multiple myeloma, an incurable malignancy with dependency on the ubiquitin proteasome system and identified OTUD6B as an oncogene that drives the G1/S-transition.

Identification of early predictors for infected necrosis in acute pancreatitis.

Background: In acute pancreatitis, secondary infection of pancreatic necrosis is a complication that mostly necessitates interventional therapy. A reliable prediction of infected necrotizing pancreatitis would enable an early identification of patients at risk, which however, is not possible yet.

Methods: This study aims to identify parameters that are useful for the prediction of infected necrosis and to develop a prediction model for early detection.

Association of C-Terminal Pro-Endothelin-1 with Mortality in the Population-Based KORA F4 Study.

Introduction: Endothelin-1 and its prohormone C-terminal pro-endothelin-1 (CT-proET-1) have been linked to metabolic alterations, inflammatory responses and cardiovascular events in selected study populations. We analyzed the association of CT-proET-1 with cardiovascular events and mortality, carotid intima-media-thickness as surrogate for early atherosclerotic lesions, biomarkers of subclinical inflammation and adipokines in a population-based study.

Methods: The cross-sectional and prospective analyses used data from the KORA F4 study with a median follow-up time of 9.

Treatment of avascular necrosis of the humeral head - Postoperative results and a proposed modification of the classification.

Background: Avascular necrosis of the humeral head after proximal humeral fracture i.e. type 1 fracture sequelae (FS) according to the Boileau classification is a rare, often painful condition and treatment still remains a challenge.

The Impact of Total Knee Replacement with a Customized Cruciate-Retaining Implant Design on Patient-Reported and Functional Outcomes.

Purpose: To treat patients with tricompartimental knee osteoarthritis (OA), a customized cruciate-retaining total knee arthroplasty (CCR-TKA) system can be used, including both individualized instrumentation and implants. The objective of this monocentric cohort study was to analyze patient-reported and functional outcomes in a series of patients implanted with the second generation of this customized implant.

Methods: At our arthroplasty center, we prospectively recruited a cohort of patients with tricompartmental gonarthrosis to be treated with total knee replacement (TKA) using a customized cruciate-retaining (CCR) implant design.

Endothelial Retargeting of AAV9 In Vivo.

Adeno-associated viruses (AAVs) are frequently used for gene transfer and gene editing in vivo, except for endothelial cells, which are remarkably resistant to unmodified AAV-transduction. AAVs are retargeted here toward endothelial cells by coating with second-generation polyamidoamine dendrimers (G2) linked to endothelial-affine peptides (CNN). G2 AAV9-Cre (encoding Cre recombinase) are injected into mTmG-mice or mTmG-pigs, cell-specifically converting red to green fluorescence upon Cre-activity.

MCT1 is a predictive marker for lenalidomide maintenance therapy in multiple myeloma.

Biomarkers that predict response to lenalidomide maintenance therapy in patients with multiple myeloma (MM) have remained elusive. We have shown that immunomodulatory drugs (IMiDs) exert anti-MM activity via destabilization of MCT1 and CD147. In this study, cell samples of 654 patients with MM who received lenalidomide (n = 455), thalidomide (n = 98), or bortezomib (n = 101) maintenance were assessed by gene expression profiling and RNA sequencing, followed by correlation of MCT1 and CD147 expression with data for progression-free survival (PFS) and overall survival (OS).